Radiotherapy Department, University Hospital S'Anna, Ferrara, Italy.
Cancer Treat Rev. 2010 Nov;36(7):539-49. doi: 10.1016/j.ctrv.2010.03.002. Epub 2010 Mar 23.
There is clear evidence from two systematic reviews that radiotherapy (RT) reduces the risk of local recurrence in patients with resectable rectal cancer, though the data on survival are still equivocal.
To assess the effects of chemotherapy combined concomitantly with radiotherapy (CRT) on the increase of overall survival, and on the prevention of local recurrence and distant metastases.
Computerized bibliographic searches of MEDLINE and CANCERLIT (1970-2008) were supplemented with hand searches of reference lists.
Studies were included if they were randomized controlled trials (RCTs) comparing preoperative or postoperative CRT to preoperative or postoperative RT alone, and if they included patients with resectable, histologically-proven, rectal adenocarcinoma without metastases. Thirteen RCTs, seven of preoperative CRT vs. preoperative RT (2787 patients), four of postoperative CRT vs. postoperative RT (726 patients) and two of postoperative CRT vs. preoperative RT (1400 patients), were analyzed.
Data on population, intervention, and outcomes were extracted from each RCT, in accordance with the intention-to-treat method, by three independent observers, and combined using the DerSimonian method and Laird method.
Preoperative CRT compared to preoperative RT alone significantly reduces the 5-year local recurrence rate (RR 1.05; 95%CI 1.01-1.10). No increase was observed in 5-year overall survival rate (RR 0.94; 95%CI 0.94-1.09), and in the occurrence of distant metastases (RR 0.97; 95%CI 0.93-1.02). Instead, postoperative CRT did not reduce local recurrence (RR 0.96; 95%CI 0.80-1.16), distant metastases (RR 1.11; 95%CI 0.94-1.31) and overall mortality (RR 1.09; 95%CI 0.83-1.41). By pooling data on postoperative CRT vs. preoperative RT a significant reduction of local recurrence was found for the preoperative approach (RR 0.93; 95%CI 0.90-0.96), though no difference was found in distant metastases rates and overall survival. Finally, the risk of mortality related to toxic events was significantly higher when adding chemotherapy to radiotherapy (RR 2.86; 95%CI 0.99-8.26).
In patients with resectable rectal cancer, CRT does not increase overall survival, despite the fact that preoperative CRT significantly reduces the risk of the local recurrence. No reduction in the distant metastases rate was found. Toxicity-related mortality is significantly increased by the concomitant approach, emphasizing the need for safer treatment combinations.
有两项系统综述明确表明放疗（RT）可降低可切除直肠癌患者的局部复发风险，但有关生存的数据仍存在争议。
评估化疗联合放疗（CRT）对提高总生存率以及预防局部复发和远处转移的作用。
计算机检索 MEDLINE 和 CANCERLIT（1970-2008 年）并辅以手工检索参考文献。
如果研究是比较术前或术后 CRT 与单纯术前或术后 RT 的随机对照试验（RCT），且纳入了可切除、组织学证实的无转移直肠腺癌患者，则将这些研究纳入。共分析了 13 项 RCT，其中 7 项为术前 CRT 对比术前 RT（2787 例患者），4 项为术后 CRT 对比术后 RT（726 例患者），2 项为术后 CRT 对比术前 RT（1400 例患者）。
由 3 位独立观察者按照意向治疗原则，从每项 RCT 中提取人群、干预和结局数据，并用 DerSimonian 法和 Laird 法进行合并。
与单纯术前 RT 相比，术前 CRT 显著降低了 5 年局部复发率（RR 1.05；95%CI 1.01-1.10）。5 年总生存率（RR 0.94；95%CI 0.94-1.09）和远处转移发生率（RR 0.97；95%CI 0.93-1.02）均无显著增加。相反，术后 CRT 并未降低局部复发率（RR 0.96；95%CI 0.80-1.16）、远处转移率（RR 1.11；95%CI 0.94-1.31）或总死亡率（RR 1.09；95%CI 0.83-1.41）。对术后 CRT 对比术前 RT 进行汇总数据分析，发现术前 CRT 可显著降低局部复发风险（RR 0.93；95%CI 0.90-0.96），但远处转移率和总生存率无差异。最后，与单纯放疗相比，放化疗联合治疗时与毒性相关的死亡风险显著增加（RR 2.86；95%CI 0.99-8.26）。
在可切除直肠癌患者中，尽管术前 CRT 可显著降低局部复发风险，但 CRT 并未提高总生存率。也未发现远处转移率降低。联合治疗的毒性相关死亡率显著增加，这强调了需要更安全的治疗组合。
