258 - First Report from the Headlight Trials: Postoperative Hypofractionated Proton Therapy for Head and Neck Cancers Unrelated to HPV
Presenter(s)
S. C. Lester1, L. A. McGee2, D. M. Routman1, M. A. Neben-Wittich1, J. M. Wilson3, K. K. Tasche4, E. J. Moore4, L. X. Yin4, K. M. Van Abel4, D. L. Price4, K. Price5, H. Fuentes Bayne3, A. V. Chintakuntlawar5, P. W. McGarrah3, C. Fazer3, R. Guenzel6, M. Dorr3, K. O. Steinert3, S. H. Patel2, and D. J. Ma1; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 3Mayo Clinic, Rochester, MN, 4Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, 5Division of Medical Oncology, Mayo Clinic, Rochester, MN, 6Mayo Clinic, Eau Claire, WI, United States
Purpose/Objective(s): The HEADLIGHT trials evaluated the efficacy and tolerability of moderate hypofractionation for locally advanced head and neck cancers unrelated to the human papillomavirus. Here we report the primary outcomes of hypofractionated proton therapy after surgical resection.
Materials/Methods: Eligible patients were newly diagnosed with squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx; salivary tumors; or skin cancers with indications for nodal treatment. 4350 cGy in 15 fractions over 19 days was administered to the operative bed and involved nodal areas; 4005 cGy in 15 fractions was administered for elective coverage. An optional boost of 4500 cGy in 15 could be employed for positive margins. Concomitant weekly chemotherapy was prescribed at the discretion of the treating medical oncologist for high-risk features. Patients had weekly evaluations for 3 weeks during and 3 weeks after radiation. The primary endpoint was 2-year locoregional recurrence rate (LRR). We hypothesized in this one-sample non-inferiority design that the LRR would not cross a predefined threshold of 14.3%. PROs included weekly mucositis (OMWQ-HN), global health (EQ5DL), swallowing (MDADI), and impact on work (WPAI) questionnaires.
Results: 75 patients prospectively enrolled from April 2022 to February 2024. 57 (75%) had oral cavity tumors, 11 (15%) had salivary tumors, and 5 (7%) had skin, 1 (1%) had hypopharynx, and 1 (1%) had oropharynx. 59 (79%) were pT3/T4a and 50 (67%) were > pN1. 50 (67%), 18 (24%), and 6 (8%) of patients started radiation within 6, between 6-8, and >8 weeks after surgery. 70 (93%) completed radiation in the specified timeframe (18-21 days) and 1 patient did not complete radiation. Chemotherapy was administered for 13 (17%) patients. All patients planned for chemotherapy completed at least 2 doses and 77% completed all 3 doses. 2-year LRR was 12% (95% CI: 5.6-21.6), Of the 6 patients with local recurrence, 5 were infield and 1 out-of-field. Of the 3 patients with regional recurrence, 1 was infield, 1 marginal, and 1 out-of-field. The 2-year disease-free and overall survival rates (95% CI) were 66% (55.9-78.7) and 84% (75.8-93.2), respectively. Grade =3 acute adverse events were seen in 21 (28%) patients. 6 (8%) patients experienced weight loss > 10% of baseline weight by 3 weeks post RT. 4 patients needed postoperative PEG tubes and 6 (8.5%) patients required PEG placement during or after radiation. There was one death during radiation therapy from a myocardial infarction. Grade 3+ solicited toxicity occurring more than 30 days from radiation completion occurred in 5 patients.
Conclusion: Hypofractionated proton therapy demonstrated non-inferior locoregional recurrence risk compared to a historical control, is effective, and is well-tolerated for postoperative treatment of head and neck cancers. Definitive and IMRT cohorts have completed enrollment and are maturing.