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.

Abstract

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. 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. 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). 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).