Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial
Yan‐Ping Mao, Shunxin Wang, Tian-Sheng Gao, Ning Zhang, Xiaoyu Liang, Fang‐Yun Xie, Yuan Zhang, Guan‐Qun Zhou, Rui Guo, Wei-Jie Luo, Yongjie Li, Shaoqiang Liang, Li Lin, Wen‐Fei Li, Xu Liu, Cheng Xu, Yu‐Pei Chen, Jia‐Wei Lv, Shao-Hui Huang, Lizhi Liu, Jibin Li, Ling‐Long Tang, Lei Chen, Ying Sun, Jun Ma
Abstract
Abstract Objectives To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma. Design Open-label, non-inferiority, multicentre, randomised, phase 3 trial. Setting Three Chinese hospitals between 20 November 2017 and 3 December 2018. Participants Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement. Interventions Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy. Main outcome measures Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than −8%. Results 568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3% v 95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of −0.2% ((one sided 97.5% confidence interval –3.6 to ∞), P non-inferiority <0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5% v 35.1%, P=0.01) and late dysphagia (24.0% v 34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference −5.6 (95% confidence interval –9.1 to –2.0), P=0.002), role functioning (−5.5 (–7.4 to –3.6), P<0.001), social functioning (−6.2 (–8.9 to –3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference). Conclusion Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma. Trial registration ClinicalTrials.gov NCT03346109