Circulating Tumor DNA Multi-Panel Testing and Circulating Tumor Cells (Liquid Biopsy)
DESCRIPTION
Liquid biopsy refers to the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) as a method of noninvasively characterizing tumors and tumor genome from the peripheral blood. This method may be used to test for single genes or multiple genes using a panel.
Both malignant and nonmalignant cells release small fragments of DNA into the blood, which is referred to as cell-free DNA. Most cell-free tumor DNA is derived from apoptotic and/or necrotic tumor cells, either from the primary tumor or metastases. Analysis of circulating tumor DNA allows multiple samples of blood to be analyzed over time to monitor the molecular changes taking place in a tumor and possibly determining sensitivity to certain treatments.
Liquid biopsy using Guardant360 in individuals with advanced non-small cell lung cancer may be a reasonable non-invasive alternative to tumor biopsy, particularly in individuals unable to undergo standard tissue biopsy or in cases where tumor tissues are lacking or insufficient for proper mutation analysis. For individuals with other types of cancer, liquid biopsy using other multi-gene panels may be used as a companion diagnostic assay to identify the presence of driver mutations and inform a decision regarding treatment selection (e.g., whether to select a targeted treatment or standard treatment).
Intact circulating tumor cells (CTCs) are released from a primary tumor and/or a metastatic site into the blood stream. The half-life of a CTC is short, approximately 1 - 2 hours. The primary reason for detecting CTCs is prognostic through quantification of circulating levels.
Note: This policy does not address using circulating tumor DNA liquid biopsy for single-gene testing.
POLICY
Detection and quantification of circulating tumor DNA (liquid biopsy) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Detection and quantification of circulating tumor DNA using liquid biopsy multi-gene panels not addressed under medical appropriateness is considered investigational.
Detection and quantification of circulating tumor cells (liquid biopsy, e.g., CellSearch®) for risk assessment or to guide the management of cancer is considered investigational.
MEDICAL APPROPRIATENESS
Detection and quantification of circulating tumor DNA (liquid biopsy) is considered medically appropriate if ANY ONE of the following are met:
Multi-gene panel testing (i.e., Guardant360®) for risk assessment or to guide the management of cancer when ALL of the following are met:
Diagnosis of metastatic or recurrent non-small cell lung cancer, biopsy confirmed
Insufficient tumor tissue is available for broad molecular profiling
Documentation that additional standard tissue biopsy is contraindicated due to clinical condition
Liquid biopsy-based companion diagnostic assays to guide in prescribing certain medications when ALL of the following are met:
Diagnosis of cancer
Treatment with a medication in which there is a liquid biopsy-based FDA- approved (e.g., FoundationOne Liquid CDx™, Guardant360® CDx ) companion diagnostic being considered
FDA label for the drug and indication being considered states companion diagnostic testing is necessary
Individual has not had previous somatic tumor testing to identify genetic change required to prescribe medication
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes 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. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
Insufficient data are available to determine if the analysis of circulating tumor cells (e.g., CellSearch®) improves health outcomes.
SOURCES
Aggarwal, C., Thompson, J.C., Black, T.A., Katz, S.I., Fan, R., Yee, S.S., et al. (2018). Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncology, 5 (2), 173 - 180. (Level 2 evidence)
American Society of Clinical Oncology / College of American Pathologists. (2018, March). Circulating tumor DNA analysis in patients with cancer: ASCO / CAP Joint Review. Received March 6, 2018 from http://jco.org.
BlueCross BlueShield Association. Evidence Positioning System. (12:2022). Somatic biomarker testing (including liquid biopsy) for targeted treatment and immunotherapy in non-small-cell lung cancer (2.04.45). Retrieved September 27, 2023 from http://www.evidencepositioningsystem.com. (151 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Evidence Positioning System. (9:2023). Circulating tumor DNA and circulating tumor cells for cancer management (liquid biopsy) (2.04.141). Retrieved September 26, 2023 from http://www.evidencepositioningsystem.com. (28 articles and/or guidelines reviewed)
Boysen, A.K., Schou, J.V., & Spindler, K.G. (2018). Cell-free DNA and preoperative chemoradiotherapy for rectal cancer: a systematic review. Clinical & Translational Oncology, 21 (7) 874 – 880. Abstract retrieved May 13, 2019 from PubMed database.
Bunduc, S., Gede, N., Váncsa, S., Lillik, V., Kiss, S., Dembrovszky, F., et al. (2022). Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 169, 103548. (Level 1 evidence)
Chen, V.L., Xu, D., Wicha, M.S., Lok, A.S., & Parikh, N.D. (2020). Utility of liquid biopsy analysis in detection of hepatocellular carcinoma, determination of prognosis, and disease monitoring: a systematic review. Clinical Gastroenterology and Hepatology: The official clinical practice journal of the American Gastroenterological Association, 18 (13), 2879-2902.e9. (Level 1 evidence)
Chidambaram, S., & Markar, S. R. (2022). Clinical utility and applicability of circulating tumor DNA testing in esophageal cancer: a systematic review and meta-analysis. Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus, 35 (2), doab046. (Level 1 evidence)
CMS.gov: Centers for Medicare & Medicaid Services. Palmetto GBA. (2021, December). MolDX: plasma-based genomic profiling in solid tumors. (LCD ID L38043). Retrieved September 22, 2023 from www.cms.gov.
eviCore healthcare. (2023, July). Lab management guidelines for investigational and experimental laboratory testing. Retrieved September 28, 2023 from www.evicore.com.
eviCore healthcare. (2023, July). Lab management guidelines for liquid biopsy testing. Retrieved September 28, 2023 from www.evicore.com. (62 articles and/or guidelines reviewed).
Feng, S. N., Cen, X. T., Tan, R., Wei, S. S., & Sun, L. D. (2021). The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis. Translational Oncology, 14 (6), 101072. (Level 1 evidence)
Herranz, R., Oto, J., Plana, E., Fernández-Pardo, Á., Cana, F., Martínez-Sarmiento, M., et al. (2021). Circulating cell-free dna in liquid biopsies as potential biomarker for bladder cancer: a systematic review. Cancers, 13 (6), 1448. (Level 1 evidence)
Jongbloed, E. M., Deger, T., Sleijfer, S., Martens, J. W. M., Jager, A., & Wilting, S. M. (2021). A systematic review of the use of circulating cell-free dna dynamics to monitor response to treatment in metastatic breast cancer patients. Cancers, 13 (8), 1811. (Level 1 evidence)
Lanman, R., Mortimer, S., Zill, O., Sebisanovic, D., Lopez, R., Blau, S., Collisson, E., et al. (2015). Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS One, 10 (10), e0140712. (Level 3 evidence)
Mao, C., Yuan, J., Yang, Z., Wu, X., & Tang, J. (2015). Blood as a substitute for tumor tissue in detecting EGFR mutations for guiding EGFR TKIs treatment of non-small cell lung cancer. Medicine, 94 (21), e775. (Level 1 evidence)
Morais, M., Pinto, D. M., Machado, J. C., & Carneiro, S. (2022). ctDNA on liquid biopsy for predicting response and prognosis in locally advanced rectal cancer: A systematic review. European Journal of Surgical Oncology, 48 (1), 218-227. Retrieved September 29, 2023 from PubMed database.
National Comprehensive Cancer Network (2023, April). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-small cell lung cancer V3.2023. Retrieved September 28, 2023 from the National Comprehensive Cancer Network.
Petit, J., Carroll, G., Gould, T., Pockney, P., Dun, M., & Scott, R.J. (2019). Cell-free DNA as a diagnostic blood-based biomarker for colorectal cancer: a systematic review. Journal of Surgical Research, 236, 184-197. Abstract retrieved May 13, 2019 from PubMed database.
U. S. Food and Drug Administration. (2005, January). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K040898 (CellSearch™). Retrieved January 4, 2012 from http://www.accessdata.fda.gov.
Wang, S., Du, H., & Li, G. (2017). Significant prognostic value of circulating tumor cells in esophageal cancer patients: A meta-analysis. Oncotarget, Advance Publications, 2017, 1-12. (Level 2 evidence)
Wu, Z. X., Liu, Z., Jiang, H. L., Pan, H. M., & Han, W. D. (2016). Circulating tumor cells predict survival benefit from chemotherapy in patients with lung cancer. Oncotarget, 7 (41), 67586-67596. (Level 1 evidence)
Zheng, Y., Zhang, C., Wu, J., Cheng, G., Yang, H., Hua, L., et al. (2016). Prognostic value of circulating tumor cells in castration resistant prostate cancer: A meta-analysis. Urology Journal, 13 (6), 2881-2888. Abstract retrieved February 17, 2017 from PubMed Database.
ORIGINAL EFFECTIVE DATE: 5/12/2005
MOST RECENT REVIEW DATE: 11/9/2023
ID_EC
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