Prospective clinical trial of upright image-guided proton therapy for locally recurrent head and neck and brain malignancies
This prospective clinical trial evaluated the feasibility, safety, and dosimetric benefits of upright image-guided proton therapy (IGPT) for patients with recurrent head and neck or brain malignancies. Conducted at the Mayo Clinic, the study included 25 patients treated between 2021 and 2024 using a novel upright positioning system integrated with image guidance and pencil beam scanning proton delivery. All participants had previously received high-dose radiotherapy and were selected for re-irradiation due to localized recurrence. Treatment planning was performed with CT and cone-beam CT acquired in the upright seated position to ensure reproducibility and accurate targeting.
The median prescribed dose was 60 Gy (RBE) in 2-Gy fractions, with adaptive planning as needed. Patients tolerated the upright setup well, reporting improved comfort and reduced treatment time compared with conventional supine positioning. Image guidance achieved submillimeter accuracy, and treatment reproducibility remained within 1 mm translational and 0.5° rotational variation. Acute toxicity was limited to grade 1–2 mucositis and fatigue, while only one case of grade 3 late toxicity (soft tissue necrosis) occurred during follow-up. Local control at one year was 78%, and overall survival was 82%, demonstrating favorable outcomes for this challenging cohort.
Dosimetric analysis showed significant sparing of critical structures—including the brainstem, optic nerves, and spinal cord—while maintaining full target coverage. The upright position also reduced setup-related anatomical deformation, especially in patients with airway obstruction or postoperative changes.
In conclusion, upright IGPT proved to be a technically feasible and clinically safe approach for re-irradiating recurrent head and neck or brain tumors. The study highlights its potential to improve patient comfort, treatment precision, and organ sparing, supporting its further development and integration into future proton therapy systems.
Radiotherapy and Oncology – Volume 211, 111097 October 2025 – Received March 17, 2025; Revised July 22, 2025; Accepted July 24, 2025; Published online August 10, 202 DOI: 10.1016/j.radonc.2025.111097
