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

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dc.contributor.authorCorrales, Luis
dc.contributor.authorMartín, Claudio
dc.contributor.authorFreitas, Helano
dc.contributor.authorCordeiro de Lima, Vladmir Cláudio
dc.contributor.authorRodríguez Ariza, July Katherine
dc.contributor.authorÁvila Coy, Jenny Mireya
dc.contributor.authorBravo, Melissa
dc.contributor.authorArchila, Pilar
dc.contributor.authorCarranza Isaza, Hernán
dc.contributor.authorVargas Báez, Carlos Alberto
dc.contributor.authorOtero, Jorge
dc.contributor.authorBarrón, Feliciano
dc.contributor.authorKarachaliou, Niki
dc.contributor.authorRosell, Rafael
dc.contributor.authorCardona-Mendoza, Andrés Felipe
dc.contributor.authorRojas Puentes, Leonardo
dc.contributor.authorZatarain Barrón, Zyanya Lucia
dc.contributor.authorRuíz-Patiño, Alejandro
dc.contributor.authorRicaurte, Luisa
dc.contributor.authorArrieta, Oscar
dc.contributor.orcidCardona-Mendoza, Andrés Felipe [0000-0002-6697-5471]
dc.contributor.orcidCarranza Isaza, Hernán [0000-0002-3593-7405]
dc.contributor.orcidVargas Báez, Carlos Alberto [0000-0002-6076-8260]
dc.contributor.orcidRojas Puentes, Leonardo [0000-0002-7865-5424]
dc.contributor.orcidRuíz-Patiño, Alejandro [0000-0003-1274-9273]
dc.contributor.orcidRodríguez Ariza, July Katherine [0000-0003-1168-595X]
dc.contributor.orcidÁvila Coy, Jenny Mireya [0000-0002-2968-7980]
dc.date.accessioned2019-09-16T18:01:13Z
dc.date.available2019-09-16T18:01:13Z
dc.date.issued2019
dc.description.abstractenglishObjectives: 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.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3389/fonc.2019.00254
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn2234-943X
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/1712
dc.language.isoeng
dc.publisherFrontiers Mediaspa
dc.publisher.journalFrontiers in Oncologyspa
dc.relation.ispartofseriesFrontiers in Oncology, 2234-943X, Vol. 9, Nro, 254, 2019 p. 1-10spa
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fonc.2019.00254/full
dc.rightsAttribution 4.0 International*
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf104
dc.rights.creativecommons2019
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.decsNeoplasias pulmonaresspa
dc.subject.decsVariación genéticaspa
dc.subject.decsCaracterísticas de la poblaciónspa
dc.subject.keywordsSmall-cell lung cancerspa
dc.subject.keywordsGenome profilespa
dc.subject.keywordsNext-generation sequencingspa
dc.titleMultigene mutation profiling and clinical characteristics of small-cell lung cancer in never-smokers vs. seavy smokers (Geno1.3-CLICaP)spa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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