Simple SummaryIn head and neck cancer, local recurrences are unfortunately common. A more intense local treatment, such as an increased radiation dose to the primary tumour, could potentially prevent some of these recurrencies. Previous studies have not shown an increased risk of side effects with a higher radiotherapy dose. However, the follow-up time in these studies is sometimes limited, and late side effects may then be missed. In our study with a relatively long patient follow-up, we compared survival and side effects in two groups with 215 patients in each group, where one group was treated with standard dose radiotherapy and the other group was treated with a higher dose of radiotherapy. In this study, we found that certain severe side effects are more common after higher doses of radiotherapy compared to after treatment with standard dose radiotherapy.AbstractPrevious studies on dose-escalated radiotherapy in head and neck cancer have shown mixed results, and it is not established which patients would benefit from dose escalation. Further, while dose escalation does not appear to increase late toxicity, this needs to be confirmed with longer follow-up. In this study, we analysed treatment outcome and toxicity in 215 patients with oropharyngeal cancer treated with dose-escalated radiotherapy (>72 Gy, EQD2, α/β = 10 Gy, boost by brachytherapy or simultaneous integrated boost) and a matched cohort of 215 patients treated with standard dose external-beam radiotherapy (68 Gy) between 2011 and 2018 at our institution. The 5-year overall survival (OS) was 77.8% (72.4–83.6) and 73.7% (67.8–80.1) in the dose-escalated and standard dose group, respectively (p= 0.24). Median follow-up was 78.1 (49.2–98.4) and 60.2 (38.9–89.4) months in the dose-escalated and standard dose groups, respectively. Grade ≥3 osteoradionecrosis (ORN) and late dysphagia were more common in the dose-escalated group compared to the standard dose group, with 19 (8.8%) vs. 4 (1.9%) patients developing grade ≥3 ORN (p= 0.001), and 39 (18.1%) vs. 21 (9.8%) patients developing grade ≥3 dysphagia (p= 0.01). No predictive factors to help select patients for dose-escalated radiotherapy were found. However, the remarkably good OS in the dose-escalated cohort, despite a predominance of advanced tumour stages, encourages further attempts to identify such factors.