ESTRO 37 Abstract book

S298

ESTRO 37

Conclusion Our results show that the tissue sparing effect of proton minibeams is highest in the superficial parts of the beam channel whereas it is possible to create almost homogenous irradiation in the tumor area, which could be used to obtain tumor control while sparing the surrounding healthy tissue. However, as even larger minibeams have significantly reduced acute side effects than a broad beam, proton minibeam radiotherapy may offer various possibilities for new approaches in clinical proton and/or heavy ion radiotherapy. Skin fibrosis as a radiation induced late effect is currently investigated 90 days after irradiation. Supported by the DFG Cluster of Excellence: Munich- Centre for Advanced Photonics. PV-0571 Transcriptomic changes in fibroblasts irradiated with proton beam scanning or Co-60 gamma rays S. Nielsen 1 , N. Bassler 2 , L. Grzanka 3 , J. Swako ń 3 , P. Olko 3 , C.N. Andreassen 1 , J. Overgaard 1 , J. Alsner 1 , B.S. Sørensen 1 1 Aarhus University Hospital, Experimental Clinical Oncology, Aarhus, Denmark 2 Stockholm University, Medical Radiation Physics- Department of Physics, Stockholm, Sweden 3 Institute of Nuclear Physics Polish Academy of Sciences, Proton Radiotherapy Group, Kraków, Poland Purpose or Objective Proton pencil beam scanning delivers a more conformal dose distribution than the best photon modality thereby diminishing low and medium dose levels to the normal tissues. Proton radiobiology studies have primarily focused on identifying the relative biological effectiveness (RBE) of proton radiation. It is becoming evident that the RBE increases along the proton track as the linear energy transfer (LET) reaches maximum levels at the distal end of the spread-out Bragg peak. Transcriptomic changes in normal tissues receiving sublethal proton radiation doses have only been scarcely studied. At this point, it is still unclear whether proton beam scanning and photon radiation induce equivalent changes in the coding transcriptome. The aim of the present study was to identify signal transduction pathways regulated differently by relatively low and high LET proton beams. These differences were also compared with pathway regulation in Co-60 irradiated fibroblasts. Material and Methods The study used 12 primary subcutaneous fibroblast cell cultures. Mono-layered fibroblasts were irradiated at positions in the entrance and SOBP distal edge of the proton beam profile. Dose was delivered in 3 fractions x 3.5 GyE (RBE 1.1). Cobalt-60 irradiation was used as reference. RNA sequencing was performed using Illumina NextSeq 500 with high-output kit. The Tuxedo suite protocol was employed for data analysis. Real-time qPCR will be performed to validate RNA-sequencing findings. Results Cytokines involved in modulation of the JAK-STAT and MAPK/ERK pathways appear to be more heavily upregulated in fibroblasts irradiated with Co-60 gamma rays than in proton irradiated fibroblasts; irrespective of LET. The profibrogenic genes COL3A1 and COL3A3 coding subunits of collagen type III are more upregulated by the relatively high LET at the distal edge of the SOBP compared with the lower LET at the entrance region. Conclusion Upcoming pathway analysis will disclose whether signal transduction is altered in pathways critical for development of normal tissue damage and secondary cancers depending on the radiation quality. An improved understanding of the transcriptomic changes in normal tissues will undoubtedly be helpful in optimizing proton therapy in the future.

PV-0572 Biological effects by the next generation of ultra-fast dose rate ionizing radiation ‘FLASH’ H. Kim 1 , B. Hong 2 , E. Shueler 3 , M. Rafat 3 , P. Maxim 3 , B.J. Loo 3 , G. Ahn 2 1 Seoul National University College of Medicine, Radiation Oncology, Seoul, Korea Republic of 2 Pohang University of Science and Technology, Integrative Biosciences & Biotechnology, Pohang, Korea Republic of 3 Stanford University School of Medicine, Radiation Oncology, Stanford, USA Purpose or Objective Ultra-fast dose rate irradiation (>50 Gy/s), the prototype called "FLASH" is currently being developed in order to see whether it could increase therapeutic effect. In this study we irradiated tumors at a single high dose either by FLASH or conventional (CONV) irradiation to determine their biological effects in tumors. Material and Methods Syngeneic Lewis lung carcinomas (LLC) were grown subcutaneously in C57BL/6 mice in the back and irradiated with either CONV or FLASH irradiation in a single dose of 15 Gy. We performed immunoflourescent staining on tumor sections that were harvested before irradiation (d-1), at 6 hours (d0), or 2 days (d2) after irradiation for endothelial cells and hypoxia by using CD31 antibodies and pimonidazole, respectively. Phosphorylated myosin light chain (MLC) or γH2AX was determined by western blot in human microdermal vascular endothelial cells (HMDVEC) and LLC in vitro. Results High dose CONV radiation resulted in a rapid and reversible tumor vasculature collapse, which did not occur with high dose FLASH irradiation as determined by CD31 area densities, indicating that the biological effects differ between CONV and FLASH. By performing western blot, 15 Gy irradiation resulted in higher expression of phosphorylated MLC, a molecule involved in cellular contraction, in LLC but not HMDVEC. Also, prolonged accumulated DNA damage, as assessed by phosphorylated γH2AX in LLC was observed at this time point. Conclusion Our results indicate that FLASH produces a novel pathway of tumor cell damage, which may lead to a significantly better therapeutic response in vivo. SP-0573 Science diffusion and education at a global level: how to tackle? V. Valentini 1 1 Università Cattolica del Sacro Cuore, Gemelli ART, Rome, Italy Abstract text Science diffusion and education at a global level: how to tackle?The recent social and technological developments open new perspectives for education and Science diffusion, representing a fascinating challenge to tackle in the contemporary global village.Science has become more accessible and communicable thanks to the information technologies developed in the last years, but their real advantages and pitfalls should still be understood.Will these technologies and the new global approaches to knowledge change our definition of Science?Would they alter our way of think, do and share Science? How will the quality of Science diffusion survive to mass-social networks, cyber incompetence and fake news?Will scientists be able to take advantage of such technologies to enhance research networking and create Symposium: Planning future global radiotherapy services