Overview
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
Description
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
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