FSRT联合替莫唑胺治疗大体积脑转移瘤的对照研究

Case-control study of fractionated stereotactic radiotherapy combined with temozolomide for largebrain metastases

目的 回顾比较应用分次立体定向放疗（FSRT）±替莫唑胺治疗大体积脑转移瘤患者疗效及安全性。方法 2009—2017年间共84例脑转移瘤患者（体积≥ 6 cm3）纳入分析,其中同步放化疗组（CRT组） 与单纯放疗组（RT组）各42例。放疗方案为52.0~52.5 Gy分13~15次,3.5~4.0 Gy/次。疗中复查脑MRI,如病灶体积明显缩小则行疗中缩野。疗后2~3个月评估疗效。主要研究终点为LRFS,次要研究终点为IPFS、PFS、OS、BMSS及不良反应。采用Kaplan-Meier法计算生存率并Logrank法检验和单因素预后分析。结果 CRT、RT组的中位GTV体积分别为16.9、15.7 cm3,疗中缩野率分别为75%、34%（P=0.000）。CRT、RT组LC率分别为100%、98%。中位随访时间为16.1个月（2.1~105.7个月）,CRT组LRFS、IPFS、PFS、OS、BMSS均显著优于RT组（P=0.040、0.022、0.045、0.013、0.006）。1—2级消化道不良反应CRT组高于RT组（33%∶26%,P=0.006）,两组均无4— 5级不良反应发生。结论 FSRT联合替莫唑胺进一步提高了大体积脑转移瘤患者的LC率及生存率且未增加严重不良反应。

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy （FSRT） combined with and without temozolomide in the treatment of large brain metastases. Methods Between 2009 and 2017,84 patients with large brain metastases （tumor size ≥ 6 cm3） were recruited and assigned into the CRT group （concurrent TMZ and FSRT,n=42） and RT group （FSRT alone, n=42）.The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions. Patients were reexamined by magnetic resonance imaging （MRI） during treatment. The radiation field would be shrunk if the gross target volume （GTV） was reduced. The clinical efficacy was evaluated at postoperative 2 to 3 months. The primary end-point event was local recurrence-free survival （LRFS） and the secondary end-point events included intracranial progression-free survival （IPFS）, progression-free survival （PFS）, overall survival （OS）, brain metastasis-specific survival （BMSS） and adverse events. The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis. Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75% of the lesions in the CRT group were reduced compared with 34% in the RT group （P=0.000）.The local control （LC） rate in the CRT and RT groups was 100% and 98%.The median follow-up time was 16.1 months （range,2.1-105.7 months）.In the CRT group, the LRFS （P=0.040）,IPFS （P=0.022）,PFS （P=0.045）,OS （P=0.013） and BMSS （P=0.006） were significantly better than those in the RT group, respectively. In the CRT group, the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33%, significantly higher compared with 26% in the RT group （P=0.006）.No grade IV-V adverse events occurred in both groups. Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.