Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.
Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.
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DOI：
10.1016/s1470-2045(16)30102-4
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
CHHiP Investigators
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作者：
Dearnaley D;Syndikus I;Mossop H;Khoo V;Birtle A;Bloomfield D;Graham J;Kirkbride P;Logue J;Malik Z;Money-Kyrle J;O'Sullivan JM;Panades M;Parker C;Patterson H;Scrase C;Staffurth J;Stockdale A;Tremlett J;Bidmead M;Mayles H;Naismith O;South C;Gao A;Cruickshank C;Hassan S;Pugh J;Griffin C;Hall E;CHHiP Investigators
前列腺癌可能具有较高的放射分割敏感性，这将使低分割治疗具有治疗优势。我们提出了一项对5年后常规放射治疗和低分割放射治疗进行比较的随机试验的疗效和副作用的预先计划分析。CHHiP是一项随机的3期非劣势试验，招募了患有局限性前列腺癌(pT1b-T3aN0M0)的男性。患者按1：1：1随机分为常规治疗组(74Gy7·4周，共37次)或两种低分割方案之一(60Gy20次，4周；57Gy19次，3·8周)，均采用调强技术。大多数患者接受放射治疗，同时接受3-6个月的新辅助治疗和雄激素抑制。通过计算机生成的随机排列块进行随机分组，按国家癌症综合网络(NCCN)风险组和放射治疗中心进行分层，治疗分配不被掩盖。主要终点是达到生化或临床失败的时间；非劣势的临界危险比(HR)为1.208。分析采用意向治疗。长期随访仍在继续。CHHiP试验注册为国际标准随机对照试验，编号为ISRCTN97182923。2002年10月18日至2011年6月17日，从71个中心招募了3216名男性患者，并随机分配(74Gy组，1065例患者；60Gy组，1074例患者；57Gy组，1077例患者)。中位随访时间62·4个月(IQR 53·9~77·0)。5年生化或临床无失败率分别为88.3%(95%CI 86·0~90·2)、90·6%(88·5~92·3)和85·9%(83·4~88·0)。60Gy值不低于74Gy值(HR0.84[90%CI 0.68-1.03]，PNI=0.0018)，但57Gy值与74Gy值相比不能算非劣值(HR1.20[0.99-1.46]，PNI=0.48)。与常规组相比，低分馏组的长期副作用相似。在使用三种临床医生报告的和患者报告的结果测量方法治疗5年后，副作用的比例或累积发生率没有显著差异。放疗肿瘤学(RTOG)2级及以上肠、膀胱不良事件5年累积发生率分别为13.7%(111次)和9.1%(66次)，11.9%(105次)和11.7%(88次)，11.3%(95次)和6.6%(57次)。没有与治疗相关的死亡报告。20次60Gy超分割放射治疗并不逊色于37次74Gy超分割放射治疗，被推荐为局部前列腺癌外放射治疗的新标准。英国癌症研究所、卫生部和国家健康研究所癌症研究网络。
Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up. CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b–T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923. Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9–77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0–90·2) in the 74 Gy group, 90·6% (88·5–92·3) in the 60 Gy group, and 85·9% (83·4–88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68–1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99–1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported. Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer. Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.