Late toxicities (LT) in patients affected by locally advanced (LA) oropharyngeal carcinoma (OPC) treated with definitive (chemo)radiotherapy (C)RT: Risk factors and pattern of adverse effects.

e18111 Background: Treatment with CRT has a high burden of acute toxicities in OPCs patients, but data regarding LT are scarce. The more favourable prognosis of HPV-positive OPCs increases the importance to evaluate LT. Methods: We conducted a multinational, retrospective analysis of a consecutive series of LA OPCs treated with definitive RT with/without induction and/or concurrent CT, without any relapse or second primary cancer. We analysed the different patterns of LT in terms of type, number and grade (CTCAE v 5.0), as well as the baseline and treatment-related risk factors associated with LT development. We assessed with generalized linear model and binary logistic regression the impact of clinical and treatment related parameters on the number of LT and the development of at least one grade >2 toxicity. Two different models were created, one including the main clinical factors (alcohol consumption, smoking status, body-mass index, weight loss in past 6 months, stage, p16, p16 x smoking status, primary subsite, caregiver presence) and one considering the treatment-related variables (RT fractionation, type of concurrent CT, use of induction CT). Results: We analysed data from 275 patients (81% HPV-positive) treated with C(RT), with a median total dose of 70 Gy, at 14 European centres between 2007 and 2019. With a median follow-up of 6.4 years (range: 0.8–14.9 years), 201 (73%) experienced at least one treatment-related LT (median 2, range 1-5) of any grade. Overall, xerostomia and dysphagia were the most frequent LT, while weight loss and osteoradionecrosis were the most common ≥G3 toxicities. The incidence and severity of each LT are reported in Table 1. The n° of LT was significantly higher in pts who received conventional fractionation vs moderately acceleration or hyperfractionation, and for the primary subsite of soft palate. Conclusions: With the limitation of a retrospective analysis, xerostomia and dysphagia are the most frequent toxicities complained by the patients in the long term follow up of OPC treated with (C)RT. The number of LT is significantly higher in pts who received conventional fractionation, potentially related to the use of less conformal RT techniques, and for primary subsite in soft palate. This pattern of LT represents the benchmark to be compared with what obtained with de-escalation treatments. Pts with LT. Total n° of pts 275 (100%) N (%) N tox G1 N tox G2 N tox G3-4 N° of pts with any-grade of LT (%) 201 (73.1%) 135 (49.1%) 113 (41.1%) 19 (6.9%) Xerostomia 138 (50.1%) 88 (32.0%) 49 (17.8%) 1 (0.3%) Dysphagia 68 (24.7%) 49 (17.8%) 16 (5.8%) 3 (1.1%) Musculoskeletal fibrosis 63 (22.8%) 38 (13.8%) 24 (8.7%) 1 (0.3%) Hypothyroidism 45 (16.4%) 11 (4.0%) 34 (12.4%) 0 Weight loss 37 (13.4 %) 19 (6.9%) 10 (3.6%) 8 (2.9%) Osteoradionecrosis 21 (7.6%) 11 (4.0%) 3 (1.1%) 7 (2.5%) Pain 9 (3.2%) 6 (2.2%) 2 (0.7%) 1 (0.3%)