Genetic Testing Oncology

Transcription

1 Genetic Testing Oncology Policy Number: Original Effective Date: MM /01/2010 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST Integration 05/01/2014 Section: Medicine Place(s) of Service: Outpatient I. Description Genetic testing involves the analysis of chromosomes, DNA (deoxyribonucleic acid), RNA (ribonucleic acid), genes or gene products to detect inherited (germline) or non-inherited (somatic) genetic variants related to disease or health. This is accomplished several ways: Direct DNA or RNA mutation analysis (also known as molecular testing) that examines the direct base pair sequence of a gene for specific gene mutations. Indirect DNA or RNA testing is possible when a marker has been identified as being associated with a disease. Chromosome analysis (also known as cytogenetics) which looks for chromosome abnormalities. For the purpose of this policy, first-degree relatives are defined as parents, full siblings, and offspring. Second-degree relatives are defined as grandparents, grandchildren, aunts, uncles, nephews, nieces, half-siblings and third-degree relatives are defined as great-grandparents, greataunts, great-uncles, first cousins. II. Criteria/Guidelines A. Genetic testing is covered (subject to Limitations/Exclusions and Administrative Guidelines) when all of the following criteria are met: 1. There must be a reasonable expectation based on family history, pedigree analysis, risk factors, and/or symptomatology that a genetically inherited condition exists. 2. The genotypes to be detected by a genetic test must be shown by scientifically valid methods to be associated with the occurrence of the disease, and the analytical and clinical validity of the test must be established. 3. The clinical utility of the test must be established (e.g., test results will influence decisions concerning disease treatment or prevention). B. Genetic testing is covered (subject to Limitations/Exclusions and Administrative Guidelines) when the following criteria are met: 1. A positive or negative test will influence treatment decisions, course of treatment or medical management of the patient; or

2 Genetic Testing - Oncology 2 2. Used to link DNA with known cancer susceptibility. 3. Patient has a cancer or strong suspicion of cancer for the following conditions: a. Acute myeloid leukemia b. Acute promyelocytic leukemia c. Chronic lymphocytic leukemia d. Ewing's sarcoma e. Hereditary Diffuse Gastric Syndrome (CDH1 gene) f. Medullary thyroid carcinoma g. Multiple Myeloma h. Myelodysplastic syndrome i. Myeloproliferative neoplasms j. Non-Hodgkin's lymphoma k. Non-small cell lung cancer l. Small lymphocytic lymphoma m. Breast cancer (see policies for Oncotype DX and Genetic Testing for Hereditary Breast and/or Ovarian Cancer) n. Lynch Syndrome/Colorectal Cancer (see policy for Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes) III. Limitations/Exclusions A. Genetic testing is not covered for the following: 1. Family members of subscribers, who themselves are not subscribers 2. Members if the results of the genetic testing are for the benefit of family members who are not covered by HMSA 3. In the absence of associated signs, symptoms or complaints 4. Home genetic testing is not covered. 5. Cytochrome P-450 with the exception of members being considered for treatment with Plavix (see policy for Cytochrome p450 Genotyping). 6. Chemoresistance and chemosensitivity (e.g., ChemoFx) 7. UGT1A1 Molecular Assay (Invader) 8. Pathfinder (Genetic fingerprinting/dna fingerprinting) and any other genetic expressing test not supported by NCCN) 9. Detection of circulating tumor cells in the management of patients with cancer B. Genetic counseling is not a covered benefit. C. For a known deleterious mutation, HMSA will only cover a targeted single site analysis genetic test not a full analysis (i.e., testing for the mutation that has been identified in the family). D. Most genetic tests are performed once per life time but neuro-oncologic therapies may warrant repeat testing and coverage based on current national clinical practices and guidelines. E. Laboratories that conduct genetic testing must be CLIA certified. F. Because of the rapidly evolving field of genetic testing, this policy does not address every genetic test available. All other conditions not mentioned in this policy will be reviewed based on medical necessity and the policy criteria.

3 Genetic Testing - Oncology 3 IV. Administrative Guidelines Precertification is not required. Documentation supporting the medical necessity should be legible, maintained in the patient's medical record and must be made available to HMSA upon request. HMSA reserves the right to perform retrospective review using the above criteria to validate if services rendered met payment determination criteria. ICD-9 Codes Description Malignant neoplasm of stomach, unspecified site 162.2, 162.3, 162.4, 162.5, 162.8, Malignant neoplasm of the lung Malignant neoplasm of bone and articular cartilage, unspecified (Ewing's sarcoma) 193 Malignant neoplasm of thyroid gland Small lymphocytic lymphoma Non-Hodgkin's lymphoma Multiple Myeloma Lymphoid leukemia 205.0, 205.1, Myeloid leukemia Acute promyelocytic leukemia Carcinoma in situ of other specified sites (includes thyroid gland) Other lymphatic and hematopoietic tissues V10.61 Lymphoid leukemia V10.62 Myeloid leukemia V10.71 Lymphosarcoma and reticulosarcoma V10.72 Hodgkin's disease V10.79 Other lymphatic and hematopoietic neoplasms V10.87 Personal history of malignant neoplasm of thyroid CPT Codes Description BCR/ABL1 (t(9;22)) (eg, chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (eg, chronic myelogenous leukemia) translocation analysis; minor breakpoint, qualitative or quantitative

4 Genetic Testing - Oncology BCR/ABL1 (t(9;22)) (eg, chronic myelogenous leukemia) translocation analysis; other breakpoint, qualitative or quantitative EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) FLT3 (FMS-related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis, internal tandem duplication (ITD) variants (ie, exons 14, 15) IGH (immunoglobulin heavy chain locus) (eg, leukemias and lymphomas, B- cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (eg, polymerase chain reaction) ;direct probe methodology (eg, southern blot) ;variable region somatic mutation analysis IGK(immunoglobulin kappa light chain locus) (eg, leukemia and lymphoma, b-cell), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) JAK2 (Janus Kinase 2) (eg, myeloproliferative disorder) gene analysis, P.VAL617PHE (V617F) variant NPM1 (Nucleophosmin) (eg, acute myeloid leukemia) gene analysis, exon 12 variants PML/RARALPHA, (T(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (eg, promyelocytic leukemia) translocation analysis; common breakpoints (eg, intron 3 and intron 6), qualitative or quantitative ;single breakpoint (eg, intron 3, intron 6 or exon 6), qualitative or quantitative TRB (T cell antigen receptor, beta) (eg, leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using amplification methodology (eg, polymerase chain reaction) ;using direct probe methodology (eg, southern blot) TRG(T cell antigen receptor, gamma) (eg, leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) Tissue culture for non-neoplastic disorders; lymphocyte skin or other solid tissue biopsy Tissue culture for neoplastic disorders; bone marrow, blood cells Cryopreservation, freezing and storage of cells, each cell line Thawing and expansion of frozen cells, each aliquot

5 Genetic Testing - Oncology Chromosome analysis for breakage syndromes; baseline Sister Chromatid Exchange (SCE), cells baseline breakage, score cells, count 20 cells, 2 karyotypes (e.g., for ataxia telangiectasia, Fanconi anemia, fragile X) score 100 cells, clastogen stress (e.g., diepoxybutane, mitomycin C, ionizing radiation, UV radiation) Chromosome analysis; count 5 cells, 1 karyotype, with banding count cells, 2 karyotypes, with banding count 45 cells for mosaicism, 2 karyotypes, with banding Analyze cells Molecular cytogenetics, DNA probe, each (e.g., FISH) chromosomal in situ hybridization, analyze 3-5 cells (e.g., for derivatives and markers) chromosomal in situ hybridization, analyze cells (e.g., for microdeletions) interphase in situ hybridization, analyze cells interphase in situ hybridization, analyze cells Chromosome analysis; additional karyotypes, each study additional specialized banding technique (e.g., NOR, C-banding) additional cells counted, each study additional high resolution study Cytogenetics and molecular cytogenetics, interpretation and report HCPCS Codes S3840 S3841 Description DNA analysis for germline mutations of the RET proto-oncogene for susceptibility to multiple endocrine neoplasia type 2 Genetic testing for retinoblastoma Codes that do not meet payment determination CPT Codes Description UGT1A1 (UDP Glucuronosyltransferase 1 family, polypeptide A1) (eg, irinotecan metabolism), gene analysis, common variants (eg, *28, *36, *37) Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); deleted codes

6 Genetic Testing - Oncology Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); physician interpretation and report, when required deleted codes Modifiers (These are listed for information purposes only) Description -0N TP53, commonly called p53-1c FLI1, ERG, ETV1, or EWSR1 (Ewing s sarcoma, desmoplastic round cell) -2A RUNX1 or CBFA2T1, commonly called AML1 or ETO, genes associated with t(8;21) AML1-also ETO (acute myelogenous leukemia) -2B BCR or ABL1, genes associated with t(9;22) (chronic myelogenous or acute leukemia) BCR-also ABL (chronic myeloid, acute lymphoid leukemia) -2C PBX1 or TCF3, genes associated with t(1;19) (acute lymphoblastic leukemia) CGF1-2D CBFB or MYH11, genes associated with inv 16 (acute myelogenous leukemia) CBF beta (leukemia) -2E MLL (acute leukemia) -2F PML or RARA, genes associated with t(15;17) (acute promyelocytic leukemia) PML/RAR alpha (promyelocytic leukemia) -2G ETV6, commonly called TEL, gene associated with t(12;21) (acute leukemia) TEL (Leukemia) -2H BCL20 (B cell lymphoma, follicle center cell origin) bcl-2 (Lymphoma) -2I CCND1, commonly called BCL1, cyclin D1 (Mantle cell lymphoma, myeloma) bcl-1 (lymphoma) -2J MYC (Burkitt s lymphoma) c-myc (lymphoma) -2K IgH (lymphoma/leukemia) -2L IGK (lymphoma/leukemia) -2M TRB, T cell receptor beta (lymphoma/leukemia) -2N TRG, T cell receptor gamma (lymphoma/leukemia) -2O SIL or TAL1 (T cell leukemia) -2T BCL6 (B cell lymphoma) -2Q API1 or MALT1 (MALT lymphoma) -2R NPM or ALK, genes associated with t(2;5) (anaplastic large cell lymphoma)

7 Genetic Testing - Oncology 7-2S FLT3 (Acute myelogenous leukemia) -4O Microsatellite loss (los of heterozygosity) ICD-10 codes are provided for your information. These will not become effective until the ICD-10 compliance date. ICD-10 Codes Description C16.9 Malignant neoplasm of stomach, unspecified C34.00 Malignant neoplasm of main bronchus, unspecified side C34.01 Malignant neoplasm of right main bronchus C34.02 Malignant neoplasm of left main bronchus C34.10 Malignant neoplasm of upper lobe, bronchus or lung, unspecified side C34.11 Malignant neoplasm of upper lobe, right bronchus or lung C34.12 Malignant neoplasm of upper lobe, left bronchus or lung C34.2 Malignant neoplasm of middle lobe, right bronchus or lung C34.30 Malignant neoplasm of lower lobe, bronchus or lung, unspecified side C34.31 Malignant neoplasm of lower lobe, right bronchus or lung C34.32 Malignant neoplasm of lower lobe, left bronchus or lung C34.80 Malignant neoplasm of overlapping sites of bronchus and lung C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung C34.90 Malignant neoplasm of bronchus or lung, unspecified, unspecified side C34.91 Malignant neoplasm of right bronchus or lung, unspecified C34.92 Malignant neoplasm of left bronchus or lung, unspecified C41.9 Malignant neoplasm of bone and articular cartilage, unspecified C73 Malignant neoplasm of thyroid gland C82.90 Follicular lymphoma, unspecified, unspecified site C82.99 Follicular lymphoma, unspecified, extranodal and solid organ sites C82.91 Follicular lymphoma, unspecified, lymph nodes of head, face, and neck C82.92 Follicular lymphoma, unspecified, intrathoracic lymph nodes C82.93 Follicular lymphoma, unspecified, intra-abdominal lymph nodes C82.94 Follicular lymphoma, unspecified, lymph nodes of axilla and upper limb

8 Genetic Testing - Oncology 8 C82.95 Follicular lymphoma, unspecified, lymph nodes of inguinal region and lower limb C82.96 Follicular lymphoma, unspecified, intrapelvic lymph nodes C82.97 Follicular lymphoma, unspecified, spleen C82.98 Follicular lymphoma, unspecified, lymph nodes of multiple sites C85.80 Other specified types of non-hodgkin lymphoma, unspecified site C85.89 Other specified types of non-hodgkin lymphoma, extranodal and solid organ sites C85.81 Other specified types of non-hodgkin s lymphoma, lymph nodes of head, face, and neck C85.82 Other specified types of non-hodgkin lymphoma, intrathoracic lymph nodes C84.93 Mature T/NK-cell lymphomas, unspecified, intra-abdominal lymph nodes C85.83 Other specified types of non-hodgkin lymphoma, intra abdominal lymph nodes C85.84 Other specified types of non-hodgkin lymphoma, lymph nodes of axilla and upper limb C85.85 Other specified types of non-hodgkin lymphoma, lymph nodes of inguinal region and lower limb C85.86 Other specified types of non-hodgkin lymphoma, intrapelvic lymph nodes C85.87 Other specified types of non-hodgkin lymphoma, spleen C85.88 Other specified types of non-hodgkin lymphoma, lymph nodes of multiple sites C90.00 Multiple myeloma not having achieved remission C90.01 Multiple myeloma in remission C90.02 Multiple myeloma in relapse C91.10 Chronic lymphocytic leukemia of B-cell type not having achieved remission C91.11 Chronic lymphocytic leukemia of B-cell type in remission C91.12 Chronic lymphocytic leukemia of B-cell type in relapse C91.Z0 C91.Z1 C91.Z2 Other lymphoid leukemia not having achieved remission Other lymphoid leukemia in remission Other lymphoid leukemia, in relapse C92.00 Acute myeloblastic leukemia, not having achieved remission

9 Genetic Testing - Oncology 9 C92.40 Acute promyelocytic leukemia, not having achieved remission C92.50 Acute myeolomonocytic leukemia, not having achieved remission C92.01 Acute myeloblastic leukemia, in remission C92.41 Acute promyelocytic leukemia, in remission C92.51 Acute myeolomonocytic leukemia, in remission C92.02 Acute myeloblastic leukemia, in relapse C92.42 Acute promyelocytic leukemia, in relapse C92.52 Acute myeolomonocytic leukemia, in relapse C92.10 Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission C92.11 Chronic myeloid leukemia, BCR/ABL-positive, in remission C92.12 Chronic myeloid leukemia, BCR/ABL-positive, in relapse C92.20 Atypical chronic myeloid leukemia, BCR/ABL-negative, not having achieved remission C92.21 Atypical chronic myeloid leukemia, BCR/ABL-negative, in remission C92.22 Atypical chronic myeloid leukemia, BCR/ABL-negative, in relapse D09.3 Carcinoma in situ of thyroid and other endocrine glands D09.8 Carcinoma in situ of other specified sites D47.3 Essential (hemorrhagic) thrombocythemia D46.0 Refractory anemia without ring sideroblasts, so stated D46.1 Refractory anemia with ring sideroblasts D46.20 Refractory anemia with excess of blasts, unspecified D46.21 Refractory anemia with excess of blasts 1 D46.A D46.B Refractory cytopenia with multilineage dysplasia Refractory cytopenia with multilineage dysplasia and ring sideroblasts D46.22 Refractory anemia with excess of blasts 2 D46.C Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality D46.9 Myelodysplastic syndrome, unspecified D47.1 Chronic myeloproliferative disease D47.Z1 Post-transplant lymphoproliferative disorder (PTLD) C94.40 Acute panmyelosis with myelofibrosis not having achieved remission

10 Genetic Testing - Oncology 10 C94.41 Acute panmyelosis with myelofibrosis, in remission C94.42 Acute panmyelosis with myelofibrosis, in relapse D47.1 Chronic myeloproliferative disease D47.9 Neoplasm of uncertain behavior of lymphoid, hematopoietic and related tissue, unspecified D47.Z9 Other specified neoplasm of uncertain behavior of lymphoid, hematopoietic and related tissue Z85.6 Personal history of leukemia Z85.6 Personal history of leukemia Z85.71 Personal history of Hodgkin lymphoma Z85.79 Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues Z Personal history of malignant neoplasm of soft tissue Z Personal history of malignant neoplasm of thyroid Z80.8 Family history of malignant neoplasm of other organs or systems V. Scientific Background Many genetic tests are imperfect predictors of either existing disease or disease susceptibility, particularly when used in the context of population screening, where individuals without family histories of disease, risk factors or symptoms are tested. For example, the probability exists that a disease may still occur, even when a negative test result is obtained. Conversely, a specific disease may not occur when there is a positive test result. While these concepts hold true for at-risk individuals as well, the probability of both these occurrences is greater in population screening, so test results are more difficult to interpret in a manner that will meaningfully affect health outcomes. With a few limited exceptions (e.g., PKU testing), general screening of populations for diseases that can be attributed to genetic mutations is not advocated in the published scientific literature. The genotypes to be detected by a genetic test must be shown by scientifically valid methods to be associated with the occurrence of the disease, and the analytical and clinical validity of the test must be established. Analytical validity Analytical validity is an indicator of how well a test measures the property or characteristic it is intended to measure, and it is made up of three components Analytical sensitivity: the test is positive when the relevant gene mutation is present. Analytical specificity: the test is negative when the gene mutation is absent and reliability: the test obtains the same result each time. Clinical Validity Clinical validity in genetic testing is a measurement of the accuracy with which a test identifies or predicts a clinical condition and involves the following:

11 Genetic Testing - Oncology 11 a. Clinical sensitivity: the probability that the test is positive if the individual being tested actually has the disease or a predisposition to the disease. b. Clinical specificity: the probability that the test is negative if the individual does not have the disease or a predisposition to the disease. c. Positive predictive value: the probability that an individual with positive test results will get the disease. d. Negative predictive value: the probability that an individual with negative test results will not get the disease. e. Heterogeneity: different mutations within the same gene may cause the same disease and can result in different degrees of disease severity; a failure to detect all diseaserelated mutations reduces a test's clinical sensitivity. f. Penetrance: the probability that the disease will appear when a disease-related genotype is present. Penetrance is incomplete when other genetic or environmental factors must be present for a disease to develop. There are both benefits and risks associated with genetic tests. Genetic tests that are not fully assessed for analytical and clinical validity prior to their use in clinical practice have the potential for causing harm to patients. For example, patients who are wrongly classified as atrisk may be subjected to increased and unnecessary surveillance or treatments, some of which may be harmful, or even irreversible. Likewise, false negative test results may lead to delays in diagnosis and treatment. The development of genetic tests that can diagnose or predict disease occurrence has far outpaced the development of interventions to treat, ameliorate or prevent those same diseases. Clinical utility refers to the ability of genetic test results, either positive or negative, to provide information that is of value in the clinical setting. Specifically for positive test results, this could involve instituting treatments or surveillance measures, making decisions concerning future conception, or avoiding harmful treatments. Negative test results can have clinical utility in that unnecessary treatments or surveillance can be avoided. In the absence of such interventions, the benefits of testing are limited, and in fact, can cause psychological harm. VI. Important Reminder The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii s Patients Bill of Rights and Responsibilities Act (Hawaii Revised Statutes 432E-1.4), generally accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with

12 Genetic Testing - Oncology 12 HMSA s determination as to medical necessity in a given case, the physician may request that HMSA consider the application of this Medical Policy to the case at issue. VII. References 1. AHRQ Update on emerging genetic tests currently available for clinical use in common cancer. Technology Assessment Program. Final Report July 19, AHRQ Quality, regulation and clinical utility of laboratory-developed molecular tests. Technology Assessment Program. Final Report ASCO Policy Statement Update: Genetic Testing for Cancer susceptibility. June 15, Journal of Clinical Oncology. 21(12): Blue Cross Blue Shield Regence #20, Genetic and Molecular Diagnostic Testing. December Ford, JM. Inherited susceptibility to gastric cancer: Advances in genetics and guidelines for clinical management. ASCO Educational Sessions: pp (2002). 6. Hereditary Diffuse Gastric Cancer Syndrome (CDH1). Stanford Medicine: A National Cancer Institute Designated Cancer Center. Available at: 7. Secretary's Advisory Committee on Genetic Testing. A public consultation on oversight of genetic tests. December 1, January 31, National Institutes of Health. Accessed on November 30,