Liquid Biopsy Form

. Liquid biopsy is a test usually performed on blood samples, but may be performed on other body fluid samples. It purportedly analyzes the presence of cancer cells released from a tumor that are circulating or fragments of deoxyribonucleic acid (DNA) from tumor cells in the fluid. It may be used to manage treatment, assist in drug selection, determine prognosis as well as therapy response and be used as a minimally invasive alternative to tumor biopsy. The test may have the potential to diagnose cancer at an early stage. Liquid biopsy may identify 2 main biomarkers in an individual with cancer: circulating cell-free DNA (cfDNA), also known as circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs). cfDNA are DNA fragments from a tumor that circulate in the blood or body fluid of an individual who has cancer. Examples of cfDNA tests include, but may not be limited to, Agilent Resolution ctDx FIRST, GeneStrat, Guardant Tests, LiquidHALLMARK and NavDx. (Refer to Coverage Limitations section)

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 2 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body. Testing purportedly aids in the monitoring of an individual with cancer. Examples include, but may not be limited to CellSearch, which is US Food & Drug Administration (FDA) cleared, and Oncocee. For information regarding liquid biopsy for prostate cancer, please refer to Genetic Testing and Liquid Biopsy for Prostate Cancer Medical Coverage Policy. (Refer to Coverage Limitations section) Liquid biopsy test may also analyze additional biomarkers such as autoantibodies, cell free ribonucleic acid (RNA) and tumor antigens. These are purported to have the potential to stratify cancer risk or diagnose cancer at an early stage. Examples include, but may not be limited to:
• Avantect Pancreatic Cancer test is a blood test that purportedly detects epigenomic and genomic profiles of cfDNA associated with pancreatic cancer. Results indicate whether a cancer signal is detected and treatment recommendations. (Refer to Coverage Limitations section) • BTG Early Detection of Pancreatic Cancer is a blood test that analyizes 59 methylation haplotype block markers in plasma using next-generation sequencing, purportedly the results are reported as cancer signal detected or not detected. (Refer to Coverage Limitations section) • Coloscape Colorectal Cancer Detection test is a blood test purported to evaluate mutations in 8 genes (APC, BRAF, CTNNB1, KRAS, NRAS, PIK3CA, SMAD4, and TP53) and 7 methylation markers (C9ORF50, CLIP4, FLI1, KCNQ5, MYO1G, TWIST1 and ZNF132) to report a risk score for advanced adenoma or colorectal cancer (CRC). (Refer to Coverage Limitations section) • ColonSentry is a blood test intended to measure RNA transcript expression of 6 genes (ANXA3, CLEC4D, LMNB1, PRRG4, TNFAIP6, and VNN1) and pairs with the expression level of reference gene IL2RB to create a genetic signature. An individual can be stratified for CRC risk. (Refer to Coverage Limitations section) • Helioliver is a blood test purportedly used for surveillance of hepatocellular See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 3 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. carcinoma (HCC) in a high-risk individual, by an analysis of methylation patterns on cfDNA combined with measurement of serum of AFP/AFP-L3 and oncoprotein des-gamma-carboxy-prothrombin (DCP), algorithm reported as normal or abnormal result. (Refer to Coverage Limitations section) • LungLB is a blood test that uses a predictive algorithm to generate an evaluation reported as a decreased or increased risk for lung cancer. These results are purported to bring certainty into early stage diagnosis confirming for clinicians whether to refer on to biopsy where the low-dose computed tomography (LDCT) scan reveals suspicious nodules. (Refer to Coverage Limitations section) • OncobiotaLUNG is a blood test used to measure microbial DNA by NGS, carcinoembryonic antigen and osteopontin by immunoassay. It is purported to detect malignancy risk for lung nodules in early-stage disease. (Refer to Coverage Limitations section) • Protein Assay Utilizing Lung Cancer Analytes (PAULAs) test is a multiplex immunoassay blood test consisting of 4 biomarkers including a group of 3 tumor antigens (CEA, CA-125, Cyfra) and 1 tumor autoantibody (NY-ESO-1). It is purported to determine risk for asymptomatic, current or former smokers who are at least 50 years of age or older with at least a 20 pack- year smoking history. The composite PAULAs test score categorizes an individual into lung cancer risk categories. The results are to be used in conjunction with other clinical data to determine the appropriate diagnostic follow up. (Refer to Coverage Limitations section) Additional liquid biopsy tests that may aid in predicting an individual’s response to therapy include, but may not be limited to:
• RadTox is a quantitative DNA amplification test intended for monitoring radiation therapy toxicity in an individual with cancer, enabling providers to monitor side effect severity and tumor response. (Refer to Coverage Limitations section) Any state mandates for liquid biopsy take precedence over this medical coverage policy. Coverage Determination See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 4 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. Please refer to the member’s applicable pharmacy benefit to determine benefit availability and the terms and conditions of coverage for medication for the treatment of cancer. Humana members may be eligible under the Plan for Guardant360 CDx (0242U) when the following criteria are met:
• Individual diagnosed with advanced or metastatic, ER-positive, HER2-negative, breast cancer; AND • Progression following at least 1 line of endocrine therapy; AND • Testing performed as a companion diagnostic prior to initiation of treatment with elacestrant (Orserdu) For information regarding Orserdu, please refer to Orserdu (elacestrant) Pharmacy Coverage Policy. Coverage Limitations Humana members may NOT be eligible under the Plan for liquid biopsy (eg, cfDNA, ctDNA, CTC tests) for any indications or tests other than those listed above including, but may not be limited to: • Agilent Resolution ctDx FIRST (0397U) • Avantect Pancreatic Cancer Test (0410U) • BTG Early Detection of Pancreatic Cancer (0405U) • CellSearch (86152, 86153)
o CellSearch Circulating Multiple Myeloma Cell (CMMC) (0337U) o CellSearch HER2 Circulating Tumor Cell (CTC-HER2) (0338U) • CNSide See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 5 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. • ColonSentry • ColoScape Colorectal Cancer Detection Test (0368U) • FirstSightCRC (0091U) • FoundationOne Liquid (including FoundationOne Liquid CDx [0239U]) • Galleri • GeneStrat • GPS Cancer (NantHealth Liquid GPS) • Guardant Tests (eg, Guardant360 [0326U], Guardant360 Response, Guardant Reveal, Guardant Shield) • HelioLiver (0333U) • InVisionFirst LUNG (0388U) • LiquidHALLMARK (0409U) • LungLB (0317U) • NavDx (0356U) • OncobiotaLUNG (0395U) • Papgene • PAULAs test • Promoter methylation analysis (BCAT1 or IKZF1) (eg, Colvera [0229U]) • RadTox (0285U) See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 6 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. • Resolution ctDx Lung (0179U) • SEPT9 DNA methylation assay (eg, ColoVantage [81327], Epi proColon) • Signatera (0340U) • Tempus xF • Trovera BRAF • Trovera KRAS These are considered experimental/investigational as they have not been identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language. Background Additional information about cancer may be found from the following websites: • American Cancer Society • National Cancer Institute • National Comprehensive Cancer Network • National Library of Medicine Medical Alternatives Alternatives to liquid biopsy include, but may not be limited to, the following: • Tumor biopsy Physician consultation is advised to make an informed decision based on an individual’s health needs. Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care. See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 7 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. Provider Claims Codes Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure. CPT® Code(s) 81327 Description SEPT9 (Septin9) (eg, colorectal cancer) promoter methylation analysis 81479 Unlisted molecular pathology procedure 81599 Unlisted multianalyte assay with algorithmic analysis 82378 Carcinoembryonic antigen (CEA) 86152 86153 Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); physician interpretation and report, when required 86304 Immunoassay for tumor antigen, quantitative; CA 125 0091U Oncology (colorectal) screening, cell enumeration of circulating tumor cells, utilizing whole blood, algorithm, for the presence of adenoma or cancer, reported as a positive or negative result Comments Not Covered Not Covered if used to report any test outlined in this medical coverage policy Not Covered if used to report any test outlined in this medical coverage policy Not Covered if used to report any test outlined in this medical coverage policy Not Covered Not Covered Not Covered if used to report any test outlined in this medical coverage policy Not Covered See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 8 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. 0179U 0229U 0239U 0242U 0285U 0317U 0326U 0333U Oncology (non-small cell lung cancer), cell-free DNA, targeted sequence analysis of 23 genes (single nucleotide variations, insertions and deletions, fusions without prior knowledge of partner/breakpoint, copy number variations), with report of significant mutation(s) BCAT1 (Branched chain amino acid transaminase 1) or IKZF1 (IKAROS family zinc finger 1) (eg, colorectal cancer) promoter methylation analysis Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311 or more genes, interrogation for sequence variants, including substitutions, insertions, deletions, select rearrangements, and copy number variations Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free circulating DNA analysis of 55-74 genes, interrogation for sequence variants, gene copy number amplifications, and gene rearrangements Oncology, response to radiation, cell-free DNA, quantitative branched chain DNA amplification, plasma, reported as a radiation toxicity score Oncology (lung cancer), four-probe FISH (3q29, 3p22.1, 10q22.3, 10cen) assay, whole blood, predictive algorithm- generated evaluation reported as decreased or increased risk for lung cancer Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free circulating DNA analysis of 83 or more genes, interrogation for sequence variants, gene copy umber amplifications, gene rearrangements, microsatellite instability and tumor mutational burden Oncology (liver), surveillance for hepatocellular carcinoma (HCC) in high-risk patients, analysis of methylation patterns on circulating cell-free DNA (cfDNA) plus measurement of serum of AFP/AFP-L3 and oncoprotein des-gamma-carboxy-prothrombin (DCP), algorithm reported as normal or abnormal result Not Covered Not Covered Not Covered Not Covered Not Covered Not Covered Not Covered See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 9 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. 0337U 0338U 0340U Oncology (plasma cell disorders and myeloma), circulating plasma cell immunologic selection, identification, morphological characterization, and Oncology (solid tumor), circulating tumor cell selection, identification, morphological characterization, detection and enumeration based on differential EpCAM, cytokeratins 8, 18, and 19, and CD45 protein biomarkers, and quantification of HER2 protein biomarker–expressing cells, peripheral blood Oncology (pan-cancer), analysis of minimal residual disease (MRD) from plasma, with assays personalized to each patient based on prior next-generation sequencing of the patient’s tumor and germline DNA, reported as absence or presence of MRD, with disease-burden correlation, if appropriate 0356U Oncology (oropharyngeal), evaluation of 17 DNA biomarkers using droplet digital PCR (ddPCR), cell-free DNA, algorithm reported as a prognostic risk score for cancer recurrence 0368U 0388U 0395U Oncology (colorectal cancer), evaluation for mutations of APC, BRAF, CTNNB1, KRAS, NRAS, PIK3CA, SMAD4, and TP53, and methylation markers (MYO1G, KCNQ5, C9ORF50, FLI1, CLIP4, ZNF132 and TWIST1), multiplex quantitative polymerase chain reaction (qPCR), circulating cell-free DNA (cfDNA), plasma, report of risk score for advanced adenoma or colorectal cancer Oncology (non-small cell lung cancer), next-generation sequencing with identification of single nucleotide variants, copy number variants, insertions and deletions, and structural variants in 37 cancer-related genes, plasma, with report for alteration detection Oncology (lung), multi-omics (microbial DNA by shotgun next- generation sequencing and carcinoembryonic antigen and osteopontin by immunoassay), plasma, algorithm reported as malignancy risk for lung nodules in early-stage disease Not Covered Not Covered Not Covered Not Covered New Code Effective 01/01/2023 Not Covered New Code Effective 04/01/2023 Not Covered New Code Effective 07/01/2023 Not Covered New Code Effective 07/01/2023 See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 10 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. 0397U 0405U 0409U Oncology (non-small cell lung cancer), cell-free DNA from plasma, targeted sequence analysis of at least 109 genes, including sequence variants, substitutions, insertions, deletions, select rearrangements, and copy number variations Oncology (pancreatic), 59 methylation haplotype block markers, next-generation sequencing, plasma, reported as cancer signal detected or not detected Oncology (solid tumor), DNA (80 genes) and RNA (36 genes), by next-generation sequencing from plasma, including single nucleotide variants, insertions/deletions, copy number alterations, microsatellite instability, and fusions, report showing identified mutations with clinical actionability 0410U Oncology (pancreatic), DNA, whole genome sequencing with 5- hydroxymethylcytosine enrichment, whole blood or plasma, algorithm reported as cancer detected or not detected Not Covered New Code Effective 07/01/2023 Not Covered New Code Effective 10/01/2023 Not Covered New Code Effective 10/01/2023 Not Covered New Code Effective 10/01/2023 CPT® Category III Code(s) No code(s) identified HCPCS Code(s) Description Comments Description Comments References

1. Aggarwal C, Thompson J, Black TA, et al. Clinical implications of plasma- based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. https://www.ncbi.nlm.nih.gov. Accessed December 23, 2022.
2. American College of Gastroenterology (ACG). ACG Clinical Guidelines: colorectal cancer screening 2021. https://gi.org. Published March 2021. Accessed December 16, 2022.

3. American Society of Clinical Oncology (ASCO). Biomarkers for adjuvant See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

   Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 11 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing. endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. https://www.asco.org. Published April 19, 2022. Accessed December 15, 2022. American Society of Clinical Oncology (ASCO). Biomarkers for systemic therapy in metastatic breast cancer: ASCO guideline update. https://www.asco.org. Published May 2, 2022. Accessed September 1, 2023. American Society of Clinical Oncology (ASCO). Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology clinical oncology and College of American Pathologists joint review. https://www.asco.org. Published March 5, 2018. Accessed September 1,

   2023. American Society of Clinical Oncology (ASCO). Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer. https://www.asco.org. Published April 1, 2020. Accessed September 1, 2023.
         American Society of Clinical Oncology (ASCO). Somatic genomic testing in patients with metastatic or advanced cancer: ASCO provisional clinical opinion. https://www.asco.org. Published February 17, 2022. Accessed September 1, 2023.
         American Society of Colon and Rectal Surgeons (ASCRS). The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of colon cancer. https://www.fascrs.org. Published February
   2024. Accessed September 1, 2023. Association for Molecular Pathology (AMP). Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? https://www.amp.org. Published May 2015. Accessed September 12, 2023.

10. Association for Molecular Pathology (AMP). Molecular biomarkers for the evaluation of colorectal carcinoma: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. https://www.amp.org. Published February 6, 2017. Accessed December 16,

    2022. See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

    Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 12 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

11. Bidard F, Kaklamani V, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. https://www.ncbi.nlm.nih.gov. Accessed March 13, 2023.
12. ClinicalKey. Clinical Overview. Colorectal cancer. https://www.clinicalkey.com. Updated August 26, 2022. Accessed August 29, 2023.
13. ClinicalKey. Clinical Overview. Colorectal cancer, screening and prevention. https://www.clinicalkey.com. Updated September 9, 2022. Accessed December 16, 2022.
14. College of American Pathologists (CAP). Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. https://www.cap.org. Updated March 2018. Accessed December 16, 2022.
15. ECRI Institute. Clinical Evidence Assessment. NavDx Assay (Naveris, Inc.) for detecting recurrence of HPV-associated cancers. https://www.ecri.org. Published June 1, 2020. Updated March 16, 2023. Accessed August 28, 2023.
16. ECRI Institute. ECRIgene Genetic Test Assessment. CellSearch CTC Test (Menarini Silicone Biosystems, Inc.) for monitoring metastatic colorectal cancer treatment response and evaluating prognosis. https://www.ecri.org. Published June 2020. Accessed August 28, 2023.

17. ECRI Institute. ECRIgene Genetic Test Assessment. Circulating tumor DNA tests for colorectal cancer minimal residual disease. https://www.ecri.org. Published November 2022. Accessed September 1,

    2023. See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

    Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 13 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

18. ECRI Institute. ECRIgene Genetic Test Assessment. Colvera (Clinical Genomics Pathology, Inc.) liquid biopsy test to monitor for recurrent colorectal cancer. https://www.ecri.org. Published October 21, 2021. Accessed December 12, 2022.
19. ECRI Institute. ECRIgene Genetic Test Assessment. FirstSightCRC (CellMax Life) for colorectal cancer screening. https://www.ecri.org. Published June 2021. Accessed December 12, 2022.
20. ECRI Institute. ECRIgene Genetic Test Assessment. FoundationOne liquid (Foundation Medicine, Inc.) genomic profiling and liquid biopsy test for guiding targeted therapy for solid tumors. https://www.ecri.org. Published September 3, 2019. Accessed December 12, 2022.
21. ECRI Institute. ECRIgene Genetic Test Assessment. Galleri Multicancer Early Detection Test (Grail, LLC) for cancer screening. https://www.ecri.org. Published October 2022. Accessed December 12, 2022.
22. ECRI Institute. ECRIgene Genetic Test Assessment. GeneStrat (Biodesix, Inc.) liquid biopsy test to guide targeted therapy for non-small cell lung cancer. https://www.ecri.org. Published October 21, 2021. Accessed December 12, 2022.
23. ECRI Institute. ECRIgene Genetic Test Assessment. Guardant Reveal (Guardant Health, Inc.) liquid biopsy test for assessing minimal residual disease and monitoring recurrence of colorectal cancer. https://www.ecri.org. Published April 2022. Accessed December 12, 2022.
24. ECRI Institute. ECRIgene Genetic Test Assessment. Guardant360 (Guardant Health, Inc.) test for informing management of advanced solid tumor cancers. https://www.ecri.org. Published August 2020. Accessed March 10, 2023.

25. ECRI Institute. ECRIgene Genetic Test Assessment. HelioLiver test (Fulgent Genetics) for aiding diagnosis of liver cancer. https://www.ecri.org. Published May 2023. Accessed August 28, 2023.
    See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

    Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 14 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

26. ECRI Institute. ECRIgene Genetic Test Assessment. InVisionFirst-Lung (Inivata Ltd) genomic profiling and liquid biopsy test for guiding targeted therapy for non-small cell lung cancer. https://www.ecri.org. Published June 2021. Accessed August 28, 2023.
27. ECRI Institute. ECRIgene Genetic Test Assessment. LiquidHallmark (Lucence Health, Inc.) for guiding targeted therapy selection for lung cancer. https://www.ecri.org. Published June 2023. Accessed August 28, 2023.
28. ECRI Institute. ECRIgene Genetic Test Assessment. Signatera (Natera, Inc.) ctDNA test for molecular residual disease assessment and recurrence monitoring of solid tumor cancers. https://www.ecri.org. Published April 2020. Updated June 2023. Accessed August 28, 2023.
29. ECRI Institute. ECRIgene Genetic Test Assessment. Tempus xF (Tempus) to guide targeted therapy for solid tumor cancers. https://www.ecri.org. Published October 2020. Accessed December 12, 2022.
30. ECRI Institute. ECRIgene Genetic Test Product Brief. GPS cancer test (NantHealth, Inc.) for informing management of solid tumors. https://www.ecri.org. Published March 2017. Accessed December 9, 2022.
31. ECRI Institute. ECRIgene Genetic Test Product Brief. Trovera BRAF (Trovagene, Inc.) liquid biopsy test for informing management of BRAF- associated disorders. https://www.ecri.org. Published November 2016. Accessed December 12, 2022.
32. ECRI Institute. ECRIgene Genetic Test Product Brief. Trovera KRAS (Trovagene, Inc.) liquid biopsy test for informing management of KRAS- associated cancers. https://www.ecri.org. Published March 2017. Accessed December 12, 2022.

33. Giulia S, Connor J, Shohreh V, et al. Cell free HPV DNA provides an accurate and rapid diagnosis of HPV-associated head and neck cancer. Clin Cancer Res. 2022;28(4):719-727. https://www.ncbi.nlm.nih.gov. Accessed September 1, 2023. See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

    Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 15 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

34. Grossi F, Rijavec E, Genova C, et al. Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy. Br J Cancer. 2017;36-43. https://www.ncbi.nlm.nih.gov. Accessed December 23, 2022.
35. Hayes, Inc. Clinical Utility Evaluation. Liquid biopsy tests for colorectal cancer screening. https://evidence.hayesinc.com. Published March 26, 2020. Updated May 17, 2022. Accessed December 13, 2022.
36. Hayes, Inc. Genetic Test Evaluation (GTE) Synopsis. GPS Cancer (NantHealth). https://evidence.hayesinc.com. Published February 2, 2017. Accessed December 10, 2021.
37. Hayes, Inc. Health Technology Brief (ARCHIVED). CellSearch circulating tumor cell (CTC) Kit (Janssen Diagnostics LLC) for monitoring metastatic breast cancer. https://evidence.hayesinc.com. Published October 23, 2014. Updated August 31, 2016. Accessed August 28, 2023.
38. Hayes, Inc. Molecular Test Assessment. ColonSentry (Stage Zero Life Sciences). https://evidence.hayesinc.com. Published December 11, 2018. Updated March 25, 2022. Accessed December 13, 2022.
39. Hayes, Inc. Molecular Test Assessment. Colvera (Clinical Genomics Pathology Inc.). https://evidence.hayesinc.com. Published November 14, 2018. Updated July 1, 2022. Accessed December 13, 2022.
40. Hayes, Inc. Molecular Test Assessment. Epi proColon (Epigenomics Inc.). https://evidence.hayesinc.com. Published September 30, 2020. Updated October 14, 2022. Accessed December 13, 2022.
41. Hayes, Inc. Molecular Test Assessment. FirstSightCRC (CellMax Life). https://evidence.hayesinc.com. Published August 7, 2020. Updated July 1, 2022. Accessed December 13, 2022.

42. Hayes, Inc. Molecular Test Assessment. GeneStrat (Biodesix Inc.). https://evidence.hayesinc.com. Published December 5, 2017. Updated August 6, 2021. Accessed December 13, 2022. See the DISCLAIMER. All Humana member health plan contracts are NOT the same. All legislation/regulations on this subject may not be included. This document is for informational purposes only.

    Liquid Biopsy Effective Date: 05/25/2023 Revision Date: 05/25/2023 Review Date: 02/02/2023 Policy Number: HUM-0555-025 Page: 16 of 21 Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

43. Hayes, Inc. Molecular Test Assessment. Guardant360 (Guardant Health Inc.). https://evidence.hayesinc.com. Published December 11, 2018. Updated November 19, 2021. Accessed December 13, 2022.
44. Hayes, Inc. Molecular Test Assessment. NavDx (Naveris). https://evidence.hayesinc.com. Published August 15, 2023. Accessed August 28, 2023.
45. Hayes, Inc. Molecular Test Assessment. Signatera (Natera Inc.). https://evidence.hayesinc.com. Published January 18, 2023. Accessed August 28, 2023.
46. Hayes, Inc. Molecular Test Assessment (ARCHIVED). FoundationOne Liquid (Foundation Medicine Inc.). https://evidence.hayesinc.com. Published June 13, 2019. Updated April 6, 2021. Accessed December 13, 2022.
47. Hayes, Inc. Precision Medicine Research Brief. Galleri: multi-cancer early detection test (Grail Inc.). https://evidence.hayesinc.com. Published May 26, 2021. Accessed December 13, 2022.
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