Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma

Pisani, Carla; Vigna, L.; Mastroleo, Federico; Loi, G.; Amisano, V.; Masini, Laura; Deantonio, Letizia; Valletti, Paolo Aluffi; Sacchetti, Gian Mauro; Krengli, Marco

doi:10.21203/rs.3.rs-127931/v1

Cited by 1 publication

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References 20 publications

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“…Third, both intensity-modulated and image-guided radiotherapy (IMRT and IGRT, respectively) are standard of care for almost twenty years now, and have led to signi cant irradiation volume reduction without compromising clinical outcome [14]. Analysis of IMRT treatment reveals that recurrences are predominantly within the high dose target areas [33]. Optimizing local control without increasing toxicity can thus be achieved by redistributing the radiation dose, creating inhomogeneous dose distribution towards the most (FDG-avid) active part of the tumor, instead of a conventional homogenous dose distribution with 1cm margin around the tumor area.…”

Section: Discussionmentioning

confidence: 99%

HYpofractionated, Dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase-I HYDRA trial

Elbers

Gunsch

Vulpen

et al. 2023

Preprint

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Background: Radiotherapy (RT) is standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%. Despite strong biological rationale, combining RT with immune checkpoint inhibitors does not result in a survival benefit. Our hypothesis is that the combination of these individually effective treatments fails because of radiation-induced immunosuppression and lymphodepletion. By integrating modern radiobiology and innovative radiotherapy concepts, the patient’s immune system could be maximally retained by: (1) increasing the dose per fraction so that the total-dose and number of fractions can be reduced (HYpofractionation), (2) redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective lymphatic field dose (Dose-redistribution), and by (3) using RAdiotherapy with protons instead of photons (HYDRA). Methods: The primary aim of this multicenter study is to determine the safety of HYDRA proton- and photon radiotherapy by conducting two parallel phase-I trials. Both HYDRA arms are randomized with standard of care for longitudinal immune profiling. There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated immuno-radiotherapy trials. The HYDRA dose prescriptions (in 20 fractions) are 40 Gy elective dose and 55 Gy simultaneous integrated boost on the clinical target volume with a 59 Gy focal boost on the tumor center. A total of 100 patients (25 per treatment group) will be recruited, the final analysis will be performed one year after the last patient has been included. Discussion: In the context of HNSCC, hypofractionation has historically only been reserved for small tumors out of fear for late normal tissue toxicity. To date, hypofractionated radiotherapy may also be safe for larger tumors as both the radiation dose and volume can be reduced by the combination of advanced imaging for better target definition, novel accelerated repopulation models and high-precision radiation treatment planning and dose delivery. HYDRA’s expected immune sparing effect may lead to improved outcome by allowing for future effective combination treatment with immunotherapy. Trial registration: The trial is registered at ClinicalTrials.gov; NCT05364411 (registered on May 6th, 2022).

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Section: Discussionmentioning

confidence: 99%