Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas

Yolanda Prezado,Catherine Sebrie,Annalisa Patriarca,Dalila Labiod,Wilfredo Gonzalez,Marjorie Juchaux,Catherine Nauraye,Laurene Jourdain,Frederic Pouzoulet,Gregory Jouvion,Consuelo Guardiola,Remi Dendale,Charlotte Lamirault

doi:10.1038/s41598-018-34796-8

Abstract

Proton minibeam radiation therapy (pMBRT) is a novel strategy which has already shown a remarkable reduction in neurotoxicity as to compared with standard proton therapy. Here we report on the first evaluation of tumor control effectiveness in glioma bearing rats with highly spatially modulated proton beams. Whole brains (excluding the olfactory bulb) of Fischer 344 rats were irradiated. Four groups of animals were considered: a control group (RG2 tumor bearing rats), a second group of RG2 tumor-bearing rats and a third group of normal rats that received pMBRT (70 Gy peak dose in one fraction) with very heterogeneous dose distributions, and a control group of normal rats. The tumor-bearing and normal animals were followed-up for 6 months and one year, respectively. pMBRT leads to a significant tumor control and tumor eradication in 22% of the cases. No substantial brain damage which confirms the widening of the therapeutic window for high-grade gliomas offered by pMBRT. Additionally, the fact that large areas of the brain can be irradiated with pMBRT without significant side effects, would allow facing the infiltrative nature of gliomas.

Highlights

Radiotherapy (RT) has a key role in cancer treatment
No comparison with conventional PT has been performed since such high mean doses would not be tolerated27. iii) a third group of normal rats (n = 9) that received proton minibeam radiation therapy (pMBRT) with the same dose and configuration than group ii); iv) a second control group of normal rats (n = 5)
This section reports on the tumor control effectiveness of pMBRT as well as on the long-term side effects of irradiated rats

Summary

Introduction

Radiotherapy (RT) has a key role in cancer treatment. about half of the patients will receive RT at some point during their illness[1]. The central dogma of conventional RT, namely that the cytotoxic effects of radiation are primarily due to the production of DNA double-strand breaks followed by some form of cell death (apoptosis, necrosis, autophagy, senescence), is being abandoned This paradigm shift is led by the recent shreds of evidence of the importance of cell signaling[7,8] and the role of the vascular[9], stromal and immunological changes[10] induced by the radiation in treatment outcome. To profit from the benefits of MBRT, we have recently proposed to explore the synergies of proton therapy and the spatial fractionation of the dose[22] This novel therapeutic approach is called proton minibeam radiation therapy (pMBRT). Even though the beam energy is not clinically relevant (a 20 MeV proton beam only penetrates 1 mm in the body), this work provided another indication of the advantages of this approach

Objectives

Methods

Results

Conclusion