EviCore Oncology Imaging Guidelines - Effective 2/14/2020

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CLINICAL GUIDELINESOncology Imaging PolicyVersion 1.0Effective February 14, 2020eviCore healthcare Clinical Decision Support Tool Diagnostic Strategies: This tool addresses common symptoms and symptom complexes. Imaging requests for individualswith atypical symptoms or clinical presentations that are not specifically addressed will require physician review. Consultation with the referring physician, specialist and/orindividual’s Primary Care Physician (PCP) may provide additional insight.CPT (Current Procedural Terminology) is a registered trademark of the American Medical Association (AMA). CPT five digit codes, nomenclature and other data arecopyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in the CPT book. AMA doesnot directly or indirectly practice medicine or dispense medical services. AMA assumes no liability for the data contained herein or not contained herein. 2019 eviCore healthcare. All rights reserved.

Oncology Imaging GuidelinesOncology Imaging GuidelinesAbbreviations for Oncology GuidelinesONC-1: General GuidelinesONC-2: Primary Central Nervous System TumorsONC-3: Squamous Cell Carcinomas of the Head and NeckONC-4: Salivary Gland CancersONC-5: Melanomas and Other Skin CancersONC-6: Thyroid CancerONC-7: Small Cell Lung CancerONC-8: Non-Small Cell Lung CancerONC-9: Esophageal CancerONC-10: Other Thoracic TumorsONC-11: Breast CancerONC-12: Sarcomas – Bone, Soft Tissue and GISTONC-13: Pancreatic CancerONC-14: Upper GI CancersONC-15: Neuroendocrine Cancers and Adrenal TumorsONC-16: Colorectal CancerONC-17: Renal Cell Cancer (RCC)ONC-18: Transitional Cell CancerONC-19: Prostate CancerONC-20: Testicular, Ovarian and Extragonadal Germ CellTumorsONC-21: Ovarian CancerONC-22: Uterine CancerONC-23: Cervical CancerONC-24: Anal Cancer & Cancers of the External GenitaliaONC-25: Multiple Myeloma and PlasmacytomasONC-26: Leukemias, Myelodysplasia and MyeloproliferativeNeoplasmsONC-27: Non-Hodgkin LymphomasONC-28: Hodgkin LymphomaONC-29: Hematopoietic Stem Cell TransplantationONC-30: Medical Conditions with Cancer in the DifferentialDiagnosisONC-31: Metastatic Cancer, Carcinoma of Unknown PrimarySite, and Other Types of CancerONC-32: Medicare Coverage Policies for 4181191198206213220231238244254259263269285 2019 eviCore healthcare. All Rights Reserved.Page 2 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.com

Oncology Imaging GuidelinesV1.0Abbreviations for Oncology GuidelinesACTHadrenocorticotropic hormoneAFPalpha-fetoproteinbetaHCGbeta human chorionic gonadotropinCA 125APanteroposteriorcancer antigen 125 testCA 19-9cancer antigen 19-9CA 15-3cancer antigen 15-3CA 27-29 cancer antigen 27-29CBCcomplete blood countCEAcarcinoembryonic antigenCRcomplete responseCTAcomputed tomographyangiographyDLBCLdiffuse large B cell lymphomasDRECNScentral nervous systemDCISductal carcinoma in situdigital rectal examEGDesophagogastroduodenoscopyENTear, nose, throatEOTend of therapyERCPendoscopic retrograde cholangiopancreatographyESRerythrocyte sedimentation rateEUSendoscopic ultrasoundFDGfluorodeoxyglucoseFUOfever of unknown originGEgastroesophagealGUgenitourinaryGTRgross total resectionHIVhuman immunodeficiency diseaseHRPChormone refractory prostatecancerhypermet hypermetabolicIFRTInvolved field radiation therapyinvinvasiveLARlow anterior resectionLCISlobular carcinoma in situLDHlactate dehydrogenaseLFTliver function testsLNDLymph node dissectionMALTmucosa associated lymphoidtissuemaintmaintenanceEUAexam under anesthesiaFNAfine needle aspirationGIgastrointestinalHGhigh grade 2019 eviCore healthcare. All Rights Reserved.Page 3 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.com

Oncology Imaging GuidelinesV1.0MENmultiple endocrine neoplasiaMGMGUSmonoclonal gammopathy of unknown significanceMIBGI-123 metaiodobenzylguanidine scintigraphyMRAmagnetic resonance angiographyMUGA‘multiple gated acquisition’ cardiac nuclear scanMWAmicrowave ablationNaFSodium FluorideNETNeuroendocrine tumorNCCN National Comprehensive Cancer NetworkNHLnon-Hodgkin’s lymphomaNSABPNational Surgical Adjuvant Breast and Bowel ProjectNSAIDSnonsteroidal anti-inflammatory drugsNSCLCnon-small cell lung cancerNSGCTnon-seminomatous germ celltumorPCIprophylactic cranial irradiationPETMRINPCmyasthenia gravismagnetic resonance imagingnasopharyngeal carcinomaPAposteroanteriorpositron emission tomographyCOGChildren’s Oncology GroupPSAprostate specific antigenRFAradiofrequency ablationRPLNDretroperitoneal lymph node dissectionSqCCasquamous cell carcinomaSIADHsyndrome of inappropriate secretion of antidiuretic hormoneTCCtransitional cell carcinomaTLHtotal laparoscopic hysterectomyTNMtumor node metastasis staging systemTSHthyroid-stimulating hormoneTURBTtrans-urethral resection of bladder tumorVIPomavasoactive intestinal polypeptideWB-MRIwhole body MRIWMWaldenstrom’s macroglobulinemia WBXRTSCLCWLEsmall cell lung cancerwide local incisionWhole brain radiation therapy 2019 eviCore healthcare. All Rights Reserved.Page 4 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.com

Oncology Imaging GuidelinesV1.0ONC-1: General GuidelinesONC-1.1: Key PrinciplesONC-1.2: Phases of Oncology Imaging and General PhaseRelated ConsiderationsONC-1.3: Nuclear Medicine (NM) Imaging in OncologyONC-1.4: PET Imaging in OncologyONC-1.5: Unlisted Procedure Codes in OncologyONC-1.6: Predisposition Syndromes 2019 eviCore healthcare. All Rights Reserved.Page 5 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.com

Oncology Imaging GuidelinesV1.0ONC-1.1: Key PrinciplesAge of Individual 18 years old at initialdiagnosis 18 years old at initialdiagnosis15 to 39 years old atinitial diagnosis (definedas Adolescent andYoung Adult (AYA)oncology individuals)AGE APPROPRIATE GUIDELINESAppropriate Imaging Guidelines Adult Oncology Imaging Guidelines, except where directedotherwise by a specific guideline section Pediatric Oncology Imaging Guidelines, except where directedotherwise by a specific guideline section When unique guidelines for a specific cancer type exist only ineither Oncology or Pediatric Oncology, AYA individuals shouldbe imaged according to the guideline section for their specificcancer type, regardless of the individual’s age When unique guidelines for a specific cancer type exist in bothOncology and Pediatric Oncology, AYA individuals should beimaged according to the age rule in the previous bullet A recent clinical evaluation (within 60 days) (history and physical examination,laboratory studies, non-advanced imaging studies) or meaningful contact (telephonecall, electronic mail or messaging) should be performed prior to consideringadvanced imaging, unless the patient is undergoing guideline-supported scheduledoff therapy surveillance evaluation or cancer screening. The clinical evaluation mayinclude a relevant history and physical examination, including biopsy, appropriatelaboratory studies, and non-advanced imaging modalities. Advanced imaging is not indicated for monitoring disease in individuals who chooseto not receive standard oncologic therapy, but may be receiving alternative therapiesor palliative care and/or hospice. All advanced imaging indicated for initial staging ofthe specific cancer type can be approved once when the patient is consideringinitiation of a standard therapeutic approach (surgery, chemotherapy, or radiationtherapy). Routine imaging of brain, spine, neck, chest, abdomen, pelvis, bones, or other bodyareas is not indicated except where explicitly stated in a diagnosis-specific guidelinesection, or if one of the following applies: Known prior disease involving the requested body area New or worsening symptoms or physical exam findings involving the requestedbody area (including non-specific findings such as ascites or pleural effusion) New finding on basic imaging study such as plain x-ray or ultrasound New finding on adjacent body area CT/MRI study (i.e., pleural effusion observedon CT abdomen) 2019 eviCore healthcare. All Rights Reserved.Page 6 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.comOncology Imaging Conventional Imaging (mostly CT, sometimes MRI or bone scan) of the affectedarea(s) drives much of initial and re-staging and surveillance. PET is not indicatedfor surveillance imaging unless specifically stated in the diagnosis-specific guidelinesections

Oncology Imaging GuidelinesV1.0 Brain imaging is performed for signs or symptoms of brain disease MRI Brain without and with contrast (CPT 70553) is the recommended study forevaluation of suspected or known brain metastases. If a non-contrast CT headshows suspicious lesion, MRI brain may be obtained to further characterize thelesion CT without and with contrast (CPT 70470) can be approved when MRI iscontraindicated or not available, or if there is skull bone involvement Certain malignancies including, but not limited to melanoma, lung cancer andrenal cell cancer have indications for brain imaging for asymptomatic patients If stage IV disease is demonstrated elsewhere or if systemic diseaseprogression is noted, refer to disease specific guidelines Initiation of angiogenesis therapy is not an indication for advanced imaging ofthe brain in asymptomatic patients (Avastin/Bevacizumab; 3% risk of bleedingand 1% risk of serious bleeding) Patients receiving cardiotoxic chemotherapy (such as doxorubicin, trastuzumab,pertuzumab, mitoxantrone, etc.) may undergo cardiac evaluation – at baseline andfor monitoring while on active therapy. eviCore guidelines support using Echocardiography (CPT 93306, CPT 93307,or CPT 93308) rather than MUGA scan for determination of LVED and/or wallmotion EXCEPT in one of the circumstances described previously in CD-3.4:MUGA Study – Cardiac Indications. The timeframe should be determine by the provider, but no more often thanbaseline and at every 6 weeks. May repeat every 4 weeks if cardiotoxic chemotherapeutic drug is withheld forsignificant left ventricular cardiac dysfunction. If the LVED is 50% on echocardiogram than follow up can be done withMUGA at appropriate intervals. See also: CD-12.1: Oncologic Indications for Cancer Therapeutics-RelatedCardiac Dysfunction (CTRCD) Adults ( 18 years) with a diagnosis of Li-Fraumeni Syndrome (LFS) may bescreened for malignancy with a Whole Body MRI (CPT 76498) on an annual basis.Annual Brain MRI (CPT 70553) may be performed as part of Whole Body MRI or asa separate exam. Due to lack of standardization of technique, interpretation, andavailability of Whole Body MRI, individuals with LFS are encouraged to participate inclinical trials. CTA or MRA of a specific anatomic region is indicated when requested for surgicalplanning when there is suspected vascular proximity to proposed resection margin. 2019 eviCore healthcare. All Rights Reserved.Page 7 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.comOncology Imaging Bone scan supplemented by plain x-rays are the initial imaging modalities forsuspected malignant bone pain. For specific imaging indications, see also: ONC-1.3: Nuclear Medicine (NM) Imaging in Oncology ONC-31.5: Bone (including Vertebral) Metastases ONC-31.6: Spinal Cord Compression ONC-31.7: Carcinoma of Unknown Primary Site

Oncology Imaging GuidelinesV1.0Use of Contrast CT imaging should be performed with contrast for known or suspected body regions,unless contraindicated. Shellfish allergy is not a contraindication to contrast. Patients with knownshellfish allergy do not have contrast reaction any more often than other atopicindividuals or patients with other food allergies. For iodinated contrast dye allergy, either CT scans without contrast or MRIscans without and with contrast are indicated. If CT scanning is considered strongly indicated in a patient with known contrastallergy, CT with contrast may be considered to be safely performed followingprednisone premedication over a 24 hour period prior to the study. For patients with renal insufficiency which precludes contrast use, CT withoutcontrast appropriate disease-specific areas should be offered. Further imaging (suchas MRI) may be indicated if noncontrast CT results are inconclusive. Severe renal insufficiency, i.e. an eGFR less than 30, is a contraindication for anMRI using a gadolinium-based contrast agent (GBCA) as well. In patients with eGFRgreater than 40, GBCA administration can be safely performed. GBCA administeredto patients with acute kidney injury or severe chronic kidney disease can result in asyndrome of nephrogenic systemic fibrosis (NSF), but GBCAs are not considerednephrotoxic at dosages approved for MRI. Gadolinium deposition has been found in patients with normal renal functionfollowing the use of gadolinium based contrast agents (GBCAs). The U.S. Food and Drug Administration (FDA) is investigating the risk of braindeposits following repeated use of GBCAs. The FDA has noted that, “It is unknown whether these gadolinium deposits areharmful or can lead to adverse health effects.” and have recommended: To reduce the potential for gadolinium accumulation, health careprofessionals should consider limiting GBCA use to clinical circumstances inwhich the additional information provided by the contrast is necessary. Health care professionals are also urged to reassess the necessity ofrepetitive GBCA MRIs in established treatment protocols. The use of MRI in place of CT scans to reduce risk of secondary malignancy is notsupported by the peer-reviewed literature. Unless otherwise specified in theGuidelines, MRI in place of CT scans for this purpose alone is not indicated. In someinstances (i.e., testicular cancer surveillance), MRI may be considered inferior to CTscans. 2019 eviCore healthcare. All Rights Reserved.Page 8 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.comOncology ImagingRadiation Exposure

Oncology Imaging GuidelinesV1.0ONC-1.2: Phases of Oncology Imaging and General PhaseRelated ConsiderationsPhases ofOncology ImagingDefinitionScreeningImaging requested for patients at increased risk for a particularcancer in the absence of known clinical signs or symptomsSuspected DiagnosisImaging requested to evaluate a suspicion of cancer, prior tohistological confirmationInitial work-up andStagingImaging requested after biopsy confirmation and prior to startingspecific treatmentTreatment response orInterim RestagingImaging performed during active treatment with chemotherapy,endocrine therapy or maintenance therapyRestaging of locallytreated lesionsImaging performed to evaluate primary or metastatic lesions withablation using radiofrequency, radioactive isotope, microwave orchemotherapyRestaging / SuspectedRecurrenceImaging requested when there is suspicion for progression orrecurrence of known cancer based on clinical signs/symptoms,laboratory tests or basic imaging studiesSurveillanceImaging performed in patients who are asymptomatic or havechronic stable symptoms, and are not receiving active treatmentGeneral phase-related considerations: Imaging performed prior to diagnosis should not be repeated unless there is a delayof at least 6 weeks since previous imaging and treatment initiation or there are newor significantly worsening clinical signs or symptomsImaging Timeframe Follow surveillance guidelines Follow surveillance guidelines See disease-specific guidelines Every 2 cycles (generally every 6 to8 weeks) Every 3 months Every 3 months Every 3 months Imaging typically not indicatedbeyond 5 years from completion oftreatment for metastatic disease 2019 eviCore healthcare. All Rights Reserved.Page 9 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.comOncology ImagingPhaseAfter definitive local therapy of primary tumor(surgery or radiation therapy)During adjuvant chemotherapyAfter ablative therapyDuring chemotherapy or immunotherapy formeasurable diseaseDuring endocrine/hormonal therapyMeasurable metastatic disease being monitoredoff therapyMinimal metastatic disease on maintenancetherapySurveillance for history of metastatic disease withcomplete response and being observed offtherapy

Oncology Imaging GuidelinesV1.0ONC-1.3: Nuclear Medicine (NM) Imaging in Oncology This section does not apply to PET imaging. PET imaging considerations can befound in ONC-1.4: PET Imaging in Oncology Bone Scan: Primarily used for evaluation of bone metastases in patients with solidmalignancies. Indications for bone scan in patients with history of malignancy include – bonepain, rising tumor markers, elevated alkaline phosphatase or in patients withprimary bone tumor. For evaluation of suspected or known bony metastases, CPT 78306 (Nuclearbone scan whole body), may be approved. Radiopharmaceutical Localization scan (CPT 78803) may be approved as anadd-on test for further evaluation of a specific area of interest. CPT codes 78300 (Nuclear bone scan limited), 78305 (Nuclear bone scanmultiple areas) or 78315 do not have any indications in oncology nuclearmedicine imaging. Bone marrow imaging: This study is rarely performed for evaluation of the entire bone marrow inconditions like myeloproliferative disorders, sickle cell bone infarct or ischemia,avascular necrosis or myeloma The correct CPT code for this study is CPT 78104 (Diagnostic NuclearMedicine Procedures on the Hematopoietic, Reticuloendothelial and LymphaticSystem) Brain imaging SPECT with Technetium-99m or thallium-201 (CPT 78803): Immunocompromised patients with mass lesion detected on CT or MRI fordifferentiation between lymphoma and infection In distinguishing recurrent brain tumor from radiation necrosis Immunocompromised patients with mass lesion detected on CT or MR fordifferentiation of lymphoma and infection 2019 eviCore healthcare. All Rights Reserved.Page 10 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.comOncology Imaging Octreotide scan: Specific for low and intermediate grade neuroendocrine tumors which expressspecific cell surface somatostatin receptors. See cancer specific guidelines forrecommended use. One of the following codes may be approved when Octreotide scan isrequested: CPT 78802 (Radiopharmaceutical localization of tumor whole body singleday study) CPT 78804 (Radiopharmaceutical localization of tumor whole body two ormore days) In addition to one of the above CPT codes, CPT 78803 (Radiopharmaceuticallocalization of tumor SPECT) may be approved as an add-on test for furtherevaluation of a specific area of interest.

Oncology Imaging GuidelinesV1.0 Radiopharmaceutical localization of tumor or distribution of radiopharmaceuticalagent(s): CPT 78800, CPT 78801, CPT 78802, CPT 78804, CPT 78803 (SPECT), orCPT 78830, CPT 78831, or CPT 78832 (SPECT/CT) For evaluation of fever of unknown origin and osteomyelitis For suspected infections such as infected central lines, grafts or shuntsOncology Imaging Gallium Isotope Scan: Radiopharmaceutical Localization of tumor (CPT 78800, CPT 78801, CPT 78802, CPT 78803, or CPT 78804) This may be rarely used in place of PET/CT scan when PET/CT scan notavailable and PET/CT is indicated by guidelines for lymphoma, sarcoma,melanoma or myeloma 2019 eviCore healthcare. All Rights Reserved.Page 11 of 295400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924www.eviCore.com

Oncology Imaging GuidelinesV1.0ONC-1.4: PET Imaging in OncologyNOTE: Some payors have specific restrictions on PET imaging, and those coveragepolicies may supersede the recommendations for PET imaging in these guidelines. CPT codes: PET imaging in oncology should use PET/CT fusion imaging (CPT 78815 or

Oncology Imaging Brain imaging is performed for signs or symptoms of brain disease MRI Brain without and with contrast (CPT 70553) is the recommended study for evaluation of suspected or known brain metastases.

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