Clinical Appropriateness Guidelines Positron Emission Testing, Other PET Applications, Including Oncologic Tumor Imaging Effective Date: April 21, 2014

Clinical Appropriateness Guidelines Positron Emission Testing, Other PET Applications, including Oncologic Tumor Imaging Effective Date: April 21, 2014

Proprietary and Confidential

Date of Origin: 03/30/2005 Last reviewed: 11/14/2013 Last revised: 01/15/2013

Clinical Appropriateness Guidelines 8600 W Bryn Mawr Avenue South Tower - Suite 800 Chicago, IL 60631 P. 773.864.4600 Copyright © 2014. AIM Specialty Health. All Rights Reserved www.aimspecialtyhealth.com Table of Contents

Administrative Guideline...... 3 Disclaimer...... 3 Use of AIM’s Diagnostic Imaging Guidelines...... 4 Multiple Simultaneous Imaging Requests...... 5 General Imaging Considerations...... 6

PET - Other PET Applications, Including Oncologic Tumor Imaging...... 8

PET Bibliography...... 12

BY ACCEPTING THESE DOCUMENTS, I ACKNOWLEDGE ACCEPTANCE OF THE FOLLOWING TERMS AND CONDITIONS FOR ACCESS AND USE OF THE CLINICAL GUIDELINES:

AIM Specialty Health (AIM) has developed proprietary clinical appropriateness guidelines (together with any updates, referred to collectively as the “Guidelines”). The Guidelines are designed to evaluate and direct the appropriate utilization of high technology diagnostic imaging services. They are based on data from the peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations. Access to these Guidelines is being provided for informational purposes only. AIM is under no obligation to update its Guidelines. Therefore, these Guidelines may be out of date.

The Guidelines are protected by copyright of AIM as permitted by and to the full extent of the law. These rights are not released, transferred, or assigned as a result of allowing access. You agree that you do not have any ownership rights to the Guidelines and you are expressly prohibited from selling, assigning, leasing, licensing, reproducing or distributing the Guidelines, unless authorized in writing by AIM.

The Guidelines do not constitute medical advice and/or medical care, and do not guarantee results or outcomes. The Guidelines are not a substitute for the experience and judgment of a physician or other health care professionals. Any clinician seeking to apply or consult the Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The Guidelines do not address coverage, benefit or other plan specific issues.

The Guidelines are provided “as is” without warranty of any kind, either expressed or implied. AIM disclaims all responsibility for any consequences or liability attributable or related to any use, non-use or interpretation of information contained in the Guidelines.

AIM’s Clinical Appropriateness Guidelines Define the Optimal Approaches for Diagnostic Imaging Utilization During Individualized Case Review

Use of AIM’s Diagnostic Imaging Guidelines: AIM’s proprietary clinical appropriateness guidelines are designed to evaluate and direct the appropriate utilization of elective, high technology diagnostic imaging services. In the process, multiple functions are accomplished: ●● To promote the most efficient and cost-effective use of diagnostic imaging services ●● To assist the practitioner as an educational tool ●● To encourage standardization of medical practice patterns and reduce variation in clinical evaluation ●● To curtail the performance of inappropriate, elective diagnostic imaging studies ●● To reduce the performance of duplicate diagnostic imaging studies ●● To advocate biosafety issues, including unnecessary radiation exposure (for CT and plain film radiography) and MRI safety concerns ●● To enhance quality of healthcare for elective diagnostic imaging studies, using evidence-based medicine and outcomes research from numerous resources

AIM Guideline Development Process and Resources: The development of AIM’s proprietary practice guidelines involves integration of medical information from multiple sources to support the reproducible use of high quality and state-of-the-art advanced diagnostic imaging services. The process for criteria development is based on technology assessment, peer-reviewed medical literature including clinical outcomes research and consensus opinion in medical practice. The primary resources used for AIM guideline development include: ●● American College of Radiology (ACR) Appropriateness Criteria ●● American College of Cardiology (ACC) Appropriateness Criteria ●● American Heart Association (AHA) ●● American Institute of Ultrasound in Medicine (AIUM) ●● American Cancer Society (ACS) ●● American Academy of Neurology (AAN) ●● American Academy of Pediatrics (AAP) ●● Society of Interventional Radiology (SIR) ●● Society of Nuclear Medicine (SNM) ●● Agency for Healthcare Research and Quality (AHRQ) ●● National Guideline Clearinghouse ●● Centers for Medicare and Medicaid Services (CMS) * When variances occur, Medicare NCD and LCD determinations will be used instead of AIM guidelines for Medicare Advantage patients

Guideline Review: AIM’s proprietary guidelines for appropriate diagnostic imaging utilization are reviewed routinely by: ●● Independent Physician Review Board: AIM’s External Advisory Panel ●● Health Plan Medical Directors ●● Local Imaging Advisory Council (representing local physician communities) ●● Physician Review Panels, under the governance of our clients’ State Regulatory Agencies

Standard Anatomic Coverage for Multiple Simultaneous Imaging Requests The major area of concern is contiguous body parts where clinical signs and symptoms may be coming from abnormalities involving either region or different modalities can be considered to evaluate the same anatomy for the same clinical problem. These are areas where ordering multiple tests before the results of any of the tests are known lead to inappropriate imaging. General Considerations for Multiple Simultaneous Imaging Requests Rapid breakthroughs in technology, with attendant rise of new imaging tests available to improve patient management, have created a dilemma for clinicians. Many factors in choosing the right test now come into play. One must consider basic data in the decision-making process. Considerations include the possible effect on patient management, the pretest probability that the patient is affected by a particular disease, the prevalence of the disease in the population, and the accuracy (sensitivity/specificity) of the test. When a screening approach is adopted, rather than targeting the particular test or anatomic site with the highest pretest probability of success, the possibility of one or more of the tests being superfluous and not contributing meaningfully to patient management increases to an unacceptable level. For this reason, simultaneous ordering of multiple examinations may subject these examinations to more intensive levels of review than would be the case if these same tests were ordered sequentially. Depending on the clinical situation, one or more of the requested studies might not meet medical necessity criteria until the results of the lead study are known. Common Indications for Multiple Simultaneous Imaging Requests ●● The initial diagnosis/staging or follow-up of oncology patients ●● Follow-up of patients who have had operative procedures on multiple anatomic sites ●● Patients in whom the suspected anatomic abnormality might extend into multiple regions, such as diverticulitis or suspected syringomyelia Common Inappropriate Multiple Simultaneous Imaging Requests ●● Brain MRA ordered routinely with brain MRI without vascular indications ●● Brain CT ordered simultaneously with sinus CT for headache ●● Multiple levels of spine MRI’s or CT’s for diffuse back pain or radicular symptoms ●● Cervical spine and shoulder MRI’s ordered simultaneously for shoulder pain ●● Pelvic or hip MRI’s ordered simultaneously with lumbar spine MRI for hip pain ●● Pelvic CT ordered routinely with abdominal CT for suspected upper quadrant disease processes ●● CT Angiography (CTA) utilizes the data obtained from standard CT imaging. Request for a CT exam, in addition to CT Angiography of the same anatomic area AND during the same imaging session, is inappropriate.

●● Duplicative testing or repeat imaging of the same anatomic area with same or similar technology may be subject to high- level review and may not be medically necessary unless there is a persistent diagnostic problem or there has been a change in clinical status (e.g., deterioration) or there is a medical intervention which warrants interval reassessment. ●● Request for re-imaging due to technically limited exams is the responsibility of the imaging providers. ●● In general, follow-up exams should be performed only when there is a clinical change, with new signs or symptoms. ●● AIM’s clinical guidelines do not supersede the enrollee’s health plan medical policy specific to a given exam for a given anatomic structure. Imaging Considerations Specific to CT and CTA

●● Advantages of CTA over MRA include higher sensitivity for detection of mural calcification; usually shorter scan time, which results in less motion, pulsation and turbulent flow artifact; avoidance of MRA in-plane flow as a cause of apparent exaggerated stenosis; more facile detection of surgical clips and stents. ●● Disadvantages of CTA include radiation exposure and use of intravascular iodinated contrast material. ●● Multi-detector row CT is preferred but not required in the performance of CTA, when compared with single detector CT. ●● CTA studies are typically performed through acquisition of thin CT sections, during intravenous bolus infusion of iodinated contrast material. ●● Contrast-enhancement for CT/CTA may be contraindicated in certain circumstances, such as a documented allergy to intravenous contrast material and renal insufficiency. Special consideration should also be given to patients with multiple myeloma. ●● CT Angiography (CTA) utilizes imaging data from standard CT acquisitions. Request for a CT exam in addition to CT Angiography of the same anatomic area during the same imaging session is inappropriate. Imaging Considerations Specific to MRI and MRA Patient Compatibility Issues: ●● Artifact due to patient motion may have a particularly significant impact on exam quality. ●● Metallic implants present in spine and brain. ●● Eye and brain for metallic foreign bodies. ●● Breath hold requirements: ○○ Some imaging sequences require breath holding and this may be difficult or impossible for some patients. ●● Claustrophobic patients: ○○ Patients with claustrophobia may need to be premedicated in order to tolerate the imaging procedure. Rarely patients with severe claustrophobia will not be suitable candidates for imaging.

Biosafety Issues: ●● Ordering and imaging providers are responsible for considering biosafety issues prior to MRI/MRA examination, to ensure patient safety. Among the generally recognized contraindications to MRI/MRA exam performance are permanent pacemakers (some newer models are MRI/MRA compatible and others may be safe depending on sequences used; contact imaging facility for substantiation), implantable cardioverter-defibrillators (ICD), intracranial aneurysm surgical clips that are not compatible with MR imaging, as well as other devices considered unsafe in MRI scanners (including certain implanted materials in the patient as well as external equipment, such as portable oxygen tanks). ●● Contrast utilization is at the discretion of the ordering and imaging providers.

Administrative Guideline | Copyright © 2014. AIM Specialty Health. All Rights Reserved. 6 Ordering Issues: ●● The CPT code assignment for an MRI procedure is based on the anatomic area imaged. Requests for multiple MRI exams of the same anatomic area to address patient positional changes, additional sequences or equipment are not allowed. These variations or extra sequences are included within the original imaging request. ●● There are rare circumstances when both CT and MRI exams should be ordered for the same clinical presentation. The specific rationale for each study must be delineated at the time of request. ●● There are uncommon circumstances when both MRA and CTA should be ordered for the same clinical presentation. The specific rationale must be delineated at the time of request. ●● Advantages of MRA, compared with CTA include avoidance of radiation exposure as well as intravascular administration of iodinated contrast material. ●● Disadvantages of MRA, compared with CTA, include lower sensitivity for detection of mural calcification; usually longer scanning time, with potential for greater motion, pulsation and turbulent flow artifact; in-plane flow causing apparent exaggerated stenosis; greater difficulty in identifying surgical clips and stents. Reference/Literature Review

1. Bossuyt PM, Irwig L, Craig J, Glasziou P. Comparative accuracy: assessing new tests against existing diagnostic pathways. BMJ. 2006;332(7549):1089-1092. 2. Centers for Medicare and Medicaid Services. National Coverage Determination for Magnetic Resonance Imaging (NCD 220.2). Medicare Coverage Database. Effective July 7, 2011; Implementation September 26, 2011. http://www.cms.gov/ medicare-coverage-database/details/ncd-details.aspx?NCDId=177. Accessed October 27, 2011. 3. Dodd JD. Evidence-based practice in radiology: steps three and four–appraise and apply diagnostic radiology literature. Radiology. 2007;242(2):342-354. 4. Dubilet PM, Cain KC. The superiority of sequential over simultaneous testing. Med Decis Making. 1985;5(4):447-451. 5. Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making. 1991;11(2):88-94. 6. Hollingworth W, Jarvik JG. Technology assessment in radiology: putting the evidence in evidence-based radiology. Radiology. 2007;244(1):31-38. 7. Kuhns LR, Thornberry JR, Freyback DG. Decision Making in Imaging. Chicago: Year Book Medical Publishers;1989. 8. Ng CS, Palmer CR. Analysis of diagnostic confidence and diagnostic accuracy: a unified framework. Br J Radiol. 2007;80(951):152-160. 9. Owens DK, Qaseem A, Chou R, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. High-value, cost-conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions. Ann Intern Med. 2011;154(3):174-180.

Administrative Guideline | Copyright © 2014. AIM Specialty Health. All Rights Reserved. 7 Positron Emission Tomography Other PET Applications, Including Oncologic Tumor Imaging CPT Codes Dedicated PET Imaging: 78811 �� PET imaging, limited area 78812 �� PET imaging, skull to mid-thigh 78813 �� PET imaging, whole body

PET/CT Imaging: 78814 �� PET imaging, with concurrently acquired CT for attenuation correction and anatomic localization; limited area 78815 �� PET imaging, with concurrently acquired CT for attenuation correction and anatomic localization; skull base to mid-thigh 78816 �� PET imaging, with concurrently acquired CT for attenuation correction and anatomic localization; whole body Commonly Used Radiopharmaceutical/Scanner

●● 2-(fluorine-18) fluoro-2-deoxy-d-glucose (FDG), performed on a dedicated PET or integrated (hybrid) PET/CT scanner. Imaging Considerations

●● For PET tumor imaging, AIM’s Guidelines will use the definitions for initial treatment strategy (diagnosis, staging), and subsequent treatment strategy (restaging and treatment response monitoring) as provided in the CMS National Coverage Determination for PET Scans. PET for tumor staging is covered subject to the conditions below. ●● CMS has determined that the available evidence is sufficient to determine that FDG PET imaging for subsequent anti- tumor treatment strategy for all other tumor types other than breast, colorectal, esophagus, head and neck (non-CNS/ thyroid), lymphoma, melanoma, non-small cell lung, ovarian, cervical, and myeloma, may be nationally covered as research under §1862(a)(1)(E) of the Act through CED. ●● AIM’s Guidelines do not imply enrollee benefit coverage for all diagnoses and/or indications. Benefit coverage is determined solely by the enrollee’s health plan. Common Diagnostic Indications The following diagnostic indications for PET Tumor Imaging (which includes dedicated PET and PET/CT Exams) are accompanied by pre-test considerations as well as supporting clinical data and prerequisite information.

PET or PET/CT is considered medically necessary when used for the following oncologic indications: INITIAL TREATMENT STRATEGY PET or PET/CT for a member with a biopsy-proven solid tumor listed below or myeloma, or one of the tumors listed below which is strongly suspected based on other diagnostic testing AND imaging results are required to determine at least one of the following: ●● Whether the patient is a candidate for an invasive diagnostic or therapeutic procedure, such as biopsy; OR ●● The optimal anatomic location for an invasive procedure; OR ●● The anatomic extent of malignancy when recommended therapy reasonably depends upon the extent of malignancy; An initial treatment strategy PET may be requested following a surgical therapeutic procedure if results from surgery indicate the need for further staging or intervention, or if the intervention also served as the diagnostic intervention; OR ●● In the setting of proven or highly suspected new recurrence, after a disease-free period when a patient was treated with curative intent, a request for PET imaging should be handled as a new initial treatment strategy.

List of malignancies appropriate for initial treatment strategy PET or PET/CT (with exceptions/special considerations noted in parentheses for melanoma, breast, and cervix): ●● Head and neck, including: ○○ Lip, oral cavity, and pharynx ○○ Nasal cavity, ear, and sinuses ○○ Eye ○○ Larynx ●● Brain and spinal cord ●● Digestive system, including: ○○ Esophagus ○○ Stomach ○○ Small intestine ○○ Liver and intrahepatic bile ducts ○○ Gallbladder & extrahepatic bile ducts ○○ Pancreas ○○ Retroperitoneum and peritoneum ○○ Colon and rectum ○○ Anus ●● Thorax, including: ○○ Lung, Non-small cell ○○ Lung, small cell ○○ Pleura ○○ Thymus, heart, mediastinum ●● Bone/cartilage and connective/other soft tissue, including gastrointestinal stromal tumors (GIST) ●● Skin, including: ○○ Melanoma (PET or PET/CT is non-covered for initial staging of regional lymph nodes in patients with melanoma, but is covered for detection of distant metastatic disease in high-risk patients with melanoma) ○○ Non-melanoma skin (includes basal cell and squamous cell) ○○ Kaposi’s sarcoma ●● Female and male breast ○○ PET or PET/CT is non-covered for “diagnosis” of breast cancer to evaluate a suspicious breast mass or for initial staging of non-palpable axillary lymph nodes in patients with breast cancer. ○○ PET or PET/CT is covered for initial treatment strategy evaluation of a patient with axillary nodal metastasis of unknown primary origin ○○ PET or PET/CT is covered for the detection of distant (non-axillary) metastatic disease in high-risk patients with known breast cancer. This includes, but is not limited to: ■■ Patients with clinically suspicious axillary lymph nodes (palpable, matted, or highly suspicious on imaging study), to avoid the need for an unnecessary lymph node procedure in a patient who might already have metastatic disease or would require chemotherapy prior to surgery. ■■ Patients with locally advanced disease prior to planned neoadjuvant therapy (prior to surgery), particularly when standard imaging is equivocal or suspicious

●● Urogenital organs, including: ○○ Uterus and adnexa ○○ Cervix (only if a prior CT or MRI has been negative for extrapelvic metastatic disease) ○○ Placenta ○○ Ovary ○○ Other female genitalia ○○ Testis ○○ Penis and other male genitalia ○○ Bladder ○○ Kidney ●● Thyroid and other endocrine glands and related structures (includes pituitary and adrenal) ●● Cancer of unknown primary origin ●● Lymphoma (Hodgkin’s and non-Hodgkin’s) ○○ Initial PET is useful in patients with a history of chronic lymphocytic leukemia or low grade lymphoma with suspected or biopsy-proven Richter’s transformation to a more aggressive lymphoma ●● Myeloma ●● Neuroendocrine tumor ●● Other solid tumor not listed except prostate and leukemia which are not medically necessary PET or PET/CT for SUBSEQUENT TREATMENT STRATEGY (to assist the physician in the determination of optimal subsequent anti-tumor treatment strategies) is medically necessary only for the following malignancies ●● Head and neck (non-CNS) including: ○○ Lip, oral cavity, and pharynx ○○ Nasal cavity, ear, and sinuses ○○ Larynx ●● Esophagus ●● Colon and rectum ●● Lung, non-small cell only ●● Melanoma ●● Female and male breast ●● Cervix ●● Ovary ●● Lymphoma ●● Myeloma ●● Gastrointestinal Stromal Tumors (GIST), when standard imaging has not been helpful in determining response to therapy ●● Thyroid (for follicular cell origin only) ○○ With prior treatment including thyroidectomy and radioiodine ablation; AND ○○ With a current serum thyroglobulin > 10 ng/mL ■■ In the setting of documented anti-thyroglobulin antibodies, thyroglobulin level may not rise, and therefore this criteria does not need to be met; AND ○○ With a negative whole-body I-131 scan in the past

PET or PET/CT | Copyright © 2014. AIM Specialty Health. All Rights Reserved. 10 Common Diagnostic Indications Paraneoplastic syndrome including neurologic syndrome ●● PET or PET/CT is indicated for initial evaluation of individuals with paraneoplastic syndrome

Surveillance of asymptomatic patients after therapy for malignancy PET or PET/CT is considered not medically necessary for patients who have completed therapy twelve (12) or more months ago for lymphoma or six (6) or more months ago for all other malignancies unless the patient demonstrates signs, symptoms, laboratory or other objective findings suggestive of recurrence or spread of the original malignancy

Screening: PET or PET/CT is not covered as a screening test (i.e., for evaluation of patients without specific signs and symptoms of disease)

PET for screening or diagnosis of breast cancer is not a covered benefit by CMS or multiple health plans

PET Imaging of Infectious Processes

For diagnosis of chronic osteomyelitis involving the axial skeleton

Other Considerations

PET mammography is an evolving technology under clinical development. This technology and its impact on health outcomes will continue to undergo review as new evidence-based studies are published. Interval routine coverage for PET mammography is not generally available and is not considered medically appropriate at this time

PET bone scanning is currently only a covered benefit by the Centers for Medicare and Medicaid services with CED. PET bone scanning is an evolving technology under clinical development. This technology and its impact on health outcomes will continue to undergo review as new evidence-based studies are published. Interval routine coverage for PET bone scanning is not generally available and is not considered medically appropriate at this time

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