• Aaron C Tan, Gillianne G Y Lai, Gek San Tan, Shou Yu Poon, Brett Doble, Tse Hui Lim, Zaw Win Aung, Angela Takano, Wan Ling Tan, Mei-Kim Ang, Bien Soo Tan, Anantham Devanand, Chow Wei Too, Apoorva Gogna, Boon-Hean Ong, Tina P T Koh, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Tanujaa Rajasekaran, Alvin S T Lim, Wan Teck Lim, Chee Keong Toh, Eng-Huat Tan, LimTony Kiat HonTKHDivision of Pathology, Singapore General Hospital, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore., and TanDaniel S WDSWDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore. Electronic address: daniel.tan.s.w@singhealth.com.sg..
• Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
• Lung Cancer. 2020 Jan 1; 139: 207-215.

ObjectivesThere is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients.Materials And MethodsWe identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted.ResultsA total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 % had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time.ConclusionsThis study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.Copyright © 2019. Published by Elsevier B.V.

42 keywords...

hide…