瑞典Umeå大学Anders Widmark研究团队，宣布他们提出了前列腺癌的超低分割放疗与常规分割放疗：低RT-PC随机、非劣效、3期试验的5年结果。该成果于2019年8月2日发表在国际学术期刊《柳叶刀》上。

课题组研究人员报告了Scandinavian低RT-PC三期试验的结果，目的是显示超低分馏与常规分馏的非劣效性。在瑞典和丹麦的12个中心进行的这项开放标签、随机、3期非劣效性试验中，研究组招募了年龄在75岁以下、患有中度至高风险前列腺癌的男性，世卫组织将他们的表现定为0至2。患者随机分为超低分割组(7个分割组42·7 Gy，每周3天，共2·5周)或常规分割放疗组(39个分割组78·0 Gy，每周5天，共8周)。不允许使用雄激素剥夺疗法。主要终点是生化或临床失败的时间，分析在每个方案的人群。5年后，预先指定的非劣效界限为4%，对应的临界危险率(HR)限值为1·338。根据放射治疗肿瘤组(RTOG)的发病率量表和前列腺癌症状量表(PCSS)的患者报告结果测量，测量医生记录的毒性。

2005年7月1日至2015年11月4日，将1200例患者随机分为常规分级(n=602)和超低分级(n=598)，其中1180例(591例常规分级和589例超低分级)为每方案人群。1054人(89%)为中度风险，126人(11%)为高风险。中位随访时间5·0年(IQR 3·1-7·0)。两组患者5年无失败生存率均为84% (95% CI 80-87)，平均生存时间为1·002 (95% CI 0·758-1·325);log-rank p = 0·99)。在放射治疗结束时，超低分馏率组(569例患者中158例[28%]，578例患者中132例[23%])的急性医生报告的RTOG 2级或更严重的尿毒性发生率增加的证据不足;p = 0·057)。没有明显差异在2级或者更糟尿或肠晚期毒性两治疗组之间的任何时候放疗后,除了增加尿毒性超低分馏组相比传统的分馏组1年随访(32(6%)的528名患者和13 529例(2%);(p = 0·0037)。课题组人员观察到，在RTOG 2级或更严重的尿毒性发生5年后，各组之间的频率没有差异(超低分级组243例中有11例[5%]，常规分级组249例中有12例[5%];p=1·00)和肠毒性(244例中有3例[1%]，249例中有9例[4%];p = 0·14)。患者报告结果显示的水平明显高于急性尿和肠道症状超低分馏组相比，传统的分馏组但没有显著的晚期症状被发现，除了增加尿症状1年随访,符合医生评估的毒性。在无失败生存率方面，超低分割放疗并不比传统分割放疗差。早期副作用更明显的超低分馏与传统分馏相比，而晚期毒性是相似的，在两个治疗组。研究结果支持超低分馏技术在前列腺癌放疗中的应用。

据悉，前列腺癌低分馏放疗因其高辐射分馏敏感性而受到越来越多的关注。最近的研究报告比较中度低分割和常规低分割放疗支持中度低分割的临床主题。迄今为止，还没有发表关于超低分割放疗的随机研究。
 

附：英文原文

Title: Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial

Author: Anders Widmark, Adalsteinn Gunnlaugsson, Lars Beckman, Camilla Thellenberg-Karlsson, Prof Morten Hoyer, Magnus Lagerlund

Issue&Volume: 2 August 2019

Abstract:

Background
Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.

Methods
In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.

Findings
Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.

Interpretation
Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer.

DOI: https://doi.org/10.1016/S0140-6736(19)31131-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31131-6/fulltext#