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The rules say that plans must pay for a medical service or item if regular Medicare would pay for it in this case. 
You can find this rule at 42 Code of Federal Regulations (CFR) Section 422.101. 
 
The rules state that covered clinical types of application(s) are identified below as diagnostic (DX), prognostic 
(PROG) or predictive (PRED). 
  
   
1.  Colorectal Cancer 
 
        KRAS (12/13) - PRED of resistance to an anti-EGFR agent 
        KRAS codon 61 - PRED of resistance to an anti-EGFR agent 
        KRAS codon 146 - PRED of resistance to an anti-EGFR agent 
        NRAS - PRED of resistance to an anti-EGFR agent 
        BRAF - PRED of resistance to an anti-EGFR agent + DX (sporadic vs. Lynch syndrome) 
        PIK3CA - PRED of resistance to an anti-EGFR agent + PROG for local recurrence 
        MSI by PCR - PRED of 5-FU resistance + DX 
        MLH1 promoter hypermethylation - PRED of 5-FU resistance + DX 
        mRNA (oncotype-Colon)  PRED for the recurrence risk for patients with Stage II colon cancer 
        Hereditary colon cancer disorders 
        Sept9 
 
ColonSeq 
 
This testing provides information to the patient and provider regarding potential treatment options and 
implications for RAS and BRAF mutations. 
 
Please refer to DA52986-Billing and Coding: Biomarkers for Oncology regarding coding and billing 
information. 
 
2.  Non-Small Cell Lung Cancer (NSCLC) 
 
        EGFR- PRED of anti-EGFR response 
        KRAS (12/13) - PRED of anti-EGFR resistance 
        KRAS codon 61 - PRED of anti-EGFR resistance 
        KRAS codon 146 - PRED of anti-EGFR resistance 
        BRAF - PROG + PRED for anti-RAF inhibitor 
 
        ThermoFisher Oncomine DX Target Test for Non-Small Cell Lung Cancer (NSCLC) is a 23 gene panel 
including a 3 gene target test (companion test) approved by the FDA in June 2017 for NSCLC from tissue 
specimens.  It can simultaneously identify the three gene variants that are a key to targeted therapy selection: 
BRAF and ROS1, and EGFR.  The targeted therapies are dabrafenib (Tafinlar) in combination with trametinib 
(Mekinist), crizotinib (Xalkori), and gefitinib (Iressa), respectively.  These three drugs are approved therapies 
for NSCLC patients with the above gene variants. Oncomine DX Target Test is the only FDA approved 
companion test that detects ROS1 fusions and that detects BRAF V600E, but it does not detect ALK fusions. 
Coverage is limited as specified in NCD 90.2, Next Generation Sequencing (NGS) for Patients with Advanced 
Cancer. Please refer to the NCD at https://www.cms.gov/medicare-coverage-database/details/ncd-
details.aspx?NCDId=372&ncdver=1&bc=AAAAQAAAAAAA  
 
         for full coverage details. 
 
LungSeq 
 
Testing for genetic alteration in these genes can determine targeted therapy options that have the potential to 
decrease tumor burden, decrease symptoms, increase survival, and dramatically improve the quality of life for 
patients with specific genetic alterations. 
 
Please refer to A52986, Billing and Coding: Biomarkers for Oncology regarding coding and billing 
information.  
3.  Melanoma 
 
        BRAF - PRED of response to Vemurafenib 
        KIT - PRED of response to Imatinib (TKI) 
        NRAS - PROG + PRED for anti-MEK inhibitor 
      
    4.  Uveal Melanoma 
        GNAQ  PROG 
        GNA11 - PROG  
 
5.  Brain 
 
        BRAF - PRED 
        EGFR - PRED 
        MGMT - PRED 
        IDH1 - DX + PROG 
        IDH2 - DX + PROG 
        PIK3CA - PRED 
        PTEN - PRED 
        CIMP - PRED 
        TERT - DX 
 
6.  Thyroid 
 
        BRAF - DX + PRED 
        KRAS - PRED for Selumetinib 
        HRAS - PRED for Selumetinib 
        NRAS - PRED for Selumetinib 
        PIK3CA - PRED 
        RET - DX 
        PAX8/PPARG- DX 
 
ThyraMIR Thyroid miRNA classifier (aPCR based microRNA gene expression classifier) (PRED) evaluates 
the expression levels of 10miRNA genes within an FNA biopsy: miR-29b-1-5p, miR-31-5p, miR-138-1-3p, 
miR-139-5p, miR-146b-5p, miR-155, miR-204-5p, miR-222-3p, miR-375, and miR-551b-3p. 
 
Oncology Thyroid, provides gene expression analysis of 142 genes utilizing fine needle aspirate, algorithm 
reported as a categorical result (Afirma - PRED). 
 
ThyraMIR is used as a companion test to ThyGeNEXT when ThyGeNEXT results are inconclusive. 
 
            ThyraMIR, ThyGeNEXT and Afirma services will be considered reasonable and necessary for patients 
with any of the following conditions: 
 
                An indeterminate pathology on fine needle aspiration 
                Patients with one or more thyroid nodules with a history or characteristics suggesting malignancy 
such as: 
                    Nodule growth over time 
                    Family history of thyroid cancer 
                    Hoarseness, difficulty swallowing or breathing 
                    History of exposure to ionizing radiation                     Hard nodule compared with rest of gland consistency 
                    Presence of cervical adenopathy 
            RosettaGX Reveal thyroid MicroRNA test, an assay used for the classification of indeterminate thyroid 
nodules, will be considered reasonable and necessary when the conditions outlined above for ThyraMIR, 
ThyGeNEXT and Afirma are met. 
            ThyroSeq is a test utilized to better define the need for thyroid surgery and the type of such surgery. 
ThyroSeq will be considered reasonable and necessary when the conditions outlined above for ThyraMir, 
ThyGeNEXT and Afirma are met. 
 
7.  Ovary/Fallopian Tube/Peritoneum 
 
            AKT1 - PRED for PI3K/AKT/mTOR inhibitors 
            BRAF - DX + PROG 
            KRAS - DX + PROG 
            MLH1 promoter hypermethylation - DX 
            MSI by PCR - DX 
            PIK3CA - PRED for PI3K/AKT/mTOR inhibitors 
            PTEN - PRED for PI3K/AKT/mTOR inhibitors 
            TP53 - DX + PROG 
 
8.  Uterus 
 
            AKT1 - PRED for PI3K/AKT/mTOR inhibitors 
            BRAF - PRED 
            KRAS - PRED 
            MLH1 promoter hypermethylation - DX 
            MSI by PCR - DX 
            PIK3CA - PRED for PI3K/AKT/mTOR inhibitors 
            PTEN - PRED for PI3K/AKT/mTOR inhibitors + DX + PROG 
            TP53 - DX + PROG 
 
9.  Urinary Tract 
 
            FGFR3 - PROG 
            MSI by PCR - DX 
            MLH1 promoter hypermethylation - DX 
 
10.  Prostate 
 
            The PROGENSA PCA3 Assay (PRED) is an FDA-approved, automated molecular test (assay) that 
helps physicians determine the need for repeat prostate biopsies in men who have had a previous negative 
biopsy. 
            PTEN  PROG and THER 
            RB1  DX and PROG 
            TP53 - PROG 
 
11.  Gastrointestinal Stomal Tumor 
 
            KIT - PRED for Sumatinib + DX 
            PDGFRA - PRED for Sumatinib + DX 
 
12.  Cancer of Unknown Primary (CUP)  
        Molecular testing, using the Rosetta Cancer Origin TestTM (PROG), is considered reasonable and 
necessary in the pathologic diagnoses of CUP when a conventional surgical pathology/imaging work-up is 
unable to identify a primary neoplastic site. Other applications of this technology are considered not reasonable 
and necessary and are considered investigational in the use of diagnosis of specific tumor types such as NSCLC 
and renal cancers. 
 
        TUO CTID (Cancer Type ID) (DX) is considered reasonable and necessary in the pathologic diagnoses of 
CUP when a conventional surgical pathology/imaging work-up is unable to identify a primary neoplastic site. 
Other applications of this technology are considered not reasonable and necessary and are considered 
investigational in the use of diagnosis of specific tumor types such as NSCLC and renal cancers. 
 
13.  Leukemias and Lymphomas 
 
            Acute lymphoid leukemia (ALL) 
                JAK1 
                JAK2 
                BCR/ABL1 - DX 
                ABL1 (kinase domain) - PROG 
                IGH - DX 
                TCRB - DX 
                TCRG - DX 
                TP53 - PROG 
                MLL/AF4 - DX 
                E2A/PBX1 - DX 
                ETV6/RUNX1 - DX 
                KRAS 
                NRAS 
                NOTCH1 
                FBXW7 
            Acute myeloid leukemia (AML, and including acute promyelocytic leukemia): All PROG, except 
where noted below. 
                TP53 
                PML/RARA - DX 
                RUNX1/RUNX1T1 - DX 
                CBFB/MYH11 - DX 
                FLT3 ITD 
                FLT3 D835 
                NPM1 
                KRAS 
                NRAS 
                KIT 
                CEBPA 
                IDH1 
                IDH2 
                DNMT3A 
                JAK2 (p.V617F) 
                JAK2 (exon 12) 
                MPL 
                DEK/CAN - DX 
                ASXL1 
                EZH2                 TET2 
                PML/RARalpha 
                U2AF1 
                SRSF2 
                ZRSR2 
            Hairy cell leukemia 
                BRAF 
                IGH somatic hypermutation - PROG 
                IGH - DX 
            Aplastic anemia 
                TCRB - DX 
                TCRG - DX 
            Burkitts lymphoma 
                IGH - DX 
                TP53 - PROG 
            Myeloproliferative diseases (MPD - essential thrombocytosis [ET], myelofibrosis & polycythemia vera 
[PV]) 
                KIT 
                TP53 
                BCR/ABL1 - DX 
                JAK2 (p.V617F) - DX 
                JAK2 (exon 12) - DX 
                MPL - DX 
                CALR - DX 
                CSF3R - DX 
                ASXL1 - PROG 
                TET2 - PROG 
                EZH2 - PROG 
                Calr (exon 9) 
            Chronic myeloid leukemia (CML) and chronic myelomonocytic leukemia (CMML) 
                ABL1 T3151  CML only 
                KRAS - PROG 
                NRAS - PROG 
                BCR/ABL1 - DX 
                ABL1 (kinase domain) - PRED for Imatinib 
                FLT3 ITD - PROG 
                FLT3 D835 - PROG 
                KIT - PROG 
                JAK2 (p.V617F) - PROG 
                JAK2 (exon 12) - PROG 
            Chronic lymphoid leukemia (CLL) 
                IGH - DX 
                IGH somatic hypermutation - PROG 
                TP53 - PROG 
                IGH direct probe method 
                BTK 
                PLCG2 
                BIRC3 
                BTK 
                NOTCH1 
                SF3B1 
            Follicular lymphoma                 IGH/BCL2 - DX 
            Hypereosinophilia Syndrome (HES) 
                KIT (including p.D816V) - PROG + DX 
                FIP1L1/PDGFRA Fusion - DX 
            Mantle cell lymphoma 
                CCND1/IGH - DX 
            Mastocytosis 
                KIT (including p.D816V) - PROG + DX 
                FIP1L1/PDGFRA Fusion - DX 
                TCRG - DX 
            T-cell prolymphocytic leukemia 
                JAK1 
                JAK3 
                TCRB - DX 
                TCRG - DX 
            T-cell large granular lymphocytic leukemia(TLGLL) 
                STAT3 
                STAT5B 
            Myelodysplastic syndrome (MDS): All below biomarkers are PROG. 
                FLT3 ITD 
                FLT3 D835 
                NPM1 
                KRAS 
                NRAS 
                KIT 
                CEBPA 
                IDH1 
                IDH2 
                DNMT3A 
                JAK2 (p.V617F) 
                JAK2 (exon 12) 
                MPL 
                ASXL1 
                EZH2 
                TET2 
            Cytogenomic microarray analysis, or alternatively, a single nucleotide polymorphism (SNP) array for 
the same testing, is covered for the identification of various mutations. These tests are used in the 
diagnosis/prognosis of various hematological malignancies. 
 
            Waldenstrom's Lymphoplasmacytic Lymphoma 
                MYD88 
 
14.  Myeloma Gene Expression Profile (MyPRS) (PROG) isolates plasma cells from myeloma patients, 
extracts DNA, which is then subjected to MicroArray testing and application of validated software programs to 
identifying patterns of genetic abnormalities. Seventy highly predictive genes have been identified and 
correlated to myeloma early relapse. MyPRS gives a predictive risk signature as high-risk or low-risk at this 
time. A high-risk score predicts a less than 20% three-year complete remission where as a low-risk predicts a 
five-year complete remission of greater than 60%. The predictive value for the stratification of therapeutic 
interventions allows these patients to be treated in a more personalized manner based on their own genetic 
profile. 
 
This test is considered reasonable and necessary only after the initial diagnosis of multiple myeloma has been made and will be available to be used in the stratification of therapeutic interventions. It would be inappropriate 
to use this test as a diagnostic tool or as a monitoring device of ongoing therapy. Other testing is available for 
this function. 
 
The coverage is set to include only two clinical settings: 
 
        Once after initial diagnosis is made. In the event MyPRS was not tested at diagnosis of myeloma and there 
is ongoing initial therapy with persistent disease, MyPRS can be done still as an initial test. 
 
        OR 
 
        If relapse has occurred and a change in the therapeutic modalities is contemplated. 
 
Please refer to the limitations section of this policy for frequency limitations. 
 
15.  Hereditary neuroendocrine tumor disorders - Must include 6 genes with genomic sequence analysis NEX 
GEN including: 
 
        MAX 
        SDHB 
        SDHC 
        SDHD 
        TMEM127 
        VHL 
 
Please refer to the limitations section of this policy for frequency limitations. 
 
16.  Hereditary neuroendocrine tumor disorders; duplication/deletion analysis panel - must include analysis for: 
 
        SDHB 
        SDHC 
        SDHD 
        VHL 
 
17. Neuroendocrine Tumors 
 
        MGMT - PROG 
        PTEN  PROG and THER 
        RB1  DX and PROG 
        TP53  DX and PROG 
        TSC2 - PROG 
 
18.  Prosigna breast cancer gene signature assay (PROG) 
 
You can find this information in the Local Coverage Determination (LCD) Biomarkers for Oncology L35396. 
 
If you want to read these Medicare rules, you can go to this website www.medicareappeal.com.