Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial
Authors: Mao Yan-Ping , Wang Shun-Xin , Gao Tian-Sheng , Zhang Ning , Liang Xiao-Yu , Xie Fang-Yun , Zhang Yuan , Zhou Guan-Qun , Guo Rui , Luo Wei-Jie , Li Yong-Jie , Liang Shao-Qiang , Lin Li , Li Wen-Fei , Liu Xu , Xu Cheng , Chen Yu-Pei , Lv Jia-Wei , Huang Shao-Hui , Liu Li-Zhi , Li Ji-Bin , Tang Ling-Long , Chen Lei , Sun Ying , Ma Jun 
Published: February 2023

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