Jon Zugazagoitia1, Daniel Rueda2, Nuria Carrizo2, Ana Belen Enguita3, David Gómez-Sánchez2, Asunción Díaz-Serrano4, Elisabeth Jiménez4, Antonio Mérida4, Rosa Calero5, Ricardo Lujan6, Eduardo De Miguel6, Pablo Gámez7, Vicente Díaz-Hellín7, Juan Antonio Nuñez4, Lara Iglesias4, Irene Ferrer8, Luis Paz-Ares9, Santiago Ponce-Aix10. 1. Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Electronic address: jonzuga@gmail.com. 2. Biochemistry Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain. 3. Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 4. Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain. 5. Radiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Pulmonology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 7. Department of Thoracic Surgery, Hospital Universitario 12 de Octubre, Madrid, Spain. 8. Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. 9. Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain; Complutense University, Madrid, Spain. 10. Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Abstract
INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs. RESULTS: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials. CONCLUSION: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.
INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs. RESULTS: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials. CONCLUSION: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.
Authors: Els Van Valckenborgh; Aline Hébrant; Aline Antoniou; Wannes Van Hoof; Johan Van Bussel; Patrick Pauwels; Roberto Salgado; Waltruda Van Doren; Anouk Waeytens; Marc Van den Bulcke Journal: Arch Public Health Date: 2018-09-06