Multigene mutation profiling and clinical characteristics of small-cell lung cancer in never-smokers vs. Heavy smokers (GENO1.3-clicap)
Por:
Cardona A.F., Rojas L., Zatarain-Barrón Z.L., Ruiz-Patiño A., Ricaurte L., Corrales L., Martín C., Freitas H., De Lima V.C.C., Rodriguez J., Avila J., Bravo M., Archila P., Carranza H., Vargas C., Otero J., Barrón F., Karachaliou N., Rosell R., Arrieta O.
Publicada:
1 ene 2019
Resumen:
Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46-81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5-34.6] vs. 17.3 months [4.8-29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41-0.80), limited-stage disease (HR 0.56, 95% CI 0.40-0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60-0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset. Copyright © 2019 Cardona, Rojas, Zatarain-Barrón, Ruiz-Patiño, Ricaurte, Corrales, Martín, Freitas, Cordeiro de Lima, Rodriguez, Avila, Bravo, Archila, Carranza, Vargas, Otero, Barrón, Karachaliou, Rosell and Arrieta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Filiaciones:
Cardona A.F.:
Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia
Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia
Rojas L.:
Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia
Zatarain-Barrón Z.L.:
Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico
Ruiz-Patiño A.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Ricaurte L.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Corrales L.:
Department of Oncology, Hospital San Juan de Dios, San José, Costa Rica
Martín C.:
Medical Oncology Group, Fleming Institute, Buenos Aires, Argentina
Freitas H.:
Department of Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
De Lima V.C.C.:
Department of Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
Rodriguez J.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Avila J.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Bravo M.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Archila P.:
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Carranza H.:
Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia
Vargas C.:
Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia
Otero J.:
Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia
Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia
Barrón F.:
Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico
Karachaliou N.:
Instituto Oncológico Dr. Rosell (IOR), Quirón-Dexeus University Institute, Barcelona, Spain
Instituto Oncológico Dr. Rosell (IOR), Sagrat Cor Hospital, Barcelona, Spain
Rosell R.:
Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Barcelona, Spain
Arrieta O.:
Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico
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