顺铂辅助化疗方案已经成为可以手术切除的非小细胞肺癌的标准治疗方案。因为其晚期效应是多变的，发表在《Ann Oncol》的一项研究重新分析了国际肺癌辅助治疗试验的远期数据来详细描述辅助化疗的作用。文献阅读：Ann Oncol 2014 Sep 5.

患者和方法

在国际肺癌辅助治疗试验中，1867位患者被随机分配到顺铂辅助化疗组或对照组，随访时间的中位数为7.5年。这些患者中，来自132个诊疗中心的1687位患者愿意报告癌症相关事件的次数。我们应用事件史分析方法来评估辅助化疗对局部复发、远处转移和死亡风险的影响。

Figure 1. Number of events and event sequences in the IALT study — both arms. For example: a total of 202 bDM were observed, 177 as first event, 12 concomitantly with LR, and 13 after LR; among the 177 patients with bDM only, 7 had LR later, 155 died, and 15 were censored; among the 32 patients with both bDM and LR, 31 died and 1 was censored. DM: distant metastasis; LR: local relapse. The numbers in the grey boxes are the number of patients whose follow-up data were censored (c=). Note that only the time to the first metastasis, either brain or non-brain, was available for each patient. Events on the arrows to intersections of event sets (for instance those 12 patients from randomization to LR+bDM) denote simultaneous events; other events occurred sequentially, like those 7 patients having LR after bDM. 

研究结果

辅助化疗对控制局部复发 (HR=0.73; 95% CI: 0.60–0.90; P=0.003)和脑部以外的转移灶 (HR=0.79; 95% CI: 0.66–0.94; P=0.008)非常有效，但是对控制脑转移无效(HR=1.1; 95% CI: 0.82–1.4; P=0.61)。在前5年内对非癌症死亡的影响不明显(HR=1.1; 95% CI: 0.81–1.5; P=0.29)，但是随后非癌症死亡的风险上升(HR=3.6; 95% CI: 2.2–5.9; P<0.001)。然而，8年里，这种有害的效应可能影响到2%左右的患者。

Figure 2. Summary of results (hazard ratios) regarding the chemotherapy (CT) effect a compared to control (Ctrl) and the effect of events on each other, from the three multistate models: (1) the model for death with intermediate recurrences (solid arrows), which also estimated the residual (= remaining after taking into account the effect of chemotherapy on recurrences) effect of chemotherapy on death, before and after five years. (2) The model for local relapse (LR), with non-simultaneous intermediate distant metastases (DM, dotted arrows). (3) The model for brain and non-brain metastasis (bDM, nbDM), with non-simultaneous intermediate local relapse (dashed arrows). Grey-colored HRs are not significantly different from 1 at a 95% level. Black HRs are significantly lower/higher than 1. Significance codes: *** = <0.001, ** = 0.001 to 0.01, * = 0.01 to 0.05 

结论

顺铂辅助化疗可以降低局部复发和非脑转移的风险，从而延长生存期。这种治疗方案在前5年内对死亡率没有任何残余效应，但是此后非癌症死亡风险明显上升。强烈推荐在随机试验中对所有患者进行详细的远期随访，来评估非小细胞肺癌辅助治疗的效果。