Cardona Andrés F, Rojas Leonardo, Zatarain-Barrón Zyanya Lucia, Ruiz-Patiño Alejandro, Ricaurte Luisa, Corrales Luis, Martín Claudio, Freitas Helano, Cordeiro de Lima Vladmir Cláudio, Rodriguez July, Avila Jenny, Bravo Melissa, Archila Pilar, Carranza Hernán, Vargas Carlos, Otero Jorge, Barrón Feliciano, Karachaliou Niki, Rosell Rafael, Arrieta Oscar
Clinical and Translational Oncology Group, Clinica del Country, Bogotá, Colombia.
Foundation for Clinical and Applied Cancer Research, Bogotá, Colombia.
Front Oncol. 2019 Apr 17;9:254. doi: 10.3389/fonc.2019.00254. eCollection 2019.
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. To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers ( = 10) and never/ever-smokers ( = 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. Median age was 63 years (46-81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases ( = 0.04) and were older ( = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were (80%), (40%), (30%), and (30%). Smoker patients had more (80%, = 0.04), (30%, = 0.05), and (30%, = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers ( = 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]; = 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. 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 , and mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.
肺癌是一种异质性疾病。已知其临床表现和预后会因多种因素而有所不同，如基因和人口统计学特征等。小细胞肺癌在从不吸烟者中的发病率正在上升。然而，与有吸烟史的患者相比，这一人群中的疾病表型有所不同。为了进一步研究这一患者亚组的临床和基因特征，一组小细胞肺癌患者被分为吸烟者（n = 10）和从不/曾经吸烟者（n = 10）。使用全面的二代测序分析获得了体细胞突变谱。采用Kaplan-Meier方法和Cox比例模型比较临床结局。中位年龄为63岁（46 - 81岁），40%为男性，90%患有广泛性疾病。与非吸烟患者相比，吸烟患者有更多的脑转移（P = 0.04）且年龄更大（P = 0.03）。对于从不/曾经吸烟者，主要的基因突变有RB1（80%）、TP53（40%）、NOTCH1（30%）和MYC（30%）。吸烟患者有更多的RB1（80%，P = 0.04）、NOTCH1（30%，P = 0.05）和MYC（30%，P = 0.05）突变。依托泊苷加顺铂/卡铂一线治疗的缓解率在吸烟者中为50%，在从不/曾经吸烟者中为90%（P = 0.141）。从不吸烟者的中位总生存期显著长于吸烟者（29.1个月[23.5 - 34.6]对17.3个月[4.8 - 29.7]；P = 0.0054）。从不/曾经吸烟史（HR 0.543，95% CI 0.41 - 0.80）、局限期疾病（HR 0.56，95% CI 0.40 - 0.91）和对一线铂类化疗的反应（HR 0.63，95% CI 0.60 - 0.92）与良好预后独立相关。我们的数据支持，与吸烟患者相比，患有小细胞肺癌的从不/曾经吸烟者预后更好。此外，患有小细胞肺癌的从不/曾经吸烟史患者与吸烟者相比有不同的突变谱，包括RB1、TP53和MYC突变的高频率。需要进一步研究来评估这种差异突变谱是否是疾病发病不同病理机制的结果。
