Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

Methods

Pre-specified five year analysis of an open label, non-inferiority, multicentre, randomised phase 3 trial.

预先设定的开放标签、非劣效性、多中心、随机的III期试验的五年分析。

Three Chinese medical centres between 20 November 2017 and 3 December 2018.

2017年11月20日至2018年12月3日，三家中国医疗中心。

Adults (18-65 years) with untreated, non-keratinising, non-metastatic nasopharyngeal carcinoma without MRLN involvement.

18至65岁的成年人，患有未经治疗的、非角化型、非转移性鼻咽癌，且无咽旁淋巴结（MRLN）受累。

Eligible patients were randomised (1:1; block size of four) to MRLN sparing radiotherapy or standard radiotherapy.

符合条件的患者按1:1的比例（每组四人）随机分配接受MRLN保护性放疗或标准放疗。

Randomisation was stratified by institution and treatment modality (radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy).

随机分组按照机构和治疗方式（仅放疗、同步放化疗，或诱导化疗加放疗或同步放化疗）进行分层。

The primary outcome was local relapse-free survival. The three year local relapse-free survival to assess the non-inferiority, with a margin of 8%, of MRLN sparing radiotherapy compared with standard radiotherapy has been reported previously.

主要结果是局部无复发生存率。先前报告了与标准放疗相比，MRLN保护性放疗在三年局部无复发生存率上非劣效性的评估，非劣效性边界为8%。

This updated report focuses on five year survival, toxicity, and quality of life.

本更新报告重点介绍了五年生存率、毒性和生活质量。

Additionally, a videofluoroscopic swallowing study and magnetic resonance imaging (MRI) measurements of pharyngeal contractors were used as objective measures of dysphagia RESULTS: This trial enrolled 285 patients in the MRLN sparing group and 283 patients in the standard group.

此外，使用了视频透视吞咽研究和磁共振成像（MRI）测量咽部收缩肌作为吞咽困难的客观指标

At a median follow-up of 70 months, the MRLN sparing and standard groups had similar five year local relapse-free survival (89.2% (95% confidence interval(CI) 85% to 92%) versus 90.6% (87% to 94%); stratified hazard ratio1.03 (95% CI 0.61 to 1.74); P=0.90) and overall survival(89.2% (85% to 93%) versus 90.3% (87% to 94%); stratified hazard ratio1.06 (0.68 to 1.68); P=0.79).

在中位随访70个月时，MRLN保护组和标准组的五年局部复发无病生存率相似（89.2%（95%置信区间（CI）85%至92%）与90.6%（87%至94%）；分层风险比1.03（95% CI 0.61至1.74）；P=0.90）以及总生存率（89.2%（85%至93%）与90.3%（87%至94%）；分层风险比1.06（0.68至1.68）；P=0.79）。

Updated safety profiles of the MRLN sparing group showed a lower rate of grade ≥1 dysphagia (45/206 (22%) v 70/216 (32%); P=0.01) and grade ≥2 dry mouth (33/206 (16%) v 55/216 (25%); P=0.02) and enhanced swallowing related quality of life (mean difference -11.9; P<0.001).

更新的 MRLN 保护组的安全性资料表明，1级及以上吞咽困难的发生率较低（206例中有45例（22%）对比216例中有70例（32%）；P=0.01），2级及以上口干的发生率也较低（206例中有33例（16%）对比216例中有55例（25%）；P=0.02），并且吞咽相关的生活质量有所提高（平均差异为-11.9；P<0.001）。

Videofluoroscopy showed a lower prevalenceof vallecular residue (49/66 (74%) v 62/62 (100%); P<0.001), pyriform sinus residue (32/66 (48%) v 45/62 (73%); P=0.01), coating of pharyngeal wall (7/66 (11%) v 17/62 (27%); P=0.01), pharyngeal transit time >1.0 s (1/66 (2%) v 7/62 (11%); P=0.03), and aspiration (8/66 (12%) v 18/62 (29%); P=0.03) in the MRLN sparing group.

视频透视检查显示，在 MRLN 保护组中，舌盲孔残留的发生率较低（66例中有49例（74%）对比62例中有62例（100%）；P<0.001），梨状隐窝残留的发生率也较低（66例中有32例（48%）对比62例中有45例（73%）；P=0.01），咽壁涂层的发生率较低（66例中有7例（11%）对比62例中有17例（27%）；P=0.01），咽部转运时间超过1.0秒的发生率较低（66例中有1例（2%）对比62例中有7例（11%）；P=0.03），以及吸入的发生率较低（66例中有8例（12%）对比62例中有18例（29%）；P=0.03）。

Additionally, MRI detectable late atrophy in the superior pharyngeal constrictor (mean thickness: 1.80 v 1.65 mm; P=0.005) and middle pharyngeal constrictor (2.34 v 2.15 mm; P=0.01) was less severe after MRLN sparing radiotherapy.

此外，MRI可检测到的晚期萎缩在上咽缩肌（平均厚度：1.80对1.65毫米；P=0.005）和中咽缩肌（2.34对2.15毫米；P=0.01）在保留MRLN放射治疗后较不严重。

Conclusions

MRLN sparing radiotherapy maintained uncompromised efficacy and better long term swallowing function by reducing radiation damage to pharyngeal contractors, supporting its use as a standard of care for non-metastatic nasopharyngeal carcinoma.

通过减少对咽缩肌的放射性损伤，MRLN保护性放射治疗维持了未受损害的疗效和更好的长期吞咽功能，支持将其作为非转移性鼻咽癌的标准治疗方法。

trial_registration

ClinicalTrials.gov NCT03346109.

临床试验注册号：NCT03346109。