Characterization of never-smoking and its association with clinical outcomes in Chinese patients with small-cell lung cancer
Introduction
Lung cancer is the most common incident cancer and the leading cause of cancer-related death worldwide [1]. Tobacco smoking has been regarded as the most important risk factor for lung cancer. The relationship between smoking and lung cancer is one of the most thoroughly investigated issues in biomedical research, and evidence has been set up since middle of the 20th century to indicate that smoking is the predominant factor for lung cancer [2], [3]. Although lung cancer is commonly viewed as a smoker’s disease, approximately 10%-15% patients worldwide are never-smokers [4], [5]. The prevalence is different geographically and histologically. The proportion of never-smokers in Asian patients is higher than in non-Asian patients [4]. Several studies have shown that small-cell lung cancer (SCLC) is highly associated with smoking among the four major lung cancer histological types [6], [7].
Globally, SCLC accounts for 13%-15% of all lung cancers [8]. SCLC is known to be clinically different from non-small cell lung cancer (NSCLC) with a short doubling time, a high growth fraction, and early development of widespread metastases, which contribute to the extremely poor prognosis [8]. Tobacco exposure is strongly associated with the development of SCLC, with only 2% to 5% patients being never-smokers worldwide [9]. With the implementation of strategies for smoking cessation, the incidence of SCLC has been declined in the past decades [10]. It is now well recognized that never-smokers with NSCLC tend to have better survival than smokers [11]. Unlike NSCLC, due to the limited number of cases, there are few prospective and large-scale clinical studies to investigate both the predictive and prognostic relevance of smoking status in patients with SCLC [9], [12], [13], and no study was carried out in Chinese population. Therefore, we performed this study to investigate the proportion of never-smokers with SCLC in Chinese population and the effect of smoking history on clinical outcomes in these patients.
In addition, brain metastases remain the common issue in patients with SCLC. Intracranial metastases will eventually occur in more than 50% of patients with SCLC during the course of their disease [14].Previous results from randomized controlled trials and meta-analysis have shown that prophylactic cranial irradiation (PCI) could decrease the incidence of brain metastases and bring survival benefit in SCLC populations [15], [16]. However, recently a phase III trail drew a different conclusion that PCI did not result in longer overall survival than observation in extensive-stage (ES)-SCLC [17]. Hence, we also evaluated the effect of PCI in the treatment of SCLC patients, especially patients with ES-SCLC in real world.
Section snippets
Patients inclusion
We performed a retrospective study of 389 patients who were histologically diagnosed with SCLC and treated at the Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University between January 2014 and October 2015. Patients received surgical resection or with missing data on follow-up were excluded in this study. Finally, a total of 303 patients were enrolled. For all the 303 patients, baseline characteristics, comorbidities, treatments and clinical outcomes were extracted from
Patient characteristics
A total of 303 patients with histologically or cytologically diagnosed SCLC and treated at Shanghai Pulmonary Hospital between January 2014 and October 2015 were enrolled in this study. Of them, 69 (22.8%) patients were never-smokers and 234 (77.2%) cases had a positive history of smoking. Among the 234 smokers, the median smoking amount was 40 pack-years (one pack-year = 20 cigarettes per day during 1 year). The median age at diagnose of smokers was 63 years compared with 60 years of
Discussion
To our knowledge, this is arguably the first retrospective and large-scale study to investigate the proportion of never-smokers with SCLC in Chinese population and whether never-smoking status is a significant prognostic factor in patients with SCLC. In this study, our results suggested that in all populations, never-smokers with SCLC show statistically significant better PFS and OS than smokers, and a positive smoking history is an independent poor prognostic factor for PFS in SCLC patients by
Conflict of interest
The authors declare no conflict of interest. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant support for this work that could have influenced its outcomes.
Authors’ contributions
Xiaozhen Liu, Tao Jiang, Chunxia Su and Caicun Zhou designed this study. Xiaozhen Liu, Tao Jiang, Wei Li, Xuefei Li, Chao Zhao, Jinpeng Shi, Sha Zhao, Yijun Jia, Meng Qiao, Limin Zhang, Jiawei Luo, Guanghui Gao, Fei Zhou, Fengying Wu, Xiaoxia Chen, and Yayi He collected the clinical data. Xiaozhen Liu, Tao Jiang, and Wei Li performed the statistical analyses. Xiaozhen Liu, Tao Jiang, Chunxia Su, Shengxiang Ren, and Caicun Zhou drafted the manuscript. Chunxia Su, Shengxiang Ren, and Caicun Zhou
Acknowledgement
This study was sponsored by grants from the National Natural Science Foundation of China (No. 81672286, 81401890 and 81772467), “Shuguang Program” supported by Shanghai Education Development Foundation andShanghai Municipal Education Commission (No. 16SG18), the Chronic Diseases Program of Shanghai Shen Kang Pharmaceutical Development Co. Ltd (No. SHDC 12015314), Shanghai Committee of Science and Technology, China (No. 134119b1001) and the Outstanding Young Doctor Program of the Shanghai
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The first three authors contributed equally to this work.