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02/01/2023

Clinical perspectives on lung cancer

Clinical Practices for utilizing next-generation sequencing (NGS) in lung cancer patients

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Hear from Dr. Wade T. Iams of Vanderbilt-Ingram Cancer Center and Dr. Mary Jo Fidler of Rush Medical Center as they discuss their own view on best practices for implementing NGS testing approaches to inform optimized care decisions for their lung cancer patients.

Utilizing different NGS testing approaches in lung cancer

Solid tumor next generation sequencing (NGS) and liquid biopsy testing are common approaches to full genomic profiling in lung cancer care. A concurrent testing approach may help to optimize assessment for lung cancer biomarkers while expediting test results to initiate appropriate precision therapies without delay. Testing approaches should be individualized for the patient based on clinical history and health status. Listen to what these lung cancer specialists have to say about their testing practices1.

Liquid biopsy testing to assess for cancer resistance

Liquid biopsy testing has proven to be a complementary approach to solid tumor molecular profiling to maximize the potential of identifying targeted mutations for treatment selection when performed concurrently. This blood-based test is a minimally invasive, practical tool to assess for acquired resistance to commonly initiated targeted kinase inhibitors, such as EGFR TKIs. Mechanisms of acquired resistance are diverse and implementing a strategy for longitudinal testing using liquid biopsy may inform future treatment strategies4.

The value of RNA sequencing in lung cancer

Studies have shown RNA-based sequencing may improve the sensitivity of detecting actionable alterations such as chromosomal rearrangements and fusions over DNA sequencing. Additionally, wIth multiple FDA-approved targeted therapies associated with these alterations, should DNA and RNA sequencing be standard for patients in non-small cell lung cancer? Hear what Dr. Iams has to say2.

What is unique about Tumor/Normal match sequencing?

Tumor normal matched sequencing is a method to compare tumor mutations to the matched normal sample to identify the true somatic variants that may act as the oncogenic drivers in the patient’s cancer. A Tempus published paper demonstrated Tempus xT tumor/normal match sequencing had a 28% reduction in somatic false-positive calls, improving accuracy compared to tumor-only analysis. Other benefits to parallel tumor/normal match sequencing are being researched such as incidental germline findings and estimations of tumor mutational burden (TMB). Learn more in this video3.

 

1. Based on a retrospective study involving a cohort of randomly selected patients with breast cancer, CRC, NSCLC, and prostate cancer. Mackay M, Mitsiades N, Chae YK, et al. Dual tissue and plasma testing to improve detection of actionable variants in patients with solid cancers. JCO. 2022;40(16_suppl):3017.
2. Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no driver alteration detected by DNA sequencing and low tumor mutation burden. Clinical Cancer Research, 2019. Based on a retrospective study involving a cohort of randomly selected patients with tumor types including low grade glioma, sarcoma, glioblastoma, bladder, NSCLC and biliary tract cancer. Michuda J, Park BH, Cummings AL, et al. Use of clinical RNA-sequencing in the detection of actionable fusions compared to DNA-sequencing alone. Journal of Clinical Oncology. 2022;40(16_suppl):3077).
3. Based on a retrospective study involving a cohort of randomly selected patients with tumor types including brain, breast, colorectal, lung, ovarian, endometrial, pancreatic and prostate cancer. Beaubier N, Bontrager M, Huether R, et al. Integrated genomic profiling expands clinical options for patients with cancer. Nature Biotechnology. 2019;37(11):1351-1360. Based on a retrospective study involving a cohort of randomly selected patients treated in geographically diverse brain, lung, cholangiocarcinoma, head and neck, breast, ovarian, pancreatic, prostate, endometrial and colorectal. Yap TA, Ashok A, Stoll J, et al. Prevalence of among tumors from cancer types lacking hereditary testing guidelines. JAMA Network Open. 2022;5(5). Carson KR, Salahudeen A, Fidler MJJ, et al. Paired tumor/normal sequencing to overcome racial differences in tumor mutational burden (Tmb). JCO. 2022;40(16_suppl):3138-3138.
4. Schoenfeld AJ, Chan JM, Kubota D, et al. Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in egfr-mutant lung cancer. Clinical Cancer Research. 2020;26(11):2654-2663. Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: Mechanisms of resistance and management. Nature Reviews Clinical Oncology. 2022;19(8):499-514.

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