Yin Zhenzhen, You Jinqiang, Wang Youyou, Zhao Jinlin, Jiang Shengpeng, Zhang Ximei, Wang Peiguo, Tao Zhen, Wang Xin, Yuan Zhiyong
Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China,
Onco Targets Ther. 2019 Feb 15;12:1259-1268. doi: 10.2147/OTT.S181067. eCollection 2019.
To determine the efficacy and late toxicities of moderate (2.5-4 Gy) hypofractionated radiotherapy (H-RT) in localized prostate cancer, a meta-analysis of published randomized clinical trials comparing moderate H-RT with conventional fractionated RT (C-RT) was performed.
Systematic search on published randomized clinical trials in English according to Cochrane review guidelines in databases of Pubmed, Embase, Cochrane, web of science, and Wiley Online Library was carried out. Outcomes of interests were biochemical and clinical disease failure (BCDF), biochemical failure (BF), overall survival (OS), and late toxicities.
Seven of the 365 studies fulfilled inclusion criteria with 8,156 participants. Compared with C-RT, moderate H-RT showed a lower BF rate (risk ratio [RR] =0.80, 95% CI: 0.68-0.95, =0.009), while did not improve OS (RR =0.68, 95% CI: 0.78-1.02, =0.10). There was no significant difference in BCDF rates between H-RT and C-RT (RR =0.92, 95% CI: 0.82-1.02, =0.12). The H-RT was deeply grouped into dose-escalated H-RT (with a higher biologically effective dose [BED] than C-RT) and no dose-escalated H-RT; dose-escalated H-RT significantly decreased BCDF rate compared with C-RT (RR =0.84, 95% CI: 0.73-0.96, =0.01). Regarding late toxicities, there is no significant difference in late gastrointestinal (GI; RR =0.97, 95% CI: 0.71-1.33, =0.85) and genitourinary (GU) toxicities (RR =1.04, 95% CI: 0.87-1.24, =0.69). When subgrouped into dose-escalated H-RT (with a higher BED compared with C-RT) and no dose-escalated H-RT, dose-escalated H-RT increased GI toxicity (RR =1.62, 95% CI: 1.26-2.09, =0.0002) and GU toxicity (RR =1.28, 95% CI: 1.05-1.55, =0.01), while no dose-escalated H-RT significantly lowered GI toxicity (RR =0.81, 95% CI: 0.70-0.94, =0.005) and placed no influence on GU toxicity (RR =1.02, 95% CI: 0.88-1.20, =0.77).
This meta-analysis provides reliable evidence that moderate H-RT decreases BF rate, while does not improve OS. Compared with C-RT, H-RT with an increase in BED improved BCDF rates significantly, and accordingly, an increase in BED will result in elevated late GI and GU toxicities.
为了确定中度（2.5 - 4 Gy）超分割放疗（H-RT）治疗局限性前列腺癌的疗效和晚期毒性，我们对已发表的比较中度H-RT与传统分割放疗（C-RT）的随机临床试验进行了荟萃分析。
根据Cochrane综述指南，在PubMed、Embase、Cochrane、科学网和Wiley Online Library数据库中对已发表的英文随机临床试验进行系统检索。感兴趣的结局指标为生化和临床疾病失败（BCDF）、生化失败（BF）、总生存期（OS）和晚期毒性。
365项研究中有7项符合纳入标准，共8156名参与者。与C-RT相比，中度H-RT的BF率较低（风险比[RR]=0.80，95%置信区间：0.68 - 0.95，P = 0.009），但未改善OS（RR = 0.68，95%置信区间：0.78 - 1.02，P = 0.10）。H-RT和C-RT的BCDF率无显著差异（RR = 0.92，95%置信区间：0.82 - 1.02，P = 0.12）。H-RT进一步分为剂量递增的H-RT（生物等效剂量[BED]高于C-RT）和未剂量递增的H-RT；与C-RT相比，剂量递增的H-RT显著降低了BCDF率（RR = 0.84，95%置信区间：0.73 - 0.96，P = 0.01）。关于晚期毒性，晚期胃肠道（GI；RR = 0.97，95%置信区间：0.71 - 1.33，P = 0.85）和泌尿生殖系统（GU）毒性无显著差异（RR = 1.04，95%置信区间：0.87 - 1.24，P = 0.69）。当分为剂量递增的H-RT（与C-RT相比BED更高）和未剂量递增的H-RT时，剂量递增的H-RT增加了GI毒性（RR = 1.62，95%置信区间：1.26 - 2.09，P = 0.0002）和GU毒性（RR = 1.28，95%置信区间：1.05 - 1.55，P = 0.01），而未剂量递增的H-RT显著降低了GI毒性（RR = 0.81，95%置信区间：0.70 - 0.94，P = 0.005）且对GU毒性无影响（RR = 1.02，95%置信区间：0.88 - 1.20，P = 0.77）。
这项荟萃分析提供了可靠的证据，表明中度H-RT可降低BF率，但不能改善OS。与C-RT相比，BED增加的H-RT显著提高了BCDF率，因此，BED增加会导致晚期GI和GU毒性升高。
