ESTRO 2020 Abstract Book

S270 ESTRO 2020

Purpose or Objective Synchrotron Microbeam Radiation Therapy (MRT) is a pioneering radiotherapy technique that spatially fractionates the beam of synchrotron X-rays into an array of quasi-parallel micro-planar beamlets. MRT is effective at delaying and even suppressing the growth of several types of tumors, with minor collateral effects on the normal tissue. One of our studies, conducted in rodents, demonstrated that MRT elicited a minor degree of pulmonary fibrosis compared to synchrotron Broad Beam (BB) radiotherapy even at 600 Gy peak-dose and one year post-irradiation (pi). The aim of this project is to elucidate the early cellular and molecular mechanisms responsible for comprehensive tissue repair and minor degree lung fibrosis after MRT. Material and Methods To identify the underlying mechanisms, we established an ex-vivo mouse model of lung tissue slices (Fig.1). To the latter synchrotron MRT was applied (50 µm wide beams; 400 µm center to center) with peak-doses of 100, 200, 400 and 800 Gy. Immunostaining and confocal microscopy were performed at different time points: 1h, 4h, 12h, 24h and 48h pi.

Results A strong correlation between LET and RBE was found for prostate carcinoma- and melanoma cells (α/β < 4.5)(Figure 2). For both low α/β cell lines RBE values between 1.28 and 1.76 were determined, with highest RBE values at the distal SOBP positions. Cell lines with a high α/β ratio showed only a marginal LET-dependency; however, RBE values between 1 and 1.3 were observed for head-and- neck cancer squamous cell carcinoma cells and normal keratinocytes (α/β > 10).

Results The γH2A.X staining revealed persistent robust DNA damage in the cellular compartments exclusively within the beam paths after all doses up to 24h pi. Staining for type IV collagen does not reveal any structural damage to the basement membrane and ECM at all time points (Fig.2). Accumulation of macrophages negative for γH2A.X were observed along the beam paths over time suggesting that macrophages migrated from the “valley” regions between the beams.

Conclusion The intrinsic α/β ratio of a tissue appears to be a primary influencing factor for the RBE of protons and its sensitivity towards LET changes. These findings indicate a rational patient stratification according to the individual malignancy type and location. Patients with tumours with comparably lower α/β ratios than the surrounding normal tissues may benefit most from proton therapy. Tumours with high α/β ratios in close proximity to organs at risk with low α/β ratios, may respond less while an increased risk for developing significant late adverse effects can be expected. PH-0480 Early repair mechanisms after Synchrotron Microbeam Radiation Therapy in normal lung tissue V. Trappetti 1 , C. Fernandez-Palomo 1 , P. Pellicioli 2 , V. Djonov 1 1 University of bern, Institute of Anatomy, Bern, Switzerland ; 2 Grenoble Alpes University, European Synchrotron Radiation Facility, Grenoble, France

Conclusion The presented data support our hypothesis: (i) microbeams damage the cellular components within the beam path. (ii) The intact macrophages from the surrounding “valley” regions infiltrate and remove cell debris from the beam path. (iii) In the next step, the unaffected lung cells repopulate the “beam” region using the basal membranes as a scaffold. PH-0481 Synchrotron Microbeam Radiation Therapy increases the therapeutic index for brain tumor treatment. L. Eling 1 , A. Bouchet 1 , A. Ocadiz 1 , J. Adam 1 , H. Elleaume 1 , M. Krisch 2 , J.A. Laissue 3 , J. Balosso 4 , R.