3515 - Combined Proton/Photon Therapy in Skull-Base Approximating Head and Neck Cancers

Purpose/Objective(s): Management of head and neck cancers (HNCs) involving or approximating the skull base represent unique therapeutic challenges due to proximity to critical neurologic structures. While proton therapy offers dosimetric advantages, concerns remain regarding the distal-range RBE and potential late toxicity near sensitive CNS structures. To balance conformality with biologic uncertainty, our institution implemented a combined proton-photon treatment approach. In this institutional cohort, we report early safety, toxicity and response outcomes with this strategy combining proton and photon therapy.

Materials/Methods: Thirty-one patients with newly diagnosed Stage II–IV HNC received combined photon-proton treatment from November 2019 to September 2025. Twenty-three patients who met inclusion criteria, had tumors involving or approximating the skull base, paranasal sinuses, nasopharynx, or orbits, and received combined 50% proton and 50% photon treatment were analyzed. Proton therapy was delivered first, followed by sequential photon therapy via SIB technique. All acute adverse events (AEs) were prospectively evaluated at point of care and graded per the CTCAE v5.0. Response was evaluated using RECIST v1.1 criteria and Flexible Nasopharyngoscopy examination. DVH values were evaluated for dose delivered to the patient.

Results: Median age was 60 years (range: 26-84), and most patients had T4 disease (78.2%). The most common histology and site was squamous cell carcinoma (73.9%) and nasopharynx (34.8%), respectively. Median prescription dose was 70 Gy (range: 60-76.80 Gy). Median follow-up was 17 months from end of treatment to most recent radiographic follow-up. Eleven grade 3 acute AEs were recorded, but no acute grade 4-5 events. One (4.3%) patient required PEG placement, 2 weeks post-radiation. One (4.3%) late grade 4 event involved a patient with right frontal lobe radionecrosis, successfully managed with surgery and hyperbaric oxygen 2 years post-radiation. No other cases of CNS necrosis, osteoradionecrosis, or optic neuropathy occurred to date. Initial complete and partial response rates were 65.2% and 26.1%, respectively. Local control rate was 86.0%. Local recurrence and distant failure rates were each 8.6%. Three (13%) patients in our cohort died, 2 (8.7%) from disease progression and 1 (4.3%) from sepsis, 3 months after last concurrent chemotherapy administration.

Conclusion: Combined proton-photon treatment represents an emerging approach for HNCs at or approximating paranasal sinus or skullbase, with early promising toxicity and response results. This is the first, and largest, series in the United States detailing this approach and its safety and efficacy. Delivery technique, rationale, and outcomes are presented. Further evaluation is needed, including larger patient cohort, histology-focused subanalysis, and longer follow-up. Late toxicity analysis is ongoing and will be available as data matures.