Medical Policy

 

Subject: Positron Emission Tomography (PET) and PET/CT Fusion
Document #: RAD.00002 Publish Date:    08/29/2018
Status: Reviewed Last Review Date:    07/26/2018

Description/Scope

This document addresses the use of PET scans and PET/CT fusion. Positron Emission Tomography (PET) is an imaging modality that produces an image of the body's soft structures, including metabolic and/or chemical information. The CT scan produces an image of body structures, including bone and tissue. The PET/CT fusion combines the two images to show both hard structures, such as bone, and soft structures, such as growing tissue or tumors.

Note: For additional information and documents relevant to PET imaging, see:

Position Statement

Medically Necessary:

Positron emission tomography (PET) is considered medically necessary for the identification or localization of seizure foci in individuals who are surgical candidates for neurosurgical treatment of intractable epilepsy.

PET scan with or without PET/CT fusion is considered medically necessary to diagnose chronic osteomyelitis of the axial skeleton.

Cardiac Applications:

PET is considered medically necessary for the following cardiac conditions when results of the PET scan can reasonably be expected to influence clinical management of the individual’s condition:

  1. To assess myocardial viability in those with severe global left ventricular dysfunction to determine candidacy for a cardiac surgery procedure including coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA) and transplantation;
    or
  2. To assess myocardial perfusion in the diagnosis of coronary artery disease when any of the following are present:
    1. Unavailable or inconclusive single photon emission computed tomography (SPECT) or stress echocardiogram; or
    2. Body habitus or other conditions for which SPECT or stress echocardiogram may have attenuation problems, (for example, body mass index [BMI] of greater than or equal to 40 kg/m2, large breasts, left mastectomy, breast implant, chest wall deformity, left pleural or pericardial effusion, circulatory problems in inferior-septal areas of the heart) or other technical difficulty (extensive prior myocardial infarction); or
    3. Conditions for which angiography may be associated with high risk for morbidity (for example, allergy to contrast medium, poor arterial access, significant renal dysfunction).
      or
  3. To assess suspected cardiac sarcoidosis when magnetic resonance imaging (MRI) is contraindicated.

Oncologic Applications:

A.  Diagnosis* or Staging* (*see the Definitions section)

PET scan with or without PET/CT fusion, is considered medically necessary when used for diagnosis or staging of cancer when ALL (1, 2, and 3) of the following criteria are met:

  1. Imaging results are required to determine at least one of the following:
    1. Whether the individual is a candidate for an invasive diagnostic or therapeutic procedure of an internal body structure (for example, biopsy of a pancreas lesion not merely a superficial lymph node); or
    2. The appropriate anatomic location for an invasive procedure; or
    3. The extent of malignancy when recommended therapy, (for example, local vs. systemic therapy, use of neo-adjuvant therapy) reasonably depends upon the extent of malignancy;
      and
  2. More standard imaging modalities, (for example, CT, MRI, or ultrasound) are either not indicated or provided inconclusive results;  
    and
  3. The tumor in question is a suspected or proven malignancy from any of the following primary locations:
    1. Brain; or
    2. Breast (except initial staging of axillary lymph nodes); or
    3. Cervix; or
    4. Colorectal; or
    5. Esophageal; or
    6. Head and Neck (excluding Central Nervous System and Thyroid); or
    7. Lung:        
      1. Non-Small Cell (NSCLC)
      2. Small Cell (SCLC)
      3. Evaluation of Solitary Pulmonary Nodule with diameter 8-30 mm; or
    8. Lymphoma: Hodgkin’s or Non-Hodgkin’s; or
    9. Melanoma (excluding the initial evaluation of regional lymph nodes); or
    10. Musculoskeletal (including Soft Tissue Sarcoma); or
    11. Myeloma; or
    12. Neuroblastoma; or
    13. Neuroendocrine Tumor, poorly differentiated; or
    14. Pancreas; or
    15. Thyroid; or
    16. Cancer of Unknown Primary; or
    17. Suspected Paraneoplastic Syndrome.

B.   Restaging* or Monitoring* (*see the Definitions section)

PET scan with or without PET/CT fusion, is considered medically necessary when used for restaging or monitoring of cancer when ALL (1, 2, 3, 4 and 5) of the following criteria are met:

  1. Initial therapy has been completed;
    and
  2. Imaging results are required to assess therapeutic success, in order to establish the need for, or scope of, any subsequent therapy, by determining at least one of the following:
    1. Presence or extent of residual disease; or
    2. Presence or extent of recurrent disease; or
    3. Presence or extent of metastasis; or
    4. Other assessment of tumor response;
      and
  3. More standard imaging modalities (for example, CT, MRI, or ultrasound) are either not indicated or provided inconclusive results;
    and
  4. The tumor in question is a primary malignancy from any of the following locations:
    1. Brain; or
    2. Breast; or
    3. Cervix; or
    4. Colorectal; or
    5. Esophageal; or
    6. Head and Neck (excluding Central Nervous System & Thyroid); or
    7. Lung – Non-Small Cell (NSCLC); or
    8. Lymphoma: Hodgkin’s or Non-Hodgkin’s; or
    9. Melanoma; or
    10. Myeloma; or
    11. Musculoskeletal (including Soft Tissue Sarcoma); or
    12. Neuroblastoma; or
    13. Neuroendocrine Tumor, poorly differentiated; or
    14. Ovarian; or
    15. Testicular; or
    16. Thyroid;
      and
  5. When prior PET scan has been performed, the results demonstrated hypermetabolic uptake by the tumor (if no prior PET or prior PET positive, then this criteria is met).

C.  Other Malignancies

PET scan, with or without PET/CT fusion, is considered medically necessary for other (not included in the lists in section A or B) malignancies if ALL of the following criteria are met:

  1. Imaging results are required to determine at least one of the following:
    1. Whether the individual is a candidate for an invasive diagnostic or therapeutic procedure of an internal body structure (for example, biopsy of a pancreas lesion not merely a superficial lymph node); or
    2. The appropriate anatomic location for an invasive procedure; or
    3. The extent of malignancy when recommended therapy, (for example, local vs. systemic therapy, use of neo-adjuvant therapy) reasonably depends upon the extent of malignancy; or
    4. When major surgery or curative local high-dose radiation is being recommended, and a PET or PET/CT scan may identify the presence of metastatic disease that may change management of the individual; or
    5. After completion of initial therapy for malignancy, imaging results are required to assess therapeutic success, in order to establish the need for, or scope of, any subsequent therapy, by determining at least one of the following:
      1. Presence or extent of residual disease; or
      2. Presence or extent of recurrent disease; or
      3. Presence or extent of metastasis; or
      4. Other assessment of tumor response;
        and
  2. More standard imaging modalities, (for example, CT, MRI, or ultrasound) are either not indicated or unable to conclusively provide the required information;
    and
  3. Imaging is NOT for any of the following clinical situations (or scenarios):
    1. Diagnosis or staging for ovarian cancer or testicular cancer; or
    2. Restaging or monitoring for small cell lung cancer (SCLC) or pancreatic cancer.

D.  Interim Scanning

For Non-Hodgkin’s lymphoma (NHL), other than follicular lymphoma, interim PET or PET/CT is considered medically necessary no more frequently than every two cycles of chemotherapy to a maximum of 3 times during a treatment course when needed to guide treatment decision making.

For Hodgkin’s lymphoma (HL), other than stage Ia HL, interim PET or PET/CT is considered medically necessary no more frequently than every two cycles of chemotherapy to a maximum of 3 times during a treatment course when needed to guide treatment decision making.

E.   Surveillance

Intermittent surveillance (see Definitions section) scanning for Ewing Sarcoma is considered medically necessary.

Investigational and Not Medically Necessary:

All other uses of PET scan with or without PET/CT fusion, other than as set forth above, are considered investigational and not medically necessary including, but not limited to, the following:

  1. Malignancies that do not meet the criteria in the Medically Necessary sections above; or
  2. Interim (see Definitions section) PET scanning to evaluate response to treatment during a course of treatment except when criteria above are met; (Note: Interim PET scanning is not considered restaging.); or
  3. Screening for any malignancies in an individual not yet diagnosed with cancer, other than as described in the criteria for “Solitary Pulmonary Nodule” above; or
  4. Surveillance of asymptomatic individuals, except for Ewing Sarcoma (without abnormal physical findings, lab tests, or other imaging findings related to malignancy recurrence) after completion of therapy for malignancy; or
  5. Alzheimer’s disease and other dementias (for example, multi-infarct dementia, fronto-temporal dementia) using beta amyloid (β-amyloid) or other PET tracers; or
  6. Cerebrovascular disease, (for example, carotid artery disease, aneurysms, arteriovascular malformations, ischemic cerebrovascular disease or assessment of arterial vasospasm subsequent to subarachnoid hemorrhage); or
  7. Autism Spectrum Disorders; or
  8. Parkinson’s Disease.

PET scanning of the bone using Sodium fluoride F 18 (NaF-18) is considered investigational and not medically necessary for all applications including, but not limited to, the evaluation of suspected metastasis to bone.

PET scanning of the prostate using C-11 choline radiotracer or any other radiopharmaceutical, (such as FDG-PET) is considered investigational and not medically necessary for all applications, including, but not limited to, initial staging, confirming the diagnosis, restaging or monitoring for recurrence of prostate cancer.

The use of PET Mammography (PEM) for the detection of breast cancer or subsequent monitoring of breast cancer is considered investigational and not medically necessary.

Rationale

Neurologic Applications

PET has been shown to be useful for localizing seizure foci in selected individuals for whom neurosurgical treatment of refractory epilepsy is contemplated (ACR, 2011).  The most appropriate candidates are those with complex temporal lobe partial seizures who have failed to respond to medical therapy.  In addition, a PET scan may eliminate the need for extended preoperative EEG recordings with implanted electrodes.

The use of PET scans in Alzheimer’s disease (AD) has been investigated for use in the differentiation of AD from certain other dementias, such as fronto-temporal dementia (FTD).  There is a lack of studies that specifically look at the incremental benefit of PET over standard clinical evaluation alone, which is accurate in up to 90% of cases.  Finally, there is no evidence in the peer reviewed literature to indicate that the use of PET scans contributes to improved outcomes in any group with dementia (Durand-Martel, 2010; Kovacs, 2008; Laforce, 2010; Mosconi, 2010). 

In addition to diagnosis, PET has been proposed as a technique to predict the progression of dementia.  There are several concerns about this use.  First, the predictive models for the rate of cognitive decline have not been appropriately validated.  The studies tend to have small sample sizes and often significant loss to follow-up.  In 2008, results of a large multicenter study examined the use of 18F-fluorodeoxyglucose (FDG) PET measures in the differential diagnosis of AD, FTD, and dementia with Lewy bodies (DLB) from normal aging and from each other (total subjects n=548, which included 110 healthy elderly referred to in this study as “normals”).  Disease-specific PET patterns yielded 96% accuracy in discriminating normal findings from AD, DLB, and FTD subjects in the testing cohort.  The percentage of subjects correctly classified was consistent across the groups, with 94% in healthy elderly, 95% with AD, 92% with DLB, and 94% with FTD.  Subjects with mild cognitive impairment (MCI) showed primarily posterior cingulate cortex and hippocampal hypometabolism (81%), whereas neocortical abnormalities varied according to neuropsychological profiles.  An AD PET pattern was observed in 79% MCI with deficits in multiple cognitive domains and 31% amnesic MCI.  FDG PET heterogeneity in MCI with non-memory deficits ranged from absent hypometabolism to FTD and DLB PET patterns.  The authors concluded that standardized automated analysis of FDG PET scans may provide an objective and sensitive support to the clinical diagnosis in early dementia.  However, 29% of DLB subjects and 35% of FTD subjects showed a pattern of cortical deficits similar to that of AD subjects.  Therefore, the presence of cortical abnormalities discriminated AD from DLB and FTD, with a high sensitivity (> 90%) though a lower specificity (71% and 65%, respectively) (Mosconi, 2008).

Another study of 50 subjects in a university-based cognitive disorders clinic was conducted to compare assessment of regional cerebral metabolic changes with [(11) C] dihydrotetrabenazine (DTBZ)-PET measurement of regional cerebral blood flow [K (1)] and FDG PET measurement of regional cerebral glucose uptake (CMR[glc]) in a clinically representative sample of subjects with mild dementia and MCI.  The DTBZ-PET regional K(1) and FDG PET CMR(glc) measurements were compared with standard correlation analysis.  The overall patterns of DTBZ-PET K(1) and FDG PET CMR(glc) deficits were assessed with stereotaxic surface projections (SSPs) of parametric images.  The DTBZ-PET regional K(1) and FDG PET CMR(glc) measurements were highly correlated, both within and between subjects. The SSP maps of deficits in DTBZ-PET regional K(1) and FDG PET CMR(glc) measurements were markedly similar.  The DTBZ-PET K(1) SSP maps exhibited a mild decrease in sensitivity relative to FDG PET CMR(glc) maps.  The authors concluded that both DTBZ-PET K(1) and FDG PET CMR(glc) measurements provide comparable information in the assessment of regional cerebral metabolic deficits in mild dementia and MCI and that blood flow measures can assess regional cerebral metabolism deficits accurately in mild dementia and MCI (Albin, 2010).  Despite the results of these and other small studies, the use of PET imaging in the evaluation of AD and other early dementias needs further study to further define its role in the management of these conditions (Aizenstein, 2008).

In addition, there is interest in beta amyloid (β-amyloid) PET tracers, because preliminary evidence has noted a correlation between the retention of β-amyloid during PET imaging and AD plaque in the brain.  Eli Lilly and Co. (Indianapolis, IN) acquired the manufacturing company, Avid Radiopharmaceuticals Inc., (Philadelphia, PA) and obtained FDA approval on April 6, 2012 to market the agent, florbetapir F 18 (under the branded name Amyvid), as a β-amyloid detection agent and not directly as a tool to diagnose Alzheimer's disease.  Amyvid is designed to be used in individuals undergoing PET, in order to "light up" areas of the brain that contain β-amyloid on imaging scans.  β-amyloid is a protein contained in clumps or plaques seen in the brains of people who have died of Alzheimer's complications, but it's not clear what role the plaque plays in the development and progression of the disease.  The FDA-approved labeling for Amyvid is as follows:  “Amyvid is a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s Disease (AD) and other causes of cognitive decline” (FDA, 2012).  The FDA limitations of use note that, “A positive florbetapir scan does not confirm the diagnosis of AD or any other cognitive disorder.”  This is because a positive florbetapir scan, which indicates the presence of moderate to frequent amyloid plagues in the brain, may be seen in persons with AD or other causes of cognitive decline, as well as in persons with normal cognition.  

According to the FDA press release:

Amyvid is not a test for predicting the development of AD-associated dementia and is not for monitoring patient responses to AD therapy.  Amyvid does not replace other diagnostic tests used in the evaluation of cognitive impairment.  This is a new type of nuclear medicine test, and images should be interpreted only by healthcare professionals who successfully complete a special training program developed by the manufacturer… Amyvid is an adjunct to other diagnostic evaluations…A positive Amyvid scan indicates moderate to frequent plaques.  However, a positive Amyvid scan does not establish a diagnosis of AD because, although patients with AD always have an increased brain content of plaque, the test also may be positive in patients with other types of neurologic conditions, as well as in older people with normal cognition. (FDA, 2012).

Additional tracer agents have obtained FDA approval for PET imaging of the brain to estimate the β-amyloid plaque density in adults being evaluated for AD and other causes of cognitive decline.  These include Vizamyl (flutemetamol F 18 injection), which is manufactured for GE Healthcare by Medi-Physics, Inc., Arlington Heights, IL (FDA approved October 25, 2013) and Neuraceq(florbetaben F 18 injection), Piramal Imaging, Matran Switzerland (FDA approved March 19, 2014).

Preliminary research has suggested that abnormal β-amyloid accumulation, as evidenced by PET imaging, has implications for both present and future cognitive performance (Clark, 2011; Doraiswamy, 2012; Fleisher, 2011; Joshi, 2012; Wolk, 2018).  Although large longitudinal studies, like the ongoing Alzheimer’s Disease Neuroimaging Initiative (ADNI) trial, will be required for definitive evaluation, present data suggest that PET amyloid imaging has the potential to promote earlier and more specific diagnosis of dementia.  The ADNI study, (which is comprised of a consortium of academic medical centers), is being conducted by the National Institute on Aging, in conjunction with other federal agencies and private-sector corporations and organizations. The ADN1 and 2 are described as the National Institutes of Health’s (NIH) largest public-private partnership on brain research and includes scientists at 55 research centers in the U.S. and Canada.  Currently the study involves over 800 study participants from those without memory problems to mild cognitive impairment to AD.  The study results are expected to provide researchers with a better understanding of AD progression in its earliest stages (Jagust, 2010; Kadir, 2011).  

In 2013, the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the Alzheimer’s Association  jointly published Appropriate Use Criteria for β-amyloid PET scanning to aid in the diagnosis of people with suspected AD.  An Amyloid Imaging Taskforce (AIT), consisting of dementia and imaging experts, reviewed the scientific literature currently available and concluded that the decision whether or not to order amyloid imaging should be made only after a comprehensive evaluation by a physician experienced in the assessment and diagnosis of cognitive impairment and dementia, and only if the presence or absence of amyloid would increase certainty in the diagnosis and alter the treatment plan.  Although some potential benefits to amyloid PET imaging were identified, the AIT concluded that:

Amyloid PET results will not constitute and is not equivalent to a clinical diagnosis of AD dementia.  Imaging is only one tool among many that clinicians should use judiciously to manage patients, and that amyloid PET imaging does not substitute for a careful history and examination. The AIT recognized that studies suggest amyloid imaging may have a role in stratifying patients into their risk of developing cognitive decline and that, someday, as longitudinal research studies accumulate data, amyloid imaging may become useful to predict future clinical conditions, such as the risk of developing cognitive decline or of transitioning into clinical states, such as mild cognitive impairment (MCI) or dementia… At this point, data are simply incomplete to support using amyloid imaging to provide prognostic information to persons with AD risk factors such as age, family history of dementia, APOE ε4 status, genetic mutation carrier status, and cognitive complaint that is unconfirmed on clinical examination, or to asymptomatic persons (Johnson, 2013). 

On September 27, 2013 the Centers for Medicare and Medicaid Services (CMS) posted its final decision memo regarding β-amyloid PET in Dementia and Neurodegenerative Disease in which CMS determined that:

There is sufficient evidence that the use of PET Aβ imaging is promising in two scenarios: (1) to exclude Alzheimer’s disease (AD) in narrowly defined and clinically difficult differential diagnoses, such as AD versus frontotemporal dementia (FTD); and (2) to enrich clinical trials seeking better treatments or prevention strategies for AD, by allowing for selection of patients on the basis of biological, as well as clinical and epidemiological factors…Therefore, CMS will cover one PET Aβ scan per patient through coverage with evidence development (CED regulatory statute), in clinical studies that meet the criteria, as set forth in the Decision Summary (CMS, 2013).

It is notable within the CMS Decision Summary regarding AD:

Currently, there is no effective treatment for AD.  Existing interventions do not prevent, modify or cure the disease process.  Some medications, such as memantine and cholinesterase inhibitors, can temporarily improve cognitive and neuropsychiatric symptoms in some patients with AD, (as well as certain other dementias).  Care is, therefore, primarily supportive and increases as functional impairment progresses, eventually leading to round-the-clock supervision which can be needed for years (CMS, 2013).

Cardiac Applications

The 2003 American College of Cardiology /American Heart Association/American Society of Nuclear Cardiology Guidelines for the Clinical Use of Cardiac Radionuclide Imaging describes several cardiac applications of PET scanning.  These uses include assessment of myocardial viability and as an adjunct in diagnosing coronary artery disease in selected individuals.  Myocardial viability studies are useful to identify those with significant left ventricular dysfunction who may be candidates for transplantation, as opposed to those who may benefit from revascularization (Ghesani, 2005).  With regard to the use of PET in coronary artery disease, this guideline indicates that PET and SPECT scanning share many indications but does not make definitive statements, as to their relative value.  It also notes that, at this time, there is not a robust database of head to head comparison of these two techniques.  Thus, PET is often used when other diagnostic procedures or modalities, (including SPECT and stress echocardiogram) are inconclusive or cannot be performed, (e.g., when obesity causes attenuation problems for other imaging tests in cases of the BMI being greater than or equal to 40 km/m2).  However, one review article noted that:

Although myocardial perfusion PET imaging is an option for all patients requiring stress perfusion imaging, there are identifiable patient groups difficult to image with conventional single-photon emission computed tomography imaging that are particularly likely to benefit from PET imaging, such as obese patients, women, patients with previous nondiagnostic tests, and patients with poor left ventricular function attributable to coronary artery disease considered for revascularization (Mechac, 2005).

Oncologic Applications

PET and PET/CT are used for diagnosis, staging, restaging, and monitoring tumor response to treatment. However, the efficacy of PET and the sensitivity and specificity of the technology varies with the type of tumor and, thus, the use of PET is only supported for specific indications. PET scanning for oncologic applications is generally only medically necessary when other imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography, are inconclusive.

In 2008, the University of Alberta Evidence-based Practice Center (UA-EPC) under contract with the Agency for Healthcare Research and Quality (AHRQ) reviewed and synthesized evidence on the use of PET in the assessment and treatment of nine types of cancer (Bladder, Brain, Cervical, Kidney, Ovarian, Pancreatic, Prostate, Small Cell Lung, Testicular) for determining diagnosis, staging, restaging, and monitoring of response to treatment.  Relevant aspects of the technology assessment include:

On April 3, 2009 the Centers for Medicare and Medicaid Services (CMS) issued revised national coverage determination (NCD) policy (#220.6) for most solid tumors and for myeloma with policy now titled -- PET for Solid Tumors, following a period for public comments and review of input from multiple sectors.  This updated CMS NCD is based, in large part, on the results of the AHRQ Technology Assessment Report described above. Within this revised policy, the CMS has reorganized and adopted a coverage framework that replaces the former four-part categories, (that is, diagnosis, staging, restaging and monitoring response to treatment) with a two-part framework that differentiates PET imaging used to inform the initial anti-tumor treatment strategy from other uses related to guiding subsequent anti-tumor treatment strategies after the completion of initial treatment.  This revised NCD policy replaces prior CMS policy for the following indications:  lung cancer, esophageal cancer, colorectal cancer, head/neck cancers (excluding CNS and thyroid tumors), lymphoma, melanoma, breast, thyroid, soft tissue sarcoma, brain, cervical, ovarian, pancreatic, SCLC, testicular, and CMS policy on all other cancer indications with disease-specific exceptions.  Notably, this new CMS policy does not replace prior NCD for all oncologic indications (please refer to the CMS web site for further information) (CMS, 2009).  On March 7, 2013 CMS issued a decision memo which determined that, unless there is a specific NCD, local Medicare Administrative Contractors (MACs) may determine coverage within their respective jurisdictions for PET using radiopharmaceuticals for their Food and Drug Administration (FDA) approved labeled indications for oncologic imaging.  The effect of this decision is to remove the national noncoverage for FDA approved labeled oncologic uses of radiopharmaceuticals that are not more specifically determined nationally by CMS.  This decision does not change coverage for any use of PET using radiopharmaceuticals FDG (2-deoxy-2-[F-18] fluoro-D-Glucose fluorodeoxyglucose), NaF-18 (fluorine-18 labeled sodium fluoride), ammonia N-13, or rubidium-82 (Rb-82).  This decision does not prevent CMS from determining national coverage for any uses of any radiopharmaceuticals in the future, and if such determinations are made, a future determination would supersede local contractor determination (CMS, 2013).  

On June 11, 2013 CMS revised its NCD (#220.6.17) for oncologic conditions to end the requirement for prospective data collection by the National Oncologic PET Registry (NOPR) for those cancers or cancer types that had been covered under Coverage with Evidence Development (CED) regulatory requirements.  In addition, this revision also provided the following:

CMS has determined that three FDG PET scans are covered under § 1862(a)(1)(A) when used to guide subsequent management of anti-tumor treatment strategy after completion of initial anticancer therapy. Coverage of any additional FDG PET scans (that is, beyond three) used to guide subsequent management of anti-tumor treatment strategy after completion of initial anti-tumor therapy will be determined by local Medicare Administrative Contractors (CMS, 2013).

It was noted by CMS that:

The scope of the first part of this reconsideration determination (described above as subsequent management after completion of initial anticancer therapy) is limited to those oncologic indications of FDG PET to guide subsequent anti-tumor treatment strategy, which had been covered only under CED.

However, the scope of the second part of this reconsideration determination (described above as coverage of additional FDG PET scans beyond three) includes any oncologic use(s) of FDG PET to guide subsequent antitumor treatment strategy, and specifically includes all types of solid tumors, not only those that had been covered under CED (CMS, 2013).

Interim Scanning

The use of PET in the lymphomas (Hodgkin lymphoma [HL] and Non-Hodgkin’s lymphoma [NHL]) has been proposed as an interim scanning strategy during chemotherapy and/or radiation therapy regimens, usually after two cycles of chemotherapy, to assist the oncologists in determining response to treatment, prognosis and subsequent treatment planning.  Although the evidence for PET and interim monitoring remains inconclusive, as noted in Andre (2011), “The use of interim PET after a few cycles of chemotherapy may allow treatment reduction for good responders, leading to lesser treatment toxicities, as well as early treatment adaptation for bad responders with a potential higher chance for cure.”  This notion was also concluded by Ceriani and colleagues in 2018. There is some support in the NCCN guidelines for interim scanning with PET in NHL, other than follicular lymphoma, and in HL, other than stage Ia, when imaging is needed to guide treatment decision making.  However, the updated 2017 NCCN guidelines for both HL and NHL recommend repeat biopsy if the PET results are positive prior to additional therapy and before changing a course of treatment.  The 2017 NCCN guidelines for HL states:

PET scans are useful in upstaging of stage I and II disease. In cases of PET positivity outside of the disease already identified or if the PET positive sites are inconsistent with the usual presentation of HL, additional clinical evaluation may be required to stage the patient. PET scans are usually positive in patients with HIV infection even in the absence of HL.

Several trials are ongoing both for localized and advanced disease to evaluate the FDG-PET potential for early treatment monitoring and tailoring which will further inform regarding the most appropriate and standardized use of FDG-PET in response assessment and interim therapy monitoring for lymphoma (Avigdor, 2010; Cheson, 2011; Dann, 2007; Juweid, 2011; Kasamon, 2011; Le Roux, 2011; Michallet, 2010).

Regarding the use of PET scans for initial staging of individuals with lymphomas, including HL, and for evaluating residual masses at the end of treatment, the 2017 NCCN update adds:

PET/CT has become an important tool for initial staging and for response assessment at the completion of treatment in patients with HL. Complete response should be documented including the reversion of PET to ‘negative’ within three months following completion of therapy.  PET positivity at the end of treatment has been shown to be a significant adverse risk factor in patients with early stage, as well as advanced stage disease.  In classical HL stage III/IV, interim restaging with PET/CT may be considered after two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) with a possible de-escalation of therapy (4 cycles of ABVD [doxorubicin, bleomycin, vinblastine and dacabazine]) in patients with a negative interim PET/CT.  Early interim PET/CT after chemotherapy has been shown to be a sensitive prognostic indicator of treatment outcome in patients with advanced disease (stage II with unfavorable risk factors [with or without bulky disease] or in stage III to IV disease).  Initial results from retrospective analyses have failed to demonstrate the prognostic significance of interim PET/CT in patients with stage I/II favorable disease.  More recent reports suggest that interim response assessment with interim PET/CT after 2 or 3 cycles of chemotherapy, based on the 5-PS (Deauville criteria) is a good prognostic indicator  in patients with early stage disease.  However, the value and timing of interim PET scans remains unclear for many clinical scenarios, and all measures of response should be considered in the context of management decisions (NCCN, 2017). 

The 2017 NCCN PET/CT Task Force conclusions continue to recommend using PET for initial staging of lymphomas, including HL, and for evaluating for residual mass and treatment response for restaging at the end of treatment adding:

The role of PET/CT in post-therapy surveillance remains controversial and further studies are need to determine its role.  Until those studies are completed, PET scans are not recommended for routine surveillance due to the risk for false positive findings and unnecessary diagnostic interventions and/or radiation exposure…Management decisions should not be based on PET scan alone; clinical or pathologic correlation is needed (NCCN, 2017).

Regarding NHL, the updated NCCN guidelines recommend PET/CT for initial staging of all FDG-avid lymphomas.

PET/CT scans are now employed for initial staging, restaging and end-of-treatment response assessment in the majority of NHL types.  Biopsy of affected sites remains the gold standard for confirming new or persistent disease at the end of therapy (NCCN, 2017).  

Breast Cancer

Updated 2017 NCCN guidance for breast cancer retains a Category 2B* recommendation for PET and PET/CT and indicates that PET/CT is not indicated in the staging of clinical stage I, II, and operable III disease. 

FDG PET/CT is most helpful in situations where standard staging studies are equivocal or suspicious especially in the setting of locally advanced or metastatic disease.  FDG PET/CT may also be helpful in identifying unsuspected regional nodal disease and/or distant metastasis in locally advanced breast cancer when used in addition to standard staging studies (NCCN, 2017).

Ovarian Cancer

Updated 2017 NCCN guidance for ovarian cancer (including Fallopian Tubes and primary peritoneal cancer) retains the prior recommendations that consider PET and PET/CT imaging a Category 2B* recommendation, in the follow-up of the individual after completion of primary treatment. This recommendation is for monitoring response to treatment and as part of the evaluation for recurrent disease, if deemed clinically appropriate by the treating physicians.  In the 2014 NCCN update, a footnote was added for PET/CT scanning in the initial workup as “May be indicated for indeterminate lesions if results will alter management.” This was retained in the 2017 update (NCCN, 2017).

Cervical Cancer

An NCCN Task Force Report on PET identified studies that support use of PET for initial staging and identification and staging of recurrent disease in cervical cancer.  NCCN guidelines indicate, “PET-CT may aid in treatment planning but is not accepted for formal staging purposes.”  The NCCN guidelines recommend a single PET-CT scan be done at 3 to 6 months following therapy for locally advanced cervical cancer for detecting early or asymptomatic persistent or recurrent disease that is potentially curable but PET-CT is not recommended for surveillance.  For follow-up imaging of stage II and greater disease, PET/CT is considered preferable and can be considered in stage I disease if metastasis is suspected.  Staging is recommended for Stage IB2, IIA2 or advanced stage tumors (NCCN, 2017).

Testicular Cancer

Updated 2017 NCCN guidance for testicular cancer continues to recommend PET/CT in the post-chemotherapy management of pure seminoma stages IIA, IIB, IIC and III.  The role of PET/CT in this setting is for evaluating for residual viable tumor when there is a residual mass greater than 3 cm in size and normal serum tumor markers.  PET is typically performed at least 6 weeks following completion of chemotherapy to reduce the incidence of false-positive results.  “PET scanning has limited predictive value in nonseminoma disease” (NCCN, 2017).  

Pancreatic Cancer

The updated NCCN guideline for pancreatic adenocarcinoma reiterates:

The role of PET/CT scan remains unclear.  PET/CT may be considered after formal pancreatic CT protocol in ‘high risk patients’ to detect extra pancreatic metastases…The role of PET/CT in this setting is evolving and has not yet been established.  It is not a substitute for high quality contrast enhanced CT, although it can be considered as an adjunct to a formal pancreatic CT protocol in high risk patients (NCCN, 2017).

Solitary Pulmonary Nodule

Solitary pulmonary nodules (SPN) are also referred to as “coin lesions.”  These are usually round lesions and, by definition, less than 3 cm (that is 30 mm) in diameter and completely surrounded by pulmonary parenchyma, without other abnormalities.  Lesions larger than 3 cm are called masses and are often malignant (Ost, 2003).  PET and PET/CT may be used to determine the metabolic activity of SPNs that have adequate tissue volume for imaging resolution which can be used to estimate the likelihood that the lesion is malignant and that intervention is appropriate.  According to the updated NCCN guideline for NSCLC:

PET has a low sensitivity for nodules with less than 8 mm of solid component…In the workup of pulmonary nodules detected with CT in a high risk lung cancer screening population, the roles of contrast-enhanced CT and PET/CT are still in evolution.  Consider PET if the solid component is greater than 10 mm. Biopsy if PET positive (NCCN, 2017). 

In 2007, the American College of Chest Physicians (ACCP) released Guidelines for the Evaluation of  Solitary Pulmonary Nodules, based primarily on nodule size and individual risk factors for cancer, which provides recommendations for PET and PET/CT imaging of SPNs that includes all aspects of clinical management.  Within this ACCP document, the definition of a SPN is provided as:

A single, spherical, well circumscribed, radiographic opacity that measures < 3 cm (30 mm) in diameter and is surrounded completely by aerated lung.  There are no associated atelectasis, hilar enlargement, or pleural effusion…Focal pulmonary lesions that are > 3 cm (30 mm) in diameter are called lung masses and are presumed to represent bronchogenic carcinoma until proved otherwise…We further distinguish small subcentimeter nodules from the classical SPN because, compared with larger nodules, nodules that measure < 8-10 mm in diameter are much less likely to be malignant, typically defy accurate characterization by imaging tests, and are often difficult to approach by needle biopsy (Gould, 2007).

This ACCP guideline provided recommendations for imaging of SPNs when it is considered appropriate, which were updated in 2013 with the release of another ACCP guideline entitled, Diagnosis and Management of Lung Cancer, 3rd edition (Detterbeck, 2013).  This updated guideline changed its recommendations regarding SPNs from “We recommend…” to “We suggest…” for solid nodules that measure greater than 8 mm and also downgraded the evidence from Grade 1B* to 2C** saying:

According to the ACCP Guidelines for Diagnosis and Management of Lung Cancer, 3rd edition, Supplement for Methodology for Development of Guidelines for Lung Cancer (Lewis, 2013), the strength of recommendations grading system includes the following:
Grade 1A:        Strong recommendation, high-quality evidence;
*Grade 1B:      Strong recommendation, moderate-quality evidence;
Grade 1C:        Strong recommendation, low-quality evidence;
Grade 2A:        Weak recommendation, high-quality evidence;
Grade 2B:        Weak recommendation, moderate-quality evidence;
**Grade 2C:    Weak recommendation, low-quality evidence (Lewis, ACCP, 2013).

The 2007 ACCP guideline also noted that, “PET seems to be less sensitive for nodules that measure less than 8-10 mm in diameter, so its use in such nodules should be discouraged outside investigational settings.”  It is noted that PET imaging of a SPN does not confirm the diagnosis; the ACCP consider PET imaging most useful when the clinical pretest probability and CT results are discordant:

…Especially when pretest probability is relatively low and CT characteristics are indeterminate (not clearly benign)…In patients with indeterminate nodules by CT and high pretest probability, negative PET results do not reliably exclude malignancy…PET/CT results can help distinguish between hilar and mediastinal lymph nodes and identify invasion of the chest wall or mediastinal structures but the role of PET/CT scanners in the management of SPNs has not been well defined (Gould, 2007). 

A special feature review that provided an algorithmic approach to the diagnosis and management of SPNs was published in 2013, in which the following was noted:

PET scans are recommended only for nodules that are > 8 to 10 mm in diameter because the sensitivity decreases for the smaller pulmonary nodules.  Nodules < 1 cm and GGN (ground glass nodules) have a high rate of false negative interpretation (Patel, 2013a and 2013b).    

In 2018, Evangelista and colleauges published a retrospective study that concluded PET/CT is not recommended for GGN less than 5 mm.

Small Cell Lung Cancer

Concerning small cell lung cancer (SCLC), the updated NCCN 2018 guideline states that:

In the initial evaluation of SCLC and combined SCLC and NSCLC of primary or metastatic sites, PET/CT is recommended if limited stage disease is suspected to assess for distant metastasis.  If extensive stage is established, further staging evaluation is optional. For additional workup of limited stage disease (any T, any N, M0, except T 3-4 due to multiple nodules that do not fit in a tolerable radiation field), PET/CT is recommended to identify distant disease and to guide mediastinal evaluation if not previously done.  PET can increase staging accuracy in SCLC, however, pathologic confirmation is still required for lesions detected by PET/CT that alter the stage.  PET/CT is superior to PET alone.  For most metastatic sites, PET/CT is superior to standard imaging, however, PET/CT is inferior to MRI or CT for detection of brain metastasis.  PET/CT is not recommended for routine follow-up of disease status.

Regarding radiation therapy treatment planning, the 2018 NCCN guideline reiterates:

Radiation target volumes can be defined based on the pretreatment PET scan and CT scan obtained at the time of radiotherapy planning…PET/CT should be obtained preferably within 4 weeks, and no more than 8 weeks, before treatment.  For the imaging workup evaluation of neuroendocrine lung tumors, PET scanning is undergoing evaluation in clinical trials and should only be considered as a supplement, and not as a replacement, for other imaging studies (NCCN, 2018).

Non-small Cell Lung Cancer

The NCCN 2017 updated guideline for non-small cell lung cancer (NSCLC) reiterates prior comments regarding use of PET/CT in radiation therapy treatment planning, stating “PET/CT significantly improves targeting accuracy, especially for patients with significant atelectasis and when IV CT contrast is contraindicated…PET/CT should be obtained preferably within 4 weeks before treatment.”  Regarding surgical treatment planning, “CT and PET used for staging should be within 60 days before proceeding with surgical evaluation.”  PET/CT is even more sensitive than PET and is recommended for the evaluation and staging of NSCLC.  Regarding restaging after induction therapy, “…CT +/- PET should be performed to exclude disease progression or interval development of metastatic disease.”  PET was found to be more sensitive than CT in identifying mediastinal node disease, and PET/CT has been shown to be useful in restaging after adjuvant therapy.  However, positive PET/CT findings for distant disease need pathologic or other radiologic confirmation.  “If the PET/CT scan is positive in the mediastinum, the lymph node status needs pathologic confirmation” (NCCN, 2017).

Prostate Cancer

According to the NCCN 2017 updated guideline for prostate cancer:

PET/CT using C-11 choline tracer should be considered and may identify sites of metastatic disease in men with biochemical recurrence after primary treatment failure…Further study is needed to determine the best use of C-11 choline PET/CT imaging in men with prostate cancer...Oncologic PET/CT is typically done using 18F-FDG tracer. In certain clinical settings, the use of FDG-PET may provide useful information but should not be used routinely since data on the utility of FDG-PET/CT for prostate cancer is limited…C-11 choline PET/CT has been used to detect and differentiate prostate cancer from benign tissue...C-11 choline PET/CT may be useful to detect distant metastasis in these patients…FDG and fluoride PET is not recommended for initial assessment of prostate cancer and should not be used routinely for initial assessment or in other settings, due to limited evidence of clinical utility (NCCN, 2017).  

On September 12, 2012, the FDA approved C-11 choline radiotracer (Mayo Clinic, PET Radiochemistry Facility, [MCPRF] Rochester, MN) for the following indications:

Choline C 11 injection is a radioactive diagnostic agent for positron emission tomography (PET) imaging of patients with suspected prostate cancer recurrence and non-informative bone scintigraphy, computerized tomography (CT) or magnetic resonance imaging (MRI). In these patients, 11 C-choline PET imaging may help identify potential sites of prostate cancer recurrence for subsequent histologic confirmation. Suspected prostate recurrence is based upon elevated blood prostate specific antigen (PSA) levels following initial therapy. In clinical studies, images were produced with PET/CT coregistration. Choline C 11 PET imaging is not a replacement for histologic verification of recurrent prostate cancer (FDA, 2012).

Guidance from the European Association of Urology guidelines for prostate cancer indicate that 11C-choline PET/CT has limited value unless PSA levels exceed 1.0 ng/mL (Heidenreich, 2014).  The published evidence currently available from systematic reviews and meta-analysis regarding PET and PET/CT imaging with 11C-choline and 18F-FDG for staging and restaging individuals considered at high risk for prostate cancer is limited in terms of clinical applications, and warrants further study (Treglia, 2014; Umbehr, 2013; von Eyben, 2014).  

On May 27, 2016 the FDA approved another radiotracer proposed for use in prostate scanning for cancer recurrence, AXUMIN (fluciclovine F 18, Blue Earth Diagnostics, Ltd., Oxford, United Kingdom).  To date, the evidence to support utility for this tracer is lacking.  The FDA information is as follows:

Axumin is a radioactive diagnostic agent indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment (FDA, 2016).

Paraneoplastic Syndrome

Paraneoplastic syndromes are rare disorders that develop in some people with cancer, most commonly in people with lung, breast or ovarian cancer.  Some of these disorders are believed to occur when cancer-fighting antibodies mistakenly attack normal cells in the nervous system.  Symptoms usually appear when cancer is still in its early stages and can be manifest before the diagnosis of cancer has been confirmed.  Treatment of the underlying cancer may eliminate the symptoms of a paraneoplastic syndrome, although successful treatment may require medications to suppress the immune system.

Evaluation of neurologic paraneoplastic syndrome was investigated in a retrospective, medical record review conducted at a single institution for 56 consecutive subjects with suspected disease who underwent whole body PET/CT imaging after negative findings on standard diagnostics including conventional CT.  The Mayo Clinic medical records linkage system was retrospectively searched for all relevant records between January 1, 2005 and December 31, 2008.  This list was then cross-referenced with the Mayo Clinic Department of Radiology nuclear medicine imaging database where 112 subjects were identified where whole body PET/CT had been requested to search for cancer.  This resulted in the exclusion of 56 subjects who had PET/CT performed for cancer staging.  The remaining 56 all had a neurologic disorder suspected to be paraneoplastic in etiology, due to symptoms, history (of either cancer or smoking), inflammatory spinal fluid, or the presence of a paraneoplastic antibody detected in serum or in cerebrospinal fluid (CSF).  Whole body PET/CT was suggestive of cancer in 22 subjects (39%), 20 of whom then went on to have more targeted evaluations (biopsy, laryngoscopy).  Cancer was confirmed histologically in 10 subjects (18%) which represented half of all trial participants who had PET findings suggestive of cancer.  All 10 subjects were also seropositive for a paraneoplastic autoantibody.  No cancer was detected in 12 of the 56 trial subjects (55%) who had PET/CT abnormalities suggestive of cancer.  The median time from neurologic symptom onset to PET/CT did not differ for subjects where cancer was found (8.5 months; range 3-12 months) and those where cancer was not found (9 months; range 1-16 months).  It was noted that the association of a neuronal nuclear or cytoplasmic paraneoplastic autoantibody, detected by means of immunofluorescence, and a successful cancer search using PET/CT was significant (p<0.001).  Seven of 10 with cancer (70%) and 6 of 44 without cancer (14%) were seropositive.  No other statistically significant associations with cancer detection by PET/CT were identified.  The authors concluded that, despite acknowledged trial limitations (including small sample size, retrospective design, and potential for selection bias related to the inclusion of only subjects with detectable neural autoantibodies), the study results favor the use of PET/CT for initial oncologic evaluation of individuals with strongly suspected paraneoplastic neurologic etiology (McKeon, 2010).      

Surveillance Scanning

With regard to surveillance of individuals without signs or symptoms suggestive of recurrence after therapy has been completed, a review of the literature and specialty society guidelines has not found evidence that supports routine use of PET or PET/CT for regular follow-up in these clinical settings, except as an alternative to bone scan in soft tissue and bone sarcomas.  In a 2009 NCCN Task Force paper that examined the current state of clinical utility for PET and PET/CT for a variety of tumor types, it was noted that data supporting a definitive role for PET in disease surveillance is still lacking and, therefore, exploratory use of PET should be restricted to well-designed clinical trials (Podoloff, 2009).  However, in cases of Ewing Sarcoma Family of Tumors (ESFT), the current NCCN guidelines for bone cancer state, “Use the same imaging techniques that were performed in the initial workup.” Regarding surveillance following primary treatment and also following adjuvant/additional therapy:    

Surveillance of patients with Ewing Sarcoma Family of Tumors (ESFT) should include a physical exam, CBC and other laboratory studies and imaging of the chest and primary site every 2 to 3 months.  Surveillance intervals should be increased after 2 years.  Long-term surveillance should be performed annually after 5 years (Recommendation: Category 2B; NCCN, 2017). 

Osteomyelitis

A review and meta-analysis of the literature was conducted to evaluate diagnostic imaging modalities for evaluation of chronic osteomyelitis.  The diagnostic imaging techniques that were reviewed for the assessment of chronic osteomyelitis were radiography, computed tomography, magnetic resonance imaging (MRI), leukocyte scintigraphy, bone scintigraphy, gallium scintigraphy, PET and combined techniques, such as combined bone and leukocyte scintigraphy and combined bone and gallium scintigraphy.  A total of 23 clinical studies were included in the review.  Pooled sensitivity demonstrated that PET was the most sensitive technique with a sensitivity of 96% (95% confidence interval [CI], 88% to 99%), compared with 82% (95% CI, 70% to 89%) for bone scintigraphy; 61% (95% CI, 43% to 76%) for leukocyte scintigraphy; 78% (95% CI, 72% to 83%) for combined bone and leukocyte scintigraphy; and 84% (95% CI, 69% to 92%) for MRI.  Pooled specificity demonstrated that bone scintigraphy had the lowest specificity with 25%, compared with 60% for MRI; 77% for leukocyte scintigraphy; 84% for combined bone and leukocyte scintigraphy; and 91% for PET.  The sensitivity of leukocyte scintigraphy in detecting chronic osteomyelitis in the peripheral skeleton was 84%, compared with 21% for its detection in the axial skeleton.  The specificity of leukocyte scintigraphy in the axial skeleton was 60%, compared with 80% for the peripheral skeleton.  The authors concluded that while leukocyte scintigraphy has appropriate diagnostic accuracy in detecting chronic osteomyelitis of the peripheral skeleton, PET is superior for detecting chronic osteomyelitis in the axial (central) skeleton (Termaat, 2005).

Other Conditions

For the conditions and indications listed as investigational, including, but not limited to, scanning to evaluate in Parkinson’s Disease or as part of the evaluation of Autism Spectrum Disorder, there has not been adequate evidence in the medical literature to support the use of PET.  In most circumstances, there has not been sufficient numbers of well-conducted clinical trials evaluating the efficacy and utility of PET in either diagnosing or guiding the treatment of such conditions.  Finally, PET has not been shown to be effective as a screening modality for asymptomatic individuals for any condition.

NaF-18 for PET Scanning of Bone

Sodium fluoride F 18 (NaF-18) is a positron emitting radiopharmaceutical that has been used for diagnostic purposes, in conjunction with PET imaging, for bone scanning as a skeletal radiotracer.  Currently, the use of PET or PET/CT for imaging of bone has not demonstrated adequate evidence in the medical literature to support its safety, efficacy or superiority to conventional bone scanning for the evaluation of suspected metastatic bone disease or for any other condition.  In most circumstances, there has not been sufficient numbers of well-conducted clinical trials evaluating the efficacy and utility of PET or PET/CT using NaF-18 in either diagnosing or guiding the treatment of such conditions.  The literature on oncologic applications of NaF-18 PET scanning suggests improved ability to detect metastatic disease to bone, as compared with technetium bone scan from primary sites, such as breast, prostate, and lung.  Although the test performance data for NaF-18 PET scanning is encouraging, the number of subjects studied has been limited to date.  There is very little data, from just a few studies, suggesting that NaF-18 PET scanning may affect management decisions, and no data on how it affects actual clinical outcomes (Besheshti, 2008; Hetzel, 2003; Schirrmeister, 1999b).  There are several large ongoing studies that are designed to compare traditional technetium bone scan with NaF-18 PET scanning for oncologic bone indications.  Recently, use of NaF-18 has been investigated for detection of bone metastasis in high risk oncologic cases, such as advanced breast and prostate malignancies.  To date, the evidence has come from small, mostly prospective trials which show the potential for prognostic benefit to PET scanning with NaF-18.  However, further study is needed to demonstrate the role of NaF-18 and its impact on clinical management (Even-Sapir, 2006; Kjölhede, 2012; Withofs, 2011).  The literature on other uses of NaF-18 PET scanning, (for example, for detecting loosening of a joint prosthesis or assessing causes of back pain) is sparse, and there is no documentation or confirmation of incrementally improved clinical outcomes (Even-Sapir, 2006; Iagaru, 2009).  The updated NCCN guideline for prostate cancer refers to  NaF-18 as:

(This is) a newer technology utilized for PET or a hybrid imaging bone scan for diagnostic staging.  PET scans using NaF-18 tracer appear to have greater sensitivity than conventional bone scans.  However, there is controversy about how results should be acted upon, since all phase 3 clinical trials to date have used progression criteria for bone scans (NCCN, 2017).      

On March 26, 2010 CMS issued two transmittals to affirm that evidence is not sufficient to determine that the results of NaF-18 PET scanning to identify bone metastases improve health outcomes of beneficiaries with cancer. Effective for claims with dates of service on and after February 26, 2010:

NaF-18 PET oncologic claims to inform initial treatment strategy or subsequent treatment strategy for suspected or biopsy proven bone metastasis are covered but only in the context of a clinical study. All other claims for NaF-18 PET oncology scanning will remain non-covered (CMS, 2010).

Combined PET/CT Fusion Scanning

The fusion of PET and CT imaging into a single system has been widely reported to offer physicians improved diagnostic capabilities, especially in the field of oncology. While the results from a majority of the published studies on PET/CT fusion are preliminary and have focused on assessing technical feasibility and potential clinical applications, it can already be stated that this diagnostic tool improves upon imaging by using PET alone, because it synthesizes both structural and metabolic information. Early studies suggest that this additional information may help alter treatment decisions. From a practical perspective, there is now a movement toward utilizing PET/CT imaging for any oncologic indication where PET scanning would be indicated, i.e., for the diagnosis, staging, restaging, and monitoring of treatment for a number of different malignancies. Specifically, several small studies have suggested that PET/CT fusion has improved diagnostic ability over PET alone in lung cancer, lymphoma, malignant melanoma, and a variety of gastrointestinal, gynecological and head and neck malignancies. PET/CT fusion may be considered medically necessary for any oncologic indication where PET scanning is considered medically necessary.

Combined FDG PET and Mammography (PEM)

PET Mammography (PEM) is a form of PET that uses high-resolution, mini-camera detection technology to provide functional information on the breast.  As with PET, a radiotracer, usually FDG, is administered and a camera is used to provide a higher resolution image of a limited section of the body than would be achievable with FDG PET.  Gentle compression is used, and the detector(s) are mounted directly on the compression paddle(s). PEM allows for the detection of lesions smaller than 2 cm, which may not be possible with FDG PET.  Three-dimensional reconstruction of the PEM images is also possible.  PEM is presented as an alternative to MRI for individuals with contraindications to MRI or to the contrast agent.  PEM is also proposed as a noninvasive alternative to other imaging techniques for breast lesions that are difficult to characterize with conventional mammography, such as those with dense breast tissue, ductal carcinoma in situ (DCIS), and very small lesions.  To date, there is limited published evidence available.  One prospective, non-randomized clinical trial with 77 subjects reported that PEM had an overall accuracy of 88% to 92% compared with 71% for conventional imaging (p<0.001).  The authors concluded that this was largely due to PEM performing better for very early-stage breast cancer that had not spread beyond the site of origin (Berg, 2006).  Additional information is forming on PEM (Berg, 2011; Moadel, 2011; Raylman, 2008; Schilling, 2011; Tafra, 2005; Tafreshi, 2010).

New Radiotracer

On June 1, 2016 the FDA approved NetSpot (gallium-68 dotatate injection, Advanced Accelerator Applications , Inc. New York, NY) through the Priority Review and orphan drug designation process, which is indicated as follows:

NETSPOT, after radiolabeling with Ga 68, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients (FDA, 2016).

The evidence to support efficacy and utility for NetSpot tracer is evolving. In 2018, Castroneves and colleauges published a prospective study that evaluated the sensitivity and specificity of 68Ga PET/CT in detecting medullary thyroid cancer. The authors concluded it was not superior to currently used imaging studies. Additonal studies are needed to inform about this agent, as compared to established radiotracers used with PET and PET/CT scanning for malignancies.

Background/Overview

Description of Disease

One of the major applications of PET is for the detection and evaluation of various malignancies. The National Cancer Institute estimates that approximately 8.9 million Americans with a history of cancer were alive in January 1999. Some of these individuals were cancer-free, while others still had evidence of cancer and may have been undergoing treatment. Approximately 1.4 million new cancer cases are diagnosed annually.  In addition, this imaging technique is used in cardiology and in the localization of seizure focus for those with intractable epilepsy under consideration for neurosurgical resection.   

Description of Technology

Radiopharmaceutical agents (also called radiotracers) exhibit spontaneous disintegration of unstable nuclei by the emission of positrons and is used for providing dual photon positron emission tomographic diagnostic images.  This includes any nonradioactive reagent, reagent kit, ingredient, nuclide generator, accelerator, target material, electronic synthesizer, or other apparatus or computer program to be used in the preparation of a PET drug.  A “PET drug product” has been redefined by the FDA as a finished dosage form of a PET drug, whether or not in association with one or more other ingredients (FDA Modernization Act, 1997).

A PET scan (Positron Emission Tomography) is a highly specialized imaging technique that produces three-dimensional colored images to provide information about the body's chemistry. Unlike computed tomography (CT) or magnetic resonance imaging (MRI) scans, that look at anatomy or body form, PET studies metabolic activity or body function. The principle behind PET is that the utilization of substances, such as glucose, may differ between various tissue types or within different parts of an organ. Changes in the differential utilization of certain substances may occur in the presence of certain disease conditions, and patterns found on imaging are correlated with clinical implications.      

PET scans can be done on an outpatient basis; however, some hospitalized individuals may undergo a PET examination, if indicated. The procedure may be expected to last from 30 minutes to 2 hours, depending on the specific type of PET examination. Generally, a PET scan procedure follows this process:

  1. A small amount of radioactive material (called a tracer) is combined with a chemical, (such as glucose), and this mixture is generally injected into a vein but, on occasion, may be inhaled. The tracer emits tiny positively charged particles (positrons) that produce signals. The chemical substance and radioactive tracer chosen for the test vary according to the organ being evaluated.  A period of equilibration occurs and then images are taken. 
  2. A camera records the tracer's signals, as it travels through the body and collects in organs. A computer then converts the signals into three-dimensional images of the examined organ. The three-dimensional views can be produced from any angle and provide a clear view of an abnormality. For example, glucose or sugar, (which the body uses to produce energy), combined with a radioisotope, will show where glucose is being used in the brain, the heart muscle, or a growing tumor. Rapidly multiplying cancer cells need more sugar fuel, and, therefore, take up more of the sugar than other tissues, which show up as hot spots on the scan. When these images are combined or fused with CT or MRI scans, physicians have the most complete picture possible of the disease.

Proposed Benefits

PET scans are purported to be useful in a variety of conditions where variations in physiologic function can be detected. Major applications of PET include neurologic, (such as seizure foci detection); cardiac, (such as coronary artery disease evaluation and assessment of myocardial viability); and oncologic (tumor evaluation). The results of the scan may be used to help diagnose, localize, or evaluate the status of certain disease states, so that more informed treatment decisions may be made.

Possible Risks

There is always a slight risk of damage to cells or tissue from being exposed to any radiation, including the low level of radiation released by the radioactive tracer used for a PET scan. However, the risk of damage from the tracer is usually very low, compared with the potential benefits of the test. Most of the tracer will be eliminated from the body within 6 to 24 hours. Allergic reactions to the tracer are very rare.

PET/CT fusion refers to the imaging technique that combines the functional information from PET with the anatomical information from CT into one set of images. The PET and CT images are either “fused” by a software package that superimposes two digital images together or are processed simultaneously by combined PET/CT scanners. In either case, PET/CT fusion has been purported to allow for earlier and more accurate detection and staging of a number of malignancies.

Definitions

Applications of PET:

Intermittent Surveillance:  The term “Intermittent,” when used in the context of timeframes for surveillance of asymptomatic individuals with a history of Ewing Sarcoma, is defined as periodic or interval rescanning.  According to the 2015 NCCN guidelines for bone cancer regarding surveillance imaging following primary treatment or adjuvant/additional therapy, “Surveillance of patients with Ewing Sarcoma Family of Tumors (ESFT) should include: imaging of the chest and primary site every 2 to 3 months. Surveillance intervals should be increased after 2 years. Long-term surveillance should be performed annually after 5 years. Use the same imaging techniques that were performed in the initial workup.” (See Surveillance definition above).

Medically refractory:  This term refers to a disease or condition that does not yield to treatment with medications.

Metastases:  Cancer that started from cancer cells from another part of the body, for example: cancer that starts in the breast can spread to the lymph nodes and then be spread throughout the body.

Myocardial viability:  A measure of the functional condition of heart muscle centering on its ability to work properly.

National Comprehensive Cancer Network® NCCN Clinical Practice Guidelines in Oncology (NCCN) Categories of Evidence and Consensus:

Category 1:  The recommendation is based on high level evidence, and there is uniform NCCN consensus.

**Category 2A:  The recommendation is based on lower level evidence, including clinical experience and there is uniform NCCN consensus.

*Category 2B:  The recommendation is based on lower level evidence, including clinical experience and there is non-uniform NCCN consensus (but no major disagreement).

Category 3:  Based on any level of evidence but reflects major disagreement.

All recommendations of the NCCN are Category 2A unless otherwise noted.

Obesity:  According to the Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults Evidence Report of the Obesity Education Initiative from the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), the following BMI (body mass index) ranges should be used to classify obesity as follows:

(BMI = weight (kg)/height squared [m2].  To estimate BMI from pounds and inches use:
[weight (pounds)/ height (inches)2] x 703 528; [1 lb = 0.4536 kg]; [1 in = 2.54 cm = 0.0254 m])

Radiation necrosis:  An area of dead cells that result from complications of therapy or surgery using high-energy radiation techniques.

Resectability:  The quality of a tumor or other tissue that allows it to be safely removed in whole or part by surgery.

Revascularization:  A medical or surgical procedure that re-establishes blood supply to a part of the body.

Seizure focus:  The area of the brain from which a seizure originates.

Coding

 The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Brain PET imaging, nonspecific
When services may be Medically Necessary when criteria are met:

CPT

 

78608

Brain imaging, positron emission tomography (PET); metabolic evaluation

78609

Brain imaging, positron emission tomography (PET); perfusion evaluation

 

 

ICD-10 Diagnosis

 

C70.0

Malignant neoplasm of cerebral meninges

C70.9

Malignant neoplasm of meninges, unspecified

C71.0-C71.9

Malignant neoplasm of brain, cranial nerves, cerebral meninges

C72.20-C72.59

Malignant neoplasm of olfactory, optic, acoustic, other and unspecified cranial nerves

C72.9

Malignant neoplasm of central nervous system, unspecified

C79.31-C79.32

Secondary malignant neoplasm of brain and cerebral meninges

D43.0-D43.3

Neoplasm of uncertain behavior of brain, cranial nerves

D49.6

Neoplasm of unspecified behavior of brain

G40.011-G40.019

Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable

G40.111- G40.119

Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable

G40.211-G40.219

Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable

G40.311- G40.319

Generalized idiopathic epilepsy and epileptic syndromes, intractable

G40.A11-G40.A19

Absence epileptic syndrome, intractable

G40.B11-G40.B19

Juvenile myoclonic epilepsy, intractable

G40.411- G40.419

Other generalized epilepsy and epileptic syndromes, intractable

G40.803-G40.804

Other epilepsy, intractable

G40.813-G40.814

Lennox-Gastaut syndrome, intractable

G40.823-G40.824

Epileptic spasms, intractable

G40.911-G40.919

Epilepsy, unspecified, intractable

Z85.841

Personal history of malignant neoplasm of brain

When services are Investigational and Not Medically Necessary:
For the procedure and diagnostic codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Myocardial PET imaging
When services may be Medically Necessary when criteria are met:

CPT

 

78459

Myocardial imaging, positron emission tomography (PET), metabolic evaluation

78491

Myocardial imaging, positron emission tomography (PET), perfusion; single study at rest or stress

78492

Myocardial imaging, positron emission tomography (PET), perfusion; multiple studies at rest and/or stress

0482T

Absolute quantitation of myocardial blood flow, positron emission tomography (PET), rest and stress

 

 

ICD-10 Diagnosis

 

D86.85

Sarcoid myocarditis

I09.81

Rheumatic heart failure

I11.0

Hypertensive heart disease with heart failure

I13.0

Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease

I13.2

Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease

I20.0-I20.9

Angina pectoris

I21.01-I21.A9

Acute myocardial infarction

I22.0-I22.9

Subsequent ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction

I24.0-I24.9

Other acute ischemic heart disease

I25.10-I25.9

Chronic ischemic heart disease

I50.1-I50.9

Heart failure

I51.0-I51.9

Complications and ill-defined descriptions of heart disease

I97.130-I97.131

Postprocedural heart failure

R07.1-R07.2

Chest pain on breathing, precordial pain

R07.81-R07.89

Other chest pain

R07.9

Chest pain, unspecified

Z68.41-Z68.45

Body mass index (BMI) 40 or greater, adult

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above, when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Miscellaneous PET imaging, nonspecific
When services may be Medically Necessary when criteria are met:

CPT

 

78811

Positron emission tomography (PET) imaging; limited area (eg, chest, head/neck)

78812

Positron emission tomography (PET) imaging; skull base to mid-thigh

78813

Positron emission tomography (PET) imaging; whole body

78814

Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; limited area (eg, chest, head/neck)

78815

Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; skull base to mid-thigh

78816

Positron emission tomography (PET) with concurrently acquired computed tomography (CT) for attenuation correction and anatomical localization imaging; whole body

 

 

HCPCS

 

G0235

PET imaging, any site, not otherwise specified

 

 

ICD-10 Diagnosis

 

C00.0-C60.9

Malignant neoplasms

C62.00-D07.4

Malignant neoplasms

D07.60-D09.9

Malignant neoplasms

D13.6-D13.7

Benign neoplasm of pancreas, endocrine pancreas

D14.30-D14.32

Benign neoplasm of bronchus and lung

D16.00-D16.9

Benign neoplasm of bone and articular cartilage

D17.0-D17.9

Benign lipomatous neoplasm

D18.00-D18.1

Hemangioma and lymphangioma, any site

D19.0-D19.9

Benign neoplasm of mesothelial tissue

D20.0-D20.1

Benign neoplasm of soft tissue of retroperitoneum and peritoneum

D21.0-D21.9

Other benign neoplasms of connective and other soft tissue

D3A.090

Benign carcinoid tumor of the bronchus and lung

D37.01-D39.9

Neoplasms of uncertain behavior

D40.10-D48.9

Neoplasms of uncertain behavior

D49.0-D49.9

Neoplasms of unspecified behavior

K86.2-K86.3

Cyst, pseudocyst of pancreas

M86.30

Chronic multifocal osteomyelitis, unspecified site

M86.38-M86.39

Chronic multifocal osteomyelitis, other and multiple sites [specified as axial skeleton]

M86.40

Chronic osteomyelitis with draining sinus, unspecified site

M86.48-M86.49

Chronic osteomyelitis with draining sinus, other and multiple sites [specified as axial skeleton]

M86.50

Other chronic hematogenous osteomyelitis, unspecified site

M86.58-M86.59

Other chronic hematogenous osteomyelitis, other and multiple sites [specified as axial skeleton]

M86.60

Other chronic osteomyelitis, unspecified site

M86.68-M86.69

Other chronic osteomyelitis, other and multiple sites [specified as axial skeleton]

Q45.2

Congenital pancreatic cyst

R91.1

Solitary pulmonary nodule

R91.8

Other nonspecific abnormal findings of lung field

Z85.00-Z85.45

Personal history of malignant neoplasm

Z85.47-Z85.9

Personal history of malignant neoplasm

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met; for the diagnoses listed below and all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

ICD-10 Diagnosis

 

C61

Malignant neoplasm of prostate

D07.5

Carcinoma in situ of prostate

D40.0

Neoplasm of uncertain behavior of prostate

Z85.46

Personal history of malignant neoplasm of prostate

When services are also Investigational and Not Medically Necessary:

CPT

 

78999

Unlisted miscellaneous procedure, diagnostic nuclear medicine [when specified as PET scanning of the bone using Sodium fluoride F 18 (NaF-18) or PET mammography]

 

 

HCPCS

 

A9515

Choline c-11, diagnostic, per study dose up to 20 millicuries

A9580

Sodium fluoride F-18, diagnostic, per study dose, up to 30 millicuries [when specified as PET scanning of the bone using Sodium fluoride F 18 (NaF-18)]

A9586

Florbetapir F18, diagnostic, per study dose, up to 10 millicuries [AMYViD]

A9588

Fluciclovine f-18, diagnostic, 1 millicurie [Axumin]

Q9982

Flutemetamol F18, diagnostic, per study dose, up to 5 millicuries

Q9983

Florbetaben F18, diagnostic, per study dose, up to 8.1 millicuries

G0219

PET imaging whole body; melanoma for noncovered indications

G0252

PET imaging, full and partial-ring PET scanners only, for initial diagnosis of breast cancer and/or surgical planning for breast cancer (e.g., initial staging of axillary lymph nodes)

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

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  93. Wolfort RM, Papillion PW, Turnage RH, et al.  Role of FDG-PET in the evaluation and staging of hepatocellular carcinoma with comparison of tumor size, AFP level, and histologic grade.  Int Surg. 2010; 95(1):67-75.
  94. Wolk DA, Sadowsky C, Safirstein B, et al. Use of flutemetamol F 18-labeled positron emission tomography and other biomarkers to assess risk of clinical progression in patients with amnestic mild cognitive impairment. JAMA Neurol. 2018 May 14; [Epub ahead of print]. Available at: https://jamanetwork.com/journals/jamaneurology/fullarticle/2680669. Accessed on June 22, 2018.
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  97. Zamagni E, Nanni C, Mancuso K, et al. PET/CT improves the definition of complete response and allows to detect otherwise unidentifiable skeletal progression in multiple myeloma. Clin Can Res. 2015; 21:4384-4390.
  98. Zhao J, Qiao W, Wang C, et al.  Therapeutic evaluation and prognostic value of interim hybrid PET/CT with (18)F-FDG after three to four cycles of chemotherapy in non-Hodgkin's lymphoma.  Hematology. 2007; 12(5):423-430. 

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Amyvid (florbetapir F 18 injection).  Avid Radiopharmaceuticals, Inc., Philadelphia, PA. (Prescribing information). April 6, 2012. Available at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf. Accessed on June 22, 2018.
  2. Balk E, Lau J. Report for the Agency for Healthcare Research and Quality.  Systematic Review of Positron Emission Tomography for Follow-up of Treated Thyroid Cancer. April 2002.
  3. Beanlands RS, Chow BJ, Dick A, et al. CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced non-invasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease--executive summary. Can J Cardiol. 2007; 23(2):107-119. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650646/pdf/cjc230107.pdf. Accessed on June 22, 2018.
  4. Blue Cross and Blue Shield Association. Beta amyloid imaging with positron emission tomography (PET) for evaluation of suspected Alzheimer’s disease or other causes of cognitive decline. TEC Assessment, 2013; 27(5).
  5. Blue Cross Blue Shield Association. Special Report:  Positron Emission Tomography for the Indication of Post-Treatment Surveillance of Cancer. TEC Assessment, 2010; 25(3).
  6. Blue Cross Blue Shield Association. FDG positron emission tomography for evaluating breast cancer.  TEC Assessment, 2001; 16(5).
  7. Blue Cross Blue Shield Association. FDG PET to manage patients with occult primary carcinoma and metastasis outside the head and neck. TEC Assessment, 2002; 17(14).
  8. Blue Cross Blue Shield Association. FDG positron emission tomography for evaluating esophageal cancer. TEC Assessment, 2002; 16(21).
  9. Blue Cross and Blue Shield Association. FDG positron emission tomography in head and neck cancer. TEC Assessment, 2000; 15(4).
  10. Blue Cross and Blue Shield Association. FDG positron emission tomography in colorectal cancer. TEC Assessment, 2000; 14(25).
  11. Blue Cross and Blue Shield Association. FDG positron emission tomography in lymphoma.  TEC Assessment, 2000; 14(26).
  12. Blue Cross and Blue Shield Association. FDG positron emission tomography in melanoma. TEC Assessment, 2000; 14(27).
  13. Blue Cross and Blue Shield Association. FDG positron emission tomography in pancreatic cancer. TEC    Assessment, 2000; 14(28).
  14. Blue Cross and Blue Shield Association. FDG PET to manage patients with an occult primary carcinoma and metastasis outside the cervical lymph nodes. TEC Assessment. 2003; 17(14).
  15. Blue Cross and Blue Shield Association. FDG positron emission tomography for evaluating breast cancer. TEC Assessment. 2003; 18(14).
  16. Centers for Medicare and Medicaid Services. National Coverage Determination for PET (FDG). NCD #220.6. Effective April 3, 2009. Available at:  https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=211&ncdver=4&bc=BAABAAAAAAAA&. Accessed on June 22, 2018.
  17. Centers for Medicare and Medicaid Services. National Coverage Determination for PET (FDG) for Oncologic Conditions. NCD #220.6.17. Effective August 4, 2010. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=331&ncdver=3&bc=BAABAAAAAAAA&. Accessed on June 22, 2018.
  18. Center for Medicare and Medicaid Services. Decision Memo for Positron Emission Tomography (FDG) for Solid Tumors (CAG-00181R4). NCD#220.6.17. Effective June 11, 2013. Available at:  http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=263&NcaName=Positron+Emission+Tomography+(FDG)+for+Solid+Tumors&NCDId=211&ncdver=4&IsPopup=y&bc=AAAAAAAACAAAAA%3d%3d&. Accessed on June 22, 2018.
  19. Centers for Medicare and Medicaid Services. National Coverage Determination for Positron Emission Tomography (NaF-18) to Identify Bone Metastasis of Cancer. NCD #220.6.19. Effective February 26, 2010. Available at:  https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=336&ncdver=1&bc=BAABAAAAAAAA&. Accessed on June 22, 2018.
  20. Centers for Medicare and Medicaid Services. National Coverage Analysis (NCA) Final Decision Memo for Beta Amyloid Positron Emission Tomography in Dementia and Neurodegenerative Disease (CAG-00431N).  NCD#220.6.20. September 27, 2013. Available at:  http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=265. Accessed on June 22, 2018.
  21. Centers for Medicare and Medicaid Services. Decision Memo for Positron Emission Tomography (CAG-00065R2). March 7, 2013. Available at: http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=261. Accessed on June 22, 2018.
  22. Choline C-11 injection. Mayo Clinic, PET Radiochemistry Facility, (MCPRF) Rochester, MN. (Prescribing information). September 12, 2012. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203155s000lbl.pdf. Accessed on June 22, 2018
  23. Detterbeck FC, Lewis SZ, Diekemper R, et al. Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. Chest. 2013; 143(5):(Suppl)7S–37S
  24. Feldman MD. Positron emission tomography (PET) for the evaluation of Alzheimer's disease/dementia. Technology Assessment. San Francisco, CA: California Technology Assessment Forum; February 11, 2004.
  25. Gould MK, Fletcher J, Iannettoni MD, et al. Evaluation of patients with pulmonary nodules: when is it lung cancer?:  American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines (3rd  edition). Chest. 2013; 143(5 suppl):e93S-120S.
  26. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014; 65(2):467-479.
  27. Heller GV, Beanlands R, Merlino DA, et al. American Society of Nuclear Cardiology (ASNC) Model Coverage Policy: Cardiac positron emission tomographic imaging. J Nucl Cardiol. 2013; 20(5):916-947.
  28. Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. J Am Coll Cardiol. 2009; 53. 
  29. Ioannidis JP, Lau J. Report for the Agency for Healthcare Research and Quality. FDG-PET for the diagnosis and management of soft tissue sarcoma. April 2002.
  30. Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. J Nucl Med. 2013; 54(3):476-490. Available at:  http://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=15667.  Accessed on June 22, 2018.32.         
  31. Klocke FJ, Baird MG, Baterman TM, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging:  a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA/ASNC Committee to revise the 1995 Guidelines for the clinical use of radionuclide imaging. J Am Coll Cardiol. 2003; 42(7):1318-1333. 
  32. Lewis SZ, Diekemper R, Addrizzo-Harris DJ. Methodology for development of guidelines for lung cancer:diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):41S–50S.
  33. Matchar DB, Kulasingam SL, McCrory DC, et al. Use of positron emission tomography and other neuroimaging techniques in the diagnosis and management of Alzheimer’s disease and dementia. Report for the Agency for Healthcare Quality and Research.  December 14, 2001. Available at:  http://www.cms.hhs.gov/determinationprocess/downloads/id9TA.pdf. Accessed on June 22, 2018.
  34. Matchar DB, Kulasingam SL, Huntington A et al. Technology Assessment. Positron emission tomography, single photon emission computed tomography, computed tomography, functional magnetic resonance imaging, and magnetic resonance spectroscopy for the diagnosis and management of Alzheimer’s dementia. Duke Center for Clinical Policy Research and Evidence Practice Center. April 2004. 
  35. Matchar DB, Kulasingam SL, Havrilesky L. Agency for Healthcare Research and Quality (AHRQ) Technology Assessment: Positron emission testing for six cancers (brain, cervical, small cell lung, ovarian, pancreatic and testicular). Rockville, MD:  February 2004.
  36. Mitchell DG, Javitt MC, Glanc P, et al. ACR appropriateness criteria: staging and follow-up of ovarian cancer. J Am Coll Radiol. 2013; 10(11):822-827.
  37. Mujoomdar M, Moulton K, Nkansah E. Positron Emission Tomography (PET) in Oncology: A Systematic Review of Clinical Effectiveness and Indications for Use. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2010. Available at:  http://www.cadth.ca/media/pdf/M0001_PET_for_Oncology_L3_e.pdf. Accessed on June 22, 2018.
  38. Multiple Myeloma Research Foundation. Diagnosing. Available at: https://themmrf.org/multiple-myeloma/diagnosis/. Accessed on June 22, 2018.
  39. National Cancer Institute (NCI) and the Masonic Cancer Center at University of Minnesota. Study of Fluorodeoxyglucose Positron Emission Tomography/CT Imaging in Predicting Disease-Free Survival of Patients Receiving Neoadjuvant Chemotherapy for Soft Tissue Sarcoma.  NCT00346125. Last updated December 5, 2017. Available at: http://clinicaltrials.gov/ct/show/NCT00346125. Accessed on June 22, 2018.
  40. NCCN Clinical Practice Guidelines in Oncology. © 2018. National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on July 31, 2018.
    • Bladder Cancer (V5.2018). Revised July 21, 2018. Breast Cancer (V1.2018). Revised March 20, 2018.
    • Bone Cancer (V2.2018). Revised March 28, 2018.
    • Cervical Cancer (V2.2018). Revised June 26, 2018.
    • Colon Cancer (V2.2018). Revised March 14, 2018.
    • Lung Cancer Screening (V1.2019). Revised June 11, 2018.
    • Multiple Myeloma (V1.2019). Revised July 20, 2018.
    • Non-small Cell Lung Cancer (V5.2018). Revised June 27, 2018.
    • Small-cell Lung Cancer (V2.2018). Revised January 17, 2018.
    • Ovarian Cancer (V2.2018). Revised March 9, 2018.
    • Hodgkin Lymphoma (V3.2018). Revised April 16, 2018.
    •  Non-Hodgkin’s Lymphoma (V4.2018). Revised May 15, 2018.
    • Pancreatic Adenocarcinoma (V2.2018). Revised July 10, 2018.
    • Prostate Cancer (V3.2018). Revised June 21, 2018.
    • Testicular Cancer (V2.2018). Revised February 16, 2018.
  41. Neuraceq (florbetaben F 18 injection). Piramal Imaging, Matran Switzerland.  (Prescribing information).  March 19, 2014. Available at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204677s000lbl.pdf. Accessed on June 22, 2018.
  42. Patel VK, Naik SK, Naidich DP, et al. A practical algorithmic approach to the diagnosis and management of solitary pulmonary nodules:  part 1: radiologic characteristics and imaging modalities. Chest. 2013a; 143(3):825-839.  
  43. Patel VK, Naik SK, Naidich DP, et al. A practical algorithmic approach to the diagnosis and management of solitary pulmonary nodules:  part 2: pretest probability and algorithm. Chest. 2013b; 143(3):840-846.
  44. Podoloff DA, Advani RH, Allred C, et al. National Comprehensive Cancer Network, Inc.  (NCCN). NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer. J Natl Compr Canc Netw. 2007; 5(suppl 1):S1-22.
  45. Podoloff DA, Ball DW, Ben-Josef E, et al. NCCN task force: clinical utility of PET in a variety of tumor types.  J Natl Compr Canc Netw. 2009; 7(suppl 2):S1-26.
  46. Schnipper LE, Lyman GH, Blayney DW, et al. American Society of Clinical Oncology (ASCO) 2013 top five list in oncology. J Clin Oncol. 2013; 31(34):4362-4370.
  47. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians (ACCP). Evidence-based clinical practice guidelines.  Chest. 2013; 143(5 Suppl):e211S-250S.
  48. Society of Nuclear Medicine (SNM). Working Group, Brain Imaging Council. Effectiveness and Safety of FDG PET in the Diagnosis of Dementia: A Review of the recent Literature. January 25, 2011.
  49. U.S. Department of Health and Human Services. Agency for Healthcare Research and Quality (AHRQ). Technology Assessment: Positron Emission Testing for six cancers (brain, cervical, small cell lung, ovarian, pancreatic and testicular).  February 12, 2004. Available at: http://www.cms.gov/determinationprocess/downloads/id21TA.pdf. Accessed on June 22, 2018.
  50. U.S. Department of Health and Human Services. Agency for Healthcare Research and Quality (AHRQ). Positron Emission Tomography for Nine Cancers (Bladder, Brain, Cervical, Kidney, Ovarian, Pancreatic, Prostate, Small Cell Lung, Testicular). Health Technology Assessments. No. PETC1207. Dec., 1, 2008.  Available at:  http://www.cms.hhs.gov/determinationprocess/downloads/id54TA.pdf. Accessed on June 22, 2018.
  51. U.S. Department of Health and Human Services. Agency for Healthcare Research and Quality (AHRQ). Technology Assessment:  Systematic Review of Positron Emission Tomography for Follow-up of Treated Thyroid Cancer. April 10, 2002. Available at: http://www.cms.gov/determinationprocess/downloads/id7TA.pdf. Accessed on June 22, 2018.
  52. Vizamyl (flutemetamol F 18 injection). Med-Physics, Inc. Arlington Heights, IL. (Prescribing information). October 25, 2013. Available at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203137s000lbl.pdf. Accessed on June, 2018.
Websites for Additional Information
  1. American College of Radiology (ACR). Radiology Info: Positron Emission Tomography (PET). Last reviewed: 2016. Available at: http://www.radiologyinfo.org/en/info.cfm?pg=PET. Accessed on June 22, 2018.
  2. National Institutes of Health (NIH). University of Pennsylvania.  FDG-PET Imaging in Complicated Diabetic Foot. NCT00194298. Last updated August 29, 2016. Available at:   http://www.clinicaltrials.gov/ct2/show/NCT00194298?term=00194298&rank=1. Accessed on June 22, 2018.
Index

Axumin (18F-fluciclovine)
Choline C-11 (11C-choline)
FDG, Fluoro-D-glucose (F18)
Florbetapir F18 (or AV-45)
Florbetaben F18 (or AV-1, or BAY-94-9172)
Flutemetamol F18 (or GE-067)
FDDNP F18
13N-ammonia
15O-water
PIB, Pittsburgh Compound B C11
Neuraceq
Netspot (Gallium-68 Dotatate)Vizamyl

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

 

Reviewed

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

 

Reviewed

07/18/2018

Hematology/Oncology Subcommittee review. Updated formatting in the Position Statement section. Updated Rationale, References, and Websites sections.

 

Reviewed

11/02/2017

MPTAC review. 

 

Reviewed

11/01/2017

Hematology/Oncology Subcommittee review.  The document header wording was updated from “Current Effective Date” to “Publish Date.”  The Rationale and References sections were updated.  Updated Coding section with 01/01/2018 CPT and HCPCS changes, removed A9599 deleted 12/31/2017, C9461 deleted 12/31/2016..

 

 

10/01/2017

Updated Coding section with 10/01/2017 ICD-10-CM diagnosis code and descriptor changes.

 

Reviewed

11/03/2016

MPTAC review. 

 

Reviewed

11/02/2016

Hematology/Oncology Subcommittee review.  Updated the formatting of the Position Statements section.  The Rationale, References and Index sections were updated. Updated Coding section with 01/01/2017 HCPCS changes.

 

 

07/01/2016

Updated Coding section with 07/01/2016 HCPCS changes; removed C9458, C9459 deleted 06/30/2016.

 

 

04/01/2016

Updated Coding section with 04/01/2016 HCPCS changes.

 

Revised

11/05/2015

MPTAC review.

 

Revised

11/04/2015

Hematology/Oncology Subcommittee review.  A minor language revision was made for clarification to the section on Diagnosis/Staging to align with the Restaging/Monitoring section regarding the medically necessary criteria for oncologic PET and PET/CT to read, “When more standard imaging (for example, CT, MRI, ultrasound) are either not indicated or provided inconclusive results.”  Updated Coding section with 01/01/2016 HCPCS changes; also removed ICD-9 codes.

 

Revised

05/07/2015

MPTAC review.

 

Revised

05/06/2015

Hematology/Oncology Subcommittee review.  A definition was added regarding Intermittent Surveillance in Ewing sarcoma for clarification.  A statement was added regarding PET scanning of prostate cancer with C-11 choline or other radiopharmaceutical as investigational and not medically necessary for all applications. The Rationale, Definitions, Coding and References sections were updated.

 

Reviewed

05/15/2014

MPTAC review.

 

Reviewed

05/14/2014

Hematology/Oncology Subcommittee review.  The Rationale and References were updated.

 

 

01/01/2014

Updated Coding section with 01/01/2014 HCPCS changes.

 

Revised

05/09/2013

MPTAC. Review.

 

Revised

05/08/2013

Hematology/Oncology Subcommittee review.  Clarification of investigational and not medically necessary criteria to address:  beta amyloid (β-amyloid) PET tracer, Autism Spectrum Disorders, and Parkinson’s Disease.  The Rationale and References were updated.

 

 

01/01/2013

Updated Coding section with 01/01/2013 HCPCS changes.

 

Reviewed

08/09/2012

MPTAC review. 

 

Revised

06/27/2012

MPTAC review. 

 

Revised

06/19/2012

Hematology/Oncology Subcommittee review.  A medically necessary statement was proposed for interim PET or PET/CT scanning in HL and NHL with medically necessary criteria added.

 

Revised

05/10/2012

MPTAC review.  The Rationale, Definitions and References were updated.

 

Revised

05/09/2012

Hematology/Oncology Subcommittee review.  Revisions were proposed for initial diagnosis or staging of melanoma to clarify that initial evaluation of regional lymph nodes is excluded.  The position statements were reformatted.  Also the definitions within the position statement section for diagnosis, staging, restaging, monitoring, surveillance and interim imaging were revised for clarification and removed from the position statement section and placed in the Definitions section. 

 

 

10/01/2011

Updated Coding section with 10/01/2011 ICD-9 changes.

 

Revised

05/19/2011

MPTAC review. The cardiac applications were revised to clarify severe global left ventricular dysfunction for myocardial viability and to add assessment of suspected cardiac sarcoidosis when MRI is contraindicated. The additional revisions suggested below were also approved.  The Rationale, Definitions, Coding and Reference sections were also updated.

 

Revised

05/18/2011

Hematology/Oncology Subcommittee review.  Revisions to the oncologic applications for PET that are considered investigational and not medically necessary to include:  PET Mammography for detection or subsequent monitoring of breast cancer and interim PET scanning to evaluate response to treatment during a course of treatment.

 

Revised

11/18/2010

MPTAC review. The oncologic revision suggested by the Hematology/Oncology Subcommittee (below) was approved.  The cardiac applications for PET were clarified with the addition of stress echocardiogram to Criterion #2 a and b.  The Rationale, Definitions and References were also updated.

 

Revised

11/17/2010

Hematology/Oncology Subcommittee review.  A revision was discussed and suggested for the evaluation of suspected paraneoplastic syndrome to be added to the medically necessary oncologic applications for initial therapy when the other criteria are also met. 

 

 

10/01/2010

Updated Coding section with 10/01/2010 ICD-9 changes.

 

Revised

05/13/2010

MPTAC review.  The criterion for cardiac applications related to obesity was clarified.  A position statement has been added regarding PET scanning of bone with NaF-18 which is considered investigational and not medically necessary for all applications.  The Rationale, Definitions, and References were updated.

 

Revised

05/12/2010

Hematology/Oncology Subcommittee review.

 

Revised

11/19/2009

MPTAC review.  Approved new revisions suggested by the Hematology/Oncology Subcommittee (listed below).

 

Revised

11/18/2009

Hematology/Oncology Subcommittee review.  The revisions listed below for August and June, 2009 were presented and discussed.  Poorly differentiated neuroendocrine tumors was added to the medically necessary indications under Initial and Subsequent therapy. When prior PET has been performed was also added to the medically necessary indications under Subsequent therapy when criteria are met.  An additional revision was recommended to add intermittent surveillance scanning for Ewing sarcoma as considered medically necessary.  The definitions for restaging, monitoring and surveillance were clarified.

 

Revised

08/27/2009

MPTAC review. Accepted the recommendations of the Hematology/Oncology Subcommittee below.  The medical necessity criteria for cardiac applications regarding myocardial perfusion evaluation were clarified regarding the conditions for which angiography may be associated with high risk for morbidity. Updated coding section to include 10/01/2009 ICD-9 changes.

 

Revised

06/17/2009

Hematology/Oncology Subcommittee ad hoc review. The medical necessity criteria have been reformatted and revised to categorize into Initial Therapy (diagnosis or staging) and Subsequent Therapy (restaging or monitoring), consistent with the new framework adopted by CMS policy.

 

Revised

02/26/2009

MPTAC review.  Revisions were made to the oncologic criteria considered medically necessary for breast cancer and for colorectal cancer to clarify the language regarding evaluation of suspected recurrent disease.

 

Revised

01/13/2009

Hematology/Oncology Subcommittee ad hoc review of the above revisions. 

 

 

10/01/2008

Updated Coding section with 10/01/2008 ICD-9 changes.

 

Reviewed

05/15/2008

MPTAC review.

 

Reviewed

05/14/2008

Hematology/Oncology Subcommittee review.  No change to criteria.  References were updated.

 

 

01/01/2008

Updated Coding section with 01/01/2008 CPT changes.  The phrase “investigational/not medically necessary” was clarified to read “investigational and not medically necessary.”  This change was approved at the November 29, 2007 MPTAC meeting.

 

 

10/01/2007

Updated Coding section with 10/01/2007 ICD-9 changes.

 

Revised

05/17/2007

MPTAC review.  Criteria were expanded to add chronic osteomyelitis of the central skeleton and pediatric neuroblastoma to the medically necessary indications.  Rationale, References and coding were updated.

 

Revised

05/16/2007

Hematology/Oncology Subcommittee review.  Coding updated; removed CPT 78810 deleted 12/31/2004 and HCPCS codes deleted 03/31/2005.

 

Revised

06/08/2006

MPTAC review.  Revisions made to the medical necessity criteria to broaden and clarify the criteria under each indication. Revisions were based on recently published literature, including the Juweid/Cheson article in the NEJM 2006.  References were also updated with this and other articles and AHRQ/other technology assessment reports information.

 

Reviewed

12/01/2005

MPTAC review. 

 

Revised

11/30/2005

Hematology/Oncology Subcommittee review.  Merged RAD.00039 PET/CT fusion into this document.  Clarified use in breast cancer.

 

 

11/21/2005

Added references for Centers for Medicare and Medicaid Services (CMS) – National Coverage Determination (NCD).

 

Revised

04/28/2005

MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Updated coding: Added HCPCS codes G0210, G0212, G0213, G0216, G0219, G0220, G0226, G0228, G0252, G0336.

 

 

 

 

 

Pre-merger Organizations

Last Review Date

Document Number

Title

Anthem

07/27/2004

RAD.00002

Positron Emission Tomography

WellPoint Health Networks, Inc.

12/02/2004

4.01.10

Positron Emission Tomography (PET) Scans

 

09/23/2004

Clinical Guideline

Positron Emission Tomography (PET) for Cardiac Applications

 

09/23/2004

Clinical Guideline

Positron Emission Tomography (PET) for Neurologic Applications

 

12/02/2004

Clinical Guideline

Positron Emission Tomography (PET) for Oncologic Applications