PIRATES: Image-guided Hyper-fractioned Dose-escalation With Proton Therapy for Head and Neck Cancer

This study (PIRATES) tests whether proton therapy — a very precise form of radiation — delivered in smaller, more frequent doses (called hyper-fractionation) can improve outcomes in patients with locally advanced HPV-negative throat cancer (oropharyngeal squamous cell carcinoma). Patients receive this alongside weekly chemotherapy. **You may be eligible if...** - You have confirmed, locally advanced (stage III–IV) squamous cell carcinoma of the oropharynx (tonsil or base of tongue area) - Your cancer tests negative for HPV (p16-negative) - You are eligible for standard chemoradiation and are 18 or older - You are in reasonably good health (ECOG score up to 2) **You may NOT be eligible if...** - You have already had surgery to remove the tumor - You have had prior radiation to the head and neck - You have contraindications to chemotherapy - You have iron overload or cannot tolerate contrast agents used in MRI/CT - You have active HIV or other serious immune conditions Talk to your doctor to see if this trial is right for you.