Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Frontiers in Oncology

Niki Karachaliou¹  Rafael Rosell²  Leonardo Rojas³  Helano Freitas⁵  Vladmir Cláudio Cordeiro de Lima⁵  Luis Corrales⁶  Alejandro Ruiz-Patiño⁷  July Rodriguez⁷  Jenny Avila⁷  Luisa Ricaurte⁷  Pilar Archila⁷  Melissa Bravo⁷  Claudio Martín⁹  Carlos Vargas^1,10  Jorge Otero^1,10  Hernán Carranza^1,10  Andrés F. Cardona^1,10  Oscar Arrieta^1,11  Feliciano Barrón^1,11  Zyanya Lucia Zatarain-Barrón^1,11 

[1] 0Instituto Oncológico Dr. Rosell (IOR), Sagrat Cor Hospital, Barcelona, Spain;1Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Barcelona, Spain;Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia;Clinical and Translational Oncology Group, Clinica del Country, Bogotá, Colombia;Department of Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil;Department of Oncology, Hospital San Juan de Dios, San José, Costa Rica;Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia;Instituto Oncológico Dr. Rosell (IOR), Quirón-Dexeus University Institute, Barcelona, Spain;Medical Oncology Group, Fleming Institute, Buenos Aires, Argentina;Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad El Bosque, Bogotá, Colombia;Thoracic Oncology Unit, National Cancer Institute (INCan), Mexico City, Mexico;

关键词: small-cell lung cancer;    genome profile;    next-generation sequencing;    cancer in never-smokers;    TP53;    RB1;   

DOI  :  10.3389/fonc.2019.00254

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown