Multigene mutation profiling and clinical characteristics of small-cell lung cancer in never-smokers vs. seavy smokers (Geno1.3-CLICaP)

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.

• Autores: Corrales, Luis; Martín, Claudio; Freitas, Helano; Cordeiro de Lima, Vladmir Cláudio; Rodríguez Ariza, July Katherine; Ávila Coy, Jenny Mireya; Bravo, Melissa; Archila, Pilar; Carranza Isaza, Hernán; Vargas Báez, Carlos Alberto; Otero, Jorge; Barrón, Feliciano; Karachaliou, Niki; Rosell, Rafael; Cardona-Mendoza, Andrés Felipe; Rojas Puentes, Leonardo; Zatarain Barrón, Zyanya Lucia; Ruíz-Patiño, Alejandro; Ricaurte, Luisa; Arrieta, Oscar
• Fecha de publicación: 2019
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/1712
• Acceso en línea: http://hdl.handle.net/20.500.12495/1712; https://doi.org/10.3389/fonc.2019.00254
• Palabra clave: Neoplasias pulmonares; Variación genética; Características de la población; Small-cell lung cancer; Genome profile; Next-generation sequencing
• License: Attribution 4.0 International