Su Vincent Yi-Fong, Liu Chia-Jen, Chen Yuh-Min, Chou Teh-Ying, Chen Tzeng-Ji, Yen Sang-Hue, Chiou Tzeon-Jye, Liu Jin-Hwang, Hu Yu-Wen
Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Target Oncol. 2017 Apr;12(2):219-227. doi: 10.1007/s11523-016-0459-0.
Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available.
Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population.
We identified 52,639 patients with lung cancer and excluded 34,267 patients who had expired within one year after diagnosis. The study included 18,372 subjects with a median follow-up period of 2.24 years. 590 patients developed an SPM. The overall cancer risk was significantly increased (SIR 1.33, 95% confidence interval [CI]: 1.22-1.44, p < 0.001), and there was a significant increase in the incidences of head and neck (SIR 1.60, 95% CI 1.21-2.07, p = 0.001), bone and soft tissue (SIR 2.65, 95% CI 1.27-4.87, p = 0.011), genitourinary (SIR 1.50, 95% CI 1.27-1.76, p < 0.001), and thyroid (SIR 3.85, 95% CI 2.28-6.08, p < 0.001) cancers. Importantly, after multivariate adjustment, the use of tyrosine kinase inhibitors (TKIs) statistically significantly reduced SPM incidence (HR, 0.41; 95% CI, 0.21-0.79; p = 0.008).
Our study indicates that lung cancer may be a risk factor for SPM. TKI use was associated with a significantly lower risk of SPM development. However, because patients with epidermal growth factor receptor mutant lung adenocarcinoma (associated with non-smokers) tend to receive TKI treatment, they might have fewer smoking-related SPMs.
目前，尚无大型研究探讨接受不同治疗的肺癌患者与第二原发性恶性肿瘤（SPM）之间的关系。
利用台湾全民健康保险研究数据库，我们开展了一项基于人群的队列研究。纳入1997年至2005年间新诊断肺癌的患者，并随访至2011年12月31日。研究终点为SPM的发生。计算癌症的标准化发病率（SIR），以比较研究队列与一般人群的癌症发病率。
我们确定了52639例肺癌患者，并排除了34267例诊断后一年内死亡的患者。该研究纳入了18372名受试者，中位随访期为2.24年。590例患者发生了SPM。总体癌症风险显著增加（SIR 1.33，95%置信区间[CI]：1.22 - 1.44，p < 0.001），头颈部（SIR 1.60，95% CI 1.21 - 2.07，p = 0.001）、骨与软组织（SIR 2.65，95% CI 1.27 - 4.87，p = 0.011）、泌尿生殖系统（SIR 1.50，95% CI 1.27 - 1.76，p < 0.001）及甲状腺（SIR 3.85，95% CI 2.28 - 6.08，p < 0.001）癌症的发病率也显著增加。重要的是，经过多变量调整后，使用酪氨酸激酶抑制剂（TKI）在统计学上显著降低了SPM的发病率（HR，0.41；95% CI，0.21 - 0.79；p = 0.008）。
我们的研究表明肺癌可能是SPM的一个危险因素。使用TKI与SPM发生风险显著降低相关。然而，由于表皮生长因子受体突变型肺腺癌患者（与非吸烟者相关）倾向于接受TKI治疗，他们可能有较少的与吸烟相关的SPM。
