pirates: image-guided hyper-fractioned dose-escalation with proton therapy for head and neck cancer

Conditions: Head and Neck Cancer; Oropharyngeal Cancer

Summary: in this study the safety \& feasibility of image-guided mid-treatment hyper-fractioned dose-escalation with proton therapy will be assessed for the treatment of locally advanced hpv-negative squamous cell oropharyngeal cancer

for this study, the investigators propose a novel design to safely achieve tumor radiation dose escalation with proton therapy plus standard-of-care concomitant chemotherapy. through mid-treatment image guidance, the tumor boost dose is determined; subsequently, only that gtv boost will receive a total dose of 80 gy through hybrid hyperfractionation. this refers to twice-daily radiation in the last 15 fraction days. the combination of boost dose hyperfractionation and proton therapy is anticipated to prevent critical normal tissue damage within both the high- and intermediate-dose regions. this novel treatment approach aims to minimize critical toxicities while improving locoregional control for head and neck cancer patients who are at a higher risk of disease relapse.

Eligibility criteria:
inclusion criteria: in order to be eligible to participate in this study, a subject must meet all of the following criteria: * biopsy proven diagnosis of squamous cell carcinoma originating in the oropharynx. * routine staging procedures, including ct of the head and neck region and chest, head and neck fdg-pet/ct and mri (treatment planning allowed), and endoscopic evaluation when indicated. * negative for p16 * locally advanced disease, specifically meeting all following criteria: * stage iii-iv * t-stage 2-4 * all n-stages (n0-3) * m0 * eligible for primary concurrent chemoradiation using conventionally fractionated radiotherapy 70 gy combined with weekly cisplatin * eastern cooperative oncology group (ecog) performance score ≥2 * age ≥18 years * written informed consent exclusion criteria: a potential subject who meets any of the following criteria will be excluded from participation in this study; patients that: * underwent definitive resection of their primary tumor or nodal disease, except for incisional or excisional biopsies. received radiation therapy in the head and neck area in the past * have no detectable tumor anymore at both the primary site and lymph nodes at week 4 in treatment, because there will not be a volume to boost. * are unable or unwilling to give written, informed consent * have contra-indications for chemotherapy. this is at the discretion of the treating medical oncologist. * are unable to tolerate intravenous contrast for both ct and mri, having an estimated gfr \< 60 ml/min/1.73 m2 or any contraindications to gadolinium-based contrast agents. * have any evidence of iron overload on pre-imaging laboratory studies. * have other serious illnesses or medical conditions present at entry in the study, including (but not limited to): immunodeficiency virus (hiv) infection or other conditions of persistent immunodeficiency, neurologic or psychiatric disorders, active disseminated intravascular coagulation, unstable cardiac disease despite treatment or uncontrolled diabetes mellitus. * women who are pregnant or breast feeding

Keywords: proton therapy hyperfractionation dose-escalation image guidance therapy adaptive radiotherapy