ESTRO 36 Abstract Book

S123 ESTRO 36 2017 _______________________________________________________________________________________________

be the same for the two cohorts, supporting current RBE practice. Our alternative hypothesis (H1) was that the radiographic abnormalities would be greater for the proton cohort, suggesting an end-of-range RBE > 1.1. Material and Methods We analyzed follow-up CTs for 10 proton/X-ray patient pairs matched for age, chemotherapy regimen, disease laterality & implant status. 5 patients had a smoking history (4 X-ray, 1 proton), all 20 were prescribed 50.4 Gy in 28 fractions. For brevity, we write ‘Gy’ throughout, but for protons ‘Gy’ should be taken as ‘GyRBE assuming a fixed RBE of 1.1’. Proton TPS doses were recalculated using TOPAS Monte Carlo simulations. Deformable registrations enabled us to calculate changes in median HU value between pre- & post-treatment CTs for dose bins of 2-30 in 2 Gy increments. For each patient’s final (modality-blinded) CT, qualitative abnormality grading was performed by a radiologist. Results Quantitative datasets for a matched pair are included in Fig 1, with the linear regression fits used to calculate our endpoint: ΔHU/Gy. For all scans, Fig 2 plots this endpoint as a function of follow-up time: separation between the proton and X-ray cohorts is clear with proton scans exhibiting higher ΔHU/Gy values. To assess the effect of 'modality” on the Fig 2 data, we used the lme4 package in R to perform a linear mixed effects analysis of log transformed ΔHU/Gy. As fixed effects, we considered 'modality”, 'mean lung dose”, 'change in IV contrast”, 'change in breathhold” plus 'follow-up interval” (without interaction terms). Subject was added as a random effect. A p-value of 0.0007 was obtained for a likelihood ratio test of the full model against the model without modality. Similar results were obtained for analysis of the non- smoker sub-population. A significant difference between the two modalities also arose from our qualitative radiological scoring (Wilcoxon signed rank test, p=0.018, median abnormality score=3/9, for protons, 1.5/9 for X- rays). Conclusion Our data indicate that we should reject H0 in favor of H1, to conclude that the end-of-range proton RBE for lung- density changes >1.1. Experiments have demonstrated that, in-vitro, RBE=1.1 underestimates the capacity of end-of-range protons to kill cells. We studied asymptomatic radiographic changes rather than cell kill, but our work nonetheless supports the thesis that end-of- range variations in proton RBE prove important in-vivo as well as in-vitro.

OC-0246 Proton minibeam radiation therapy spares normal rat brain Y. Prezado 1 , G. Jouvion 2 , A. Patriarca 3 , C. Nauraye 3 , S. Heinrich 4 , J. Bergs 1 , D. Labiod 4 , L. Jourdain 5 , W. Gonzalez-Infantes 1 , M. Juchaux 1 , C. Sebrie 5 , F. Pouzoulet 4 1 CNRS-Imagerie et Modélisation en Neurobiologie et Cancérologie, New Approaches in Radiotherapy, Orsay, France 2 Institut Pasteur, HUMAN HISTOPATHOLOGY AND ANIMAL MODELS, PARIS, France 3 Institut Curie, Orsay Proton Therapy Center, Orsay, France 4 Institut Curie, Experimental radiotherapy platform, Orsay, France 5 University Paris Sud, Imagerie par Résonance Magnétique Médicale et Multi-Modalités, Orsay, France Purpose or Objective The morbidity of normal tissues continues being the main limitation in radiotherapy. To overcome it, we recently proposed a novel concept: proton minibeam radiation therapy (pMBRT) [1]. It allies the physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams (minibeam radiation therapy) [2]. We have recently implemented the technique [3] at a clinical center (Proton therapy center in Orsay). The main objective of this work was to confirm the gain in tissue sparing thanks to pMBRT. Material and Methods The whole brain of 7 week-old male Fischer 344 rats (n=16) was irradiated with 100 MeV protons. Half of the animals received conventional seamless proton irradiation (25 Gy in one fraction). The other rats were irradiated with pMBRT (58 Gy peak dose in one fraction). The average dose deposited in the same target volume was in both cases 25 Gy. The animals were followed up for 7 months. A magnetic resonance imaging (MRI) follow up (10 days, 3 months and 6 months) at a 7T small animal MRI scanner as well as histological analysis were performed. Results Rats treated with conventional proton irradiation exhibited severe moist desquamation and permanent epilation. The MRI and histology analysis showed important brain damage (extensive blood-brain barrier breakdown (BBB), hematomas, necrosis, microglial activation, etc.). See figure 1. In contrast, the pMBRT group presented no skin damage, a reversible epilation and no significant brain damage observed by MRI or histological analysis.