This retrospective study analyzed the survival of 2647 patients with lung cancer brain metastasis. The results showed that smoking affected the overall survival rate of lung cancer patients with brain metastasis. However, smoking cessation was not associated with higher survival than current smoking.
Contrary to our study, previous studies did not find an association between smoking and lung cancer brain metastasis. Kim et al. analyzed 313 nonsmall-cell lung cancer (NSCLC) patients with brain metastasis, and univariate analysis showed that smoking affected overall survival; however, there was no difference in the overall survival in the multivariate analysis[23]. In another study of patients with nonsmall cell lung cancer, only non-smokers in stage I had a significant survival advantage over smokers, and smokers who quit smoking in stage II or III disease had no significant reduction in the risk of death[24]. But our study found that smoking increased the risk of death in lung cancer patients with brain metastases. This difference in part may be explained by our large size simple to make the results more precise.
Previous studies have shown that smoking increases the risk of brain metastasis[25][17]. Nicotine promotes brain metastasis by polarizing microglia and inhibiting innate immune function[25–26]. Also, smoking affects the effect of chemotherapy in advanced patients[28], and a significant difference in tumor biology is the higher EGFR mutation rate of never smokers, which may explain the better prognosis of never smokers after treatment for EGFR gene[27]. These may be the reasons for the difference in prognosis between never smokers and patients with a history of smoking. The current study also suggests that there is a dose-dependent relationship between smoking and the survival of lung cancer patients[29–30]. In contrast to these results, our study showed that compared with light to moderate smokers, the overall survival of the heavy smoker(> 40 pack-years)was not significantly decreased.
Smoking is a main prognostic factor of lung cancer. Evidence has shown that smokers who quit smoking for more than one year had higher survival than current smokers. Zhou et al. suggested that overall survival increased with the increase of smoking cessation time among early-stage NSCLC patients. Nia et al. concluded that early-stage NSCLC patients who quit smoking were significantly less mortality than current smokers[32]. In a study of 4200 smokers in the National Comprehensive Cancer Network NSCLC cohort, Only young patients with stage IV disease who quitting smoking > 12 months before diagnosis can gained survival benefits[33]. However, we did not find the benefits of quitting smoking for lung cancer brain metastasis patients. Our study suggested that long-term continuous quitting smoking may have the trend of increasing survival. Paradoxically, when lung cancer patients have brain metastasis, the median survival time is short, so they may not get the benefits of long-term quitting smoking. However, cumulative smoking cessation time before the diagnosis of brain metastasis may be essential to improve survival.
This study has several limitations. First, the patient's smoking history and smoking cessation are from electronic medical records, which will deviate from the patient's self-report. Studies have shown that up to 50% of cancer patients' self-reported tobacco use may be inaccurate[34]. Second, our information collection on tobacco intake is based on cigarettes, ignoring alternative products such as tobacco and nicotine. Third, although the large sample size is a strength of our study, this is a study of a single agency. Therefore, the generalizability of the results to other populations is questionable.
In conclusion, unlike previous studies, this study is not limited to lung cancer patients with non-metastatic. Although the survival time of patients with metastatic lung cancer is short, our results still show the harm of smoking to patients with brain metastasis of lung cancer. The survival rate of patients with smoking is lower than that of patients without smoking. We failed to find the relationship between quitting s
moking and survival.