中山大学肿瘤防治中心马骏教授团队比较了鼻咽癌患者保留内侧咽后淋巴结区放疗与标准放疗对预后的影响。2023年2月6日，该项研究成果发表在《英国医学杂志》上。

为了探讨在鼻咽癌患者中，在选择性放疗中保留内侧咽后淋巴结（MRLN）区域的局部无复发生存率是否不劣于标准放疗，2017年11月20日至2018年12月3日，研究组在中国三家医院进行了一项开放标签、非劣效性、多中心、随机、3期临床试验，招募新诊断、非角化、非远处转移性鼻咽癌、无MRLN累及的成人（18-65岁）患者。

随机分组由中山大学癌症中心临床试验中心集中完成。符合条件的患者被随机分配（1:1；四个区块大小）接受MRLN保留放疗或标准放疗（包括内侧和外侧咽后淋巴结组），并按机构和治疗方式进行分层，如下：单独放疗；同步放化疗；诱导化疗加放疗或同步放化疗。如果三年局部无复发生存率（MRLN保留放疗减去标准放疗）绝对差异的单侧97.5%置信区间下限大于−8%，则符合非劣效性。

研究组招募了568名患者：285名在MRLN保留放疗组；标准放疗组283例。中位随访时间为42个月，意向治疗分析显示，MRLN保留放疗组的三年局部无复发生存率为95.3%，不低于标准放疗组的95.5%，分层风险比为1.04，符合非劣效性。

在安全组（n=564）中，保留组中发生≥1级急性吞咽困难（25.5%与35.1%）和晚期吞咽困难（24.0%与34.3%）的发生率显著低于标准放疗组。校正基线值后，MRLN保留放疗后三年患者报告的结果在多个领域更好：全球健康状况（平均差异−5.6）、角色功能（−5.5）、社会功能（−6.2）、疲劳（7.9）和吞咽（11.0）。吞咽评分差异具有临床意义（>10分差异）。

研究结果表明，与标准放疗相比，保留MRLN的放疗在非转移性鼻咽癌患者的局部复发风险方面表现出非劣效性，与辐射相关的毒性更小，患者报告的预后也有所改善。

附：英文原文

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

Author: Yan-Ping Mao, Shun-Xin Wang, Tian-Sheng Gao, Ning Zhang, Xiao-Yu Liang, Fang-Yun Xie, Yuan Zhang, Guan-Qun Zhou, Rui Guo, Wei-Jie Luo, Yong-Jie Li, Shao-Qiang Liang, Li Lin, Wen-Fei Li, Xu Liu, Cheng Xu, Yu-Pei Chen, Jia-Wei Lv, Shao-Hui Huang, Li-Zhi Liu, Ji-Bin Li, Ling-Long Tang, Lei Chen, Ying Sun, Jun Ma

Issue&Volume: 2023/02/06

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 ∞), 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).

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.

DOI: 10.1136/bmj-2022-072133

Source: https://www.bmj.com/content/380/bmj-2022-072133