Portal de investigación
Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)
Fecha de publicación:
Autores organización
Autores
- Zatarain-Barrón, ZL
- Ruiz-Patiño, A
- Ricaurte, L
- Corrales, L
- Martín, C
- Freitas, H
- de Lima, VCC
- Rodriguez, J
- Avila, J
- Bravo, M
- Archila, P
- Carranza, H
- Vargas, C
- Otero, J
- Barrón, F
- Karachaliou, N
- Rosell, R
- Arrieta, O
- CLICaP
Grupos de investigación
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.
Datos de la publicación
- ISSN/ISSNe:
- 2234-943X, 2234-943X
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 31058075
Frontiers In Oncology Frontiers Media S.A.
Citas Recibidas en Web of Science: 16
Documentos
- No hay documentos
Filiaciones
Keywords
- small-cell lung cancer; genome profile; next-generation sequencing; cancer in never-smokers; TP53; RB1; CYLD