Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial
Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial
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局部晚期复发鼻咽癌患者调强放疗中超分割与标准分割的比较：一项多中心、随机、开放标签的 3 期试验
DOI：
10.1016/s0140-6736(23)00269-6
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ming
中科院分区：
文献类型：
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作者：
R. You;You;Yu;Chao Lin;C. Duan;Dong;YI Pan;Bin Qi;X. Zou;Ling Guo;Jing;Yi;Zhi;Yong;Y. Ouyang;Kai Wen;Qi Yang;Ruo;Hui;Xiaoming Duan;X. Ding;L. Peng;Si;Jiong;Zheng;Tian;Rui;Rou Jiang;Chen;Rong;R. Sun;Xin Yang;Li;Li Ling;Qing Liu;W. Ng;Y. Hua;Pei;Ming
背景局部晚期复发性鼻咽癌在既往接受大剂量放疗后进行标准分割再照射通常与严重的晚期毒性相关，从而否定了其整体获益。因此，我们的目的是调查的有效性和安全性hyperfractionation相比，标准分割强度调制radiotherapy.MethodsThis多中心，随机，开放标签，3期试验在中国广州的三个中心。符合条件的患者年龄为18-65岁，经组织病理学证实为未分化或分化、非角化、晚期局部复发性鼻咽癌。受试者被随机分配（1：1）接受超分割（65戈伊，54次，每天两次，间隔至少6小时）或标准分割（60戈伊，27次，每天一次）。两组均采用调强放疗。通过计算机程序生成分配序列，并按照随机化时确定的治疗中心、复发肿瘤分期（T2-T3 vsT 4）和复发淋巴结分期（N 0 vsN 1-N2）对随机化进行分层。两个主要终点是重度晚期并发症的发生率，定义为安全性人群中放疗完成后3个月至末次随访期间发生的3级或更严重晚期放射诱导并发症的发生率，以及总生存期，定义为意向治疗人群中从随机化至全因死亡的时间间隔。该试验注册于ClinicalTrials.gov，NCT 02456506。结果在2015年7月10日至2019年12月23日期间，对178例患者进行了资格筛选，其中144例入组并随机分配至超分割或标准分割组（每组n=72）。35名（24%）参与者为女性，109名（76%）参与者为男性。中位随访45.0个月后（IQR 37·3-53·3），超分割组中3级或更严重的晚期放射诱导毒性的发生率显著较低（68例患者中的23例[34%]）与标准分割组相比（68例患者中的39例[57%];组间差异-23% [95%CI-39至-7]; p= 0.023）。超分割组患者的3年总生存率优于标准分割组（74.6%[95%CI 64.4 ~ 84.8] vs55.0%[43.4 ~ 66.6];死亡风险比0.54 [95%CI 0.33 ~ 0.88]; p= 0.014）。超分割组5级晚期并发症较少（5例[7%]鼻出血）（16例[24%]，包括2例[3%]鼻咽坏死，11例[16%]鼻出血，和三个[4%]颞叶坏死）。解释超分割强度-调制式放疗可明显降低局部晚期复发鼻咽癌患者的严重晚期并发症发生率，提高总生存率。我们的研究结果表明，超分割调强放射治疗可以作为这些患者的治疗标准。基金广东省重点领域研究与发展，国家自然科学基金，中山大学肿瘤防治中心高层次人才特别支持计划，广州市科技计划项目，以及国家万人计划科技创新领军人才、中山大学临床研究5010计划。
BackgroundReirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy.MethodsThis multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3vsT4), and recurrent nodal stage (N0vsN1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506.FindingsBetween July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference –23% [95% CI –39 to –7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8]vs55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis).InterpretationHyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients.FundingKey-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
DOI：
10.1016/j.ijrobp.2013.12.027
发表时间：
2014-05-01
期刊：
International journal of radiation oncology, biology, physics
影响因子：
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作者：
Beitler JJ;Zhang Q;Fu KK;Trotti A;Spencer SA;Jones CU;Garden AS;Shenouda G;Harris J;Ang KK
通讯作者：
Ang KK
DOI：
10.1016/s0360-3016(99)00550-7
发表时间：
2000-03-15
影响因子：
7
作者：
Dawson, LA;Anzai, Y;Eisbruch, A
通讯作者：
Eisbruch, A
DOI：
10.1016/s1470-2045(17)30458-8
发表时间：
2017-09
期刊：
The Lancet. Oncology
影响因子：
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作者：
Lacas B;Bourhis J;Overgaard J;Zhang Q;Grégoire V;Nankivell M;Zackrisson B;Szutkowski Z;Suwiński R;Poulsen M;O'Sullivan B;Corvò R;Laskar SG;Fallai C;Yamazaki H;Dobrowsky W;Cho KH;Beadle B;Langendijk JA;Viegas CMP;Hay J;Lotayef M;Parmar MKB;Aupérin A;van Herpen C;Maingon P;Trotti AM;Grau C;Pignon JP;Blanchard P;MARCH Collaborative Group
通讯作者：
MARCH Collaborative Group