| Autor: |
Cardona AF; Clinical and Translational Oncology Group, Clinica 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., Rojas L; Clinical and Translational Oncology Group, Clinica del Country, Bogotá, Colombia.; Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia.; Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia., Zatarain-Barrón ZL; Thoracic Oncology Unit, National Cancer Institute (INCan), Mexico 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., Cordeiro de Lima VC; 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, Clinica 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, Clinica 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, Clinica 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), Mexico 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), Mexico City, Mexico. |
| Abstrakt: |
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. |
