111 - HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA) with Protons or Photons vs. Standard of Care for Head and Neck Squamous Cell Carcinoma: A Randomized Trial
Presenter(s)
P. A. Gunsch1, M. Kroesen1,2, R. Debets3, S. Keereweer4, E. Van Meerten5, J. Zindler2,6, E. Van Werkhoven1, M. S. Hoogeman1,7, G. M. Verduijn1, R. A. Nout1, and J. Elbers1,2; 1Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 2Department of Radiotherapy, HollandPTC, Delft, Netherlands, 3Department of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 4Department of Otorhinolaryngology, Head & Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 5Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 6Department of Radiotherapy, Haaglanden Medical Center, The Hague, Netherlands, 7Department of Medical Physics & Informatics, HollandPTC, Delft, Netherlands
Purpose/Objective(s): Definitive (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) may cause severe radiation-induced lymphopenia (RIL), which is associated with worse survival. We aim to reduce RIL without increasing late toxicity using HYpofractionation and Dose-redistribution in patients treated with proton or photon RAdiotherapy.
Materials/Methods: Patients with cT1-4N0-3M0 oropharyngeal, hypopharyngeal, or laryngeal squamous cell carcinoma treated with radiotherapy (+/- concurrent systemic therapy) with curative-intent were enrolled. Referral for proton therapy was determined by Dutch model-based selection, resulting in two parallel cohorts (protons and photons). Patients were then randomized to HYDRA or standard-of-care (SOC) fractionation for exploratory translational immune profiling. This phase I trial was not powered for statistical comparison of clinical outcomes. HYDRA consisted of 20 fractions delivering 40 Gy to elective volumes, 55 Gy to macroscopic tumor (GTV)+5 mm and 59 Gy to GTV-3 mm (boost in GTV center).
Results: 108 patients were randomized to HYDRA (photon: n = 40, proton: n = 13) and SOC (photon: n = 39, proton: n = 16). 58% was HPV positive, 43% had stage III-IV disease, and 58% received concurrent systemic therapy (all equally balanced between HYDRA and SOC). Although RIL at nadir was similar between treatments (independent of concurrent chemotherapy), there was a significant increase in CD8? T cells from nadir to 3 months after treatment with HYDRA (122% vs 86%, p = 0.029). Acute toxicity in HYDRA was transient and manageable: 33% required tube feeding during treatment and 4% at three months (29% and 4% after SOC, respectively). At a median follow-up of 18 months (range 2–37), there was 6% (95% CI 2%–15%) late grade =3 toxicity after HYDRA vs 10% (95% CI 4%–20%) after SOC. In-field locoregional control (LRC) at 1 year was 90% (95% CI 77%–96%) after HYDRA vs 96% (95% CI 84%–99%) after SOC. Five out of six in-field recurrences after HYDRA were in patients with HPV negative stage III-IV disease (n = 15 in HYDRA arm).
Conclusion: HYDRA radiotherapy resulted in similar RIL at nadir but significantly higher increase in CD8? T cells at 3 months. Longitudinal in-depth immune profiling is ongoing. Acute toxicity was transient and manageable. Late toxicity was comparable to SOC, but longer follow-up is needed. HYDRA appears particularly suitable for HPV positive disease, with excellent LRC and reduced treatment burden by omitting 15 radiotherapy fractions and 3 chemotherapy cycles. (HYDRA trial, NCT05364411)