ESTRO 2025 - Abstract Book

S958

Clinical – Head & neck

ESTRO 2025

Material/Methods: The ongoing multicenter phase I HYDRA trial (NCT05364411) evaluates the safety of HYDRA radiotherapy with/without concurrent radiosensitizer in patients with T1-4N0-3bM0 oropharyngeal and hypopharyngeal carcinomas. Proton therapy eligibility is determined by model-based comparison of clinically accepted proton and photon treatment plans according to Dutch guidelines, resulting in parallel HYDRA-proton and HYDRA-photon arms. Both HYDRA arms are randomized against standard of care (SOC) arms for longitudinal immune profiling. The HYDRA treatment constitutes 20 fractions with 40 Gy elective dose, 55 Gy on the clinical target volume (GTV+5 mm) and a 59 Gy boost on the center of the tumor (GTV−3 mm). We report on (1) intra-patient treatment plan comparison of HYDRA versus SOC and (2) the planned interim safety analysis of the HYDRA-photon arm. Results: In March 2024, the predefined interim safety analysis for the HYDRA-photon arm was reached when the tenth patient had 6 months of follow-up. In that period, 45 patients were included (HYDRA-photon: n = 15; SOC-photon: n = 18; HYDRA-proton: n = 5; SOC-proton: n = 7). Intra-patient comparison of the HYDRA and SOC treatment plans showed that HYDRA delivered a focal boost to the tumor while on average, organs at risk received a lower dose compared to conventional fractionation (in EQD2). The planned interim safety analysis of the first ten HYDRA photon patients found manageable acute toxicity requiring opioid use in 70% and tube feeding in 20%. With a median follow-up of 10.6 months, one patient experienced late grade ≥3 toxicity (grade 3 osteoradionecrosis). Locoregional recurrence was observed in 2 patients. Based on these findings, the independent data safety monitoring board approved protocollary expansion of HYDRA-photon arm eligibility to include laryngeal carcinomas.