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 differ...

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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
Tipo de recurso:
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
Rights
License
Attribution 4.0 International
Description
Summary: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.