First Evaluation of Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy of Glioma-Bearing Rats
by
, , and
Annaïg Bertho
1,2,†, 
Ramon Ortiz
1,2,†,
Marjorie Juchaux
1,2,
Cristèle Gilbert
1,2,
Charlotte Lamirault
3,
Frederic Pouzoulet
3,
Laura Polledo
4,
Alethea Liens
4,
Nils Warfving
4,
Catherine Sebrie
5,
Laurène Jourdain
5,
Annalisa Patriarca
6,
Ludovic de Marzi
6,7 and
Yolanda Prezado
1,2,* 
1
Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France
2
Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France
3
Translational Research Department, Institut Curie, Experimental Radiotherapy Platform, Université Paris Saclay, 91400 Orsay, France
4
AnaPath GmbH, AnaPath Services, Hammerstrasse 49, 4410 Liestal, Switzerland
5
CEA, CNRS, Inserm, Service Hospitalier Frédéric Joliot, BIOMAPS Université Paris-Saclay, 91401 Orsay, France
6
Centre de Protonthérapie d’Orsay, Radiation Oncology Department, Campus Universitaire, Institut Curie, PSL Research University, 91898 Orsay, France
7
Institut Curie, Campus Universitaire, PSL Research University, University Paris Saclay, INSERM LITO, 91898 Orsay, France
*
Author to whom correspondence should be addressed.
†
These authors equally contributed.
Cancers 2021, 13(19), 4865; https://doi.org/10.3390/cancers13194865
Submission received: 2 September 2021
/
Revised: 22 September 2021
/
Accepted: 23 September 2021
/
Published: 28 September 2021
(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)
Simple Summary
Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach based on a distinct dose delivery method: the dose distributions follow a pattern with regions of peaks (high doses) and valleys (low doses). pMBRT was shown to be able to widen the therapeutic window in glioma-bearing rats. In previous studies the irradiation was performed in one single fraction. The work reported in this manuscript is the first evaluation detailing the response of glioma-bearing rats to a temporal fractionation in proton minibeam radiation therapy, delivered under a crossfire geometry. A significant increase of the median survival time was obtained when the dose was delivered over two sessions as opposed to in a single fraction. This result could facilitate the path towards pMBRT treatments.
Abstract
(1) Background: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy technique using spatially modulated narrow proton beams. pMBRT results in a significantly reduced local tissue toxicity while maintaining or even increasing the tumor control efficacy as compared to conventional radiotherapy in small animal experiments. In all the experiments performed up to date in tumor bearing animals, the dose was delivered in one single fraction. This is the first assessment on the impact of a temporal fractionation scheme on the response of glioma-bearing animals to pMBRT. (2) Methods: glioma-bearing rats were irradiated with pMBRT using a crossfire geometry. The response of the irradiated animals in one and two fractions was compared. An additional group of animals was also treated with conventional broad beam irradiations. (3) Results: pMBRT delivered in two fractions at the biological equivalent dose corresponding to one fraction resulted in the highest median survival time, with 80% long-term survivors free of tumors. No increase in local toxicity was noted in this group with respect to the other pMBRT irradiated groups. Conventional broad beam irradiations resulted in the most severe local toxicity. (4) Conclusion: Temporal fractionation increases the therapeutic index in pMBRT and could ease the path towards clinical trials.
