Dose de-escalation of elective neck irradiation in head and neck cancer: A secondary analysis of acute toxicity findings from the randomized controlled UPGRADE-RT trial

Background: The multicenter, randomized UPGRADE-RT trial (NCT02442375) evaluated the safety and clinical benefit of elective neck radiotherapy with reduced versus standard dose in head and neck squamous cell carcinoma (SCC). This is a secondary analysis of acute toxicity. Methods: Three hundred patients with cT2-4 N0-2 M0 SCC of the oropharynx, larynx or hypopharynx received definitive accelerated radiotherapy alone (34 fractions of 2 Gy in 5.5 weeks). Dose for elective neck irradiation was randomly assigned (ratio 2:1 to dose reduction, 43 Gy versus control, 50 Gy). Radiation induced acute toxicity was scored according to the CTC v2.0 until 90 days after start of radiotherapy. Results: The analysis included 295 evaluable patients (dose reduction, 196 and control, 99). Dysphagia grade = 3 (requiring tube feeding) occurred significantly less in the dose reduction group compared to controls (RR, 0.56, [95 % CI, 0.32 to 0.98], p = 0.046). A mean dose = 45 Gy to the pharyngeal mucosal epithelium was associated with increased rates of mucositis grade = 3 (RR, 1.41, [95 % CI, 1.17 to 1.70], p < 0.001) and dysphagia grade = 3 requiring tube feeding (RR, 3.61, [95 % CI, 1.72 to 7.57], p < 0.001). Less patients in the dose reduction group had a pharyngeal mucosal epithelium mean dose = 45 Gy (RR, 0.80, [95 % CI, 0.65 to 0.99], p = 0.041). Conclusion: Reduced elective dose resulted in significantly more patients with a pharyngeal mucosal epithelium mean dose below 45 Gy. This was associated with a reduced rate of grade = 3 pharyngeal mucositis and a lower rate of acute dysphagia grade = 3 (requiring tube feeding).