Abstract
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.
Highlights
IntroductionAside from the high incidence, lung cancer leads the list in terms of mortality, with the highest number of cancer-related deaths attributed to this tumor type
Lung cancer is the most common neoplasia worldwide
Small cell lung carcinoma (SCLC) appears to have the strongest correlation with smoking status compared with other histological subtypes [4, 5]
Summary
Aside from the high incidence, lung cancer leads the list in terms of mortality, with the highest number of cancer-related deaths attributed to this tumor type In this sense, lung cancer accounts for the lowest 5-year survival rate among other prevalent neoplasms, and represents a significant healthcare burden worldwide [1, 2]. Cigarette smoking is the best characterized lung cancer risk factor, and it is associated with a 19-fold increase in the risk of developing the disease, especially in women [3]. It is responsible for 80–90% of lung cancer cases. Environmental tobacco smoke exposure, ionizing radiation, radon gas, inherited genetic susceptibility and oncogenic viruses are risk factors that have been implicated in the development of non-small cell lung carcinoma (NSCLC), these associations have not been fully elucidated in SCLC [1, 7, 10]
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