Aaron C Tan1, Gillianne G Y Lai1, Gek San Tan2, Shou Yu Poon1, Brett Doble3, Tse Hui Lim2, Zaw Win Aung1, Angela Takano4, Wan Ling Tan1, Mei-Kim Ang5, Bien Soo Tan6, Anantham Devanand7, Chow Wei Too6, Apoorva Gogna6, Boon-Hean Ong8, Tina P T Koh1, Ravindran Kanesvaran5, Quan Sing Ng1, Amit Jain5, Tanujaa Rajasekaran5, Alvin S T Lim4, Wan Teck Lim5, Chee Keong Toh5, Eng-Huat Tan5, Tony Kiat Hon Lim4, Daniel S W Tan9. 1. Division of Medical Oncology, National Cancer Centre Singapore, Singapore. 2. Division of Pathology, Singapore General Hospital, Singapore. 3. Duke-NUS Medical School, National University of Singapore, Singapore. 4. Division of Pathology, Singapore General Hospital, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore. 5. Division of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore. 6. Duke-NUS Medical School, National University of Singapore, Singapore; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore. 7. Duke-NUS Medical School, National University of Singapore, Singapore; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore. 8. Duke-NUS Medical School, National University of Singapore, Singapore; Department of Cardiothoracic Surgery, National Heart Centre Singapore, Singapore. 9. Division 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.
Abstract
OBJECTIVES: There 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 METHODS: We 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. RESULTS: A 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. CONCLUSIONS: This 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.
OBJECTIVES: There 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 METHODS: We 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. RESULTS: A 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. CONCLUSIONS: This 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.
Authors: Charu Aggarwal; Christian D Rolfo; Geoffrey R Oxnard; Jhanelle E Gray; Lynette M Sholl; David R Gandara Journal: Nat Rev Clin Oncol Date: 2020-09-11 Impact factor: 66.675
Authors: Anna Michelotti; Marco de Scordilli; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208
Authors: Mariano Provencio; Manuel Cobo; Delvys Rodriguez-Abreu; Virginia Calvo; Enric Carcereny; Alexandra Cantero; Reyes Bernabé; Gretel Benitez; Rafael López Castro; Bartomeu Massutí; Edel Del Barco; Rosario García Campelo; Maria Guirado; Carlos Camps; Ana Laura Ortega; Jose Luis González Larriba; Alfredo Sánchez; Joaquín Casal; M Angeles Sala; Oscar Juan-Vidal; Joaquim Bosch-Barrera; Juana Oramas; Manuel Dómine; Jose Manuel Trigo; Remei Blanco; Julia Calzas; Idoia Morilla; Airam Padilla; Joao Pimentao; Pedro A Sousa; Maria Torrente Journal: BMC Cancer Date: 2022-07-05 Impact factor: 4.638
Authors: Amanda O L Seet; Aaron C Tan; Tira J Tan; Matthew C H Ng; David W M Tai; Justina Y C Lam; Gek San Tan; Apoorva Gogna; Chow Wei Too; Bien Soo Tan; Angela Takano; Alvin Lim; Tse Hui Lim; Soon Thye Lim; Rebecca Alexandra Dent; Mei Kim Ang; Yoon-Sim Yap; Iain B H Tan; Su Pin Choo; Chee Keong Toh; Elaine H Lim; Mohamad Farid; Anders Jacobsen Skanderup; N Gopalakrishna Iyer; Wan Teck Lim; Eng Huat Tan; Tony K H Lim; Daniel S W Tan Journal: JCO Precis Oncol Date: 2021-05-18
Authors: Lin Niu; Chunyan Dang; Lin Li; Na Guo; Ying Xu; Xiangling Li; Qian Xu; Luyang Cheng; Li Zhang; Lei Liu Journal: Oncol Lett Date: 2021-06-07 Impact factor: 2.967