A multidimensional cohort study of late toxicity after intensity modulated radiotherapy for sinonasal cancer.

Purpose: To evaluate the occurrence of late toxicity after curatively intended intensity modulated radiotherapy (IMRT) for sinonasal cancer and assess dose-response associations.

Methods: Patients treated with IMRT in 2008-2016 were included. Cross sectional examinations of toxicity from the optic pathway, the brain, the pituitary gland and the nose were performed along with quality of life - (QoL) and dose-response analyses.

Results: Twenty-seven patients were enrolled; median age was 67 years (range 47-83). Five patients (19%) had radiation-related ocular toxicity. The risk of visual acuity impairment increased with increasing dose (grade 2 odds ration (OR) 1.12, p = 0.01; grade 3 OR 1.14, p = 0.02) and dose constraint violations (grade 2, OR = 21, p < 0.01; grade 3, OR = 41, p < 0.01). Six patients (22%) exhibited evidence of radiation-related hypopituitarism, but no dose-response association was detected. Seventeen patients (63%) had impaired olfactory function. The risk of olfactory impairment increased with higher stage (OR = 3.32, p = 0.03). Three patients (11%) had structural abnormalities in irradiated areas of the brain, and impaired cognitive function was present in 17 patients (63%). Cognitive, physical, role functioning as well as fatigue and insomnia were affected the most in QOL analyses. Fifteen patients (56%) had grade 2 radiation-related impairment in at least one organ. Grade 3 toxicity was only present in patients with toxicities in >3 organs and in patients initially treated for T4 tumours. Three patients (11%) had radiation-related impaired function in all examined OARs.

Conclusion: Late toxicity after radiotherapy was substantial in all examined organs, with dose-response associations between visual acuity impairment and the optic nerve. The results have led to changed praxis for follow-up examinations in Denmark.