中山大学癌症中心陈明远教授团队比较了局部晚期复发鼻咽癌调强放疗中超分割与标准分割对患者预后的影响。2023年2月23日出版的《柳叶刀》杂志发表了这一最新研究成果。

对局部晚期复发性鼻咽癌进行标准分割后，在先前的高剂量放疗过程中再次进行放疗，通常会导致严重的晚期毒性，从而否定其整体益处。因此，该研究团队旨在研究超分割与标准分割在调强放疗中的有效性和安全性。

这项多中心、随机、开放标签的三期临床试验在中国广州的三个中心进行。符合条件的患者年龄为18-65岁，经组织病理证实为未分化或分化、无角化、局部复发的晚期鼻咽癌。参与者被随机分配（1:1）接受超分割（54分割，65 Gy，每天两次，组间时间间隔至少6小时）或标准分割（27分割，60 Gy，每日一次）。两组均采用调强放疗。

计算机程序生成了分配序列，随机化按治疗中心、复发肿瘤分期（T2–T3 vs T4）和复发淋巴结分期（N0 vs N1–N2）进行分层，在随机分组时确定。两个主要终点是严重晚期并发症的发生率，其定义为在安全人群中完成放疗后3个月至最近一次随访期间发生的3级或更严重的晚期放射性并发症的发生，以及总体生存率，其被定义为从随机化到治疗人群全因死亡的时间间隔。

2015年7月10日至2019年12月23日，178名患者进行了资格筛选，其中144名患者入组并随机分配到超分割或标准分割（每组72名）。35名（24%）参与者为女性，109名（76%）参与者为男性。在45.0个月的中位随访后，与标准分割组（68名患者中有39名[57%]）相比，超分割组3级或更严重的晚期辐射诱导毒性发生率显著降低（68名病人中有23名[34%]）。超分割组患者的3年总生存率高于标准分割组（74.6% vs 55.0%；死亡风险比为0.54）。超分割组的5级晚期并发症（5例[7%]鼻出血）少于标准分割组（16例[24%]，包括2例[3%]鼻咽坏死、11例[16%]鼻溢血和3例[4%]颞叶坏死）。

研究结果表明，超分割调强放疗可显著降低晚期严重并发症的发生率，提高局部晚期复发鼻咽癌患者的总体生存率。超分割调强放疗可作为这些患者的标准治疗。

附：英文原文

Title: 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

Author: Rui You, You-Ping Liu, Yu-Long Xie, Chao Lin, Chong-Yang Duan, Dong-Ping Chen, Yi Pan, Bin Qi, Xiong Zou, Ling Guo, Jing-Yu Cao, Yi-Nuan Zhang, Zhi-Qiang Wang, Yong-Long Liu, Yan-Feng Ouyang, Kai Wen, Qi Yang, Ruo-Qi Xie, Hui-Feng Li, Xiao-Tong Duan, Xi Ding, Lan Peng, Si-Yuan Chen, Jiong-Lin Liang, Zheng-Kai Feng, Tian-Liang Xia, Rui-Ling Xie, Rou Jiang, Chen-Mei Gu, Rong-Zeng Liu, Rui Sun, Xin Yang, Li-Zhi Liu, Li Ling, Qing Liu, Wai Tong Ng, Yi-Jun Hua, Pei-Yu Huang, Ming-Yuan Chen

Issue&Volume: 2023-02-23

Abstract:

Background

Reirradiation 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.

Methods

This 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–T3 vs T4), and recurrent nodal stage (N0 vs N1–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.

Findings

Between 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] vs 55·0% [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).

Interpretation

Hyperfractionated 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.

DOI: 10.1016/S0140-6736(23)00269-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00269-6/fulltext