Hypofractionated, dose-redistributed radiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma

Principal Investigator: dr. Jos Elbers (Erasmus MC)

PhD students: P. Gunsch (Erasmus MC)

Funding: Daniel den Hoed 2021

Description

Radiotherapy for advanced-stage head and neck squamous cell carcinoma (HNSCC) results in an unfavorable 5-year overall survival of 40%, and there is a strong biological rationale for improving outcome by combinatorial treatment with immunotherapy. However, also immunosuppressive effects of radiotherapy have been reported and recently a randomized phase-III trial failed to show any survival benefit following the combination of a PD-L1 inhibitor with chemoradiotherapy. Our hypothesis is that the combination of these individually effective treatments failed because of radiation-induced lymphodepletion and that the key therefore lies in reforming conventional radiotherapy, which typically consists of large lymphotoxic radiation fields of 35 fractions. By integrating modern radiobiology and individually established innovative radiotherapy concepts, the patient’s immune system could be maximally retained. This will be achieved by 1) increasing the radiation dose per fraction so that the total number of fractions can be reduced (HYpofractionation), 2) by redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective-field dose (Doseredistribution) and 3) by using RAdiotherapy with protons instead of photons (HYDRA).

In this study, it is proposed a HYpofractionated Dose-redistributed RAdiotherapy (HYDRA) by 20 fractions instead of the conventional 35 fractions. Before HYDRA can be clinically applied as a combinatorial treatment strategy with immunotherapy, there are two main research questions that need to be answered first, namely:

1. Can hypofractionated radiotherapy in 4 instead of 7 weeks be safely applied by the newly defined dose prescriptions
2. II) What is the additional effect of HYDRA with protons on anti-tumor immunity, in comparison to HYDRA with photons and conventional fractionated radiotherapy