Abstract
IntroductionRadiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. MethodsThe PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues.The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. DiscussionThe PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk.Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021.Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021.
Highlights
Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities
Outcome rates remain relatively poor for locally advanced human papillomavirus (HPV)negative HNC patients treated with chemo-radiotherapy [10]
We propose a novel method for safe dose-escalation: Proton Imageguided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients (PIRATES)
Summary
Head and neck cancer (HNC) affects approximately 650,000 people, accounting for 350,000 deaths annually [1]. Multiple studies have shown that the primary site local regional recurrence originates in the central regions that receive the high cura tive radiation dose (i.e. 70 Gy) [5,8,9]. This suggests that increasing the radiation dose to the tumor volume (e.g. from 70 to 80 Gy) is needed to improve cure rates in high-risk locally advanced HNC patients. Defining the dose-escalation “boost” target volume with MR-guided mid-treatment adaptation based on tumor shrinkage This facilitates the boost dose levels being applied to the (usually) smaller volume of still visible tumor. Using iso-effective organ-at-risk sparing to prevent the mucosa and mandible within the target area from receiving the boost dose, i.e. these organ-at-risk (OAR) should receive similar doses as with con ventional treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
