Purpose/Objective: Here we report the prospectively documented short-and long-term health-related quality of life (HRQoL) of a large cohort of patients with advanced laryngeal cancer. The patients were treated in a randomized trial comparing accelerated radiotherapy with carbogen and nicotinamide (ARCON) against accelerated radiotherapy alone (AR). Materials and Methods: Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to AR and 171 to ARCON. HRQoL was assessed using the

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... uropean Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire-C30 (QLQ-C30) and the Head&Neck cancer module (QLQ-H&N35) at baseline, at completion of radiotherapy and at 6, 12, and 24 months post-baseline. Tumor-and patient related factors with potential impact on quality of speech and swallowing were analyzed separately. Data were analyzed two years after inclusion of the last patient. Results: Compliance with completion of questionnaires at different time-points was high (AR: 60-79%; ARCON 70-81%). Significant clinical impact (>10 effect-points) was observed for nearly all items of the QLQ-C30 and QLQ-H&N35 between baseline and end of treatment. At 6 months, scores returned to baseline level for all items with exception of dry mouth, sticky saliva, taste-and smell perception. No difference in HRQoL score between AR and ARCON was observed at any of the time points. The rate of patients reporting 'quite a bit' or 'very much' complaints of dry mouth, sticky saliva, or changes in taste-and smell perception for AR vs ARCON is limited to 26% vs 33%, 20% vs 23% and 20% vs 17% at 2 years, respectively. At 2 years from diagnosis, the majority of patients treated by AR vs ARCON, have 'not at all' or 'a little' complaints of swallowing (77% vs 81%; P=.37) or speech (64 vs 63%, P=.51). Long-term function of speech and swallowing for patients presenting with T4 tumors was not impaired compared to T2-T3 tumors. The use of a feeding tube at 2 years from diagnosis was limited to 6% vs 4% of AR vs ARCON patients, respectively. Conclusions: With ARCON, a high local control (± 80%) and a significantly improved regional control rate are observed while maintaining excellent speech and swallowing function for the majority of patients, independent of T-stage. Long term dry mouth, sticky saliva and changes in taste and smell perception are limited to one quarter of patients and not different between both treatment arms.