Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial

• Published in: BMJ (Online) Vol. 380; p. e072133
• Main 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
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 06.02.2023; BMJ Publishing Group LTD
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biopsy; Boundaries; Cancer therapies; Chemoradiotherapy; Chemotherapy; Clinical trials; Deglutition Disorders; Dysphagia; Humans; Lymph nodes; Lymph Nodes - pathology; Lymphatic system; Metastases; Metastasis; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - radiotherapy; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - radiotherapy; Neoplasm Recurrence, Local - radiotherapy; Patients; Planning; Public health; Quality of life; Radiation therapy; Regions; Survival; Survival analysis; Swallowing; Throat cancer; Toxicity
• ISSN: 1756-1833; 1756-1833
• DOI: 10.1136/bmj-2022-072133

AbstractObjectivesTo 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.DesignOpen-label, non-inferiority, multicentre, randomised, phase 3 trial.SettingThree Chinese hospitals between 20 November 2017 and 3 December 2018.ParticipantsAdults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement.InterventionsRandomisation 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 measuresNon-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%.Results568 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 ∞), Pnon-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).ConclusionCompared 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 registrationClinicalTrials.gov NCT03346109