Yan-Ping Mao, et al. Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial. BMJ 2023;380:e072133

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

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

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.

Comments by Dr Amarnath

Reproducibility on a daily basis is very important in accuracy of radiation therapy delivery. You require a millimeter accuracy. If we discuss right from patient counselling to planning CT scan on a dedicated unit with selection of appropriate immobilization devices, iv contrast Injection at the right time of running the scan, to contouring with extreme patience, planning by the physicist, patient-specific QA and delivery of treatment under image guidance on a daily basis. If all these are done with dedication you will see the desired long-term results in. Quality of life is equally important to post Radiation therapy. One should not ride with overconfidence. Experience is the key. The treatment right from start to finish should be a team effort. A visiting or part-time consultant should share and seek opinions regarding his or her patient with the department team members. You should always do what is best and for the patient. And what’s more in that way you will have robust data for publications.

In the beginning, I was a little hesitant to spare the medial retropharyngeal lymph nodes in selected patients with nasopharyngeal ca. The entire team in the chain needs to be very skilled. At present having gained enough experience in patient counselling, Radiation delivery with higher-end techniques and accurate reproducibility on a daily basis we can safely practice with minimal long-term side effects

amarnath

Dr G. Amarnath

Radiation Oncologist

 

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