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Movement Disorders and Neurodegenerative Diseases

Introduction/Background Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death and may involve the cortex, deep gray nuclei, subcortical white matter, brainstem, cerebellum, and spinal cord, along with connections to associated motor pathways in the cortex or extrapyramidal system. Movement disorders can present as either hypokinetic disorders, which include the Parkinsonian syndromes (idiopathic and atypical), or hyperkinetic disorders, which include Huntington disease (HD), prion disease, and neurodegeneration with brain iron accumulation (NBIA). Motor neuron diseases are a related group of syndromes that involve degeneration of upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and is characterized by degeneration of both the upper and lower motor neurons. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult because of the variable and complex features of these conditions, the unusual clinical presentations of some of these patients, and the overlapping symptoms and characteristics. A combination of imaging techniques is often needed for complete evaluation of the patient and to help establish the most likely diagnosis. Initial assessment using structural imaging, with MRI preferred over CT, is helpful not only to look for patterns of atrophy, parenchymal abnormality, or abnormal substance deposition but also to exclude other potential etiologies, including underlying structural or vascular lesions, autoimmune or infectious processes, drug or medication toxicity, or hydrocephalus.

Movement Disorders and Neurodegenerative Diseases. Introduction/Background Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death and may involve the cortex, deep gray nuclei, subcortical white matter, brainstem, cerebellum, and spinal cord, along with connections to associated motor pathways in the cortex or extrapyramidal system. Movement disorders can present as either hypokinetic disorders, which include the Parkinsonian syndromes (idiopathic and atypical), or hyperkinetic disorders, which include Huntington disease (HD), prion disease, and neurodegeneration with brain iron accumulation (NBIA). Motor neuron diseases are a related group of syndromes that involve degeneration of upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and is characterized by degeneration of both the upper and lower motor neurons. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult because of the variable and complex features of these conditions, the unusual clinical presentations of some of these patients, and the overlapping symptoms and characteristics. A combination of imaging techniques is often needed for complete evaluation of the patient and to help establish the most likely diagnosis. Initial assessment using structural imaging, with MRI preferred over CT, is helpful not only to look for patterns of atrophy, parenchymal abnormality, or abnormal substance deposition but also to exclude other potential etiologies, including underlying structural or vascular lesions, autoimmune or infectious processes, drug or medication toxicity, or hydrocephalus.

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More advanced MRI techniques, including diffusion tensor imaging, magnetization transfer ratio imaging, and postprocessing techniques such as quantitative volumetric analysis, may be useful in the evaluation of the microstructural makeup of the brain parenchyma, including the integrity of gray matter, white matter, and their connecting neural pathways. Nuclear medicine studies can be used to evaluate for abnormal patterns of glucose metabolism, buildup of abnormal particles or proteins within neurons, dysfunction or loss of specific categories of neurons, or individual neurochemical deficits. Discussion of Procedures by Variant Variant 1: Rapidly progressive dementia; suspected Creutzfeldt-Jakob disease. Initial imaging. Rapidly progressive dementias (RPDs) are a group of conditions that result in onset of dementia over weeks or months. Although prion diseases, such as Creutzfeldt-Jakob disease (CJD), are the prototypical example of RPD, the differential diagnosis of RPD is robust, including both reversible and irreversible causes. For instance, a study out of the Memory and Aging Center at the University of California, San Francisco, showed that the diagnostic breakdown of RPDs in their patient population was 62% prion disease (all forms), 15% other neurodegenerative diseases, 8% autoimmune, 4% infectious, 2% psychiatric, 2% cancer, 2% toxic-metabolic, 2% vascular, and 4% of undetermined etiology, often representing leukoencephalopathies [1]. Importantly, 17% of their patients had potentially treatable etiologies (50% autoimmune, 13% infectious, 13% psychiatric, 13% cancer, and 10% toxic- metabolic). aMassachusetts General Hospital, Boston, Massachusetts. bResearch Author, Massachusetts General Hospital, Boston, cUT Southwestern Medical Center, Dallas, Texas. Massachusetts. dPanel Chair, Montefiore Medical Center, Bronx, New York. eUC San Diego Health, San Diego, California.

Movement Disorders and Neurodegenerative Diseases. More advanced MRI techniques, including diffusion tensor imaging, magnetization transfer ratio imaging, and postprocessing techniques such as quantitative volumetric analysis, may be useful in the evaluation of the microstructural makeup of the brain parenchyma, including the integrity of gray matter, white matter, and their connecting neural pathways. Nuclear medicine studies can be used to evaluate for abnormal patterns of glucose metabolism, buildup of abnormal particles or proteins within neurons, dysfunction or loss of specific categories of neurons, or individual neurochemical deficits. Discussion of Procedures by Variant Variant 1: Rapidly progressive dementia; suspected Creutzfeldt-Jakob disease. Initial imaging. Rapidly progressive dementias (RPDs) are a group of conditions that result in onset of dementia over weeks or months. Although prion diseases, such as Creutzfeldt-Jakob disease (CJD), are the prototypical example of RPD, the differential diagnosis of RPD is robust, including both reversible and irreversible causes. For instance, a study out of the Memory and Aging Center at the University of California, San Francisco, showed that the diagnostic breakdown of RPDs in their patient population was 62% prion disease (all forms), 15% other neurodegenerative diseases, 8% autoimmune, 4% infectious, 2% psychiatric, 2% cancer, 2% toxic-metabolic, 2% vascular, and 4% of undetermined etiology, often representing leukoencephalopathies [1]. Importantly, 17% of their patients had potentially treatable etiologies (50% autoimmune, 13% infectious, 13% psychiatric, 13% cancer, and 10% toxic- metabolic). aMassachusetts General Hospital, Boston, Massachusetts. bResearch Author, Massachusetts General Hospital, Boston, cUT Southwestern Medical Center, Dallas, Texas. Massachusetts. dPanel Chair, Montefiore Medical Center, Bronx, New York. eUC San Diego Health, San Diego, California.

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fOttawa Hospital Research Institute and the Department of Radiology, The University of Ottawa, Ottawa, Ontario, Canada; Canadian Association of Radiologists. gUniversity of Kansas Medical Center, Kansas City, Kansas. hEinstein Healthcare Network, Philadelphia, Pennsylvania. iUniversity of California San Diego Medical Center, San Diego, California. jOregon Health & Science University, Portland, Oregon. kUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina; American Academy of Neurology. lNorthwestern University Feinberg School of Medicine, Chicago, Neurosurgery Expert. mWalter Reed National Military Medical Center, Bethesda, Maryland. nUIC Medical Center, Chicago, Illinois; Neurosurgery Expert. oColumbia University Medical Center, New York, New York. pSpecialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Movement Disorders and Neurodegenerative Diseases Human prion diseases, also known as transmissible spongiform encephalopathies, represent the most common cause of RPD and are a group of uniformly fatal neurodegenerative disorders associated with accumulation of a misfolded form of the normal prion protein. CJD is the most common human transmissible spongiform encephalopathy and can be either infectious or neurogenetic in nature. Four distinct types are currently recognized: sporadic, familial/genetic (mutations of the prion protein gene), iatrogenic, and variant.

Movement Disorders and Neurodegenerative Diseases. fOttawa Hospital Research Institute and the Department of Radiology, The University of Ottawa, Ottawa, Ontario, Canada; Canadian Association of Radiologists. gUniversity of Kansas Medical Center, Kansas City, Kansas. hEinstein Healthcare Network, Philadelphia, Pennsylvania. iUniversity of California San Diego Medical Center, San Diego, California. jOregon Health & Science University, Portland, Oregon. kUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina; American Academy of Neurology. lNorthwestern University Feinberg School of Medicine, Chicago, Neurosurgery Expert. mWalter Reed National Military Medical Center, Bethesda, Maryland. nUIC Medical Center, Chicago, Illinois; Neurosurgery Expert. oColumbia University Medical Center, New York, New York. pSpecialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Movement Disorders and Neurodegenerative Diseases Human prion diseases, also known as transmissible spongiform encephalopathies, represent the most common cause of RPD and are a group of uniformly fatal neurodegenerative disorders associated with accumulation of a misfolded form of the normal prion protein. CJD is the most common human transmissible spongiform encephalopathy and can be either infectious or neurogenetic in nature. Four distinct types are currently recognized: sporadic, familial/genetic (mutations of the prion protein gene), iatrogenic, and variant.

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Movement Disorders and Neurodegenerative Diseases

Sporadic is the most common type, comprising approximately 85% of the cases, with an annual incidence of 1 to 2 cases/million and peak age of onset from 55 to 75 years [2]. The most common clinical course of sporadic CJD is rapidly worsening dementia, which may be followed by myoclonic jerks and akinetic mutism. Sporadic CJD has a median survival of approximately 5 months [2]. The diagnosis of CJD is multifactorial and includes clinical history, physical examination, electroencephalography, diagnostic imaging, cerebrospinal fluid analysis for real-time quaking-induced conversion (CSF RT-QuIC), 14-3-3, and tau proteins, and PRNP gene sequencing [3]. FDG-PET/CT Brain PET using the tracer fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) may be helpful in the evaluation of a patient with suspected CJD. FDG-PET/CT demonstrates widespread cerebral hypometabolism, even early on in the disease process, which has been noted to correspond with histopathological astrocytosis, neuronal death, and spongiform changes [4,5]. However, the lack of specificity of the findings limit its utility as the initial imaging study. MR Spectroscopy Head Although not indicated as the initial imaging study, MR spectroscopy of the brain may be helpful in providing additional information for more atypical cases of CJD. MR spectroscopy has shown decreased absolute levels of N- acetyl aspartate and ratios of N-acetyl aspartate to other metabolites in a pattern similar to the signal abnormalities seen on T2-weighted and diffusion-weighted imaging, particularly later in the disease course [6,7]. MRI Functional (fMRI) Head There is no relevant literature for functional MRI (fMRI) of the brain in the initial imaging evaluation of a patient with RPD or suspected CJD. MRI Head In patients with RPD or suspected prion disease, MRI of the brain is the optimal imaging modality, with the most sensitive sequences being diffusion weighted and T2-fluid-attenuated inversion recovery (FLAIR) [8,9].

Movement Disorders and Neurodegenerative Diseases. Sporadic is the most common type, comprising approximately 85% of the cases, with an annual incidence of 1 to 2 cases/million and peak age of onset from 55 to 75 years [2]. The most common clinical course of sporadic CJD is rapidly worsening dementia, which may be followed by myoclonic jerks and akinetic mutism. Sporadic CJD has a median survival of approximately 5 months [2]. The diagnosis of CJD is multifactorial and includes clinical history, physical examination, electroencephalography, diagnostic imaging, cerebrospinal fluid analysis for real-time quaking-induced conversion (CSF RT-QuIC), 14-3-3, and tau proteins, and PRNP gene sequencing [3]. FDG-PET/CT Brain PET using the tracer fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) may be helpful in the evaluation of a patient with suspected CJD. FDG-PET/CT demonstrates widespread cerebral hypometabolism, even early on in the disease process, which has been noted to correspond with histopathological astrocytosis, neuronal death, and spongiform changes [4,5]. However, the lack of specificity of the findings limit its utility as the initial imaging study. MR Spectroscopy Head Although not indicated as the initial imaging study, MR spectroscopy of the brain may be helpful in providing additional information for more atypical cases of CJD. MR spectroscopy has shown decreased absolute levels of N- acetyl aspartate and ratios of N-acetyl aspartate to other metabolites in a pattern similar to the signal abnormalities seen on T2-weighted and diffusion-weighted imaging, particularly later in the disease course [6,7]. MRI Functional (fMRI) Head There is no relevant literature for functional MRI (fMRI) of the brain in the initial imaging evaluation of a patient with RPD or suspected CJD. MRI Head In patients with RPD or suspected prion disease, MRI of the brain is the optimal imaging modality, with the most sensitive sequences being diffusion weighted and T2-fluid-attenuated inversion recovery (FLAIR) [8,9].

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Movement Disorders and Neurodegenerative Diseases

Although intravenous (IV) contrast is not specifically needed for the diagnosis of CJD, use of IV contrast can provide important diagnostic information for identifying other known causes of RPD, most notably including autoimmune and inflammatory etiologies. HMPAO SPECT or SPECT/CT Brain Tc-99m hexamethyl-propylamine-oxime (HMPAO) single-photon emission computed tomography (SPECT)/CT of the brain may be helpful in the evaluation of a patient with suspected CJD. Tc-99m HMPAO SPECT/CT demonstrates changes in regional cerebral blood flow that can be seen even before signal changes are apparent on MRI [18,19]. Despite the increased sensitivity for early changes, the lack of specificity of the SPECT findings limits its utility as the initial imaging study. Movement Disorders and Neurodegenerative Diseases Variant 2: Chorea; suspected Huntington disease. Initial imaging. Chorea is characterized by involuntary, flowing, nonstereotyped movements that often possess a writhing quality. HD is the prototypical choreiform disorder and the most common cause of chorea in adults. However, the differential diagnosis of chorea includes a number of additional genetic and neurodegenerative disorders in addition to myriad acquired conditions, such as cerebrovascular, infectious, autoimmune, metabolic, neurodegenerative, and drug-induced syndromes. As such, the diagnostic workup, although often focused on HD, must nonetheless consider these other potential etiologies. HD is a hereditary, autosomal dominant fatal neurodegenerative disorder with complete penetrance characterized by progressive behavioral symptoms, choreoathetosis and/or rigidity, and cognitive dysfunction.

Movement Disorders and Neurodegenerative Diseases. Although intravenous (IV) contrast is not specifically needed for the diagnosis of CJD, use of IV contrast can provide important diagnostic information for identifying other known causes of RPD, most notably including autoimmune and inflammatory etiologies. HMPAO SPECT or SPECT/CT Brain Tc-99m hexamethyl-propylamine-oxime (HMPAO) single-photon emission computed tomography (SPECT)/CT of the brain may be helpful in the evaluation of a patient with suspected CJD. Tc-99m HMPAO SPECT/CT demonstrates changes in regional cerebral blood flow that can be seen even before signal changes are apparent on MRI [18,19]. Despite the increased sensitivity for early changes, the lack of specificity of the SPECT findings limits its utility as the initial imaging study. Movement Disorders and Neurodegenerative Diseases Variant 2: Chorea; suspected Huntington disease. Initial imaging. Chorea is characterized by involuntary, flowing, nonstereotyped movements that often possess a writhing quality. HD is the prototypical choreiform disorder and the most common cause of chorea in adults. However, the differential diagnosis of chorea includes a number of additional genetic and neurodegenerative disorders in addition to myriad acquired conditions, such as cerebrovascular, infectious, autoimmune, metabolic, neurodegenerative, and drug-induced syndromes. As such, the diagnostic workup, although often focused on HD, must nonetheless consider these other potential etiologies. HD is a hereditary, autosomal dominant fatal neurodegenerative disorder with complete penetrance characterized by progressive behavioral symptoms, choreoathetosis and/or rigidity, and cognitive dysfunction.

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Movement Disorders and Neurodegenerative Diseases

The genetic basis of the disease is an abnormally increased number of CAG repeats in the huntingtin gene on the short arm of chromosome 4 (more than 38 repeats used to confirm the diagnosis), often with progressive increase in the length of the repeating sequences in successive generations, resulting in symptoms earlier in life (anticipation). The incidence is ~10/100,000, with average age of onset between 35 to 45 years and symptom progression until death within 15 to 20 years of onset [20]. Abnormal aggregates of the huntingtin protein accumulate in the brain and impair the function of a variety of transcription factors, ultimately leading to the loss of GABAergic medium spiny neurons, particularly in the striatum and cortex [20]. Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice. Patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD in concert with initial imaging, given that imaging may be normal early on in the disease course. CT Head CT is not the preferred imaging modality for suspected HD because of its limited soft-tissue characterization when compared with MRI. However, CT may be useful for excluding other etiologies of chorea, such as cerebrovascular disease or acute infectious or inflammatory processes. Contrast is typically not indicated when CT of the head is being utilized in the initial evaluation of chorea. As with MRI, CT imaging may be normal early in HD, with the progressive and disproportionate volume loss of the neostriatum only becoming apparent on later imaging studies. FDG-PET/CT Brain There is insufficient evidence to support the use of FDG-PET/CT of the brain in the initial evaluation of a patient with chorea or suspected HD. Among known HD gene carriers, FDG-PET may help demonstrate early neostriatal dysfunction (manifested as hypometabolism), which can precede neuronal loss detectable on structural imaging [21].

Movement Disorders and Neurodegenerative Diseases. The genetic basis of the disease is an abnormally increased number of CAG repeats in the huntingtin gene on the short arm of chromosome 4 (more than 38 repeats used to confirm the diagnosis), often with progressive increase in the length of the repeating sequences in successive generations, resulting in symptoms earlier in life (anticipation). The incidence is ~10/100,000, with average age of onset between 35 to 45 years and symptom progression until death within 15 to 20 years of onset [20]. Abnormal aggregates of the huntingtin protein accumulate in the brain and impair the function of a variety of transcription factors, ultimately leading to the loss of GABAergic medium spiny neurons, particularly in the striatum and cortex [20]. Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice. Patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD in concert with initial imaging, given that imaging may be normal early on in the disease course. CT Head CT is not the preferred imaging modality for suspected HD because of its limited soft-tissue characterization when compared with MRI. However, CT may be useful for excluding other etiologies of chorea, such as cerebrovascular disease or acute infectious or inflammatory processes. Contrast is typically not indicated when CT of the head is being utilized in the initial evaluation of chorea. As with MRI, CT imaging may be normal early in HD, with the progressive and disproportionate volume loss of the neostriatum only becoming apparent on later imaging studies. FDG-PET/CT Brain There is insufficient evidence to support the use of FDG-PET/CT of the brain in the initial evaluation of a patient with chorea or suspected HD. Among known HD gene carriers, FDG-PET may help demonstrate early neostriatal dysfunction (manifested as hypometabolism), which can precede neuronal loss detectable on structural imaging [21].

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Movement Disorders and Neurodegenerative Diseases

Note that FDG hypometabolism has also been noted to involve the frontal and temporal lobe cortices in both HD patients and asymptomatic carriers [21]. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with chorea or suspected HD. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with chorea or suspected HD. MRI Head MRI of the brain without IV contrast is the optimal imaging modality in patients with chorea or suspected HD, although it is often normal early on in the disease course of HD. Although often unnecessary, IV contrast may offer limited utility in certain circumstances when infectious or inflammatory conditions are among the differential diagnoses being considered. MRI findings of HD include progressive marked degeneration and atrophy of the neostriatum, particularly the head of the caudate nuclei (with enlargement of the frontal horns of the lateral ventricles), with associated abnormal signal (either T2 hyperintensity or hypointensity) [22-26]. Additionally, abnormal T2 hyperintensity may be seen in the putamen and can help to highlight more subtle changes of atrophy [22-25]. Although disproportionate volume loss of the neostriatum is the hallmark of HD, voxel-based morphometry has shown that patients with symptomatic and asymptomatic HD have significant reduction in volume in almost all brain structures when compared with normal age-matched controls [27,28]. Movement Disorders and Neurodegenerative Diseases HMPAO SPECT or SPECT/CT Brain There is insufficient evidence to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial evaluation of a patient with chorea or suspected HD. Variant 3: Parkinsonian syndromes. Initial imaging.

Movement Disorders and Neurodegenerative Diseases. Note that FDG hypometabolism has also been noted to involve the frontal and temporal lobe cortices in both HD patients and asymptomatic carriers [21]. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with chorea or suspected HD. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with chorea or suspected HD. MRI Head MRI of the brain without IV contrast is the optimal imaging modality in patients with chorea or suspected HD, although it is often normal early on in the disease course of HD. Although often unnecessary, IV contrast may offer limited utility in certain circumstances when infectious or inflammatory conditions are among the differential diagnoses being considered. MRI findings of HD include progressive marked degeneration and atrophy of the neostriatum, particularly the head of the caudate nuclei (with enlargement of the frontal horns of the lateral ventricles), with associated abnormal signal (either T2 hyperintensity or hypointensity) [22-26]. Additionally, abnormal T2 hyperintensity may be seen in the putamen and can help to highlight more subtle changes of atrophy [22-25]. Although disproportionate volume loss of the neostriatum is the hallmark of HD, voxel-based morphometry has shown that patients with symptomatic and asymptomatic HD have significant reduction in volume in almost all brain structures when compared with normal age-matched controls [27,28]. Movement Disorders and Neurodegenerative Diseases HMPAO SPECT or SPECT/CT Brain There is insufficient evidence to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial evaluation of a patient with chorea or suspected HD. Variant 3: Parkinsonian syndromes. Initial imaging.

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Parkinsonian syndromes are a group of movement disorders characterized by motor symptoms of tremor, rigidity, postural instability, and bradykinesia. Parkinson disease (PD) is the most common cause of Parkinsonism, with other common causes, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism, with a number of rarer conditions also within the differential. PD is a neurodegenerative disease and movement disorder characterized by progressive degeneration of the dopaminergic neurons in the substantia nigra/striatum. It is the most common Parkinsonism syndrome, with an annual incidence estimated at 10 to 18/100,000 in the total population and peak age of onset between 60 to 70 years [29]. PD, also known as idiopathic Parkinsonism, is a synucleinopathy with neuronal deposits of Lewy bodies (predominantly composed of alpha-synuclein and ubiquitin). Initially, Lewy body deposition is seen involving the medulla oblongata, pontine tegmentum, and olfactory system, with later involvement of the substantia nigra and other deep gray nuclei (corresponding to the onset of clinical symptoms), and finally with deposition of Lewy bodies in the cortex. The clinical presentation of PD is characterized by resting tremor, bradykinesia, and rigidity and is related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum. The estimated interval between initial loss of dopaminergic neurons and the appearance of symptoms is approximately 5 years (after approximately 40% to 50% of the dopaminergic neurons in the substantia nigra have been lost) [29]. Other features include autonomic dysfunction, behavioral changes, and dementia.

Movement Disorders and Neurodegenerative Diseases. Parkinsonian syndromes are a group of movement disorders characterized by motor symptoms of tremor, rigidity, postural instability, and bradykinesia. Parkinson disease (PD) is the most common cause of Parkinsonism, with other common causes, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism, with a number of rarer conditions also within the differential. PD is a neurodegenerative disease and movement disorder characterized by progressive degeneration of the dopaminergic neurons in the substantia nigra/striatum. It is the most common Parkinsonism syndrome, with an annual incidence estimated at 10 to 18/100,000 in the total population and peak age of onset between 60 to 70 years [29]. PD, also known as idiopathic Parkinsonism, is a synucleinopathy with neuronal deposits of Lewy bodies (predominantly composed of alpha-synuclein and ubiquitin). Initially, Lewy body deposition is seen involving the medulla oblongata, pontine tegmentum, and olfactory system, with later involvement of the substantia nigra and other deep gray nuclei (corresponding to the onset of clinical symptoms), and finally with deposition of Lewy bodies in the cortex. The clinical presentation of PD is characterized by resting tremor, bradykinesia, and rigidity and is related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum. The estimated interval between initial loss of dopaminergic neurons and the appearance of symptoms is approximately 5 years (after approximately 40% to 50% of the dopaminergic neurons in the substantia nigra have been lost) [29]. Other features include autonomic dysfunction, behavioral changes, and dementia.

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MSA can be subdivided into three distinct clinical subtypes: MSA-P (striatonigral degeneration), in which extrapyramidal/parkinsonian features predominate, MSA-C (olivopontocerebellar atrophy), in which ataxia and cerebellar symptoms predominate, and less commonly, MSA-A (Shy-Drager syndrome), in which autonomic dysfunction predominates. The majority of cases of MSA exhibit Parkinsonian symptoms at some stage of the disease, with cerebellar ataxia, pyramidal signs, and dysautonomia (including urinary incontinence) frequently reported. The typical onset is 55 to 65 years of age with a mean disease duration of almost 6 years [30]. PSP, also known as Steele-Richardson-Olszewski syndrome, is the most common atypical Parkinsonism with a prevalence of around 5/100,000 [30]. Patients classically present in the sixth or seventh decade (mean age of onset at 63) with a lurching gait and axial dystonia, manifested as unexplained falls [30]. Ocular symptoms, including blurred vision and slow saccades, can be seen early in the disease; however, the classic finding of vertical supranuclear gaze palsy is usually only seen later in the course of the disease. Correctly diagnosing a Parkinsonian syndrome on clinical features alone can be quite challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms. CT Head CT is not the preferred imaging modality for the workup of Parkinsonian syndromes because of its limited soft- tissue characterization when compared with MRI. Nonetheless, CT imaging can effectively demonstrate the patterns of regional volume loss characteristic of MSA, CBD, or PSP, as described in the MRI section. CT findings are Movement Disorders and Neurodegenerative Diseases nonspecific for PD but can help to exclude focal or regional atrophy, underlying structural lesions, or vascular disease that might signal an alternative diagnosis. Contrast is typically not indicated.

Movement Disorders and Neurodegenerative Diseases. MSA can be subdivided into three distinct clinical subtypes: MSA-P (striatonigral degeneration), in which extrapyramidal/parkinsonian features predominate, MSA-C (olivopontocerebellar atrophy), in which ataxia and cerebellar symptoms predominate, and less commonly, MSA-A (Shy-Drager syndrome), in which autonomic dysfunction predominates. The majority of cases of MSA exhibit Parkinsonian symptoms at some stage of the disease, with cerebellar ataxia, pyramidal signs, and dysautonomia (including urinary incontinence) frequently reported. The typical onset is 55 to 65 years of age with a mean disease duration of almost 6 years [30]. PSP, also known as Steele-Richardson-Olszewski syndrome, is the most common atypical Parkinsonism with a prevalence of around 5/100,000 [30]. Patients classically present in the sixth or seventh decade (mean age of onset at 63) with a lurching gait and axial dystonia, manifested as unexplained falls [30]. Ocular symptoms, including blurred vision and slow saccades, can be seen early in the disease; however, the classic finding of vertical supranuclear gaze palsy is usually only seen later in the course of the disease. Correctly diagnosing a Parkinsonian syndrome on clinical features alone can be quite challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms. CT Head CT is not the preferred imaging modality for the workup of Parkinsonian syndromes because of its limited soft- tissue characterization when compared with MRI. Nonetheless, CT imaging can effectively demonstrate the patterns of regional volume loss characteristic of MSA, CBD, or PSP, as described in the MRI section. CT findings are Movement Disorders and Neurodegenerative Diseases nonspecific for PD but can help to exclude focal or regional atrophy, underlying structural lesions, or vascular disease that might signal an alternative diagnosis. Contrast is typically not indicated.

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Amyloid PET/CT Brain There is no relevant literature to support the use of amyloid PET/CT in the initial imaging evaluation of a patient with Parkinsonian syndrome. FDG-PET/CT Brain Despite widespread use of FDG-PET/CT in clinical practice and extensive research, there is still very limited good- quality evidence for the use of FDG-PET/CT in Parkinsonian syndromes. FDG-PET is useful for discriminating PSP from idiopathic PD on the presence of a typical metabolic pattern for PSP, which is not present in PD. PSP is characterized by hypometabolism in the medial frontal and anterior cingulated cortices, striatum, and midbrain. FDG-PET may therefore be useful in early stages of the disease when the clinical diagnosis is less certain. In PD- related cognitive decline, FDG-PET have a typical pattern of hypometabolism mainly affecting the posterior cortical areas [31]. Ioflupane SPECT/CT Brain I-123 ioflupane SPECT/CT is a valuable test used to differentiate Parkinsonian syndromes (PD, MSA, PSP, CBD) from essential tremor and drug-induced tremor, demonstrating abnormality early in the disease course compared with anatomic imaging such as standard CT or MRI [32]. A normal I-123 ioflupane SPECT/CT essentially excludes Parkinsonian syndromes. I-123 ioflupane binds to the dopamine transporters and can be used to demonstrate the loss of presynaptic dopaminergic neurons in PD. It can demonstrate decreased radiotracer uptake in the striatum, usually in a posterior to anterior direction from the putamen to the caudate nuclei. I-123 ioflupane SPECT would demonstrate abnormal patterns of dopaminergic depletion for patients with PD, MSA, PSP, and CBD [33-39]. Note is made of a steady emergence of new nuclear medicine tracers, which are yet to be approved by the US FDA for clinical use, designed to target the postsynaptic dopamine receptors (D1 and D2), including 11C-raclopride-PET and I-123-iodobenzamide SPECT scans.

Movement Disorders and Neurodegenerative Diseases. Amyloid PET/CT Brain There is no relevant literature to support the use of amyloid PET/CT in the initial imaging evaluation of a patient with Parkinsonian syndrome. FDG-PET/CT Brain Despite widespread use of FDG-PET/CT in clinical practice and extensive research, there is still very limited good- quality evidence for the use of FDG-PET/CT in Parkinsonian syndromes. FDG-PET is useful for discriminating PSP from idiopathic PD on the presence of a typical metabolic pattern for PSP, which is not present in PD. PSP is characterized by hypometabolism in the medial frontal and anterior cingulated cortices, striatum, and midbrain. FDG-PET may therefore be useful in early stages of the disease when the clinical diagnosis is less certain. In PD- related cognitive decline, FDG-PET have a typical pattern of hypometabolism mainly affecting the posterior cortical areas [31]. Ioflupane SPECT/CT Brain I-123 ioflupane SPECT/CT is a valuable test used to differentiate Parkinsonian syndromes (PD, MSA, PSP, CBD) from essential tremor and drug-induced tremor, demonstrating abnormality early in the disease course compared with anatomic imaging such as standard CT or MRI [32]. A normal I-123 ioflupane SPECT/CT essentially excludes Parkinsonian syndromes. I-123 ioflupane binds to the dopamine transporters and can be used to demonstrate the loss of presynaptic dopaminergic neurons in PD. It can demonstrate decreased radiotracer uptake in the striatum, usually in a posterior to anterior direction from the putamen to the caudate nuclei. I-123 ioflupane SPECT would demonstrate abnormal patterns of dopaminergic depletion for patients with PD, MSA, PSP, and CBD [33-39]. Note is made of a steady emergence of new nuclear medicine tracers, which are yet to be approved by the US FDA for clinical use, designed to target the postsynaptic dopamine receptors (D1 and D2), including 11C-raclopride-PET and I-123-iodobenzamide SPECT scans.

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Movement Disorders and Neurodegenerative Diseases

These radiotracers compete with endogenous dopamine to bind to the postsynaptic D2 receptors and show increased uptake within the putamen and, to a lesser extent, the caudate in patients with PD when compared with normal controls. The role of these tracers in the evaluation of patients with suspected PD may grow in the future. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. MRI Head In patients with Parkinsonian syndrome, MRI of the brain without IV contrast is the optimal imaging modality because of its soft-tissue characterization and sensitivity to iron deposition [40-44]. Although IV contrast is not typically needed for the evaluation of Parkinsonian syndromes, it may be helpful for excluding additional differential considerations. Movement Disorders and Neurodegenerative Diseases In patients with CBD, MRI shows asymmetric atrophy of the frontal and parietal lobes, typically contralateral to the more affected side, as well as the striatum [42,57-60]. Faint T2/FLAIR hyperintensity can also be seen in the subcortical white matter in the atrophic regions, likely related to neuronal loss and gliosis [42,57,59,60]. In contrast to conventional MRI, advanced MRI may offer more meaningful and earlier diagnostic opportunities for patients with suspected PD and other Parkinsonian syndromes. For instance, 7-T MRI has shown promise in accurately differentiating healthy subjects from PD patients because it can demonstrate increased susceptibility in the substantia nigra and thinning of the pars compacta with blurring of the borders between the substantia nigra and red nucleus [66].

Movement Disorders and Neurodegenerative Diseases. These radiotracers compete with endogenous dopamine to bind to the postsynaptic D2 receptors and show increased uptake within the putamen and, to a lesser extent, the caudate in patients with PD when compared with normal controls. The role of these tracers in the evaluation of patients with suspected PD may grow in the future. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. MRI Head In patients with Parkinsonian syndrome, MRI of the brain without IV contrast is the optimal imaging modality because of its soft-tissue characterization and sensitivity to iron deposition [40-44]. Although IV contrast is not typically needed for the evaluation of Parkinsonian syndromes, it may be helpful for excluding additional differential considerations. Movement Disorders and Neurodegenerative Diseases In patients with CBD, MRI shows asymmetric atrophy of the frontal and parietal lobes, typically contralateral to the more affected side, as well as the striatum [42,57-60]. Faint T2/FLAIR hyperintensity can also be seen in the subcortical white matter in the atrophic regions, likely related to neuronal loss and gliosis [42,57,59,60]. In contrast to conventional MRI, advanced MRI may offer more meaningful and earlier diagnostic opportunities for patients with suspected PD and other Parkinsonian syndromes. For instance, 7-T MRI has shown promise in accurately differentiating healthy subjects from PD patients because it can demonstrate increased susceptibility in the substantia nigra and thinning of the pars compacta with blurring of the borders between the substantia nigra and red nucleus [66].

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Movement Disorders and Neurodegenerative Diseases

Additionally, recent studies in patients with PD have shown decreased magnetization transfer ratio and functional anisotropy within the substantia nigra (particularly caudally) when compared with normal controls [67]. HMPAO SPECT or SPECT/CT Brain There is no relevant literature to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. Variant 4: Suspected neurodegeneration with brain iron accumulation. Initial imaging. Although some iron accumulation within the basal ganglia and dentate nuclei can normally be seen as we age, NBIA is a distinct group of conditions characterized by excess iron deposition in the basal ganglia with progressive neuronal degeneration. Four subtypes have been defined, the most common of which is NBIA type 1, also known as pantothenate kinase-associated neurodegeneration and formerly known as Hallervorden-Spatz disease. NBIA type 1 is a rare autosomal recessive disease (annual incidence of 1/1,000,000), which classically presents in the first decade with slowly progressive gait disturbances, dystonia, dysarthria, spasticity, and pyramidal tract signs [68]. FDG-PET/CT Brain There is no relevant literature to support the use of FDG-PET/CT of the brain in the initial imaging evaluation of a patient with suspected NBIA. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with suspected NBIA. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with suspected NBIA. Movement Disorders and Neurodegenerative Diseases associated enhancement or restricted diffusion in these areas of iron deposition, although diffusion tensor imaging has shown increased fractional anisotropy in both the globus pallidus and substantia nigra in patients with NBIA [74].

Movement Disorders and Neurodegenerative Diseases. Additionally, recent studies in patients with PD have shown decreased magnetization transfer ratio and functional anisotropy within the substantia nigra (particularly caudally) when compared with normal controls [67]. HMPAO SPECT or SPECT/CT Brain There is no relevant literature to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial imaging evaluation of a patient with Parkinsonian syndrome. Variant 4: Suspected neurodegeneration with brain iron accumulation. Initial imaging. Although some iron accumulation within the basal ganglia and dentate nuclei can normally be seen as we age, NBIA is a distinct group of conditions characterized by excess iron deposition in the basal ganglia with progressive neuronal degeneration. Four subtypes have been defined, the most common of which is NBIA type 1, also known as pantothenate kinase-associated neurodegeneration and formerly known as Hallervorden-Spatz disease. NBIA type 1 is a rare autosomal recessive disease (annual incidence of 1/1,000,000), which classically presents in the first decade with slowly progressive gait disturbances, dystonia, dysarthria, spasticity, and pyramidal tract signs [68]. FDG-PET/CT Brain There is no relevant literature to support the use of FDG-PET/CT of the brain in the initial imaging evaluation of a patient with suspected NBIA. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with suspected NBIA. MRI Functional (fMRI) Head There is no relevant literature to support the use of fMRI of the brain in the initial imaging evaluation of a patient with suspected NBIA. Movement Disorders and Neurodegenerative Diseases associated enhancement or restricted diffusion in these areas of iron deposition, although diffusion tensor imaging has shown increased fractional anisotropy in both the globus pallidus and substantia nigra in patients with NBIA [74].

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Movement Disorders and Neurodegenerative Diseases

The white matter and cortex are spared in NBIA type 1. MRI may also be helpful in distinguishing the other less common subtypes of NBIA [69,71,72]. IV contrast may be useful in the initial evaluation of suspected NBIA, considering the presence of limited inflammatory etiologies among the differential diagnoses. HMPAO SPECT or SPECT/CT Brain There is no relevant literature to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial imaging evaluation of a patient with suspected NBIA. Variant 5: Suspected motor neuron disease. Initial imaging. ALS is a progressive neurodegenerative disorder characterized by degeneration of the upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts and is the most common motor neuron disease, representing ~85% of all cases [75]. The majority of cases are sporadic (85% to 90%) with an overall annual incidence of 1 to 2/100,000 and a median survival of 3 to 4 years after symptom onset [75]. Typically, patients present with hypertonicity and hyperreflexia (upper motor neuron degeneration) and muscle fasciculations, weakness, and atrophy (lower motor neuron degeneration). Electromyography and nerve conduction velocity are key tests in diagnosing ALS, with imaging relied upon mainly to exclude other conditions with similar clinical presentations rather than confirm or facilitate the diagnosis of ALS. CT Spine CT of the spine (either with, without, or without and with IV contrast) is not useful in making the diagnosis of ALS because of its limited soft-tissue characterization. FDG-PET/CT Brain There is no relevant literature to support the use of FDG-PET/CT of the brain in the initial imaging evaluation of a patient with suspected motor neuron disease. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with suspected motor neuron disease.

Movement Disorders and Neurodegenerative Diseases. The white matter and cortex are spared in NBIA type 1. MRI may also be helpful in distinguishing the other less common subtypes of NBIA [69,71,72]. IV contrast may be useful in the initial evaluation of suspected NBIA, considering the presence of limited inflammatory etiologies among the differential diagnoses. HMPAO SPECT or SPECT/CT Brain There is no relevant literature to support the use of Tc-99m HMPAO SPECT/CT of the brain in the initial imaging evaluation of a patient with suspected NBIA. Variant 5: Suspected motor neuron disease. Initial imaging. ALS is a progressive neurodegenerative disorder characterized by degeneration of the upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts and is the most common motor neuron disease, representing ~85% of all cases [75]. The majority of cases are sporadic (85% to 90%) with an overall annual incidence of 1 to 2/100,000 and a median survival of 3 to 4 years after symptom onset [75]. Typically, patients present with hypertonicity and hyperreflexia (upper motor neuron degeneration) and muscle fasciculations, weakness, and atrophy (lower motor neuron degeneration). Electromyography and nerve conduction velocity are key tests in diagnosing ALS, with imaging relied upon mainly to exclude other conditions with similar clinical presentations rather than confirm or facilitate the diagnosis of ALS. CT Spine CT of the spine (either with, without, or without and with IV contrast) is not useful in making the diagnosis of ALS because of its limited soft-tissue characterization. FDG-PET/CT Brain There is no relevant literature to support the use of FDG-PET/CT of the brain in the initial imaging evaluation of a patient with suspected motor neuron disease. MR Spectroscopy Head There is no relevant literature to support the use of MR spectroscopy of the brain in the initial imaging evaluation of a patient with suspected motor neuron disease.

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acrac_3193973_0

Staging and Post Therapy Assessment of Head and Neck Cancer

Introduction/Background Head and neck cancer comprises a heterogeneous group of malignancies that together represents the seventh most common cancer worldwide and ninth most common cancer in the United States [1]. Several anatomic sites are encompassed, including the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity, and salivary glands. There is heterogeneity in histopathology; although, the majority of the cancers are squamous cell carcinomas. Head and neck cancers are clearly associated with alcohol and tobacco consumption, with human papillomavirus (HPV) and Epstein-Barr virus (EBV) linked to oropharynx cancer and nasopharynx cancer, respectively [2]. Special Imaging Considerations For the purposes of distinguishing between CT and CT angiography (CTA), ACR Appropriateness Criteria topics use the definition in the ACR-NASCI-SIR-SPR Practice Parameter for the Performance and Interpretation of Body Computed Tomography Angiography (CTA) [7]: Reprint requests to: [email protected] Assessment of Head and Neck Cancer All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with IV contrast also include timing issues and reconstructions/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. PET/CT imaging of head and neck cancers is frequently extended beyond the skull-base to the vertex to ensure inclusion of the entirety of the tumor. Squamous cell carcinoma of the head and neck preferentially spreads to regional lymph nodes, with nodal disease conferring decreased survival rates. Presence of distant metastatic disease at the time of diagnosis has been reported in 10% to 18% of patients [10], and its occurrence is directly linked to the stage of tumor [11-13].

Staging and Post Therapy Assessment of Head and Neck Cancer. Introduction/Background Head and neck cancer comprises a heterogeneous group of malignancies that together represents the seventh most common cancer worldwide and ninth most common cancer in the United States [1]. Several anatomic sites are encompassed, including the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity, and salivary glands. There is heterogeneity in histopathology; although, the majority of the cancers are squamous cell carcinomas. Head and neck cancers are clearly associated with alcohol and tobacco consumption, with human papillomavirus (HPV) and Epstein-Barr virus (EBV) linked to oropharynx cancer and nasopharynx cancer, respectively [2]. Special Imaging Considerations For the purposes of distinguishing between CT and CT angiography (CTA), ACR Appropriateness Criteria topics use the definition in the ACR-NASCI-SIR-SPR Practice Parameter for the Performance and Interpretation of Body Computed Tomography Angiography (CTA) [7]: Reprint requests to: [email protected] Assessment of Head and Neck Cancer All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with IV contrast also include timing issues and reconstructions/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. PET/CT imaging of head and neck cancers is frequently extended beyond the skull-base to the vertex to ensure inclusion of the entirety of the tumor. Squamous cell carcinoma of the head and neck preferentially spreads to regional lymph nodes, with nodal disease conferring decreased survival rates. Presence of distant metastatic disease at the time of diagnosis has been reported in 10% to 18% of patients [10], and its occurrence is directly linked to the stage of tumor [11-13].

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Staging and Post Therapy Assessment of Head and Neck Cancer

The lungs are the most frequent site for distant metastatic disease, and when other sites of distant metastatic disease are present, pulmonary nodules are almost always present [11,14]. Skeletal metastases, most frequently of ribs and vertebrae, confers morbidity, including pain and symptoms of hypercalcemia [11]. Detection of distant metastatic disease at initial staging is crucial because it will change prognosis and typically change the management strategy toward more systemic options. An increased rate of second primary malignancy and concurrent lung malignancy among head and neck cancer patients has been linked to the intake of tobacco and alcohol [15,16]. Cancer of unknown primary of the head and neck represents 1% to 4% of patients with malignant tumors of the head and neck and is diagnosed after identification of metastatic cervical lymphadenopathy in which no primary is evident [9]. When the pathology is consistent with HPV-related squamous cell carcinoma, the primary site is presumed to localize to the oropharynx. Initial staging should include every attempt at identifying the site of primary because this impacts prognosis and treatment planning, and it is important to document the extent of nodal disease in the neck. Despite multimodality imaging and endoscopic evaluation, 2% to 9% of primary sites remain undetected [17]. Radiography Chest Chest radiography (CXR) is not useful for the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease when compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% when compared to chest CT [11].

Staging and Post Therapy Assessment of Head and Neck Cancer. The lungs are the most frequent site for distant metastatic disease, and when other sites of distant metastatic disease are present, pulmonary nodules are almost always present [11,14]. Skeletal metastases, most frequently of ribs and vertebrae, confers morbidity, including pain and symptoms of hypercalcemia [11]. Detection of distant metastatic disease at initial staging is crucial because it will change prognosis and typically change the management strategy toward more systemic options. An increased rate of second primary malignancy and concurrent lung malignancy among head and neck cancer patients has been linked to the intake of tobacco and alcohol [15,16]. Cancer of unknown primary of the head and neck represents 1% to 4% of patients with malignant tumors of the head and neck and is diagnosed after identification of metastatic cervical lymphadenopathy in which no primary is evident [9]. When the pathology is consistent with HPV-related squamous cell carcinoma, the primary site is presumed to localize to the oropharynx. Initial staging should include every attempt at identifying the site of primary because this impacts prognosis and treatment planning, and it is important to document the extent of nodal disease in the neck. Despite multimodality imaging and endoscopic evaluation, 2% to 9% of primary sites remain undetected [17]. Radiography Chest Chest radiography (CXR) is not useful for the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease when compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% when compared to chest CT [11].

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Staging and Post Therapy Assessment of Head and Neck Cancer

The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because metastatic pulmonary nodules detectable on CXR tend to be associated with late-stage disease when it is not as amenable to treatment [18]. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because metastatic pulmonary nodules detectable on CXR tend to be associated with late-stage disease when it is not as amenable to treatment [18]. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck.

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acrac_3193973_3

Staging and Post Therapy Assessment of Head and Neck Cancer

CT maxillofacial may not include the primary site in the hypopharynx or larynx and typically will not include the entire neck soft tissues, making it inadequate for the staging of regional lymphadenopathy. Assessment of Head and Neck Cancer CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. Contrast-enhanced CT (CECT) of the neck has the advantage of detailed anatomic delineation of the primary tumor site, aiding in the correct T staging as well as providing regional nodal staging of the neck. In oral cavity cancer, CECT has been shown to provide an accurate estimation of depth of invasion and tumor thickness in lesions >5 mm when compared to histopathologic findings, an important upstaging feature of oral cavity cancers [22-25], performing similar to MRI [26]. CT imaging also gives excellent delineation of osseous anatomy, including bony destruction by tumor with high sensitivity and specificity for osseous [27-29] and cartilage involvement [30], which are upstaging features. When compared to MRI, CECT of the neck performs similar or slightly better in correctly identifying osseous involvement [29,31,32].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT maxillofacial may not include the primary site in the hypopharynx or larynx and typically will not include the entire neck soft tissues, making it inadequate for the staging of regional lymphadenopathy. Assessment of Head and Neck Cancer CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. Contrast-enhanced CT (CECT) of the neck has the advantage of detailed anatomic delineation of the primary tumor site, aiding in the correct T staging as well as providing regional nodal staging of the neck. In oral cavity cancer, CECT has been shown to provide an accurate estimation of depth of invasion and tumor thickness in lesions >5 mm when compared to histopathologic findings, an important upstaging feature of oral cavity cancers [22-25], performing similar to MRI [26]. CT imaging also gives excellent delineation of osseous anatomy, including bony destruction by tumor with high sensitivity and specificity for osseous [27-29] and cartilage involvement [30], which are upstaging features. When compared to MRI, CECT of the neck performs similar or slightly better in correctly identifying osseous involvement [29,31,32].

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acrac_3193973_4

Staging and Post Therapy Assessment of Head and Neck Cancer

Conversely, MRI has been reported to have higher sensitivity than CT in detecting cartilage invasion but similar specificity, an upstaging feature of larynx and hypopharyngeal malignancies [33,34]. In comparing the ability of CECT to fluorine-18-2- fluoro-2-deoxy-D-glucose (FDG)-PET/CT to accurately diagnose regional nodal disease, CECT performs similar or slightly inferior to FDG-PET/CT [35-39]. Contrast enhancement is imperative in order to correctly identify and outline the primary site, and distinguishing it from the surrounding normal soft tissues. The puffed-cheek technique, consisting of requesting that the patient inflate their cheeks with pursed lips while undergoing CT examination, allows for a greater delineation of oral cavity tumors, particularly those along the gingiva and buccal mucosa. The maneuver allows for the separation of tumor from normal mucosa and provides a clearer picture of the size and extent of disease [40]. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease with involvement encroaching on the carotid arteries [41].

Staging and Post Therapy Assessment of Head and Neck Cancer. Conversely, MRI has been reported to have higher sensitivity than CT in detecting cartilage invasion but similar specificity, an upstaging feature of larynx and hypopharyngeal malignancies [33,34]. In comparing the ability of CECT to fluorine-18-2- fluoro-2-deoxy-D-glucose (FDG)-PET/CT to accurately diagnose regional nodal disease, CECT performs similar or slightly inferior to FDG-PET/CT [35-39]. Contrast enhancement is imperative in order to correctly identify and outline the primary site, and distinguishing it from the surrounding normal soft tissues. The puffed-cheek technique, consisting of requesting that the patient inflate their cheeks with pursed lips while undergoing CT examination, allows for a greater delineation of oral cavity tumors, particularly those along the gingiva and buccal mucosa. The maneuver allows for the separation of tumor from normal mucosa and provides a clearer picture of the size and extent of disease [40]. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease with involvement encroaching on the carotid arteries [41].

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acrac_3193973_5

Staging and Post Therapy Assessment of Head and Neck Cancer

FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site, identification of regional nodal disease, and distant metastases. FDG-PET/CT is recommended by the National Comprehensive Cancer Network for stage III and IV cancer [42]. FDG-PET/CT alone is not considered sufficient for initial staging because it may not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging [43,44]. FDG-PET/CT will typically be used in conjunction with CECT or MRI of the neck. One advantage of FDG-PET/CT is that the whole body can be imaged, and FDG-PET is more sensitive in the detection of distant metastasis and synchronous tumors over radiography, CT, and MRI [10,42,45]. Although FDG-PET/CT is sensitive (72%-96%), there are some variations in the reported specificity rate for cervical nodal metastases [36,45-48], likely due to reactive lymph nodes resulting in false-positive findings on PET. Assessment of Head and Neck Cancer The utility of FDG-PET in lower-stage cancer is more controversial. There are conflicting results when evaluating the ability of FDG-PET/CT to accurately detect occult nodal disease in clinical node-negative cancer. A range of sensitivities and specificities and contradictory results when compared to CECT and MRI are reported, either performing similar to or outperforming these modalities [35-39]. This controversy led to the American College of Radiology Imaging Network 6685 multicenter trial, which conclusively demonstrated that FDG-PET/CT confers a high negative predictive value (NPV) of 87% (visual analysis) and 94% (standardized uptake value max analysis) for lymph node metastasis in N0 cancer, with moderate to substantial reader agreement and 99% for distant metastatic disease [37,42,49]. In addition, it changed surgical management in the 20% of the study population.

Staging and Post Therapy Assessment of Head and Neck Cancer. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site, identification of regional nodal disease, and distant metastases. FDG-PET/CT is recommended by the National Comprehensive Cancer Network for stage III and IV cancer [42]. FDG-PET/CT alone is not considered sufficient for initial staging because it may not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging [43,44]. FDG-PET/CT will typically be used in conjunction with CECT or MRI of the neck. One advantage of FDG-PET/CT is that the whole body can be imaged, and FDG-PET is more sensitive in the detection of distant metastasis and synchronous tumors over radiography, CT, and MRI [10,42,45]. Although FDG-PET/CT is sensitive (72%-96%), there are some variations in the reported specificity rate for cervical nodal metastases [36,45-48], likely due to reactive lymph nodes resulting in false-positive findings on PET. Assessment of Head and Neck Cancer The utility of FDG-PET in lower-stage cancer is more controversial. There are conflicting results when evaluating the ability of FDG-PET/CT to accurately detect occult nodal disease in clinical node-negative cancer. A range of sensitivities and specificities and contradictory results when compared to CECT and MRI are reported, either performing similar to or outperforming these modalities [35-39]. This controversy led to the American College of Radiology Imaging Network 6685 multicenter trial, which conclusively demonstrated that FDG-PET/CT confers a high negative predictive value (NPV) of 87% (visual analysis) and 94% (standardized uptake value max analysis) for lymph node metastasis in N0 cancer, with moderate to substantial reader agreement and 99% for distant metastatic disease [37,42,49]. In addition, it changed surgical management in the 20% of the study population.

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Staging and Post Therapy Assessment of Head and Neck Cancer

FDG-PET/CT is considered standard of care for the evaluation of metastatic cervical adenopathy with no primary evident on clinical examination or other imaging modalities [17]. FDG-PET/CT has been demonstrated to be superior in detecting the primary site (69%) at the time of diagnosis versus 15% on CECT alone and 41% when using the combination of CECT and MRI [17]. FDG-PET/CT has been demonstrated to have a higher diagnostic accuracy than MRI and CT for the detection of small tumors [50,51]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of head and neck tumors, with FDG-PET/MRI performing similar to FDG-PET/CT [42,44,52-57]. One study found that FDG-PET/MRI outperforms FDG-PET/CT in the diagnosis of primary site in the evaluation of unknown primary [58]. MRA Neck With IV Contrast There is no relevant literature to support the use of MR angiography (MRA) with IV contrast of the neck in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA of the neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA of the neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. FDG-PET/CT is considered standard of care for the evaluation of metastatic cervical adenopathy with no primary evident on clinical examination or other imaging modalities [17]. FDG-PET/CT has been demonstrated to be superior in detecting the primary site (69%) at the time of diagnosis versus 15% on CECT alone and 41% when using the combination of CECT and MRI [17]. FDG-PET/CT has been demonstrated to have a higher diagnostic accuracy than MRI and CT for the detection of small tumors [50,51]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of head and neck tumors, with FDG-PET/MRI performing similar to FDG-PET/CT [42,44,52-57]. One study found that FDG-PET/MRI outperforms FDG-PET/CT in the diagnosis of primary site in the evaluation of unknown primary [58]. MRA Neck With IV Contrast There is no relevant literature to support the use of MR angiography (MRA) with IV contrast of the neck in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA of the neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA of the neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck.

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MRI Head With IV Contrast There is no relevant literature to support the use of MRI of the head with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI of the head without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue resolution compared to CT and with this an improved ability to delineate the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for surgical planning. The superior soft tissue contrast resolution allows for improved Assessment of Head and Neck Cancer detection of perineural spread of disease. MRI is less susceptible to metal artifact and may perform better in the oral cavity where there can be significant artifact from dental implants. Conversely, MRI offers decreased spatial resolution compared to CT and is more susceptible to motion artifact due to longer scan times.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI Head With IV Contrast There is no relevant literature to support the use of MRI of the head with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI of the head without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue resolution compared to CT and with this an improved ability to delineate the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for surgical planning. The superior soft tissue contrast resolution allows for improved Assessment of Head and Neck Cancer detection of perineural spread of disease. MRI is less susceptible to metal artifact and may perform better in the oral cavity where there can be significant artifact from dental implants. Conversely, MRI offers decreased spatial resolution compared to CT and is more susceptible to motion artifact due to longer scan times.

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When compared to CECT, MRI neck performs similarly in correctly identifying osseous involvement, with MRI better delineating marrow involvement and CT better depicting erosive cortical change [29,31]. MRI and CT achieve similar capability in the detection of extranodal extension of tumor [59] and depth of invasion in oral tongue cancer [26]. Conversely, when compared to CT, MRI has been reported to have a higher sensitivity but a similar specificity in detecting cartilage invasion, an upstaging feature of larynx and hypopharyngeal malignancies [33,34]. Accuracy of local staging of larynx cancer has been reported to be higher with MRI than CECT (80% versus 70%) [60]. MRI performs similarly to CECT in the detection of nodal metastatic disease with sensitivity ranging from 64% to 92% and specificity from 40% to 81% [61]. Most studies show superiority of FDG-PET/CT compared to MRI for detection of nodal disease [61]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary tumor, distinguishing it from surrounding normal soft tissues. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to specifically support the use of MRI orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning.

Staging and Post Therapy Assessment of Head and Neck Cancer. When compared to CECT, MRI neck performs similarly in correctly identifying osseous involvement, with MRI better delineating marrow involvement and CT better depicting erosive cortical change [29,31]. MRI and CT achieve similar capability in the detection of extranodal extension of tumor [59] and depth of invasion in oral tongue cancer [26]. Conversely, when compared to CT, MRI has been reported to have a higher sensitivity but a similar specificity in detecting cartilage invasion, an upstaging feature of larynx and hypopharyngeal malignancies [33,34]. Accuracy of local staging of larynx cancer has been reported to be higher with MRI than CECT (80% versus 70%) [60]. MRI performs similarly to CECT in the detection of nodal metastatic disease with sensitivity ranging from 64% to 92% and specificity from 40% to 81% [61]. Most studies show superiority of FDG-PET/CT compared to MRI for detection of nodal disease [61]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary tumor, distinguishing it from surrounding normal soft tissues. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to specifically support the use of MRI orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning.

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However, noncontrast MR sequences are routinely used to identify the primary tumor, define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the sinuses in the initial staging of suspected or diagnosed cancer the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. US Neck Ultrasound (US) can be a useful adjunct to cross-sectional imaging, in particular for nodal staging of head and neck cancer. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging following neck dissection [62]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. US is not typically used to stage the primary site, although there is a growing body of research demonstrating the utility of US in delineating primary tumors of the oral cavity, oropharynx, hypopharynx, and larynx. Recent studies comparing transcervical US to CT and FDG-PET/CT and US to CT and MRI demonstrated increased accuracy of US in detecting primary site in patients with HPV-related oropharyngeal carcinoma [51,66]. Intraoral US of the tongue has been proven to be accurate in the evaluation of depth of invasion, which is an important staging feature of oral cavity cancers that has prognostic and therapeutic implications [67,68]. A few studies demonstrated the utility of US in the delineation of oral cavity primary in patients in which the tumor was obscured by metal on cross- sectional imaging [25,69].

Staging and Post Therapy Assessment of Head and Neck Cancer. However, noncontrast MR sequences are routinely used to identify the primary tumor, define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the sinuses in the initial staging of suspected or diagnosed cancer the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. US Neck Ultrasound (US) can be a useful adjunct to cross-sectional imaging, in particular for nodal staging of head and neck cancer. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging following neck dissection [62]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. US is not typically used to stage the primary site, although there is a growing body of research demonstrating the utility of US in delineating primary tumors of the oral cavity, oropharynx, hypopharynx, and larynx. Recent studies comparing transcervical US to CT and FDG-PET/CT and US to CT and MRI demonstrated increased accuracy of US in detecting primary site in patients with HPV-related oropharyngeal carcinoma [51,66]. Intraoral US of the tongue has been proven to be accurate in the evaluation of depth of invasion, which is an important staging feature of oral cavity cancers that has prognostic and therapeutic implications [67,68]. A few studies demonstrated the utility of US in the delineation of oral cavity primary in patients in which the tumor was obscured by metal on cross- sectional imaging [25,69].

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In a study comparing US to CECT for the staging of hypopharyngeal cancer, US failed to detect significant findings seen on CT in 22.5% of cases, although US proved accurate in diagnosing cartilage invasion and vocal cord immobility [70]. Conversely, US was found to approach the accuracy of CECT and MRI in the evaluation of larynx primary site with 80% to 83.3% accuracy in delineating the correct T stage versus 88.8% for CECT and 76.7% for MRI [71-73]. Variant 2: Suspected or diagnosed nasopharynx cancer or EBV-associated unknown primary of the head and neck. Initial staging. Nasopharyngeal carcinoma (NPC) is a relatively rare cancer with a worldwide incidence of 0.5 to 1.0/100,00 per year [74], with higher endemic rates in Southeast Asian countries. NPC arising from the nasopharyngeal epithelium represents at least 70% of tumors of the nasopharynx and, for this reason, will be the focus of the upcoming discussion [74]. Other histologies, including nasopharyngeal lymphoma, constitute a minority of nasopharyngeal malignancies and will therefore not be emphasized in this section. The World Health Organization classifies Assessment of Head and Neck Cancer squamous cell carcinoma of the nasopharynx based on histopathologic features into keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, which is further subdivided into differentiated and undifferentiated type, and basaloid squamous cell carcinoma. Alcohol and smoking are associated with NPC, with the strongest link to keratinizing squamous cell carcinoma, which carries the worst prognosis [75]. Almost all nonkeratinizing squamous cell carcinoma and basaloid squamous cell carcinomas are associated with EBV infection with a slightly weaker association of EBV to keratinizing squamous cell carcinoma [18]. The undifferentiated subtype is most common in endemic areas, representing as many as 93% of all cases [75].

Staging and Post Therapy Assessment of Head and Neck Cancer. In a study comparing US to CECT for the staging of hypopharyngeal cancer, US failed to detect significant findings seen on CT in 22.5% of cases, although US proved accurate in diagnosing cartilage invasion and vocal cord immobility [70]. Conversely, US was found to approach the accuracy of CECT and MRI in the evaluation of larynx primary site with 80% to 83.3% accuracy in delineating the correct T stage versus 88.8% for CECT and 76.7% for MRI [71-73]. Variant 2: Suspected or diagnosed nasopharynx cancer or EBV-associated unknown primary of the head and neck. Initial staging. Nasopharyngeal carcinoma (NPC) is a relatively rare cancer with a worldwide incidence of 0.5 to 1.0/100,00 per year [74], with higher endemic rates in Southeast Asian countries. NPC arising from the nasopharyngeal epithelium represents at least 70% of tumors of the nasopharynx and, for this reason, will be the focus of the upcoming discussion [74]. Other histologies, including nasopharyngeal lymphoma, constitute a minority of nasopharyngeal malignancies and will therefore not be emphasized in this section. The World Health Organization classifies Assessment of Head and Neck Cancer squamous cell carcinoma of the nasopharynx based on histopathologic features into keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, which is further subdivided into differentiated and undifferentiated type, and basaloid squamous cell carcinoma. Alcohol and smoking are associated with NPC, with the strongest link to keratinizing squamous cell carcinoma, which carries the worst prognosis [75]. Almost all nonkeratinizing squamous cell carcinoma and basaloid squamous cell carcinomas are associated with EBV infection with a slightly weaker association of EBV to keratinizing squamous cell carcinoma [18]. The undifferentiated subtype is most common in endemic areas, representing as many as 93% of all cases [75].

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In addition to the epithelial tumors of the nasopharynx, cancers of the nasopharynx can also originate from minor salivary glands, most commonly adenoid cystic and mucoepidermoid carcinomas. Cancer of unknown primary of the head and neck represents 1% to 4% of patients with malignant tumors of the head and neck and is diagnosed after identification of metastatic lymphadenopathy in which no primary is evident [9]. When the pathology is positive for EBV, the primary site is presumed to localize to the nasopharynx. Patients often present with a neck mass or findings secondary to local invasion of structures, with symptoms such as epistaxis or nasal blockage, hearing loss secondary to Eustachian tube dysfunction, or findings of cranial nerve involvement [76]. Advanced local disease in NPC is common at presentation with skull base involvement in 25% to 35% of cases and intracranial invasion in 3% to 12% of cases [77]. Accurate staging of the primary tumor includes evaluation of involvement of osseous structures, including the skull base and extension into the adjacent soft issues such as the pterygoid musculature, which are upstaging features. NPC has a high rate of regional nodal disease at presentation, including retropharyngeal and cervical lymph nodes, with as many as 75.8% of patients presenting with nodal mass at initial presentation [78]. Identification of nodal disease is critical in staging because it confers decreased survival, and the presence of nodal disease or advanced local disease is associated with increased risk for distant metastases. NPC also has a relatively high rate of distant metastases compared with other head and neck cancers, and distant metastases are found in 5% to 11% of patients at the time of diagnosis. The most common sites of metastasis are bone (20%), lung (13%), and liver (9%) [79,80].

Staging and Post Therapy Assessment of Head and Neck Cancer. In addition to the epithelial tumors of the nasopharynx, cancers of the nasopharynx can also originate from minor salivary glands, most commonly adenoid cystic and mucoepidermoid carcinomas. Cancer of unknown primary of the head and neck represents 1% to 4% of patients with malignant tumors of the head and neck and is diagnosed after identification of metastatic lymphadenopathy in which no primary is evident [9]. When the pathology is positive for EBV, the primary site is presumed to localize to the nasopharynx. Patients often present with a neck mass or findings secondary to local invasion of structures, with symptoms such as epistaxis or nasal blockage, hearing loss secondary to Eustachian tube dysfunction, or findings of cranial nerve involvement [76]. Advanced local disease in NPC is common at presentation with skull base involvement in 25% to 35% of cases and intracranial invasion in 3% to 12% of cases [77]. Accurate staging of the primary tumor includes evaluation of involvement of osseous structures, including the skull base and extension into the adjacent soft issues such as the pterygoid musculature, which are upstaging features. NPC has a high rate of regional nodal disease at presentation, including retropharyngeal and cervical lymph nodes, with as many as 75.8% of patients presenting with nodal mass at initial presentation [78]. Identification of nodal disease is critical in staging because it confers decreased survival, and the presence of nodal disease or advanced local disease is associated with increased risk for distant metastases. NPC also has a relatively high rate of distant metastases compared with other head and neck cancers, and distant metastases are found in 5% to 11% of patients at the time of diagnosis. The most common sites of metastasis are bone (20%), lung (13%), and liver (9%) [79,80].

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Detection of distant metastatic disease at initial staging is crucial because it will change prognosis and typically convert the management strategy toward more systemic options. Radiography Chest CXR is not considered the imaging modality of choice for evaluation of pulmonary metastatic disease in suspected or diagnosed nasopharynx cancer or EBV-associated unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported to be as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis, because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastases and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the staging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be useful in patients with NPC associated with smoking and alcohol intake, given the risk for synchronous lung cancer.

Staging and Post Therapy Assessment of Head and Neck Cancer. Detection of distant metastatic disease at initial staging is crucial because it will change prognosis and typically convert the management strategy toward more systemic options. Radiography Chest CXR is not considered the imaging modality of choice for evaluation of pulmonary metastatic disease in suspected or diagnosed nasopharynx cancer or EBV-associated unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported to be as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis, because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastases and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the staging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be useful in patients with NPC associated with smoking and alcohol intake, given the risk for synchronous lung cancer.

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The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. Assessment of Head and Neck Cancer CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the staging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be useful in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in delineation of soft tissue extension of skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast.

Staging and Post Therapy Assessment of Head and Neck Cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. Assessment of Head and Neck Cancer CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the staging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be useful in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in delineation of soft tissue extension of skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast.

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CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in treated cancer of nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Although CT head may be able to delineate skull base and intracranial involvement, inclusion of the neck is useful to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT maxillofacial with IV contrast may provide sufficient evaluation of the primary site and can be particularly helpful for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed nasopharynx cancer or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in treated cancer of nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Although CT head may be able to delineate skull base and intracranial involvement, inclusion of the neck is useful to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT maxillofacial with IV contrast may provide sufficient evaluation of the primary site and can be particularly helpful for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed nasopharynx cancer or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck.

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CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG- PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of nasopharyngeal tumors as well as regional nodal staging. CT imaging is excellent for the delineation of osseous anatomy and in the detection of subtle cortical erosion. However, because of improved soft tissue contrast resolution, MRI is considered superior to CT in outlining the extent of soft tissue disease, including involvement of neighboring structures, findings that are necessary for the correct T staging of disease. Although MRI has largely surpassed the use of CECT for NPC staging with high sensitivity and specificity for correctly identifying the primary site [81,82], CT Assessment of Head and Neck Cancer has a complementary role in staging and is often used for radiation planning purposes. FDG-PET/CT is considered the imaging modality of choice for detecting cervical and distant metastases in patients with NPC [83] and demonstrates high sensitivity and specificity, when compared to CECT, in detecting nodal metastasis [82,84,85]. When CT is performed, IV contrast is recommended to better outline the soft tissue extent of the primary tumor.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG- PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of nasopharyngeal tumors as well as regional nodal staging. CT imaging is excellent for the delineation of osseous anatomy and in the detection of subtle cortical erosion. However, because of improved soft tissue contrast resolution, MRI is considered superior to CT in outlining the extent of soft tissue disease, including involvement of neighboring structures, findings that are necessary for the correct T staging of disease. Although MRI has largely surpassed the use of CECT for NPC staging with high sensitivity and specificity for correctly identifying the primary site [81,82], CT Assessment of Head and Neck Cancer has a complementary role in staging and is often used for radiation planning purposes. FDG-PET/CT is considered the imaging modality of choice for detecting cervical and distant metastases in patients with NPC [83] and demonstrates high sensitivity and specificity, when compared to CECT, in detecting nodal metastasis [82,84,85]. When CT is performed, IV contrast is recommended to better outline the soft tissue extent of the primary tumor.

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CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT neck without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA neck with IV contrast for the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. FDG-PET/CT alone is not considered sufficient in the initial staging of NPC because it does not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging, including a tendency to underestimate the involvement of the skull base, brain, cavernous sinuses, and orbits compared to MRI [74,85,86]. FDG-PET/CT has also been found to have a higher false-negative rate than MRI for detection of retropharyngeal nodal disease [82]. FDG-PET/CT is useful for detecting cervical and distant metastases in patients with NPC [83] and demonstrates high sensitivity and specificity, when compared to CECT or MRI alone, in detecting nodal metastasis [82,84,85].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated cancer of unknown primary of the head and neck. CT neck without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA neck with IV contrast for the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. FDG-PET/CT alone is not considered sufficient in the initial staging of NPC because it does not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging, including a tendency to underestimate the involvement of the skull base, brain, cavernous sinuses, and orbits compared to MRI [74,85,86]. FDG-PET/CT has also been found to have a higher false-negative rate than MRI for detection of retropharyngeal nodal disease [82]. FDG-PET/CT is useful for detecting cervical and distant metastases in patients with NPC [83] and demonstrates high sensitivity and specificity, when compared to CECT or MRI alone, in detecting nodal metastasis [82,84,85].

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Staging and Post Therapy Assessment of Head and Neck Cancer

Furthermore FDG-PET/CT has a high sensitivity and accuracy in detecting distant metastases, including osseous and pulmonary metastases [82,87,88], the most common sites for distant metastatic disease in NPC. Studies have shown that for early stage (I-II) disease, FDG-PET/CT may not confer additional benefit [74]. FDG-PET/CT is useful for the evaluation of metastatic cervical adenopathy with no primary evident on clinical examination or other imaging [17]. Comparison between FDG-PET/CT, CECT neck alone, or in combination with IV contrast-enhanced MRI, showed FDG-PET to be superior in detecting the primary site (69%) of the time versus 15% on CT alone and 41% when using the combination of CT and MRI [17]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of NPC with similar results to FDG PET/CT [53,86]. A study found that this imaging modality may provide more accurate staging than the combination of FDG-PET/CT and MRI [89]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. Furthermore FDG-PET/CT has a high sensitivity and accuracy in detecting distant metastases, including osseous and pulmonary metastases [82,87,88], the most common sites for distant metastatic disease in NPC. Studies have shown that for early stage (I-II) disease, FDG-PET/CT may not confer additional benefit [74]. FDG-PET/CT is useful for the evaluation of metastatic cervical adenopathy with no primary evident on clinical examination or other imaging [17]. Comparison between FDG-PET/CT, CECT neck alone, or in combination with IV contrast-enhanced MRI, showed FDG-PET to be superior in detecting the primary site (69%) of the time versus 15% on CT alone and 41% when using the combination of CT and MRI [17]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of NPC with similar results to FDG PET/CT [53,86]. A study found that this imaging modality may provide more accurate staging than the combination of FDG-PET/CT and MRI [89]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck.

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Staging and Post Therapy Assessment of Head and Neck Cancer

Assessment of Head and Neck Cancer MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. The coverage of an MRI of the head and MRI sequences tailored for assessment of the brain may be insufficient to completely evaluate the primary site in the nasopharynx and will not include regional nodal staging. MRI head without and with IV contrast may be used to further delineate advanced intracranial extension of disease if it is suspected based on clinical examination or other imaging modalities. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI of the orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of the tumor at the primary site. MRI provides high sensitivity and specificity for correctly identifying the primary site [81,82], and the superior soft tissue contrast resolution allows for accurate evaluation of local extent of disease, including identification of subtle skull base marrow involvement, intracranial extension, and detection of perineural spread of disease [90,91]. Furthermore, MRI has been found to correctly identify the site of the tumor in endoscopically occult disease [81,92].

Staging and Post Therapy Assessment of Head and Neck Cancer. Assessment of Head and Neck Cancer MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. The coverage of an MRI of the head and MRI sequences tailored for assessment of the brain may be insufficient to completely evaluate the primary site in the nasopharynx and will not include regional nodal staging. MRI head without and with IV contrast may be used to further delineate advanced intracranial extension of disease if it is suspected based on clinical examination or other imaging modalities. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI of the orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of the tumor at the primary site. MRI provides high sensitivity and specificity for correctly identifying the primary site [81,82], and the superior soft tissue contrast resolution allows for accurate evaluation of local extent of disease, including identification of subtle skull base marrow involvement, intracranial extension, and detection of perineural spread of disease [90,91]. Furthermore, MRI has been found to correctly identify the site of the tumor in endoscopically occult disease [81,92].

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Staging and Post Therapy Assessment of Head and Neck Cancer

MRI has demonstrated a mildly lower sensitivity than FDG-PET/CT in detecting cervical nodal disease [82] but is considered superior in detecting retropharyngeal lymph node metastases [74,82]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding soft tissues. This includes the evaluation of tumor size and local extent of disease, including the invasion of surrounding structures. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning. However, noncontrast MR sequences are routinely used to identify the primary tumor and define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the sinuses in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. US Neck US can be a useful adjunct to cross-sectional imaging, in particular for nodal staging in NPC or EBV-associated unknown primary of the head and neck. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging following neck dissection [62].

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI has demonstrated a mildly lower sensitivity than FDG-PET/CT in detecting cervical nodal disease [82] but is considered superior in detecting retropharyngeal lymph node metastases [74,82]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding soft tissues. This includes the evaluation of tumor size and local extent of disease, including the invasion of surrounding structures. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning. However, noncontrast MR sequences are routinely used to identify the primary tumor and define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the sinuses in the initial staging of suspected or diagnosed NPC or EBV-associated unknown primary of the head and neck. US Neck US can be a useful adjunct to cross-sectional imaging, in particular for nodal staging in NPC or EBV-associated unknown primary of the head and neck. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging following neck dissection [62].

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Staging and Post Therapy Assessment of Head and Neck Cancer

A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator dependent nature of this technique. US alone has been shown to be very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. One study has shown similar accuracy of US to MRI in the detection of the primary site in patients with suspected NPC, which suggests that US may have a role as a screening tool [93]. Variant 3: Suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Initial staging. Sinonasal tumors are rare neoplasms and make up only 3% of head and neck carcinomas and approximately 0.5% to 1% of all malignancies [94,95]. Despite its relatively small anatomic confine, a wide range of malignancies can arise from the sinonasal cavity. Neoplasms can be classified as either epithelial or nonepithelial. Of the epithelial tumors, squamous cell carcinoma is by far the most common malignancy and accounts for up to 80% of sinonasal cancers and, for this reason, will be the focus of the upcoming discussion. The maxillary sinus and nasal cavity Assessment of Head and Neck Cancer constitute the most common sites of origin [95,96]. The most frequent nonepithelial malignancies are malignant lymphomas, which comprise approximately 6% to 13% of extranodal lymphomas of the head and neck [95]. Additional malignancies encountered in this region include adenocarcinoma, salivary gland tumors, olfactory neuroblastoma, and melanoma, among others. Olfactory neuroblastomas are rare and constitute only around 2% of sinonasal tumors. They arise from the olfactory epithelium found at the roof of the ethmoid sinuses, cribriform plate, upper nasal septum, and superior turbinates. Because of its site of origin, olfactory neuroblastomas have a propensity to invade the anterior cranial fossa [96,97].

Staging and Post Therapy Assessment of Head and Neck Cancer. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator dependent nature of this technique. US alone has been shown to be very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. One study has shown similar accuracy of US to MRI in the detection of the primary site in patients with suspected NPC, which suggests that US may have a role as a screening tool [93]. Variant 3: Suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Initial staging. Sinonasal tumors are rare neoplasms and make up only 3% of head and neck carcinomas and approximately 0.5% to 1% of all malignancies [94,95]. Despite its relatively small anatomic confine, a wide range of malignancies can arise from the sinonasal cavity. Neoplasms can be classified as either epithelial or nonepithelial. Of the epithelial tumors, squamous cell carcinoma is by far the most common malignancy and accounts for up to 80% of sinonasal cancers and, for this reason, will be the focus of the upcoming discussion. The maxillary sinus and nasal cavity Assessment of Head and Neck Cancer constitute the most common sites of origin [95,96]. The most frequent nonepithelial malignancies are malignant lymphomas, which comprise approximately 6% to 13% of extranodal lymphomas of the head and neck [95]. Additional malignancies encountered in this region include adenocarcinoma, salivary gland tumors, olfactory neuroblastoma, and melanoma, among others. Olfactory neuroblastomas are rare and constitute only around 2% of sinonasal tumors. They arise from the olfactory epithelium found at the roof of the ethmoid sinuses, cribriform plate, upper nasal septum, and superior turbinates. Because of its site of origin, olfactory neuroblastomas have a propensity to invade the anterior cranial fossa [96,97].

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Staging and Post Therapy Assessment of Head and Neck Cancer

Paranasal sinus cancers differ from other squamous cell cancers of the upper aerodigestive tract in their risk factors, such as occupational exposures (ie, adenocarcinoma linked to wood dust exposure), and in the presence of premalignant lesions such as Schneiderian papillomas [98]. Patients most commonly present with nasal obstruction, rhinorrhea, and/or epistaxis. Symptoms can oftentimes be unilateral and can frequently be overlooked because of their overlap with more common benign etiologies [98]. Furthermore, pain is generally absent until there is associated skull base or nerve involvement. For these reasons, sinonasal tumors are commonly large at presentation [55,98]. Additionally, the sinonasal cavity has close proximity to complex skull base anatomy, the orbits, and the pterygopalatine fossae, which facilitates early disease extension. Radiography Chest CXR is not useful in the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis, because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. A heavy smoking history may also be a separate indication for CT chest imaging at initial staging, because tobacco use is a risk factor not only for squamous cell carcinoma of the head and neck but also for primary lung cancer [15,20].

Staging and Post Therapy Assessment of Head and Neck Cancer. Paranasal sinus cancers differ from other squamous cell cancers of the upper aerodigestive tract in their risk factors, such as occupational exposures (ie, adenocarcinoma linked to wood dust exposure), and in the presence of premalignant lesions such as Schneiderian papillomas [98]. Patients most commonly present with nasal obstruction, rhinorrhea, and/or epistaxis. Symptoms can oftentimes be unilateral and can frequently be overlooked because of their overlap with more common benign etiologies [98]. Furthermore, pain is generally absent until there is associated skull base or nerve involvement. For these reasons, sinonasal tumors are commonly large at presentation [55,98]. Additionally, the sinonasal cavity has close proximity to complex skull base anatomy, the orbits, and the pterygopalatine fossae, which facilitates early disease extension. Radiography Chest CXR is not useful in the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis, because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. A heavy smoking history may also be a separate indication for CT chest imaging at initial staging, because tobacco use is a risk factor not only for squamous cell carcinoma of the head and neck but also for primary lung cancer [15,20].

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Studies have shown that 7% to 14% of patients have as second lung primary at the time of initial staging of head and neck squamous cell carcinoma [15,21]. This patient population may also qualify for annual chest imaging as per the U.S. Preventative Services Task Force guidelines for annual lung cancer screening with low- dose CT in well-defined groups of high-risk smokers [20]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft-tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. A heavy smoking history may also be a separate indication for CT chest imaging at initial staging, because tobacco use is a risk factor not only for squamous cell carcinoma of the head and neck but also for primary lung cancer [15,20]. Studies have shown that 7% to 14% of patients have as second lung primary at the time of initial staging of head and neck squamous cell carcinoma [15,21]. This patient population may also qualify for annual chest Assessment of Head and Neck Cancer imaging as per the U.S. Preventative Services Task Force guidelines for annual lung cancer screening with low- dose CT in well-defined groups of high-risk smokers [20]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease.

Staging and Post Therapy Assessment of Head and Neck Cancer. Studies have shown that 7% to 14% of patients have as second lung primary at the time of initial staging of head and neck squamous cell carcinoma [15,21]. This patient population may also qualify for annual chest imaging as per the U.S. Preventative Services Task Force guidelines for annual lung cancer screening with low- dose CT in well-defined groups of high-risk smokers [20]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft-tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. A heavy smoking history may also be a separate indication for CT chest imaging at initial staging, because tobacco use is a risk factor not only for squamous cell carcinoma of the head and neck but also for primary lung cancer [15,20]. Studies have shown that 7% to 14% of patients have as second lung primary at the time of initial staging of head and neck squamous cell carcinoma [15,21]. This patient population may also qualify for annual chest Assessment of Head and Neck Cancer imaging as per the U.S. Preventative Services Task Force guidelines for annual lung cancer screening with low- dose CT in well-defined groups of high-risk smokers [20]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease.

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Staging and Post Therapy Assessment of Head and Neck Cancer

Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT of the head with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT head may provide sufficient coverage for the anatomic evaluation of the primary tumor site in the sinonasal cavity; however, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Head Without IV Contrast There is no relevant literature to support the use of CT of the head without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT maxillofacial may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity.

Staging and Post Therapy Assessment of Head and Neck Cancer. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT of the head with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT head may provide sufficient coverage for the anatomic evaluation of the primary tumor site in the sinonasal cavity; however, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Head Without IV Contrast There is no relevant literature to support the use of CT of the head without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT maxillofacial may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity.

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CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of sinonasal tumors as well as regional nodal staging. CT provides excellent delineation of the sinonasal skeleton and is superior to MRI in the depiction of osseous anatomy [96]. The presence of skull base foraminal widening, which can be detected on thin-section CT and reconstructions, may alert to perineural tumor spread [96], and the precise determination of bony destruction or remodeling may prove useful in the characterization of slow-growing versus aggressive sinonasal tumors [99]. MRI is considered superior to CT in the delineation of the soft tissue extent of disease, including involvement of neighboring structures, findings that are necessary for the correct T staging of disease. Contrast-enhanced imaging is imperative to correctly identify and outline the primary tumor, distinguishing it from the surrounding normal soft tissues.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site, in particular for the evaluation of osseous erosion. CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of sinonasal tumors as well as regional nodal staging. CT provides excellent delineation of the sinonasal skeleton and is superior to MRI in the depiction of osseous anatomy [96]. The presence of skull base foraminal widening, which can be detected on thin-section CT and reconstructions, may alert to perineural tumor spread [96], and the precise determination of bony destruction or remodeling may prove useful in the characterization of slow-growing versus aggressive sinonasal tumors [99]. MRI is considered superior to CT in the delineation of the soft tissue extent of disease, including involvement of neighboring structures, findings that are necessary for the correct T staging of disease. Contrast-enhanced imaging is imperative to correctly identify and outline the primary tumor, distinguishing it from the surrounding normal soft tissues.

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Staging and Post Therapy Assessment of Head and Neck Cancer

CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT neck without IV contrast would not provide Assessment of Head and Neck Cancer sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA with IV contrast of the head and neck in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. FDG-PET/CT alone is not considered sufficient in initial staging because it may not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging, surgical, and treatment planning [100]. Furthermore, previous authors have suggested that PET/CT may in fact overestimate the extension of the tumor [101]. However, FDG-PET/CT is recommended by the National Comprehensive Cancer Network as an adjunct in the workup of stage III and IV cancers [42]. FDG-PET/CT has shown increased sensitivity for detection of regional nodal disease, distant metastasis, and synchronous tumors over radiography and cross-sectional imaging with CT and MRI [42].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CT neck without IV contrast would not provide Assessment of Head and Neck Cancer sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA with IV contrast of the head and neck in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. FDG-PET/CT alone is not considered sufficient in initial staging because it may not provide detailed anatomic delineation of the primary site or detection of upstaging features needed for correct staging, surgical, and treatment planning [100]. Furthermore, previous authors have suggested that PET/CT may in fact overestimate the extension of the tumor [101]. However, FDG-PET/CT is recommended by the National Comprehensive Cancer Network as an adjunct in the workup of stage III and IV cancers [42]. FDG-PET/CT has shown increased sensitivity for detection of regional nodal disease, distant metastasis, and synchronous tumors over radiography and cross-sectional imaging with CT and MRI [42].

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At initial staging, one study showed that distant metastases or a secondary cancer was discovered in 22% of patients, which in turn led to adjustments in planned therapy [102]. The utility of FDG-PET in lower-stage cancer is more controversial. However, FDG-PET/CT does confer a high NPV of 87% for lymph node metastasis in N0 cancer and 99% for distant metastatic disease [37,49,85], which is valuable in directing therapy. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use in routine clinical evaluation of head and neck tumors with FDG-PET/MRI shown to have similar results to FDG- PET/CT [42,52-54,56,57]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. The coverage of an MRI of the head and the sequences used may be insufficient to completely evaluate the primary site in the paranasal sinuses or nasal cavity and will not include regional nodal staging.

Staging and Post Therapy Assessment of Head and Neck Cancer. At initial staging, one study showed that distant metastases or a secondary cancer was discovered in 22% of patients, which in turn led to adjustments in planned therapy [102]. The utility of FDG-PET in lower-stage cancer is more controversial. However, FDG-PET/CT does confer a high NPV of 87% for lymph node metastasis in N0 cancer and 99% for distant metastatic disease [37,49,85], which is valuable in directing therapy. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use in routine clinical evaluation of head and neck tumors with FDG-PET/MRI shown to have similar results to FDG- PET/CT [42,52-54,56,57]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. The coverage of an MRI of the head and the sequences used may be insufficient to completely evaluate the primary site in the paranasal sinuses or nasal cavity and will not include regional nodal staging.

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MRI head without and with IV contrast may be a useful adjunct to further delineate advanced intracranial extension of disease when suspected based on clinical grounds or prior imaging. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Assessment of Head and Neck Cancer MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of the tumor [96], which is a key component in the T staging of disease and essential for surgical planning. Perineural tumor spread is more easily recognized with MRI compared to CT, as is the regional extension to neighboring structures such as the orbits, dura, and brain, and subtle marrow involvement [96]. Furthermore, the superior soft tissue contrast resolution of MRI can better distinguish tumors from sinus inflammatory changes and retain secretions compared to CT. Advanced tools, including higher- resolution imaging, diffusion-weighted and diffusion-tensor sequences, and MR perfusion techniques such as dynamic-contrast-enhanced MRI show promise in improving anatomic and functional imaging [103-105]. These tools may help to distinguish between benign and malignant disease, however, as of now they are not consistently used in routine clinical practice. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI head without and with IV contrast may be a useful adjunct to further delineate advanced intracranial extension of disease when suspected based on clinical grounds or prior imaging. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Assessment of Head and Neck Cancer MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of the tumor [96], which is a key component in the T staging of disease and essential for surgical planning. Perineural tumor spread is more easily recognized with MRI compared to CT, as is the regional extension to neighboring structures such as the orbits, dura, and brain, and subtle marrow involvement [96]. Furthermore, the superior soft tissue contrast resolution of MRI can better distinguish tumors from sinus inflammatory changes and retain secretions compared to CT. Advanced tools, including higher- resolution imaging, diffusion-weighted and diffusion-tensor sequences, and MR perfusion techniques such as dynamic-contrast-enhanced MRI show promise in improving anatomic and functional imaging [103-105]. These tools may help to distinguish between benign and malignant disease, however, as of now they are not consistently used in routine clinical practice. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues.

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MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning. However, noncontrast MRI sequences are routinely used to identify the primary tumor and to define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. US Neck US can be a useful adjunct to cross-sectional imaging, in particular for nodal staging of head and neck cancer. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging, following neck dissection [62]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. Variant 4: Suspected or diagnosed cancer of a major salivary gland (parotid, submandibular, and sublingual glands). Initial staging. The salivary glands are classified into major and minor. The major salivary glands are paired bilateral parotid, submandibular, and sublingual glands.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site, distinguishing it from the surrounding normal soft tissues. The absence of IV contrast limits the ability to accurately delineate margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for treatment planning. However, noncontrast MRI sequences are routinely used to identify the primary tumor and to define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the initial staging of suspected or diagnosed cancer of the paranasal sinuses or nasal cavity. US Neck US can be a useful adjunct to cross-sectional imaging, in particular for nodal staging of head and neck cancer. Coupled with fine-needle aspiration and/or core-needle biopsy, nodal evaluation with US is a reliable tool and correlates well with staging, following neck dissection [62]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. Variant 4: Suspected or diagnosed cancer of a major salivary gland (parotid, submandibular, and sublingual glands). Initial staging. The salivary glands are classified into major and minor. The major salivary glands are paired bilateral parotid, submandibular, and sublingual glands.

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The minor salivary glands are located along the mucosa of the aerodigestive tract, including the oral cavity, nasal cavity, and pharynx, and tumors of the minor salivary glands occurring in various sites are included in the discussion of Variants 1, 2, and 3 above. Tumors of the major salivary glands are considered rare and account for 3% to 5% of all head and neck neoplasms and only 0.5% of all malignancies [106,107]. The most common site is the parotid gland, with about 70% arising from this site [108], followed by the submandibular gland, and lastly the sublingual gland. In general, the risk of malignancy is inversely proportional to the size of the gland. Therefore, the risk of cancer is greater in a sublingual gland lesion as opposed to a lesion in the parotid gland. The majority, approximately 70% to 80%, of these tumors are benign, with the most common benign tumor being pleomorphic adenoma (60%-70%) and Warthin tumor (5%-12%) [107]. A smaller percentage are malignant tumors, of which mucoepidermoid carcinoma, adenoid cystic carcinoma, lymphoma, and acinic cell carcinoma are the most common subtypes [107,109]. Furthermore, intraglandular lymphatic tissue predisposes the parotid glands to metastatic disease from locoregional cancers of the head and neck, as well as from distant tumors including the thyroid, breast, and lung [110]. Patients typically present with a palpable abnormality or pain. When there is perineural spread of disease, the patient may experience weakness of the facial muscles. Surgery is considered the primary treatment in the majority of salivary gland tumors and imaging is obtained in large part to determine feasibility of resection [108]. Imaging plays a crucial role in the characterization of these lesions and is aimed at determining anatomic location, relation to surrounding structures, size, multiplicity, presence of perineural spread, and internal features.

Staging and Post Therapy Assessment of Head and Neck Cancer. The minor salivary glands are located along the mucosa of the aerodigestive tract, including the oral cavity, nasal cavity, and pharynx, and tumors of the minor salivary glands occurring in various sites are included in the discussion of Variants 1, 2, and 3 above. Tumors of the major salivary glands are considered rare and account for 3% to 5% of all head and neck neoplasms and only 0.5% of all malignancies [106,107]. The most common site is the parotid gland, with about 70% arising from this site [108], followed by the submandibular gland, and lastly the sublingual gland. In general, the risk of malignancy is inversely proportional to the size of the gland. Therefore, the risk of cancer is greater in a sublingual gland lesion as opposed to a lesion in the parotid gland. The majority, approximately 70% to 80%, of these tumors are benign, with the most common benign tumor being pleomorphic adenoma (60%-70%) and Warthin tumor (5%-12%) [107]. A smaller percentage are malignant tumors, of which mucoepidermoid carcinoma, adenoid cystic carcinoma, lymphoma, and acinic cell carcinoma are the most common subtypes [107,109]. Furthermore, intraglandular lymphatic tissue predisposes the parotid glands to metastatic disease from locoregional cancers of the head and neck, as well as from distant tumors including the thyroid, breast, and lung [110]. Patients typically present with a palpable abnormality or pain. When there is perineural spread of disease, the patient may experience weakness of the facial muscles. Surgery is considered the primary treatment in the majority of salivary gland tumors and imaging is obtained in large part to determine feasibility of resection [108]. Imaging plays a crucial role in the characterization of these lesions and is aimed at determining anatomic location, relation to surrounding structures, size, multiplicity, presence of perineural spread, and internal features.

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In turn, this information in conjunction with histologic type serves to define treatment approach and management. The appropriate imaging technique is generally determined by the site Assessment of Head and Neck Cancer of origin [108]. Fine-needle aspiration remains the most definitive tool to determine the benign or malignant nature of salivary gland masses [106]. US, cross-sectional imaging (CT, MRI), and functional imaging with FDG-PET/CT may be used independently or in combination to enhance the diagnostic strength and reduce the deficiency of each modality [106]. Furthermore, imaging characteristics are particularly helpful when fine-needle aspiration cannot be performed because of inaccessible location or patient preference. In established malignancy, staging to include nodal disease and distant metastases may be warranted. Locoregional metastatic adenopathy is seen in approximately 10% to 15% of malignant salivary gland tumors and is more common in high-grade than in low- grade cancer [108]. Distant metastatic disease is identified in 10% to 50% of patients at initial staging, and both lymph node and distant metastases are more common in the setting of tumor recurrence [108]. Perineural tumor spread is especially prevalent in adenoid cystic carcinoma and is reported in >50% of patients [108]. Radiography Chest CXR is not considered useful in the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of a major salivary gland. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11].

Staging and Post Therapy Assessment of Head and Neck Cancer. In turn, this information in conjunction with histologic type serves to define treatment approach and management. The appropriate imaging technique is generally determined by the site Assessment of Head and Neck Cancer of origin [108]. Fine-needle aspiration remains the most definitive tool to determine the benign or malignant nature of salivary gland masses [106]. US, cross-sectional imaging (CT, MRI), and functional imaging with FDG-PET/CT may be used independently or in combination to enhance the diagnostic strength and reduce the deficiency of each modality [106]. Furthermore, imaging characteristics are particularly helpful when fine-needle aspiration cannot be performed because of inaccessible location or patient preference. In established malignancy, staging to include nodal disease and distant metastases may be warranted. Locoregional metastatic adenopathy is seen in approximately 10% to 15% of malignant salivary gland tumors and is more common in high-grade than in low- grade cancer [108]. Distant metastatic disease is identified in 10% to 50% of patients at initial staging, and both lymph node and distant metastases are more common in the setting of tumor recurrence [108]. Perineural tumor spread is especially prevalent in adenoid cystic carcinoma and is reported in >50% of patients [108]. Radiography Chest CXR is not considered useful in the evaluation of pulmonary metastatic disease in the initial staging of suspected or diagnosed cancer of a major salivary gland. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11].

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The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and can be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is to the lungs. A distant second are the bones followed by the liver, brain, and other sites [108]. For this reason, CT of the chest may be considered in cases of increased risk of metastatic disease, in particular in patients with high-grade malignant tumors. CT chest confers a superior spatial and contrast resolution when compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed cancer of a major salivary gland. CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is to the lungs. A distant second are the bones followed by the liver, brain, and other sites [108].

Staging and Post Therapy Assessment of Head and Neck Cancer. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and can be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is to the lungs. A distant second are the bones followed by the liver, brain, and other sites [108]. For this reason, CT of the chest may be considered in cases of increased risk of metastatic disease, in particular in patients with high-grade malignant tumors. CT chest confers a superior spatial and contrast resolution when compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aid in delineation of soft tissue extension of skeletal metastatic disease. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of suspected or diagnosed cancer of a major salivary gland. CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is to the lungs. A distant second are the bones followed by the liver, brain, and other sites [108].

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For this reason, CT of the chest may be considered in cases of increased risk of metastatic disease, in particular in patients with high-grade malignant tumors. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy and aid in delineation of the soft tissue extension of skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the routine use of CT of the head with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Head Without and With IV Contrast There is no relevant literature to support the routine use of CT of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Head Without IV Contrast There is no relevant literature to support the routine use of CT of the head without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. Assessment of Head and Neck Cancer CT Maxillofacial With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT.

Staging and Post Therapy Assessment of Head and Neck Cancer. For this reason, CT of the chest may be considered in cases of increased risk of metastatic disease, in particular in patients with high-grade malignant tumors. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy and aid in delineation of the soft tissue extension of skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the routine use of CT of the head with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Head Without and With IV Contrast There is no relevant literature to support the routine use of CT of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Head Without IV Contrast There is no relevant literature to support the routine use of CT of the head without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. Assessment of Head and Neck Cancer CT Maxillofacial With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT.

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CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Maxillofacial Without IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck can give detailed anatomic delineation of the primary tumor site and adjacent anatomy, as well as provide regional nodal staging of the neck. Soft tissue resolution of CT is considered inferior to that of MRI [108], and certain cancers such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinomas may lack significant contrast enhancement on CT, making their detection difficult by this modality [111]. Furthermore, MRI is considered superior in the detection of perineural spread and the soft tissue extent of disease [107,108], which are features needed for accurate T staging. Generally, CT is reserved for patients when there are indeterminate findings on MRI regarding osseous invasion [107,108].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Maxillofacial Without IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT maxillofacial without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy when performed alone and may best be used in combination with MRI or FDG-PET/CT. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck can give detailed anatomic delineation of the primary tumor site and adjacent anatomy, as well as provide regional nodal staging of the neck. Soft tissue resolution of CT is considered inferior to that of MRI [108], and certain cancers such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinomas may lack significant contrast enhancement on CT, making their detection difficult by this modality [111]. Furthermore, MRI is considered superior in the detection of perineural spread and the soft tissue extent of disease [107,108], which are features needed for accurate T staging. Generally, CT is reserved for patients when there are indeterminate findings on MRI regarding osseous invasion [107,108].

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CT may prove to be especially useful in the setting of suspected bone involvement because of its improved detection of cortical erosion [112]. Furthermore, CT is superior to MRI in the detection of calculus disease resulting in sialadenitis, which may behave as a tumor mimic [112]. Both CT and MRI are capable of assessing internal tumor features, extraglandular extension, enhancement, and in detecting regional adenopathy [112]. Conflicting results have been published regarding the ability of imaging to distinguish benign from malignant salivary gland tumors. Some studies suggest no statistically significant difference in diagnostic accuracy between US, CT, MRI, and PET/CT [106,113], whereas others have reported that CT is less accurate than MRI in the prediction of malignancy [107]. The use of IV contrast is recommended to better outline the extent of the primary site. CT Neck Without and With IV Contrast There is no relevant literature to support the routine use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Neck Without IV Contrast There is no relevant literature to support the routine use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT neck without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT may prove to be especially useful in the setting of suspected bone involvement because of its improved detection of cortical erosion [112]. Furthermore, CT is superior to MRI in the detection of calculus disease resulting in sialadenitis, which may behave as a tumor mimic [112]. Both CT and MRI are capable of assessing internal tumor features, extraglandular extension, enhancement, and in detecting regional adenopathy [112]. Conflicting results have been published regarding the ability of imaging to distinguish benign from malignant salivary gland tumors. Some studies suggest no statistically significant difference in diagnostic accuracy between US, CT, MRI, and PET/CT [106,113], whereas others have reported that CT is less accurate than MRI in the prediction of malignancy [107]. The use of IV contrast is recommended to better outline the extent of the primary site. CT Neck Without and With IV Contrast There is no relevant literature to support the routine use of CT neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT Neck Without IV Contrast There is no relevant literature to support the routine use of CT neck without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CT neck without IV contrast would not provide sufficient evaluation of the soft tissue extent of disease but may be complementary in the anatomic evaluation of the primary site in particular for the evaluation of osseous erosion. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. CTA of the neck can be used to identify patients at high risk of bleeding in the instance of locally advanced disease encroaching on the carotid arteries [41].

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FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. The utility of FDG-PET/CT depends on the tumor grade because low-grade salivary gland tumors have relatively low metabolism and may be occult on FDG-PET/CT. FDG-PET/CT is therefore not routinely recommended for initial staging of low-grade salivary gland tumors [108]. FDG-PET/CT has been shown to correctly identify the site of the primary tumor at a similar rate as MRI [114]. FDG-PET/CT alone is not Assessment of Head and Neck Cancer considered sufficient in the initial staging of salivary gland cancer because it does not provide detailed anatomic delineation of the primary site and detection of upstaging features needed. FDG-PET/CT is inferior to MRI for the diagnosis of perineural tumor spread because the small volume of disease and the limited spatial resolution of PET [42,115]. FDG-PET/CT in the initial staging of salivary gland tumors remains a controversial subject [108]. FDG-PET/CT may be superior to conventional cross-sectional imaging in staging of regional neck nodal disease and preoperative planning for neck dissection [114]. One study showed an increased detection rate of regional nodal metastases calculated at 100% with FDG-PET/CT versus 50% with MRI in combination with CXR [114]. Furthermore, FDG- PET/CT may be recommended in the setting of high-grade malignancy because of the increased frequency of distant metastases [108,114]. Other studies have shown that PET/CT provides additional information regarding cervical lymph nodes and distant disease in particular in patients with high-grade carcinomas [114]. The rate of change in treatment plan based on detection of regional and/or distant metastases in patients with salivary gland carcinoma with PET or PET/CT has been calculated at 15% to 47% [114].

Staging and Post Therapy Assessment of Head and Neck Cancer. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the detection and localization of primary tumor site and identification of regional nodal disease and distant metastases. The utility of FDG-PET/CT depends on the tumor grade because low-grade salivary gland tumors have relatively low metabolism and may be occult on FDG-PET/CT. FDG-PET/CT is therefore not routinely recommended for initial staging of low-grade salivary gland tumors [108]. FDG-PET/CT has been shown to correctly identify the site of the primary tumor at a similar rate as MRI [114]. FDG-PET/CT alone is not Assessment of Head and Neck Cancer considered sufficient in the initial staging of salivary gland cancer because it does not provide detailed anatomic delineation of the primary site and detection of upstaging features needed. FDG-PET/CT is inferior to MRI for the diagnosis of perineural tumor spread because the small volume of disease and the limited spatial resolution of PET [42,115]. FDG-PET/CT in the initial staging of salivary gland tumors remains a controversial subject [108]. FDG-PET/CT may be superior to conventional cross-sectional imaging in staging of regional neck nodal disease and preoperative planning for neck dissection [114]. One study showed an increased detection rate of regional nodal metastases calculated at 100% with FDG-PET/CT versus 50% with MRI in combination with CXR [114]. Furthermore, FDG- PET/CT may be recommended in the setting of high-grade malignancy because of the increased frequency of distant metastases [108,114]. Other studies have shown that PET/CT provides additional information regarding cervical lymph nodes and distant disease in particular in patients with high-grade carcinomas [114]. The rate of change in treatment plan based on detection of regional and/or distant metastases in patients with salivary gland carcinoma with PET or PET/CT has been calculated at 15% to 47% [114].

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FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging. A potential application of FDG-PET/MRI has been studied in the setting of suspected perineural tumor spread. Combining the soft tissue resolution of MRI and the functional evaluation of FDG-PET may be an attractive tool for diagnosis of the perineural spread in major salivary gland tumors [110]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head With IV Contrast There is no relevant literature to support the routine use of MRI of the head with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head Without and With IV Contrast There is no relevant literature to support the routine use of MRI of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head Without IV Contrast There is no relevant literature to support the routine use of MRI of the head without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland.

Staging and Post Therapy Assessment of Head and Neck Cancer. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging. A potential application of FDG-PET/MRI has been studied in the setting of suspected perineural tumor spread. Combining the soft tissue resolution of MRI and the functional evaluation of FDG-PET may be an attractive tool for diagnosis of the perineural spread in major salivary gland tumors [110]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head With IV Contrast There is no relevant literature to support the routine use of MRI of the head with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head Without and With IV Contrast There is no relevant literature to support the routine use of MRI of the head without and with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Head Without IV Contrast There is no relevant literature to support the routine use of MRI of the head without IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland.

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MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of tumor including the extraglandular extension of disease and perineural spread, which are key components in the T staging of disease and essential for treatment planning. Because of its superior soft tissue contrast resolution, MRI is considered the modality of choice for initial staging of major salivary gland cancer [108,112] relative to CECT. MRI overcomes many of the limitations encountered Assessment of Head and Neck Cancer by US by providing extended cross-sectional anatomic view of the area of interest and allowing for the detection of perineural tumor spread, deep-tissue extension, and marrow involvement [107]. Additionally, MRI may identify signal change and signs of extranodal extension in regional lymph nodes [112]. In the setting of sublingual and submandibular gland tumors, MRI accurately depicts the anatomy of the floor of the mouth, which is imperative in preoperative staging [107]. Because of the increased risk of malignancy of sublingual gland lesions, MRI is the imaging modality of choice [112]. Studies have reported no statistically significant difference in diagnostic accuracy between US, CT, MRI, and PET/CT to distinguish benign from malignant salivary gland tumors [106,113]. However, one meta-analysis showed MRI to have a higher sensitivity and specificity for differentiating between benign and malignant tumors [113]. The addition of advanced MRI techniques including diffusion-weighted imaging and perfusion imaging, such as dynamic contrast-enhanced, may improve the ability of MRI to distinguish benign from malignant salivary gland tumor with reported similar results to fine-needle aspiration [107], although these tools are not consistently used in routine clinical practice.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution and with this an improved ability to delineate the soft tissue extent of tumor including the extraglandular extension of disease and perineural spread, which are key components in the T staging of disease and essential for treatment planning. Because of its superior soft tissue contrast resolution, MRI is considered the modality of choice for initial staging of major salivary gland cancer [108,112] relative to CECT. MRI overcomes many of the limitations encountered Assessment of Head and Neck Cancer by US by providing extended cross-sectional anatomic view of the area of interest and allowing for the detection of perineural tumor spread, deep-tissue extension, and marrow involvement [107]. Additionally, MRI may identify signal change and signs of extranodal extension in regional lymph nodes [112]. In the setting of sublingual and submandibular gland tumors, MRI accurately depicts the anatomy of the floor of the mouth, which is imperative in preoperative staging [107]. Because of the increased risk of malignancy of sublingual gland lesions, MRI is the imaging modality of choice [112]. Studies have reported no statistically significant difference in diagnostic accuracy between US, CT, MRI, and PET/CT to distinguish benign from malignant salivary gland tumors [106,113]. However, one meta-analysis showed MRI to have a higher sensitivity and specificity for differentiating between benign and malignant tumors [113]. The addition of advanced MRI techniques including diffusion-weighted imaging and perfusion imaging, such as dynamic contrast-enhanced, may improve the ability of MRI to distinguish benign from malignant salivary gland tumor with reported similar results to fine-needle aspiration [107], although these tools are not consistently used in routine clinical practice.

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Furthermore, preprocedural assessment with advanced MRI techniques may serve to identify internal sites of greater cellularity as a target for fine-needle aspiration [107]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site. Contrast administration aids in detecting of subtle mass extension and invasion of surrounding structures and in identifying perineural tumor spread [108]. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for surgical planning. However, noncontrast MR sequences are routinely used to identify the primary tumor, define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the initial staging of suspected or diagnosed cancer of a major salivary gland. US Neck US allows for the detection and localization of major salivary gland tumors as well as regional nodal staging. US is often considered an appropriate first-line examination in the characterization of accessible salivary masses, in particular for submandibular gland tumors and masses of the superficial lobe of the parotid gland [107,108,112]. The superficial location of the major salivary glands renders their evaluation with high-resolution US an effective and safe modality for initial assessment [112,116].

Staging and Post Therapy Assessment of Head and Neck Cancer. Furthermore, preprocedural assessment with advanced MRI techniques may serve to identify internal sites of greater cellularity as a target for fine-needle aspiration [107]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site. Contrast administration aids in detecting of subtle mass extension and invasion of surrounding structures and in identifying perineural tumor spread [108]. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the initial staging of suspected or diagnosed cancer of a major salivary gland. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate the primary site. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of the tumor, which is a key component in the T staging of disease and essential for surgical planning. However, noncontrast MR sequences are routinely used to identify the primary tumor, define tumor extent, in particular marrow involvement, and are used in nodal staging. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the initial staging of suspected or diagnosed cancer of a major salivary gland. US Neck US allows for the detection and localization of major salivary gland tumors as well as regional nodal staging. US is often considered an appropriate first-line examination in the characterization of accessible salivary masses, in particular for submandibular gland tumors and masses of the superficial lobe of the parotid gland [107,108,112]. The superficial location of the major salivary glands renders their evaluation with high-resolution US an effective and safe modality for initial assessment [112,116].

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US provides information regarding tissue characterization, anatomic delineation, and intralesional vascular pattern via Doppler technique. Additionally, nodal involvement may also be established by US, and this modality may serve as guidance for fine-needle aspiration. However, some caveats exist. US may be insufficient in the detection and characterization of masses located in the deep lobe of the parotid gland [107,112]. Additional limitations of US include the inability to appropriately assess deep compartment extension, perineural tumor spread, bone invasion, and oropharyngeal/retropharyngeal nodal involvement [112]. Variant 5: Treated cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Surveillance imaging or follow-up imaging for suspected or known recurrence. Tumors of the oral cavity, oropharynx, hypopharynx, and larynx as well as tumors in which a primary site is not identified but the patient presents with metastatic cervical adenopathy are generally treated with a combination of surgery, chemotherapy, and/or radiation therapy [117]. This represents a heterogeneous group of tumors with posttreatment prognosis dependent on the site of origin and histology, although the majority of tumors are squamous cell carcinomas. As many as 40% of patients suffer recurrence after therapy, and up to 25% of patients will develop distant metastases [118,119], with the majority of recurrences occurring in the first 2 years following treatment [16]. Rate of recurrence and distant metastatic disease is directly linked to advanced stage of disease before treatment. The early detection of residual disease and recurrence, diagnosis of distant metastases, and differentiation from posttreatment changes is vital in the follow-up imaging in order to offer salvage therapy and improved survival. The exact delineation of recurrence is crucial in determining the type of salvage therapy offered.

Staging and Post Therapy Assessment of Head and Neck Cancer. US provides information regarding tissue characterization, anatomic delineation, and intralesional vascular pattern via Doppler technique. Additionally, nodal involvement may also be established by US, and this modality may serve as guidance for fine-needle aspiration. However, some caveats exist. US may be insufficient in the detection and characterization of masses located in the deep lobe of the parotid gland [107,112]. Additional limitations of US include the inability to appropriately assess deep compartment extension, perineural tumor spread, bone invasion, and oropharyngeal/retropharyngeal nodal involvement [112]. Variant 5: Treated cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. Surveillance imaging or follow-up imaging for suspected or known recurrence. Tumors of the oral cavity, oropharynx, hypopharynx, and larynx as well as tumors in which a primary site is not identified but the patient presents with metastatic cervical adenopathy are generally treated with a combination of surgery, chemotherapy, and/or radiation therapy [117]. This represents a heterogeneous group of tumors with posttreatment prognosis dependent on the site of origin and histology, although the majority of tumors are squamous cell carcinomas. As many as 40% of patients suffer recurrence after therapy, and up to 25% of patients will develop distant metastases [118,119], with the majority of recurrences occurring in the first 2 years following treatment [16]. Rate of recurrence and distant metastatic disease is directly linked to advanced stage of disease before treatment. The early detection of residual disease and recurrence, diagnosis of distant metastases, and differentiation from posttreatment changes is vital in the follow-up imaging in order to offer salvage therapy and improved survival. The exact delineation of recurrence is crucial in determining the type of salvage therapy offered.

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Cross-sectional imaging remains the mainstay of posttreatment surveillance. Additionally, imaging in the posttreatment setting may be geared to detecting complications secondary to therapy, which include but are not limited to osteoradionecrosis, Assessment of Head and Neck Cancer infection, and flap failure. The appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document. Radiography Chest CXR is not considered useful for the evaluation of pulmonary metastatic disease in treated cancer of the oral cavity or oropharynx or hypopharynx, or larynx or cancer of unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. Cross-sectional imaging remains the mainstay of posttreatment surveillance. Additionally, imaging in the posttreatment setting may be geared to detecting complications secondary to therapy, which include but are not limited to osteoradionecrosis, Assessment of Head and Neck Cancer infection, and flap failure. The appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document. Radiography Chest CXR is not considered useful for the evaluation of pulmonary metastatic disease in treated cancer of the oral cavity or oropharynx or hypopharynx, or larynx or cancer of unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of the oral cavity or oropharynx or hypopharynx or larynx or cancer of unknown primary of the head and neck. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

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Assessment of Head and Neck Cancer CT Head Without and with IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT maxillofacial will typically not include the neck and therefore would be inadequate for the staging of regional lymphadenopathy and may not include the primary site in the hypopharynx or larynx. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. Assessment of Head and Neck Cancer CT Head Without and with IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast as follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT maxillofacial will typically not include the neck and therefore would be inadequate for the staging of regional lymphadenopathy and may not include the primary site in the hypopharynx or larynx. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

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CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent tumor and the evaluation of regional nodal disease. CT is also used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Much like MRI, it has an overall low sensitivity and positive predictive value [123] for detecting recurrence. Posttreatment CECT has been shown to detect local failure and nodal recurrence earlier than clinical examination alone [124,125]. A reported high NPV of 97.7% suggests that CT is helpful in excluding recurrence [123]. CT imaging also allows for excellent delineation of osseous anatomy, including bony destruction that can be seen in the context of recurrence or as a complication of treatment such as in osteoradionecrosis. FDG-PET/CT confers increased sensitivity compared to CECT in detecting recurrence and confers similarly to slightly increased specificity [117,119,126-128]. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. The puffed-cheek technique, consisting of requesting that the patient inflate their cheeks with pursed lips while undergoing CT examination, allows for a greater delineation of oral cavity tumors, particularly those along the gingiva and buccal mucosa. The maneuver allows for the separation of the tumor from normal mucosa and provides a clearer picture of the size and extent of disease [40].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent tumor and the evaluation of regional nodal disease. CT is also used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Much like MRI, it has an overall low sensitivity and positive predictive value [123] for detecting recurrence. Posttreatment CECT has been shown to detect local failure and nodal recurrence earlier than clinical examination alone [124,125]. A reported high NPV of 97.7% suggests that CT is helpful in excluding recurrence [123]. CT imaging also allows for excellent delineation of osseous anatomy, including bony destruction that can be seen in the context of recurrence or as a complication of treatment such as in osteoradionecrosis. FDG-PET/CT confers increased sensitivity compared to CECT in detecting recurrence and confers similarly to slightly increased specificity [117,119,126-128]. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. The puffed-cheek technique, consisting of requesting that the patient inflate their cheeks with pursed lips while undergoing CT examination, allows for a greater delineation of oral cavity tumors, particularly those along the gingiva and buccal mucosa. The maneuver allows for the separation of the tumor from normal mucosa and provides a clearer picture of the size and extent of disease [40].

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CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, Assessment of Head and Neck Cancer or cancer of unknown primary of the head and neck. In the specific case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response and detection and localization of recurrence, regional nodal disease, and distant metastases. The evaluation of the posttreatment of the neck is complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Studies have shown FDG-PET/CT to have high sensitivity and specificity for detection of local and nodal recurrence, with a higher sensitivity and similar or higher specificity to CT or MRI of the neck [117,119,126-128]. FDG-PET/CT has a very high NPV and therefore is very accurate in excluding recurrence [129-131].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast for the evaluation of known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, Assessment of Head and Neck Cancer or cancer of unknown primary of the head and neck. In the specific case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response and detection and localization of recurrence, regional nodal disease, and distant metastases. The evaluation of the posttreatment of the neck is complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Studies have shown FDG-PET/CT to have high sensitivity and specificity for detection of local and nodal recurrence, with a higher sensitivity and similar or higher specificity to CT or MRI of the neck [117,119,126-128]. FDG-PET/CT has a very high NPV and therefore is very accurate in excluding recurrence [129-131].

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FDG-PET/CT has been shown to be effective in identifying subclinical recurrences in the posttreatment setting [132,133]. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT [131,134,135]. For this reason, imaging with FDG-PET/CT should ideally occur no earlier than 12 weeks after completion of therapy [117,118] to allow for treatment effects to subside, although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false-positive findings. One study found that the combination of MRI with FDG-PET/CT has the best detection of locoregional recurrence [128]. FDG-PET/CT has been found to accurately diagnose distant metastatic disease in the posttreatment setting [19,119] and may be indicated in treated advanced stage disease because of the increased rate of distant metastases. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging including in the response assessment and evaluation of recurrence following treatment of cancer of the head and neck with FDG-PET/MRI performing similar to FDG/PET CT [137,138]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. FDG-PET/CT has been shown to be effective in identifying subclinical recurrences in the posttreatment setting [132,133]. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT [131,134,135]. For this reason, imaging with FDG-PET/CT should ideally occur no earlier than 12 weeks after completion of therapy [117,118] to allow for treatment effects to subside, although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false-positive findings. One study found that the combination of MRI with FDG-PET/CT has the best detection of locoregional recurrence [128]. FDG-PET/CT has been found to accurately diagnose distant metastatic disease in the posttreatment setting [19,119] and may be indicated in treated advanced stage disease because of the increased rate of distant metastases. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging including in the response assessment and evaluation of recurrence following treatment of cancer of the head and neck with FDG-PET/MRI performing similar to FDG/PET CT [137,138]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck.

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MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the follow- up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Assessment of Head and Neck Cancer MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing tumor from treatment-related change and in evaluating local tumor response.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck with IV contrast in the follow- up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Assessment of Head and Neck Cancer MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing tumor from treatment-related change and in evaluating local tumor response.

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Evaluation of the treated neck is complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence. MRI is less susceptible to metal artifact than CT and may perform better in the oral cavity where there can be significant artifact from dental implants. Conversely, MRI offers decreased spatial resolution compared to CT and is more susceptible to motion artifact because of longer scan times. One study found that MRI, much like CT, has low sensitivity and positive predictive value for detecting recurrence in treated oropharynx cancer but has importance in excluding recurrence with a high NPV (94%) [139]. FDG-PET/CT confers increased sensitivity compared to MRI and confers similarly to slightly increased specificity when evaluating for recurrence [43]. One study found that the combination of MRI with FDG-PET/CT has the best detection of locoregional recurrence [128]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrent tumor, distinguishing it from surrounding soft tissues and treatment changes. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment- related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of tumor.

Staging and Post Therapy Assessment of Head and Neck Cancer. Evaluation of the treated neck is complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence. MRI is less susceptible to metal artifact than CT and may perform better in the oral cavity where there can be significant artifact from dental implants. Conversely, MRI offers decreased spatial resolution compared to CT and is more susceptible to motion artifact because of longer scan times. One study found that MRI, much like CT, has low sensitivity and positive predictive value for detecting recurrence in treated oropharynx cancer but has importance in excluding recurrence with a high NPV (94%) [139]. FDG-PET/CT confers increased sensitivity compared to MRI and confers similarly to slightly increased specificity when evaluating for recurrence [43]. One study found that the combination of MRI with FDG-PET/CT has the best detection of locoregional recurrence [128]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrent tumor, distinguishing it from surrounding soft tissues and treatment changes. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI of the orbits, face, and neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment- related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of tumor.

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However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. In the presence of bulky nodal disease, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy with a higher combined NPV [65]. US has been shown to perform similar to CT in detection of recurrence of head and neck squamous cell carcinomas [141] but is inherently limited by operator skill and its inability to evaluate deep neck structures. Variant 6: Treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. Surveillance imaging or follow-up imaging for suspected or known recurrence. Nasopharynx cancer and EBV-associated unknown primary of the head and neck is known to be responsive to radiotherapy and, in advanced disease, the combination of radiation and chemotherapy.

Staging and Post Therapy Assessment of Head and Neck Cancer. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of cancer of the oral cavity, oropharynx, hypopharynx, larynx, or cancer of unknown primary of the head and neck [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. In the presence of bulky nodal disease, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy with a higher combined NPV [65]. US has been shown to perform similar to CT in detection of recurrence of head and neck squamous cell carcinomas [141] but is inherently limited by operator skill and its inability to evaluate deep neck structures. Variant 6: Treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. Surveillance imaging or follow-up imaging for suspected or known recurrence. Nasopharynx cancer and EBV-associated unknown primary of the head and neck is known to be responsive to radiotherapy and, in advanced disease, the combination of radiation and chemotherapy.

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The early accurate identification of residual or recurrent disease, distant metastases, and de-differentiation from posttreatment changes is vital in posttreatment imaging and evaluation in order to determine the need for salvage therapy for improved survival. The incidence of recurrent disease following therapy has been reported to range from 6% to 16% with around half of recurrences occurring in the first 2 years [142,143]. The presence of recurrence is associated with increased risk for distant metastatic disease, reported at 30%, with distant metastatic disease the most common cause of death after treatment in NPC [142]. Direct visualization with flexible endoscopy is considered the most sensitive method for detecting mucosal recurrence. However, submucosal and deep-seated recurrences are best identified by imaging, preferably cross- sectional imaging such as MRI or functional imaging with FDG-PET/CT. Additionally, imaging in the setting of treated NPC may be geared toward detecting complications secondary to therapy, which include but are not limited to osteoradionecrosis of the skull base, brain parenchymal radiation necrosis, and infection, among others. The Assessment of Head and Neck Cancer appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document. Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11].

Staging and Post Therapy Assessment of Head and Neck Cancer. The early accurate identification of residual or recurrent disease, distant metastases, and de-differentiation from posttreatment changes is vital in posttreatment imaging and evaluation in order to determine the need for salvage therapy for improved survival. The incidence of recurrent disease following therapy has been reported to range from 6% to 16% with around half of recurrences occurring in the first 2 years [142,143]. The presence of recurrence is associated with increased risk for distant metastatic disease, reported at 30%, with distant metastatic disease the most common cause of death after treatment in NPC [142]. Direct visualization with flexible endoscopy is considered the most sensitive method for detecting mucosal recurrence. However, submucosal and deep-seated recurrences are best identified by imaging, preferably cross- sectional imaging such as MRI or functional imaging with FDG-PET/CT. Additionally, imaging in the setting of treated NPC may be geared toward detecting complications secondary to therapy, which include but are not limited to osteoradionecrosis of the skull base, brain parenchymal radiation necrosis, and infection, among others. The Assessment of Head and Neck Cancer appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document. Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11].

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The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the restaging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be indicated in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing nodes from mediastinal vessels. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases.

Staging and Post Therapy Assessment of Head and Neck Cancer. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases. Although FDG-PET/CT is preferred for the restaging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be indicated in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing nodes from mediastinal vessels. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated nasopharynx cancer or EBV-associated unknown primary of the head and neck. CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to ribs or vertebrae. NPC has a relatively high rate of distant metastases with the lung being the second most common site of distant disease after osseous metastases.

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Although FDG-PET/CT is preferred for the restaging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for the screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be indicated in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing nodes from mediastinal vessels. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Although CT head may be able to delineate skull base and intracranial involvement, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT maxillofacial may provide

Staging and Post Therapy Assessment of Head and Neck Cancer. Although FDG-PET/CT is preferred for the restaging of advanced stage NPC because it allows for simultaneous detection of metastatic disease outside the thorax, CT chest may be considered for the screening of pulmonary metastatic disease. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. CT chest may also be indicated in patients with NPC associated with smoking and alcohol intake, increasing the risk for synchronous lung cancer. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing nodes from mediastinal vessels. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT head with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Although CT head may be able to delineate skull base and intracranial involvement, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT head without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Head Without IV Contrast There is no relevant literature to support the use of CT head without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT maxillofacial may provide

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Assessment of Head and Neck Cancer sufficient coverage for the anatomic evaluation of the primary site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of nasopharyngeal tumor, treatment response assessment, and regional nodal staging. The evaluation of the posttreatment neck is often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. MRI confers improved soft tissue contrast over CT and is generally the preferred imaging modality for evaluating NPC recurrence. CT imaging does allow for excellent delineation of osseous anatomy, including bony destruction that can be seen in the context of recurrence or as a complication of treatment such as in osteoradionecrosis [144]. CT is also used to monitor treatment changes and assess for treatment complications such as infection. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes.

Staging and Post Therapy Assessment of Head and Neck Cancer. Assessment of Head and Neck Cancer sufficient coverage for the anatomic evaluation of the primary site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of nasopharyngeal tumor, treatment response assessment, and regional nodal staging. The evaluation of the posttreatment neck is often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. MRI confers improved soft tissue contrast over CT and is generally the preferred imaging modality for evaluating NPC recurrence. CT imaging does allow for excellent delineation of osseous anatomy, including bony destruction that can be seen in the context of recurrence or as a complication of treatment such as in osteoradionecrosis [144]. CT is also used to monitor treatment changes and assess for treatment complications such as infection. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes.

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CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response, detection and localization of recurrence, regional nodal disease, and distant metastases in treated NPC [75,90,145-147]. The presence of posttreatment inflammatory changes decreases the specificity of FDG-PET/CT, and, for this reason, imaging ideally occurs at a minimum of 12 weeks from completion of therapy to allow for treatment effects to subside, although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false-positive findings. The high NPV of FDG-PET/CT is very useful in excluding recurrence [147]. FDG-PET/CT has demonstrated similar detection rates of local recurrence as MRI but increased specificity of imaging findings, in particular in patients with treated advanced disease [143,145,146,148].

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast in treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response, detection and localization of recurrence, regional nodal disease, and distant metastases in treated NPC [75,90,145-147]. The presence of posttreatment inflammatory changes decreases the specificity of FDG-PET/CT, and, for this reason, imaging ideally occurs at a minimum of 12 weeks from completion of therapy to allow for treatment effects to subside, although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false-positive findings. The high NPV of FDG-PET/CT is very useful in excluding recurrence [147]. FDG-PET/CT has demonstrated similar detection rates of local recurrence as MRI but increased specificity of imaging findings, in particular in patients with treated advanced disease [143,145,146,148].

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Metabolic response on posttreatment FDG-PET/CT has been shown to be an independent prognostic indicator conferring improved survival [149]. FDG-PET/CT has a high sensitivity and accuracy in detecting distant metastases, including osseous and pulmonary metastases [82,87,88], the most common sites for distant metastatic disease in NPC. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the response assessment and evaluation of recurrence following treatment of cancer of the head and neck with FDG-PET/MR performing similarly to FDG/PET CT [137,138]. Assessment of Head and Neck Cancer MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck.

Staging and Post Therapy Assessment of Head and Neck Cancer. Metabolic response on posttreatment FDG-PET/CT has been shown to be an independent prognostic indicator conferring improved survival [149]. FDG-PET/CT has a high sensitivity and accuracy in detecting distant metastases, including osseous and pulmonary metastases [82,87,88], the most common sites for distant metastatic disease in NPC. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the response assessment and evaluation of recurrence following treatment of cancer of the head and neck with FDG-PET/MR performing similarly to FDG/PET CT [137,138]. Assessment of Head and Neck Cancer MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck.

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MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. The coverage of MRI of the head and its associated sequences may be insufficient to completely evaluate the primary site in the nasopharynx and will not include regional nodal staging. MRI head without and with IV contrast may be used to further delineate advanced intracranial extension of disease. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence, and can be helpful in distinguishing it from treatment related change and for evaluating local tumor response. The superior soft tissue contrast resolution relative to CECT is critical in distinguishing recurrence from treatment changes and in the delineation of tumor recurrence, including extension into adjacent structures such as the orbits, skull base, and intracranial compartment, and the perineural spread of disease. MRI has been reported to detect up to 27.8% of deep-seated recurrences that were occult on endoscopic evaluation [142].

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head without and with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. The coverage of MRI of the head and its associated sequences may be insufficient to completely evaluate the primary site in the nasopharynx and will not include regional nodal staging. MRI head without and with IV contrast may be used to further delineate advanced intracranial extension of disease. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence, and can be helpful in distinguishing it from treatment related change and for evaluating local tumor response. The superior soft tissue contrast resolution relative to CECT is critical in distinguishing recurrence from treatment changes and in the delineation of tumor recurrence, including extension into adjacent structures such as the orbits, skull base, and intracranial compartment, and the perineural spread of disease. MRI has been reported to detect up to 27.8% of deep-seated recurrences that were occult on endoscopic evaluation [142].

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However, posttreatment inflammatory changes, reactive mucosal change, postradiation scarring, or osteoradionecrosis may complicate MRI interpretation, and FDG-PET/CT has been shown to have increased specificity in detecting local recurrence, in particular in treated advanced disease [143,145,146,148]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrence site, distinguishing it from the surrounding soft tissues and treatment changes. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of the tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Assessment of Head and Neck Cancer Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of NPC [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique.

Staging and Post Therapy Assessment of Head and Neck Cancer. However, posttreatment inflammatory changes, reactive mucosal change, postradiation scarring, or osteoradionecrosis may complicate MRI interpretation, and FDG-PET/CT has been shown to have increased specificity in detecting local recurrence, in particular in treated advanced disease [143,145,146,148]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrence site, distinguishing it from the surrounding soft tissues and treatment changes. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated unknown primary of the head and neck. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margin and the soft tissue extent of the tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Assessment of Head and Neck Cancer Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of suspected or known recurrence of treated cancer of the nasopharynx or EBV-associated cancer of unknown primary of the head and neck. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of NPC [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique.

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US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. In the presence of bulky nodal disease in squamous cell carcinoma, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy with a higher combined NPV [65]. Variant 7: Treated cancer of the paranasal sinuses or nasal cavity. Surveillance imaging or follow-up imaging for suspected or known recurrence. Cancer of the paranasal sinuses or nasal cavity is generally treated with a combination of surgery, chemotherapy, and/or radiation therapy [117]. Despite aggressive therapy, recurrence rates may be high, estimated at up to 54% in cases of advanced head and neck squamous cell carcinomas, and these typically occur within the first 2 years following treatment [117]. Early diagnosis of recurrent disease allows for prompt treatment and for providing potential salvage options, which may portend increased survival rates [117]. However, complex posttreatment changes can distort anatomy and may interfere with the detection of subtle findings. Direct visualization with flexible endoscopy is considered the most sensitive method for detecting mucosal recurrence. However, submucosal and deep-seated recurrences are best identified by imaging, preferably cross-sectional imaging such as MRI or functional imaging with FDG-PET/CT. Imaging is also crucial for the detection of distant metastatic disease. Additionally, imaging in the setting of treated sinonasal malignancy may be geared toward detecting complications secondary to therapy, which include but are not limited to cerebrospinal fluid leaks, epistaxis, meningitis, and osteoradionecrosis of the skull base, among others. The appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document.

Staging and Post Therapy Assessment of Head and Neck Cancer. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65]. In the presence of bulky nodal disease in squamous cell carcinoma, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy with a higher combined NPV [65]. Variant 7: Treated cancer of the paranasal sinuses or nasal cavity. Surveillance imaging or follow-up imaging for suspected or known recurrence. Cancer of the paranasal sinuses or nasal cavity is generally treated with a combination of surgery, chemotherapy, and/or radiation therapy [117]. Despite aggressive therapy, recurrence rates may be high, estimated at up to 54% in cases of advanced head and neck squamous cell carcinomas, and these typically occur within the first 2 years following treatment [117]. Early diagnosis of recurrent disease allows for prompt treatment and for providing potential salvage options, which may portend increased survival rates [117]. However, complex posttreatment changes can distort anatomy and may interfere with the detection of subtle findings. Direct visualization with flexible endoscopy is considered the most sensitive method for detecting mucosal recurrence. However, submucosal and deep-seated recurrences are best identified by imaging, preferably cross-sectional imaging such as MRI or functional imaging with FDG-PET/CT. Imaging is also crucial for the detection of distant metastatic disease. Additionally, imaging in the setting of treated sinonasal malignancy may be geared toward detecting complications secondary to therapy, which include but are not limited to cerebrospinal fluid leaks, epistaxis, meningitis, and osteoradionecrosis of the skull base, among others. The appropriate imaging modality to evaluate each potential suspected complication will depend on the clinical scenario and is beyond the scope of this document.

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Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated cancer of the paranasal sinuses or nasal cavity. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Patients with recurrent head and neck squamous cell carcinoma are significantly more likely to have pulmonary metastatic disease [21,120]. Development of lung metastases is also increased in advanced stage disease [15]. CT chest confers superior spatial localization and contrast resolution when compared to radiography, allowing for the improved detection of small pulmonary nodules [15]. The use of screening CT chest in patients treated with definitive therapy have been shown to detect metastatic disease that was successfully treated with salvage therapy [121]. The rates of detection of pulmonary metastatic disease in the setting of recurrent disease for chest CT is similar to that of FDG-PET/CT [122]. The use of IV contrast allows for improved detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in the delineation of the soft tissue extension of skeletal metastatic disease.

Staging and Post Therapy Assessment of Head and Neck Cancer. Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated cancer of the paranasal sinuses or nasal cavity. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Patients with recurrent head and neck squamous cell carcinoma are significantly more likely to have pulmonary metastatic disease [21,120]. Development of lung metastases is also increased in advanced stage disease [15]. CT chest confers superior spatial localization and contrast resolution when compared to radiography, allowing for the improved detection of small pulmonary nodules [15]. The use of screening CT chest in patients treated with definitive therapy have been shown to detect metastatic disease that was successfully treated with salvage therapy [121]. The rates of detection of pulmonary metastatic disease in the setting of recurrent disease for chest CT is similar to that of FDG-PET/CT [122]. The use of IV contrast allows for improved detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in the delineation of the soft tissue extension of skeletal metastatic disease.

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There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of the paranasal sinuses or nasal cavity. Assessment of Head and Neck Cancer CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Patients with recurrent head and neck squamous cell carcinoma are significantly more likely to have pulmonary metastatic disease [21,120]. Development of lung metastases is also increased in advanced stage disease [15]. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the improved detection of small pulmonary nodules [15]. The use of screening CT chest in patients treated with definitive therapy have been shown to detect metastatic disease that was successfully treated with salvage therapy [121]. The rates of detection of pulmonary metastatic disease in the setting of recurrent disease for chest CT is similar to that of FDG-PET/CT [122]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in the delineation of the soft tissue extension of the skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT of the head with IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity.

Staging and Post Therapy Assessment of Head and Neck Cancer. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of the paranasal sinuses or nasal cavity. Assessment of Head and Neck Cancer CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Patients with recurrent head and neck squamous cell carcinoma are significantly more likely to have pulmonary metastatic disease [21,120]. Development of lung metastases is also increased in advanced stage disease [15]. CT chest confers a superior spatial localization and contrast resolution compared to radiography, allowing for the improved detection of small pulmonary nodules [15]. The use of screening CT chest in patients treated with definitive therapy have been shown to detect metastatic disease that was successfully treated with salvage therapy [121]. The rates of detection of pulmonary metastatic disease in the setting of recurrent disease for chest CT is similar to that of FDG-PET/CT [122]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy, distinguishing nodes from mediastinal vessels and aiding in the delineation of the soft tissue extension of the skeletal metastatic disease. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the use of CT of the head with IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity.

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CT head may provide sufficient coverage for the anatomic evaluation of the primary tumor site in the sinonasal cavity; however, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT of the head without and with IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Head Without IV Contrast There is no relevant literature to support the use of CT of the head without IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast for the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast for the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT head may provide sufficient coverage for the anatomic evaluation of the primary tumor site in the sinonasal cavity; however, inclusion of the neck is recommended to evaluate for cervical adenopathy for staging purposes. CT Head Without and With IV Contrast There is no relevant literature to support the use of CT of the head without and with IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Head Without IV Contrast There is no relevant literature to support the use of CT of the head without IV contrast in the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial With IV Contrast There is no relevant literature to support the use of CT maxillofacial with IV contrast for the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the use of CT maxillofacial without and with IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Maxillofacial Without IV Contrast There is no relevant literature to support the use of CT maxillofacial without IV contrast for the evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity.

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CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent sinonasal tumors, treatment response assessment, and regional nodal staging. CT provides excellent delineation of the sinonasal skeleton and is superior to MRI in the depiction of osseous anatomy [96]. The presence of skull base foraminal widening, which can be detected on thin-section CT and reconstructions, may alert to perineural tumor spread [96]. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. MRI confers improved soft tissue contrast over CT and is generally the preferred imaging modality for evaluating for sinonasal recurrence. However, CT is often used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. Assessment of Head and Neck Cancer CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent sinonasal tumors, treatment response assessment, and regional nodal staging. CT provides excellent delineation of the sinonasal skeleton and is superior to MRI in the depiction of osseous anatomy [96]. The presence of skull base foraminal widening, which can be detected on thin-section CT and reconstructions, may alert to perineural tumor spread [96]. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. MRI confers improved soft tissue contrast over CT and is generally the preferred imaging modality for evaluating for sinonasal recurrence. However, CT is often used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. Assessment of Head and Neck Cancer CT Neck Without and With IV Contrast There is no relevant literature to support the use of CT neck without and with IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. CT Neck Without IV Contrast There is no relevant literature to support the use of CT neck without IV contrast for evaluation of suspected or known recurrence of treated cancer of the paranasal sinuses or nasal cavity. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes.

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CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at a high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response, detection, and localization of recurrence, regional nodal disease, and distant metastases in treated cancer of the paranasal sinuses or nasal cavity. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT [134]. For this reason, imaging with FDG-PET/CT is preferred to occur at a minimum of 12 weeks after completion of therapy to allow for treatment effects to subside [117,118], although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false- positive findings. Because of the relatively low positive predictive values of FDG-PET/CT [150], physical examination as well as complementary imaging with MRI remains of utmost importance to elucidate findings discovered on PET/CT and to determine a degree of suspicion. FDG-PET/CT has a high NPV and therefore is very helpful in excluding recurrence [150]. One study calculated an NPV of 91% of a single PET/CT examination obtained at any time after completion of therapy for head and neck squamous cell carcinoma. NPV would increase to 98% if a second scan was also found to be negative [151]. FDG-PET/CT has been found to accurately diagnose distant metastatic disease in the posttreatment setting.

Staging and Post Therapy Assessment of Head and Neck Cancer. CTA Neck With IV Contrast There is no relevant literature to support the use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at a high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response, detection, and localization of recurrence, regional nodal disease, and distant metastases in treated cancer of the paranasal sinuses or nasal cavity. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT [134]. For this reason, imaging with FDG-PET/CT is preferred to occur at a minimum of 12 weeks after completion of therapy to allow for treatment effects to subside [117,118], although imaging as early as 8 weeks after therapy has been suggested [136]. Concurrent infection can similarly give false- positive findings. Because of the relatively low positive predictive values of FDG-PET/CT [150], physical examination as well as complementary imaging with MRI remains of utmost importance to elucidate findings discovered on PET/CT and to determine a degree of suspicion. FDG-PET/CT has a high NPV and therefore is very helpful in excluding recurrence [150]. One study calculated an NPV of 91% of a single PET/CT examination obtained at any time after completion of therapy for head and neck squamous cell carcinoma. NPV would increase to 98% if a second scan was also found to be negative [151]. FDG-PET/CT has been found to accurately diagnose distant metastatic disease in the posttreatment setting.

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In one series, distant metastases were detected in 27% of patients on FDG-PET/CT [102]. Of note, PET/CT is of limited value in cases in which the original tumor demonstrates poor FDG uptake. Tumors with low FDG metabolic activity result in suboptimal delineation of primary tumor recurrence, lymph node involvement, and distant disease [150]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the response assessment and evaluation of recurrence following treatment of cancer of the head and neck, with FDG-PET/MRI performing similarly to FDG/PET CT [137,138]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity.

Staging and Post Therapy Assessment of Head and Neck Cancer. In one series, distant metastases were detected in 27% of patients on FDG-PET/CT [102]. Of note, PET/CT is of limited value in cases in which the original tumor demonstrates poor FDG uptake. Tumors with low FDG metabolic activity result in suboptimal delineation of primary tumor recurrence, lymph node involvement, and distant disease [150]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is a new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the response assessment and evaluation of recurrence following treatment of cancer of the head and neck, with FDG-PET/MRI performing similarly to FDG/PET CT [137,138]. MRA Neck With IV Contrast There is no relevant literature to support the use of MRA neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRA Neck Without and With IV Contrast There is no relevant literature to support the use of MRA neck without and with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRA Neck Without IV Contrast There is no relevant literature to support the use of MRA neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Head With IV Contrast There is no relevant literature to support the use of MRI head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Head Without and With IV Contrast There is no relevant literature to support the use of MRI head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity.

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The coverage of MRI of the head and its included sequences may be insufficient to completely evaluate the primary site in the paranasal sinuses or nasal cavity and will not include regional nodal staging. MRI head without and with IV Assessment of Head and Neck Cancer contrast may be used to further delineate advanced intracranial extension of disease and can be considered in the follow-up of advanced stage olfactory neuroblastoma, which has a known propensity for intracranial dural-based metastases. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck Without and With IV Contrast MRI without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing it from treatment-related change and in evaluating local tumor response. Perineural tumor spread is more easily recognized with MRI compared to CT, as is regional extension of tumor to neighboring structures such as the orbits, dura, and brain, and subtle marrow involvement [96]. Evaluation of the treated neck is often complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence and may require clinical examination and complementary imaging studies such as FDG-PET/CT.

Staging and Post Therapy Assessment of Head and Neck Cancer. The coverage of MRI of the head and its included sequences may be insufficient to completely evaluate the primary site in the paranasal sinuses or nasal cavity and will not include regional nodal staging. MRI head without and with IV Assessment of Head and Neck Cancer contrast may be used to further delineate advanced intracranial extension of disease and can be considered in the follow-up of advanced stage olfactory neuroblastoma, which has a known propensity for intracranial dural-based metastases. MRI Head Without IV Contrast There is no relevant literature to support the use of MRI head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. MRI Orbits, Face, and Neck Without and With IV Contrast MRI without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing it from treatment-related change and in evaluating local tumor response. Perineural tumor spread is more easily recognized with MRI compared to CT, as is regional extension of tumor to neighboring structures such as the orbits, dura, and brain, and subtle marrow involvement [96]. Evaluation of the treated neck is often complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence and may require clinical examination and complementary imaging studies such as FDG-PET/CT.

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Advanced tools, including higher-resolution imaging, diffusion-weighted and diffusion-tensor sequences, and MRI perfusion techniques such as dynamic contrast-enhanced MRI show promise in improving anatomic and functional imaging [103-105]. These tools may help to distinguish between treatment change and recurrence; however, as of now, they are not consistently used in routine clinical practice. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margins and the soft tissue extent of tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of head and neck cancer [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65].

Staging and Post Therapy Assessment of Head and Neck Cancer. Advanced tools, including higher-resolution imaging, diffusion-weighted and diffusion-tensor sequences, and MRI perfusion techniques such as dynamic contrast-enhanced MRI show promise in improving anatomic and functional imaging [103-105]. These tools may help to distinguish between treatment change and recurrence; however, as of now, they are not consistently used in routine clinical practice. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the use of MRI orbits, face, and neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margins and the soft tissue extent of tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of the paranasal sinuses or nasal cavity. US Neck US coupled with fine-needle aspiration and/or core-needle biopsy can be a useful tool in regional nodal evaluation following treatment of head and neck cancer [140]. A range of sensitivities and specificities for detection of nodal disease are found in the literature, likely reflecting the highly operator-dependent nature of this technique. US alone has been shown to very sensitive (77.8%-96.8%) and specific (68.75%-97%) in detecting cervical nodal metastases [47,63-65].

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In the presence of bulky nodal disease in squamous cell carcinoma, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy, with a higher combined NPV [65]. Variant 8: Treated cancer of a major salivary gland (parotid, submandibular, and sublingual glands). Surveillance imaging or follow-up imaging for suspected or known recurrence. Physical examination and imaging surveillance following treatment of malignant neoplasms of the major salivary glands may be obscured or impeded by postoperative scarring and anatomic distortion. Furthermore, deep local recurrences and perineural tumor spread can be inaccessible to clinical assessment and may go overlooked, particularly in early stages [108]. Delayed diagnosis of tumor recurrence portends a poor prognosis and a decrease in long-term survival, independent of histologic type [108,152]. Because perineural tumor spread is common in malignant salivary gland tumors, in particular in adenoid cystic carcinoma, a complete radical resection may not always be feasible and postoperative radiotherapy may be indicated [152]. Regular follow-up is recommended following treatment of malignant salivary gland neoplasms [152]. The majority, approximately 70%, of recurrences of high-grade malignant salivary gland tumors occur in the first 3 years Assessment of Head and Neck Cancer following treatment [108], and these can be subclassified into local, regional, and distant. In a large cohort of 565 patients with salivary gland tumors followed over a 10 year period, local recurrence was reported in 13% of the cases, regional recurrence was seen in 22% of the cases, and distant metastases were documented in 33% of the patients [108]. Other studies reported distant disease in >50% of patients, with adenoid cystic carcinoma, adenocarcinoma, and carcinoma ex pleomorphic adenoma accounting for the majority of the cases [108].

Staging and Post Therapy Assessment of Head and Neck Cancer. In the presence of bulky nodal disease in squamous cell carcinoma, US combined with FDG-PET/CT was found to be a reliable strategy to identify patients with complete nodal response to therapy, with a higher combined NPV [65]. Variant 8: Treated cancer of a major salivary gland (parotid, submandibular, and sublingual glands). Surveillance imaging or follow-up imaging for suspected or known recurrence. Physical examination and imaging surveillance following treatment of malignant neoplasms of the major salivary glands may be obscured or impeded by postoperative scarring and anatomic distortion. Furthermore, deep local recurrences and perineural tumor spread can be inaccessible to clinical assessment and may go overlooked, particularly in early stages [108]. Delayed diagnosis of tumor recurrence portends a poor prognosis and a decrease in long-term survival, independent of histologic type [108,152]. Because perineural tumor spread is common in malignant salivary gland tumors, in particular in adenoid cystic carcinoma, a complete radical resection may not always be feasible and postoperative radiotherapy may be indicated [152]. Regular follow-up is recommended following treatment of malignant salivary gland neoplasms [152]. The majority, approximately 70%, of recurrences of high-grade malignant salivary gland tumors occur in the first 3 years Assessment of Head and Neck Cancer following treatment [108], and these can be subclassified into local, regional, and distant. In a large cohort of 565 patients with salivary gland tumors followed over a 10 year period, local recurrence was reported in 13% of the cases, regional recurrence was seen in 22% of the cases, and distant metastases were documented in 33% of the patients [108]. Other studies reported distant disease in >50% of patients, with adenoid cystic carcinoma, adenocarcinoma, and carcinoma ex pleomorphic adenoma accounting for the majority of the cases [108].

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The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is the lungs. A distant second are the bones followed by the liver, brain, and other sites [108]. Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated cancer of a major salivary gland. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Pulmonary metastatic disease is the single most common site of metastatic disease beyond the head and neck in suspected or confirmed metastatic disease at follow-up. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing the nodes from mediastinal vessels. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of a major salivary gland.

Staging and Post Therapy Assessment of Head and Neck Cancer. The most common site of metastatic involvement beyond the head and neck in up to 90% of cases is the lungs. A distant second are the bones followed by the liver, brain, and other sites [108]. Radiography Chest CXR is not considered the imaging modality of choice for the evaluation of pulmonary metastatic disease in treated cancer of a major salivary gland. Chest CT is far more sensitive in detecting pulmonary metastatic disease compared to radiography [15], with the sensitivity of CXR to detect pulmonary metastatic disease reported as low as 28% compared to chest CT [11]. The low sensitivity may in part be due to the small size of pulmonary nodules at presentation or peripheral location, in which CXR tends to be less reliable [11]. The use of CXR for detection of metastases has not been shown to improve prognosis because pulmonary metastatic disease detected on CXR tends to be diagnosed at a late stage when it is not as amenable to treatment [18]. CT Chest With IV Contrast CT chest with IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Pulmonary metastatic disease is the single most common site of metastatic disease beyond the head and neck in suspected or confirmed metastatic disease at follow-up. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing the nodes from mediastinal vessels. There is a paucity of relevant supportive literature specifically comparing the diagnostic performance of CT chest with IV contrast and CT chest without IV contrast. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast in the evaluation of treated cancer of a major salivary gland.

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CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Pulmonary metastatic disease is the single most common site of metastatic disease beyond the head and neck in suspected or confirmed metastatic disease at follow-up. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing the nodes from mediastinal vessels. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the routine use of CT of the head with IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Head Without and With IV Contrast There is no relevant literature to support the routine use of CT of the head without and with IV contrast in follow- up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Head Without IV Contrast There is no relevant literature to support the routine use of CT of the head without IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Maxillofacial With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial with IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site.

Staging and Post Therapy Assessment of Head and Neck Cancer. CT Chest Without IV Contrast CT chest without IV contrast can accurately identify pulmonary metastasis and be used to detect thoracic nodal and skeletal metastases to the ribs or vertebrae. Pulmonary metastatic disease is the single most common site of metastatic disease beyond the head and neck in suspected or confirmed metastatic disease at follow-up. CT chest confers superior spatial localization and contrast resolution compared to radiography, allowing for the detection of small pulmonary nodules [15]. The use of IV contrast may improve detection of mediastinal and hilar adenopathy by distinguishing the nodes from mediastinal vessels. Noncontrast CT chest may be considered as an alternative and is part of routine clinical practice, although there is paucity of relevant supportive literature evaluating the use of CT chest without IV contrast. CT Head With IV Contrast There is no relevant literature to support the routine use of CT of the head with IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Head Without and With IV Contrast There is no relevant literature to support the routine use of CT of the head without and with IV contrast in follow- up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Head Without IV Contrast There is no relevant literature to support the routine use of CT of the head without IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Maxillofacial With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial with IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT of the maxillofacial region may provide sufficient coverage for the anatomic evaluation of the primary tumor site.

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However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. Assessment of Head and Neck Cancer CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without and with IV contrast in follow- up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Maxillofacial Without IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent tumor and the evaluation of regional nodal disease. CT is also used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Evaluation of the treated neck is very often complicated by significant treatment related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Soft tissue resolution of CT is considered inferior to that of MRI [108], and certain cancers such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinomas may lack significant contrast enhancement on CT, rendering the detection of recurrence difficult by this modality [111]. Furthermore, MRI is considered superior in the detection of perineural spread and the soft tissue extent of disease [107,108].

Staging and Post Therapy Assessment of Head and Neck Cancer. However, CT maxillofacial will typically not include evaluation of the neck and would therefore be inadequate for the staging of regional lymphadenopathy. Assessment of Head and Neck Cancer CT Maxillofacial Without and With IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without and with IV contrast in follow- up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Maxillofacial Without IV Contrast There is no relevant literature to support the routine use of CT maxillofacial without IV contrast in follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Neck With IV Contrast Although protocols vary across institutions, for the purposes of this document, CT of the neck includes coverage from the top of the frontal sinuses down to the level of the aortic arch, with thin slices, multiplanar reformats, and both soft tissue and bony algorithms. CECT of the neck allows for the detection and localization of recurrent tumor and the evaluation of regional nodal disease. CT is also used to monitor treatment changes and assess for treatment complications such as infection or osteoradionecrosis. Evaluation of the treated neck is very often complicated by significant treatment related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Soft tissue resolution of CT is considered inferior to that of MRI [108], and certain cancers such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinomas may lack significant contrast enhancement on CT, rendering the detection of recurrence difficult by this modality [111]. Furthermore, MRI is considered superior in the detection of perineural spread and the soft tissue extent of disease [107,108].

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Staging and Post Therapy Assessment of Head and Neck Cancer

Generally, CT is reserved for the evaluation of treatment complications or when there are indeterminate findings regarding osseous invasion [107,108]. CT may prove to be especially useful in the setting of suspected bone involvement because of its improved detection of cortical erosion [112]. The use of IV contrast is recommended to better outline the extent of the primary site. CT Neck Without and With IV Contrast There is no relevant literature to support the routine use of CT neck without and with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Neck Without IV Contrast There is no relevant literature to support the routine use of CT neck without IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the routine use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response and detection and localization of recurrence, regional nodal disease, and distant metastases. The utility of FDG-PET/CT depends on the tumor grade, because low-grade salivary gland tumors tend to have relatively low metabolism and may be occult on FDG-PET/imaging. FDG- PET/CT is therefore not routinely recommended for follow-up of low-grade salivary gland tumors [108]. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT.

Staging and Post Therapy Assessment of Head and Neck Cancer. Generally, CT is reserved for the evaluation of treatment complications or when there are indeterminate findings regarding osseous invasion [107,108]. CT may prove to be especially useful in the setting of suspected bone involvement because of its improved detection of cortical erosion [112]. The use of IV contrast is recommended to better outline the extent of the primary site. CT Neck Without and With IV Contrast There is no relevant literature to support the routine use of CT neck without and with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. CT Neck Without IV Contrast There is no relevant literature to support the routine use of CT neck without IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. Contrast enhancement is imperative in order to correctly identify and delineate recurrence, distinguishing it from treatment changes. CTA Neck With IV Contrast There is no relevant literature to support the routine use of CTA of the neck with IV contrast in the follow-up imaging or evaluation of known or suspected recurrence of treated cancer of a major salivary gland. In the case of recurrent disease encroaching on the carotid arteries, CTA of the neck can be used to identify patients at high risk of bleeding [41]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT allows for the assessment of treatment response and detection and localization of recurrence, regional nodal disease, and distant metastases. The utility of FDG-PET/CT depends on the tumor grade, because low-grade salivary gland tumors tend to have relatively low metabolism and may be occult on FDG-PET/imaging. FDG- PET/CT is therefore not routinely recommended for follow-up of low-grade salivary gland tumors [108]. The presence of posttreatment inflammatory change decreases the specificity of findings on FDG-PET/CT.

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Staging and Post Therapy Assessment of Head and Neck Cancer

For this reason, imaging with FDG-PET/CT should be delayed at least 8 weeks following therapy and is preferred to occur at a minimum of 12 weeks after completion of therapy to allow for treatment effects to subside [110]. Concurrent infection can similarity give false positive findings. The use of FDG-PET/CT to evaluate for local recurrence may not confer benefit over CECT and MRI [153] but may have benefit in follow-up imaging of high-grade salivary gland tumors because of the increased frequency of distant metastases [108,114]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of major salivary gland tumor, with FDG-PET/MRI performing similarly to FDG-PET/CT. A study comparing FDG-PET/MRI to MRI concluded that FDG-PET/MRI is superior to MRI alone in the detection of local disease recurrence and locoregional nodal metastases in patients with adenoid cystic carcinoma [152]. Also, hybrid FDG-PET/MRI was found to be superior to conventional MRI in its NPV [137]. A separate study suggests FDG-PET/MRI is superior to PET/CT in the setting of salivary gland Assessment of Head and Neck Cancer tumors because of its improved characterization of internal tumor features and because of the propensity of these malignancies to present with perineural tumor spread [154]. MRA Neck With IV Contrast There is no relevant literature to support the routine use of MRA of the head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRA Neck Without and With IV Contrast There is no relevant literature to support the routine use of MRA of the head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland.

Staging and Post Therapy Assessment of Head and Neck Cancer. For this reason, imaging with FDG-PET/CT should be delayed at least 8 weeks following therapy and is preferred to occur at a minimum of 12 weeks after completion of therapy to allow for treatment effects to subside [110]. Concurrent infection can similarity give false positive findings. The use of FDG-PET/CT to evaluate for local recurrence may not confer benefit over CECT and MRI [153] but may have benefit in follow-up imaging of high-grade salivary gland tumors because of the increased frequency of distant metastases [108,114]. FDG-PET/MRI Skull Base to Mid-Thigh FDG-PET/MRI is new imaging modality with a growing body of evidence demonstrating the feasibility of use for routine clinical imaging, including the initial staging of major salivary gland tumor, with FDG-PET/MRI performing similarly to FDG-PET/CT. A study comparing FDG-PET/MRI to MRI concluded that FDG-PET/MRI is superior to MRI alone in the detection of local disease recurrence and locoregional nodal metastases in patients with adenoid cystic carcinoma [152]. Also, hybrid FDG-PET/MRI was found to be superior to conventional MRI in its NPV [137]. A separate study suggests FDG-PET/MRI is superior to PET/CT in the setting of salivary gland Assessment of Head and Neck Cancer tumors because of its improved characterization of internal tumor features and because of the propensity of these malignancies to present with perineural tumor spread [154]. MRA Neck With IV Contrast There is no relevant literature to support the routine use of MRA of the head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRA Neck Without and With IV Contrast There is no relevant literature to support the routine use of MRA of the head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland.

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Staging and Post Therapy Assessment of Head and Neck Cancer

MRA Neck Without IV Contrast There is no relevant literature to support the routine use of MRA of the head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head With IV Contrast There is no relevant literature to support the routine use of MRI of the head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head Without and With IV Contrast There is no relevant literature to support the routine use of MRI of the head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head Without IV Contrast There is no relevant literature to support the routine use of MRI of the head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the follow- up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing from treatment-related changes and evaluating local tumor response. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence. Because of the superior soft tissue contrast resolution of MRI, it is considered the modality of choice over CECT for imaging of suspected locoregional tumor recurrence.

Staging and Post Therapy Assessment of Head and Neck Cancer. MRA Neck Without IV Contrast There is no relevant literature to support the routine use of MRA of the head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head With IV Contrast There is no relevant literature to support the routine use of MRI of the head with IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head Without and With IV Contrast There is no relevant literature to support the routine use of MRI of the head with and without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Head Without IV Contrast There is no relevant literature to support the routine use of MRI of the head without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Orbits, Face, and Neck With IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck with IV contrast in the follow- up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. MRI Orbits, Face, and Neck Without and With IV Contrast MRI orbits, face, and neck without and with IV contrast has superior soft tissue contrast resolution, which facilitates assessment of local recurrence and can be helpful in distinguishing from treatment-related changes and evaluating local tumor response. Evaluation of the treated neck is very often complicated by significant treatment-related changes that can be difficult to differentiate from persistent disease after therapy or recurrence. Because of the superior soft tissue contrast resolution of MRI, it is considered the modality of choice over CECT for imaging of suspected locoregional tumor recurrence.

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Staging and Post Therapy Assessment of Head and Neck Cancer

MRI better delineates the soft tissue extension of tumor, including perineural spread of disease. The use of advanced MRI techniques such as diffusion-weighted imaging may provide further information and increase sensitivity of identifying the recurrent tumor [108]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrence and distinguish that from treatment change. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change, and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margins and the soft tissue extent of the tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. US Neck US allows for the detection and localization of recurrence following treatment of major salivary gland tumors as well as regional nodal staging. US can additionally serve as guidance for fine-needle aspiration for diagnosis of recurrent disease [108]. Evaluation of the treated neck is complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Furthermore, US has limited

Staging and Post Therapy Assessment of Head and Neck Cancer. MRI better delineates the soft tissue extension of tumor, including perineural spread of disease. The use of advanced MRI techniques such as diffusion-weighted imaging may provide further information and increase sensitivity of identifying the recurrent tumor [108]. Combined pre- and postcontrast imaging provides the best opportunity to correctly identify and delineate recurrence and distinguish that from treatment change. MRI Orbits, Face, and Neck Without IV Contrast There is no relevant literature to support the routine use of MRI orbits, face, and neck without IV contrast in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. Combined pre- and postcontrast imaging provides the best opportunity to identify and delineate local tumor recurrence, distinguishing it from treatment-related change, and in evaluating local tumor response. The absence of IV contrast limits the ability to accurately delineate the margins and the soft tissue extent of the tumor. However, noncontrast MR sequences are routinely used to identify tumor recurrence and can define tumor extent, in particular marrow involvement, and are used in nodal assessment. Radiography Paranasal Sinuses There is no relevant literature to support the use of radiography of the paranasal sinuses in the follow-up imaging or the evaluation of known or suspected recurrence of treated cancer of a major salivary gland. US Neck US allows for the detection and localization of recurrence following treatment of major salivary gland tumors as well as regional nodal staging. US can additionally serve as guidance for fine-needle aspiration for diagnosis of recurrent disease [108]. Evaluation of the treated neck is complicated by significant treatment-related changes that can be difficult to distinguish from persistent disease after therapy or recurrence. Furthermore, US has limited

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Epigastric Pain

OR Discussion of Procedures by Variant Variant 1: Epigastric pain with clinical suspicion for acid reflux or esophagitis or gastritis or peptic ulcer or duodenal ulcer. Initial imaging. GERD is a common medical disorder in the western world; it is reported that as many as 7% of Americans have episodes of heartburn every day and approximately 42% experience heartburn at least once a month [6]. Although GERD is a common disorder, its diagnosis is not straightforward; the primary reason for this is that the symptoms aNew York University Langone Medical Center, New York, New York and UT Southwestern Medical Center, Dallas, Texas. bJohns Hopkins Hospital, Baltimore, Maryland. cPanel Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. dPanel Vice-Chair, University of Alabama Medical Center, Birmingham, Alabama. eUniversity of Arizona, Banner University Medical Center, Tucson, Arizona. fDuke University Medical Center, Durham, North Carolina. gOregon Health & Science University, Portland, Oregon. hUMass Medical School, Worcester, Massachusetts. iEmory University, Atlanta, Georgia. jStanford University Medical Center, Stanford, California. kMontefiore Medical Center, Bronx, New York. lNorthwestern University Feinberg School of Medicine, Chicago, Illinois, Primary care physician. mUniversity of Connecticut, Farmington, Connecticut. nNorthShore University HealthSystem, Evanston, Illinois. oUniversity of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; American College of Emergency Physicians. pUniversity of Cincinnati Medical Center, Cincinnati, Ohio. qThe University of Mississippi Medical Center, Jackson, Mississippi; American College of Physicians. rThe Ohio State University Wexner Medical Center, Columbus, Ohio. sPhoenix Indian Medical Center, Phoenix, Arizona; American College of Surgeons. tSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia.

Epigastric Pain. OR Discussion of Procedures by Variant Variant 1: Epigastric pain with clinical suspicion for acid reflux or esophagitis or gastritis or peptic ulcer or duodenal ulcer. Initial imaging. GERD is a common medical disorder in the western world; it is reported that as many as 7% of Americans have episodes of heartburn every day and approximately 42% experience heartburn at least once a month [6]. Although GERD is a common disorder, its diagnosis is not straightforward; the primary reason for this is that the symptoms aNew York University Langone Medical Center, New York, New York and UT Southwestern Medical Center, Dallas, Texas. bJohns Hopkins Hospital, Baltimore, Maryland. cPanel Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. dPanel Vice-Chair, University of Alabama Medical Center, Birmingham, Alabama. eUniversity of Arizona, Banner University Medical Center, Tucson, Arizona. fDuke University Medical Center, Durham, North Carolina. gOregon Health & Science University, Portland, Oregon. hUMass Medical School, Worcester, Massachusetts. iEmory University, Atlanta, Georgia. jStanford University Medical Center, Stanford, California. kMontefiore Medical Center, Bronx, New York. lNorthwestern University Feinberg School of Medicine, Chicago, Illinois, Primary care physician. mUniversity of Connecticut, Farmington, Connecticut. nNorthShore University HealthSystem, Evanston, Illinois. oUniversity of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; American College of Emergency Physicians. pUniversity of Cincinnati Medical Center, Cincinnati, Ohio. qThe University of Mississippi Medical Center, Jackson, Mississippi; American College of Physicians. rThe Ohio State University Wexner Medical Center, Columbus, Ohio. sPhoenix Indian Medical Center, Phoenix, Arizona; American College of Surgeons. tSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia.

3158168

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Epigastric Pain

The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Epigastric Pain are nonspecific and overlap with other conditions [6]. GERD questionnaires, esophageal manometry, esophageal pH testing, imaging examinations, and upper endoscopy are routinely used for diagnosis [6]. PUD has an incidence of 0.1% to 0.3% [7]. Early diagnosis, treatment of Helicobacter pylori infections, and widespread use of proton pump inhibitors have all led to reducing the prevalence of PUD. It is still important to diagnose PUD, because PUD-related complications can be seen in 2% to 10% of cases, and PUD-related perforation is a surgical emergency with a mortality rate of up to 30% [7,8]. Although endoscopy is considered the standard test of choice for diagnosing these entities, patients may present with nonspecific symptoms, which may lead to an imaging study in which these entities could be identified. CT Abdomen and Pelvis Although a CT examination is not the test of choice for initial imaging if acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer is strongly suspected, patients with these entities may present with nonspecific/overlapping symptoms and may undergo a CT abdomen and pelvis as the initial diagnostic test for evaluation [7].

Epigastric Pain. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Epigastric Pain are nonspecific and overlap with other conditions [6]. GERD questionnaires, esophageal manometry, esophageal pH testing, imaging examinations, and upper endoscopy are routinely used for diagnosis [6]. PUD has an incidence of 0.1% to 0.3% [7]. Early diagnosis, treatment of Helicobacter pylori infections, and widespread use of proton pump inhibitors have all led to reducing the prevalence of PUD. It is still important to diagnose PUD, because PUD-related complications can be seen in 2% to 10% of cases, and PUD-related perforation is a surgical emergency with a mortality rate of up to 30% [7,8]. Although endoscopy is considered the standard test of choice for diagnosing these entities, patients may present with nonspecific symptoms, which may lead to an imaging study in which these entities could be identified. CT Abdomen and Pelvis Although a CT examination is not the test of choice for initial imaging if acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer is strongly suspected, patients with these entities may present with nonspecific/overlapping symptoms and may undergo a CT abdomen and pelvis as the initial diagnostic test for evaluation [7].

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acrac_3158168_2

Epigastric Pain

Findings suggestive of the diagnosis of gastritis or PUD on CT can include the following: gastric or duodenal wall thickening due to submucosal edema; mucosal hyperenhancement or fat stranding due to inflammation; fluid along the gastroduodenal region; focal outpouching of the mucosa resulting from ulcerations; focal interruption of mucosal enhancement resulting from an ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer or muscularis propria; focal perforation of a gastric ulcer with associated free air; or gastric outlet obstruction due to edema or chronic inflammatory changes near the antrum and pylorus [7,8]. Active bleeding from a peptic ulcer can be detected when hyperdense blood products accumulate at the site of the ulcer or in the stomach/duodenal lumen or as an area of active contrast extravasation [8]. PUD is the main cause of nontraumatic gastroduodenal perforation [11]. In a study by Lee et al [11], the following features were seen with perforation: extraluminal gas (97%), fluid or fat stranding along the gastroduodenal region (89%), ascites (89%), focal wall defect and/or ulcer (84%), and wall thickening (72%). Of these features, a wall defect and/or ulcer showed a positive likelihood ratio for gastroduodenal perforation of 36.83 and wall thickening showed a positive likelihood ratio of 10.52. Combined, these two features showed 95% sensitivity and 93% specificity for localization of a site of perforation [11]. If oral contrast is administered, extraluminal contrast may be seen at the site of perforation [8].

Epigastric Pain. Findings suggestive of the diagnosis of gastritis or PUD on CT can include the following: gastric or duodenal wall thickening due to submucosal edema; mucosal hyperenhancement or fat stranding due to inflammation; fluid along the gastroduodenal region; focal outpouching of the mucosa resulting from ulcerations; focal interruption of mucosal enhancement resulting from an ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer or muscularis propria; focal perforation of a gastric ulcer with associated free air; or gastric outlet obstruction due to edema or chronic inflammatory changes near the antrum and pylorus [7,8]. Active bleeding from a peptic ulcer can be detected when hyperdense blood products accumulate at the site of the ulcer or in the stomach/duodenal lumen or as an area of active contrast extravasation [8]. PUD is the main cause of nontraumatic gastroduodenal perforation [11]. In a study by Lee et al [11], the following features were seen with perforation: extraluminal gas (97%), fluid or fat stranding along the gastroduodenal region (89%), ascites (89%), focal wall defect and/or ulcer (84%), and wall thickening (72%). Of these features, a wall defect and/or ulcer showed a positive likelihood ratio for gastroduodenal perforation of 36.83 and wall thickening showed a positive likelihood ratio of 10.52. Combined, these two features showed 95% sensitivity and 93% specificity for localization of a site of perforation [11]. If oral contrast is administered, extraluminal contrast may be seen at the site of perforation [8].

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Epigastric Pain

When gastric disease is suspected, the CT examination should be performed with intravenous (IV) contrast (to assess for submucosal edema, mucosal hyperenhancement due to inflammation, a focal outpouching of the mucosal bowel lining resulting from the crater of the ulcer, focal interruption of mucosal enhancement resulting from the ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer, or muscularis propria) and a neutral oral contrast such as water or dilute barium suspension (positive oral contrast can impede assessment of mucosal enhancement and preclude assessment of intraluminal bleeding) [12]. There is limited value of performing a CT abdomen and pelvis without and with IV contrast for this indication. A CT examination without IV contrast may help in diagnosing PUD by detecting findings such as extraluminal gas, reactive fluid, fat stranding along the gastroduodenal region, ascites, focal wall defect, or a large ulcer. However, the addition of IV contrast significantly improves conspicuity of findings such as interrupted mucosal enhancement and bowel wall hyperenhancement, making the CT examination more sensitive in diagnosis. CT Abdomen Although a CT abdomen examination may provide the same clues to diagnose acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer as a CT abdomen and pelvis examination, the latter is usually chosen when overlapping or nonspecific symptoms are encountered. If gastric disease is strongly suspected, it would be appropriate to omit the pelvis from the examination. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for submucosal edema, mucosal hyperenhancement due to inflammation, a focal outpouching of the mucosal bowel Epigastric Pain

Epigastric Pain. When gastric disease is suspected, the CT examination should be performed with intravenous (IV) contrast (to assess for submucosal edema, mucosal hyperenhancement due to inflammation, a focal outpouching of the mucosal bowel lining resulting from the crater of the ulcer, focal interruption of mucosal enhancement resulting from the ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer, or muscularis propria) and a neutral oral contrast such as water or dilute barium suspension (positive oral contrast can impede assessment of mucosal enhancement and preclude assessment of intraluminal bleeding) [12]. There is limited value of performing a CT abdomen and pelvis without and with IV contrast for this indication. A CT examination without IV contrast may help in diagnosing PUD by detecting findings such as extraluminal gas, reactive fluid, fat stranding along the gastroduodenal region, ascites, focal wall defect, or a large ulcer. However, the addition of IV contrast significantly improves conspicuity of findings such as interrupted mucosal enhancement and bowel wall hyperenhancement, making the CT examination more sensitive in diagnosis. CT Abdomen Although a CT abdomen examination may provide the same clues to diagnose acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer as a CT abdomen and pelvis examination, the latter is usually chosen when overlapping or nonspecific symptoms are encountered. If gastric disease is strongly suspected, it would be appropriate to omit the pelvis from the examination. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for submucosal edema, mucosal hyperenhancement due to inflammation, a focal outpouching of the mucosal bowel Epigastric Pain

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Epigastric Pain

lining resulting from the crater of the ulcer, focal interruption of mucosal enhancement resulting from the ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer or muscularis propria) and neutral oral contrast such as water or dilute barium suspension (positive oral contrast can impede assessment of mucosal enhancement and preclude assessment of intraluminal bleeding) [12]. There is limited value of performing a CT abdomen without and with IV contrast for this indication. A CT examination without IV contrast may help in diagnosing PUD by detecting findings such as extraluminal gas, reactive fluid, fat stranding along the gastroduodenal region, ascites, focal wall defect, or a large ulcer. However, the addition of IV contrast significantly improves conspicuity of findings, such as interrupted mucosal enhancement and bowel wall hyperenhancement, making the CT examination more sensitive in diagnosis. CT Abdomen Multiphase Multiphase contrast-enhanced examinations are not routinely performed in patients with suspected acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer, but a CT angiographic protocol, including precontrast, arterial, and portal venous phases or a 2-phase dual-energy protocol with arterial and portal venous phases, may be used for patients with suspected acute gastrointestinal (GI) bleeding. These protocols may be used if GI bleeding as a complication of PUD is suspected [12]; otherwise, there would be limited utility of a multiphase examination. FDG-PET/CT Skull Base to Mid-Thigh Although patients with GERD and esophagitis may exhibit increased radiotracer uptake in the distal esophagus on fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET [13], there is no relevant literature to support the use of FDG- PET/CT in the prospective diagnosis of acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer.

Epigastric Pain. lining resulting from the crater of the ulcer, focal interruption of mucosal enhancement resulting from the ulcer crater eroding through the epithelial lining of the mucosal layer into the submucosal layer or muscularis propria) and neutral oral contrast such as water or dilute barium suspension (positive oral contrast can impede assessment of mucosal enhancement and preclude assessment of intraluminal bleeding) [12]. There is limited value of performing a CT abdomen without and with IV contrast for this indication. A CT examination without IV contrast may help in diagnosing PUD by detecting findings such as extraluminal gas, reactive fluid, fat stranding along the gastroduodenal region, ascites, focal wall defect, or a large ulcer. However, the addition of IV contrast significantly improves conspicuity of findings, such as interrupted mucosal enhancement and bowel wall hyperenhancement, making the CT examination more sensitive in diagnosis. CT Abdomen Multiphase Multiphase contrast-enhanced examinations are not routinely performed in patients with suspected acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer, but a CT angiographic protocol, including precontrast, arterial, and portal venous phases or a 2-phase dual-energy protocol with arterial and portal venous phases, may be used for patients with suspected acute gastrointestinal (GI) bleeding. These protocols may be used if GI bleeding as a complication of PUD is suspected [12]; otherwise, there would be limited utility of a multiphase examination. FDG-PET/CT Skull Base to Mid-Thigh Although patients with GERD and esophagitis may exhibit increased radiotracer uptake in the distal esophagus on fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET [13], there is no relevant literature to support the use of FDG- PET/CT in the prospective diagnosis of acid reflux, esophagitis, gastritis, peptic ulcer, or duodenal ulcer.

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acrac_3158168_5

Epigastric Pain

Fluoroscopy Biphasic Esophagram Fluoroscopy continues to be an important radiologic modality for the evaluation of patients with epigastric pain due to reflux symptoms, esophagitis, or for nonspecific abdominal pain that could be due to GERD or PUD. Depending on the symptoms, the evaluation may be performed with an esophagram/barium swallow, an upper GI series, or a combination of the two. A barium swallow/esophagram can be performed as a multiphasic examination that includes upright double-contrast views with a high density barium suspension, prone single-contrast views with a low-density barium suspension, and mucosal-relief views with either density of barium suspension [14]. The double-contrast phase optimizes the ability to detect inflammatory or neoplastic diseases, whereas the single-contrast phase optimizes the ability to detect hiatal hernias and lower esophageal rings or strictures [14]. Barium esophagram provides anatomic and functional information on esophageal length, presence, and size of hiatal hernia, diverticulum, esophageal stricture, as well as the presence of gastroesophageal reflux events with provocation [6]. Reflux esophagitis may manifest as fine nodularity or granularity of the mucosa, erosions or ulcers, thickened longitudinal folds, inflammatory esophagogastric polyps, and scarring with strictures, sacculations, or fixed transverse folds [14]. Single-contrast examinations have a reported sensitivity of 77% for detecting endoscopically proven esophagitis. Double-contrast examinations have a higher sensitivity of 80% because of their ability to reveal mucosal abnormalities that cannot be visualized on single-contrast studies. An even higher sensitivity of 88% is achieved by using a combined technique [14-16]. As such, a combined technique is most favorable for this assessment.

Epigastric Pain. Fluoroscopy Biphasic Esophagram Fluoroscopy continues to be an important radiologic modality for the evaluation of patients with epigastric pain due to reflux symptoms, esophagitis, or for nonspecific abdominal pain that could be due to GERD or PUD. Depending on the symptoms, the evaluation may be performed with an esophagram/barium swallow, an upper GI series, or a combination of the two. A barium swallow/esophagram can be performed as a multiphasic examination that includes upright double-contrast views with a high density barium suspension, prone single-contrast views with a low-density barium suspension, and mucosal-relief views with either density of barium suspension [14]. The double-contrast phase optimizes the ability to detect inflammatory or neoplastic diseases, whereas the single-contrast phase optimizes the ability to detect hiatal hernias and lower esophageal rings or strictures [14]. Barium esophagram provides anatomic and functional information on esophageal length, presence, and size of hiatal hernia, diverticulum, esophageal stricture, as well as the presence of gastroesophageal reflux events with provocation [6]. Reflux esophagitis may manifest as fine nodularity or granularity of the mucosa, erosions or ulcers, thickened longitudinal folds, inflammatory esophagogastric polyps, and scarring with strictures, sacculations, or fixed transverse folds [14]. Single-contrast examinations have a reported sensitivity of 77% for detecting endoscopically proven esophagitis. Double-contrast examinations have a higher sensitivity of 80% because of their ability to reveal mucosal abnormalities that cannot be visualized on single-contrast studies. An even higher sensitivity of 88% is achieved by using a combined technique [14-16]. As such, a combined technique is most favorable for this assessment.

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acrac_3158168_6

Epigastric Pain

Fluoroscopy Single-Contrast Esophagram Although a biphasic examination is preferred to a single-contrast examination to assess for reflux/esophagitis, a single-contrast examination may be necessary because of patient capabilities. A single-contrast examination may be helpful by revealing reflux, lower esophageal rings, or strictures [12]. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17]. Fluoroscopic evaluation of the esophagus may reveal findings of esophagitis as detailed above. In addition, evaluation of the stomach can be helpful in diagnosing gastritis, which may manifest as enlarged areae gastricae, disruption of the normal polygonal areae gastricae pattern by multiple uniform nodules, thickened gastric folds, erosions, or an ulcer with smooth folds radiating to the margin. In contrast, findings concerning for malignancy include an ulcer associated with nodularity of the adjacent mucosa, mass effect, or coarse, lobulated, or irregular radiating folds [17]. This examination should be performed when symptoms are nonspecific and differential possibilities of esophagitis, gastritis, or PUD are being considered. Epigastric Pain MRI Abdomen In general, MRI is not routinely used to diagnose GERD. For patients presenting with nonspecific symptoms when gastritis or peptic ulcer or duodenal ulcer is suspected, MRI may be able to suggest these diagnoses, but a CT examination is typically chosen over MRI because of its ability to detect free air associated with a perforated ulcer and its shorter time interval to obtain the examination. MRI Abdomen with MRCP There is no relevant literature to support the use of MR cholangiopancreatography (MRCP) sequences in the prospective diagnosis of acid reflux or esophagitis or gastritis or peptic ulcer or duodenal ulcer. Variant 2: Epigastric pain with clinical suspicion for gastric cancer. Initial imaging.

Epigastric Pain. Fluoroscopy Single-Contrast Esophagram Although a biphasic examination is preferred to a single-contrast examination to assess for reflux/esophagitis, a single-contrast examination may be necessary because of patient capabilities. A single-contrast examination may be helpful by revealing reflux, lower esophageal rings, or strictures [12]. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17]. Fluoroscopic evaluation of the esophagus may reveal findings of esophagitis as detailed above. In addition, evaluation of the stomach can be helpful in diagnosing gastritis, which may manifest as enlarged areae gastricae, disruption of the normal polygonal areae gastricae pattern by multiple uniform nodules, thickened gastric folds, erosions, or an ulcer with smooth folds radiating to the margin. In contrast, findings concerning for malignancy include an ulcer associated with nodularity of the adjacent mucosa, mass effect, or coarse, lobulated, or irregular radiating folds [17]. This examination should be performed when symptoms are nonspecific and differential possibilities of esophagitis, gastritis, or PUD are being considered. Epigastric Pain MRI Abdomen In general, MRI is not routinely used to diagnose GERD. For patients presenting with nonspecific symptoms when gastritis or peptic ulcer or duodenal ulcer is suspected, MRI may be able to suggest these diagnoses, but a CT examination is typically chosen over MRI because of its ability to detect free air associated with a perforated ulcer and its shorter time interval to obtain the examination. MRI Abdomen with MRCP There is no relevant literature to support the use of MR cholangiopancreatography (MRCP) sequences in the prospective diagnosis of acid reflux or esophagitis or gastritis or peptic ulcer or duodenal ulcer. Variant 2: Epigastric pain with clinical suspicion for gastric cancer. Initial imaging.

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acrac_3158168_7

Epigastric Pain

Gastric adenocarcinoma has an incidence rate of 7.3 per 100,000 with 27,600 new cases estimated in 2020 and a 5- year relative survival rate of 32% [18]. Although endoscopy with biopsy is the reference standard for diagnosing gastric cancer, patients often present with nonspecific symptoms and undergo an imaging test for workup of those symptoms; gastric cancer may be first detected on such imaging. CT Abdomen and Pelvis Although endoscopy is the reference standard for diagnosing gastric cancer, patients may present with nonspecific symptoms and may undergo an imaging test for workup of those symptoms; gastric cancer may be first detected on such imaging. Additionally, malignancy is now the most common cause of gastric outlet obstruction in adults because the incidence of PUD has decreased because of the widespread use of H2 blockers [12]. If a gastric outlet obstruction is suspected, a CT may be ordered for anatomic evaluation. In some cases, a gastric mass may not be well seen on CT because of gastric underdistension. However, multiple other imaging findings may nonetheless be identified on CT that are concerning for this diagnosis, such as nodular or irregular wall thickening or enhancement, soft tissue attenuation of wall thickening (rather than low attenuation thickening due to edema), perforation with an ulcerated mass, lymphadenopathy, and distant metastases [7,8,12]. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for nodular wall thickening, soft tissue attenuation of the wall thickening) and neutral oral contrast such as water or dilute barium suspension to help delineate the intraluminal space [12]. There is limited value of performing a CT abdomen and pelvis without and with IV contrast for this indication. A CT abdomen and pelvis without IV contrast will be less sensitive in establishing this diagnosis [12,19].

Epigastric Pain. Gastric adenocarcinoma has an incidence rate of 7.3 per 100,000 with 27,600 new cases estimated in 2020 and a 5- year relative survival rate of 32% [18]. Although endoscopy with biopsy is the reference standard for diagnosing gastric cancer, patients often present with nonspecific symptoms and undergo an imaging test for workup of those symptoms; gastric cancer may be first detected on such imaging. CT Abdomen and Pelvis Although endoscopy is the reference standard for diagnosing gastric cancer, patients may present with nonspecific symptoms and may undergo an imaging test for workup of those symptoms; gastric cancer may be first detected on such imaging. Additionally, malignancy is now the most common cause of gastric outlet obstruction in adults because the incidence of PUD has decreased because of the widespread use of H2 blockers [12]. If a gastric outlet obstruction is suspected, a CT may be ordered for anatomic evaluation. In some cases, a gastric mass may not be well seen on CT because of gastric underdistension. However, multiple other imaging findings may nonetheless be identified on CT that are concerning for this diagnosis, such as nodular or irregular wall thickening or enhancement, soft tissue attenuation of wall thickening (rather than low attenuation thickening due to edema), perforation with an ulcerated mass, lymphadenopathy, and distant metastases [7,8,12]. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for nodular wall thickening, soft tissue attenuation of the wall thickening) and neutral oral contrast such as water or dilute barium suspension to help delineate the intraluminal space [12]. There is limited value of performing a CT abdomen and pelvis without and with IV contrast for this indication. A CT abdomen and pelvis without IV contrast will be less sensitive in establishing this diagnosis [12,19].

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acrac_3158168_8

Epigastric Pain

CT Abdomen Although a CT abdomen examination may provide the same clues to diagnose gastric cancer as a CT abdomen and pelvis examination, the latter is usually chosen when nonspecific/overlapping symptoms are encountered. Additionally, including the pelvis may be valuable for assessing distant metastases. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for nodular wall thickening, soft tissue attenuation of the wall thickening) and neutral oral contrast such as water or dilute barium suspension [12]. There is limited value in performing a CT abdomen without and with IV contrast for this indication. A CT abdomen without IV contrast will be less sensitive in establishing this diagnosis [12,19]. CT Abdomen Multiphase Multiphase contrast-enhanced examinations are not routinely performed in patients with gastric cancer, but a CT angiographic protocol including precontrast, arterial, and portal venous phases or a 2-phase dual-energy protocol with arterial and portal venous phases may be used for patients with suspected acute GI bleeding [12]. FDG-PET/CT Skull Base to Mid-Thigh Although patients with gastric cancer may exhibit increased radiotracer uptake at the site of malignancy on FDG- PET, there is no relevant literature to support the use of FDG-PET/CT as the test of choice for initial imaging for gastric cancer. Fluoroscopy Biphasic Esophagram A biphasic esophagram does not evaluate the stomach and hence would not be useful for initial imaging for gastric cancer. Epigastric Pain Fluoroscopy Single Contrast Esophagram A single-contrast esophagram does not evaluate the stomach, and hence would not be useful for initial imaging for gastric cancer. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17].

Epigastric Pain. CT Abdomen Although a CT abdomen examination may provide the same clues to diagnose gastric cancer as a CT abdomen and pelvis examination, the latter is usually chosen when nonspecific/overlapping symptoms are encountered. Additionally, including the pelvis may be valuable for assessing distant metastases. When gastric disease is suspected, the CT examination should be performed with IV contrast (to assess for nodular wall thickening, soft tissue attenuation of the wall thickening) and neutral oral contrast such as water or dilute barium suspension [12]. There is limited value in performing a CT abdomen without and with IV contrast for this indication. A CT abdomen without IV contrast will be less sensitive in establishing this diagnosis [12,19]. CT Abdomen Multiphase Multiphase contrast-enhanced examinations are not routinely performed in patients with gastric cancer, but a CT angiographic protocol including precontrast, arterial, and portal venous phases or a 2-phase dual-energy protocol with arterial and portal venous phases may be used for patients with suspected acute GI bleeding [12]. FDG-PET/CT Skull Base to Mid-Thigh Although patients with gastric cancer may exhibit increased radiotracer uptake at the site of malignancy on FDG- PET, there is no relevant literature to support the use of FDG-PET/CT as the test of choice for initial imaging for gastric cancer. Fluoroscopy Biphasic Esophagram A biphasic esophagram does not evaluate the stomach and hence would not be useful for initial imaging for gastric cancer. Epigastric Pain Fluoroscopy Single Contrast Esophagram A single-contrast esophagram does not evaluate the stomach, and hence would not be useful for initial imaging for gastric cancer. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17].

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acrac_3158168_9

Epigastric Pain

An ulcer associated with nodularity of the adjacent mucosa, mass effect, or coarse, lobulated, or irregular radiating folds or oral contrast projecting into the mass (either inside or outside expected luminal contour) is concerning for gastric malignancy, requiring an endoscopic evaluation for a definite diagnosis [17]. Fluoroscopic examinations hold a special role in diagnosing scirrhous gastric carcinoma. Scirrhous gastric carcinomas may manifest as diffuse, long-segment, or even short-segment narrowing of a portion of the stomach. Endoscopy and biopsy have a poor sensitivity in diagnosing this entity, and a fluoroscopic examination may be essential in its diagnosis. Tumor cells invading the gastric wall result in a desmoplastic reaction that narrows the gastric lumen, making the wall rigid and nondistensible at fluoroscopy, with obliteration of gastric peristalsis [17]. MRI Abdomen Although patients with gastric cancer may exhibit nodular or irregular wall thickening or enhancement, lymphadenopathy, or distant metastases on MRI, there is no relevant literature to support the use of MRI in the prospective diagnosis of gastric cancer. MRI Abdomen with MRCP There is no relevant literature to support the use of MRCP sequences in the prospective diagnosis of gastric cancer. Variant 3: Epigastric pain with clinical suspicion for hiatal hernia. Initial imaging. In a patient with epigastric pain/discomfort and reflux symptoms, a hiatal hernia may be suspected. Hiatal hernias are reported to affect 10% to 50% of the population, with sliding hernias accounting for more than 85% of hiatal hernias and paraesophageal hernias accounting for up to 5% of all operated hiatal hernias [20]. In a relatively healthy patient with only a sliding hiatal hernia and reflux symptoms, dietary modification and a short treatment course of proton pump inhibitor may be curative with no additional testing necessary [21].

Epigastric Pain. An ulcer associated with nodularity of the adjacent mucosa, mass effect, or coarse, lobulated, or irregular radiating folds or oral contrast projecting into the mass (either inside or outside expected luminal contour) is concerning for gastric malignancy, requiring an endoscopic evaluation for a definite diagnosis [17]. Fluoroscopic examinations hold a special role in diagnosing scirrhous gastric carcinoma. Scirrhous gastric carcinomas may manifest as diffuse, long-segment, or even short-segment narrowing of a portion of the stomach. Endoscopy and biopsy have a poor sensitivity in diagnosing this entity, and a fluoroscopic examination may be essential in its diagnosis. Tumor cells invading the gastric wall result in a desmoplastic reaction that narrows the gastric lumen, making the wall rigid and nondistensible at fluoroscopy, with obliteration of gastric peristalsis [17]. MRI Abdomen Although patients with gastric cancer may exhibit nodular or irregular wall thickening or enhancement, lymphadenopathy, or distant metastases on MRI, there is no relevant literature to support the use of MRI in the prospective diagnosis of gastric cancer. MRI Abdomen with MRCP There is no relevant literature to support the use of MRCP sequences in the prospective diagnosis of gastric cancer. Variant 3: Epigastric pain with clinical suspicion for hiatal hernia. Initial imaging. In a patient with epigastric pain/discomfort and reflux symptoms, a hiatal hernia may be suspected. Hiatal hernias are reported to affect 10% to 50% of the population, with sliding hernias accounting for more than 85% of hiatal hernias and paraesophageal hernias accounting for up to 5% of all operated hiatal hernias [20]. In a relatively healthy patient with only a sliding hiatal hernia and reflux symptoms, dietary modification and a short treatment course of proton pump inhibitor may be curative with no additional testing necessary [21].

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acrac_3158168_10

Epigastric Pain

In a patient with longstanding/severe symptoms, the hernia may be large and/or of a paraesophageal type necessitating corrective surgery. In some cases, hiatal hernias may be associated with a shortened length of thoracic esophagus above the hernia, necessitating an esophageal lengthening procedure (eg, Collis gastroplasty) for successful treatment [21]. Size, subtype of the hernia, and severity of symptoms drive treatment, which ranges from medical management to corrective surgery [20]. CT Abdomen and Pelvis There is no relevant literature to support the use of CT abdomen and pelvis for initial imaging for hiatal hernia. CT Abdomen There is no relevant literature to support the use of CT abdomen for initial imaging for hiatal hernia. CT Abdomen Multiphase There is no relevant literature to support the use of multiphase CT for initial imaging for hiatal hernia. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT for initial imaging for hiatal hernia. Fluoroscopy Biphasic Esophagram Although endoscopy can be used to diagnose a hiatal hernia based on the site of the gastroesophageal junction and diaphragmatic impression on the esophagus, barium studies provide a more accurate depiction of the anatomic features of the hernia and also enable better determination of other factors that contribute to reflux symptoms, including the size of the hiatal hernia, opening of the gastroesophageal junction, and loss of the angle of Hiss [6,21- 23]. Barium studies also are better than endoscopy for differentiating sliding hiatal hernias from paraesophageal hernias [6]; this distinction is important because the surgical approach for treating a paraesophageal hernia is different from a sliding hiatal hernia [21,23]. The importance of imaging in this context is reflected in the Epigastric Pain

Epigastric Pain. In a patient with longstanding/severe symptoms, the hernia may be large and/or of a paraesophageal type necessitating corrective surgery. In some cases, hiatal hernias may be associated with a shortened length of thoracic esophagus above the hernia, necessitating an esophageal lengthening procedure (eg, Collis gastroplasty) for successful treatment [21]. Size, subtype of the hernia, and severity of symptoms drive treatment, which ranges from medical management to corrective surgery [20]. CT Abdomen and Pelvis There is no relevant literature to support the use of CT abdomen and pelvis for initial imaging for hiatal hernia. CT Abdomen There is no relevant literature to support the use of CT abdomen for initial imaging for hiatal hernia. CT Abdomen Multiphase There is no relevant literature to support the use of multiphase CT for initial imaging for hiatal hernia. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT for initial imaging for hiatal hernia. Fluoroscopy Biphasic Esophagram Although endoscopy can be used to diagnose a hiatal hernia based on the site of the gastroesophageal junction and diaphragmatic impression on the esophagus, barium studies provide a more accurate depiction of the anatomic features of the hernia and also enable better determination of other factors that contribute to reflux symptoms, including the size of the hiatal hernia, opening of the gastroesophageal junction, and loss of the angle of Hiss [6,21- 23]. Barium studies also are better than endoscopy for differentiating sliding hiatal hernias from paraesophageal hernias [6]; this distinction is important because the surgical approach for treating a paraesophageal hernia is different from a sliding hiatal hernia [21,23]. The importance of imaging in this context is reflected in the Epigastric Pain

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acrac_3158168_11

Epigastric Pain

Esophageal Diagnostic Advisory Panel Consensus of the American College of Surgeons, which states that all patients who are considered for antireflux surgery require a barium esophagram [6]. A biphasic esophagram can be useful for this indication. In addition to detecting the presence and size of a hiatal hernia, the esophagram will provide anatomic and functional information on esophageal length, esophageal stricture, presence of gastroesophageal reflux, and reflux esophagitis [6]. Reflux esophagitis may manifest as fine nodularity or granularity of the mucosa, erosions or ulcers, thickened longitudinal folds, inflammatory esophagogastric polyps, and scarring with strictures, sacculations, or fixed transverse folds [14]. Single-contrast examinations have a reported sensitivity of 77% for detecting endoscopically proven esophagitis. Double-contrast examinations have a higher sensitivity of 80% because of its ability to reveal mucosal abnormalities that cannot be visualized on single-contrast studies. An even higher sensitivity of 88% is achieved by using a combined technique [14-16]. As such, a combined technique is most favorable for this assessment. If the hiatal hernia is large, an upper GI series evaluation should be included for complete assessment of the stomach. Fluoroscopy Single Contrast Esophagram A single-contrast esophagram may be considered in some instances. Although it may not reveal the mucosal irregularity resulting from reflux disease, it may delineate the hernia, reveal reflux, lower esophageal rings, or strictures [14]. If the hiatal hernia is large, an upper GI series evaluation should be included for complete assessment of the stomach. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17]. A double-contrast upper GI series is the most useful test for diagnosing a hiatal hernia.

Epigastric Pain. Esophageal Diagnostic Advisory Panel Consensus of the American College of Surgeons, which states that all patients who are considered for antireflux surgery require a barium esophagram [6]. A biphasic esophagram can be useful for this indication. In addition to detecting the presence and size of a hiatal hernia, the esophagram will provide anatomic and functional information on esophageal length, esophageal stricture, presence of gastroesophageal reflux, and reflux esophagitis [6]. Reflux esophagitis may manifest as fine nodularity or granularity of the mucosa, erosions or ulcers, thickened longitudinal folds, inflammatory esophagogastric polyps, and scarring with strictures, sacculations, or fixed transverse folds [14]. Single-contrast examinations have a reported sensitivity of 77% for detecting endoscopically proven esophagitis. Double-contrast examinations have a higher sensitivity of 80% because of its ability to reveal mucosal abnormalities that cannot be visualized on single-contrast studies. An even higher sensitivity of 88% is achieved by using a combined technique [14-16]. As such, a combined technique is most favorable for this assessment. If the hiatal hernia is large, an upper GI series evaluation should be included for complete assessment of the stomach. Fluoroscopy Single Contrast Esophagram A single-contrast esophagram may be considered in some instances. Although it may not reveal the mucosal irregularity resulting from reflux disease, it may delineate the hernia, reveal reflux, lower esophageal rings, or strictures [14]. If the hiatal hernia is large, an upper GI series evaluation should be included for complete assessment of the stomach. Fluoroscopy Upper GI Series The double-contrast upper GI series is a beneficial diagnostic test for evaluating structural and functional abnormalities of the esophagus, stomach, and duodenum [17]. A double-contrast upper GI series is the most useful test for diagnosing a hiatal hernia.

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acrac_69359_0

Suspected Spine Trauma PCAs

Introduction/Background Cervical Spine Imaging An estimated 3% to 4% of patients presenting to the emergency department with blunt trauma have sustained an injury to the cervical spine [1,2]. Cervical spine injuries can range from stable minor soft-tissue injuries to unstable complex injury patterns resulting in complete disruption of the cervical spine with possible neurologic or vascular injury. The wide spectrum of injury patterns can make the decision process for when to perform imaging and what type of imaging to perform challenging. Overutilization of MRI and CT imaging of the cervical spine can result in an extended emergency center visit while awaiting imaging as well as iatrogenic injuries related to prolonged cervical collar placement [3], exposure to intravenous (IV) contrast, and exposure to radiation and high-power magnetic fields. On the other hand, failure to identify an unstable cervical spine or cervical vascular injury can result in poor clinical outcomes. The National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian Cervical Rules (CCR) are well-established clinical criteria for exclusion of clinically significant cervical spine injury. In their original application of the NEXUS criteria, Hoffman et al [4] found the NEXUS criteria to have a 99.6% sensitivity for detecting clinically significant cervical injury. The CCR criteria has a similar sensitivity for identifying cervical spine injury with the initial study by Stiell et al [5] that applied the CCR criteria identifying 100% of clinically significant cervical spine injuries. Since their inception, a few studies have directly compared the CCR and NEXUS criteria and have found the CCR to slightly outperform NEXUS in selecting patients at risk for cervical spine injury [6,7]. However, multiple studies have validated the sensitivity of both the NEXUS and CCR criteria for identifying clinically significant cervical spine injuries [7-12].

Suspected Spine Trauma PCAs. Introduction/Background Cervical Spine Imaging An estimated 3% to 4% of patients presenting to the emergency department with blunt trauma have sustained an injury to the cervical spine [1,2]. Cervical spine injuries can range from stable minor soft-tissue injuries to unstable complex injury patterns resulting in complete disruption of the cervical spine with possible neurologic or vascular injury. The wide spectrum of injury patterns can make the decision process for when to perform imaging and what type of imaging to perform challenging. Overutilization of MRI and CT imaging of the cervical spine can result in an extended emergency center visit while awaiting imaging as well as iatrogenic injuries related to prolonged cervical collar placement [3], exposure to intravenous (IV) contrast, and exposure to radiation and high-power magnetic fields. On the other hand, failure to identify an unstable cervical spine or cervical vascular injury can result in poor clinical outcomes. The National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian Cervical Rules (CCR) are well-established clinical criteria for exclusion of clinically significant cervical spine injury. In their original application of the NEXUS criteria, Hoffman et al [4] found the NEXUS criteria to have a 99.6% sensitivity for detecting clinically significant cervical injury. The CCR criteria has a similar sensitivity for identifying cervical spine injury with the initial study by Stiell et al [5] that applied the CCR criteria identifying 100% of clinically significant cervical spine injuries. Since their inception, a few studies have directly compared the CCR and NEXUS criteria and have found the CCR to slightly outperform NEXUS in selecting patients at risk for cervical spine injury [6,7]. However, multiple studies have validated the sensitivity of both the NEXUS and CCR criteria for identifying clinically significant cervical spine injuries [7-12].

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acrac_69359_1

Suspected Spine Trauma PCAs

The ACR does not take a position on the relative merits of the two sets of criteria; however, the ACR recognizes both are in widespread clinical practice and produce concordant predictions for most patients. Thus, either NEXUS or CCR may be applied to this ACR Appropriateness Criteria document. The NEXUS criteria identify 5 clinical factors that either place patients at increased risk for cervical spine injury or limit clinical assessment of injury (Table 1). Under the NEXUS criteria, imaging evaluation of the cervical spine is not indicated if none of the 5 clinical factors are present. The strength of the NEXUS criteria is its high sensitivity (99.6%) and negative predictive value (99.9%) for identifying significant cervical spine injury [4]. However, the NEXUS criteria have very low specificity (12.9%) [4]. A patient who meets the NEXUS criteria for cervical imaging is not necessarily likely to have sustained a significant cervical spine injury. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Suspected Spine Trauma Table 1. NEXUS Criteria for Cervical Spine Imaging [4] The CCR criteria use a more complex algorithm for guiding cervical spine imaging in trauma patients than the NEXUS criteria. In the CCR criteria, patients deemed as high risk (Table 2) for cervical spine injury automatically undergo imaging evaluation of the cervical spine. Table 3. CCR Low-Risk Factors for Cervical Spine Injury [5] Simple rear-end motor vehicle crash Patient in sitting position in emergency center Patient ambulatory at any time after trauma Delayed onset of neck pain Absence of midline cervical spine tenderness

Suspected Spine Trauma PCAs. The ACR does not take a position on the relative merits of the two sets of criteria; however, the ACR recognizes both are in widespread clinical practice and produce concordant predictions for most patients. Thus, either NEXUS or CCR may be applied to this ACR Appropriateness Criteria document. The NEXUS criteria identify 5 clinical factors that either place patients at increased risk for cervical spine injury or limit clinical assessment of injury (Table 1). Under the NEXUS criteria, imaging evaluation of the cervical spine is not indicated if none of the 5 clinical factors are present. The strength of the NEXUS criteria is its high sensitivity (99.6%) and negative predictive value (99.9%) for identifying significant cervical spine injury [4]. However, the NEXUS criteria have very low specificity (12.9%) [4]. A patient who meets the NEXUS criteria for cervical imaging is not necessarily likely to have sustained a significant cervical spine injury. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Suspected Spine Trauma Table 1. NEXUS Criteria for Cervical Spine Imaging [4] The CCR criteria use a more complex algorithm for guiding cervical spine imaging in trauma patients than the NEXUS criteria. In the CCR criteria, patients deemed as high risk (Table 2) for cervical spine injury automatically undergo imaging evaluation of the cervical spine. Table 3. CCR Low-Risk Factors for Cervical Spine Injury [5] Simple rear-end motor vehicle crash Patient in sitting position in emergency center Patient ambulatory at any time after trauma Delayed onset of neck pain Absence of midline cervical spine tenderness

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