ESTRO 38 Abstract book

S6 ESTRO 38

to find agents less toxic to the normal tissues. Preclinical studies are useful in this regard and use of image-guided radiotherapy in small animals allows the treatment to more closely mimic the radiotherapy delivered in human patients. We have used our small animal radiation research platform (SARRP) to both treat orthotopic tumours in the bladder and to investigate normal tissue toxicity. As longer term in vivo studies of bladder cancer irradiation are hampered by the need to avoid small intestine, we have developed a method of irradiating bladder and large intestine/rectum only by treating the mice head down, which employs gravity to move the small intestine from the radiotherapy field. Image guidance allows us to verify that there is no small intestine in the proposed field. We also use image guidance to treat mice for longer term toxicity studies, which include histological endpoints in the bladder and intestine evaluated by a veterinary pathologist and also functional assays including stool assessments. Much of this work has only been made possible with the advent of small animal image-guided radiotherapy. SP-0015 RBE of protons: what can we learn from preclinical models? C.P. Karger 1 1 German Cancer Research Center DKFZ, Department of Medical Physics, Heidelberg, Germany Abstract text Proton therapy allows highly conformal tumor irradiation and thereby sparing of neighboring healthy tissues. Compared to photon treatments, proton irradiation exhibit a higher biological effectiveness, which is currently considered by a fixed RBE of 1.1. Recent in-vitro data, however, indicate that the RBE at the distal edge of the Bragg-peak may increase up to values of 2 [1] and beyond and models have been developed [2-5], which describe this increase as a function of LET, dose and cell- specific parameters. This increase could potentially increase the risk of side effects in normal tissue structure behind the distal edge of the spread-out Bragg-peak. While the clinical relevance and the need to introduce these models in patient treatments is controversially discussed [6, 7], strong supportive data from in-vivo experiments and patients are still lacking. This presentation gives an overview on existing data in animal models and discusses their impact and limitations on clinical conclusions. The needs for further research will be outlined. References 1. Britten, R.A., et al., Radiat Res, 2013. 179(1): p. 21-8. 2. Jones, B., Acta Oncol, 2017. 56(11): p. 1374-1378. 3. Carabe, A., et al., Phys Med Biol, 2012. 57(5): p. 1159- 72. 4. McNamara, A.L., et al. Phys Med Biol, 2015. 60(21): p. 8399-416. 5. Wedenberg, M., et al., Acta Oncol, 2013. 52(3): p. 5808. 6. Buchsbaum, J.C., Int. J. Radiat. Oncol. Biol. Phys, 2017. 97(5): p. 1085-1086. 7. Paganetti, H., Int J Radiat Oncol Biol Phys, 2015. 91(5): p. 892-4. SP-0016 Dynamics Changes in Immune Cells During Glioblastoma Response to Treatment: Macrophages at Play L. Akkari 1 1 Netherlands Cancer Institute, Tumor Biology and Immunology, Amsterdam, The Netherlands Abstract text New insights into the role of innate immune subsets in cancer requires a thorough investigation of the molecular mechanisms responsible of their evolution in the course of

Biol Phys. 2013 [10]Nwankwo O et al Radiat Oncol. 2015 [13]Arimura H et al. J Radiat Res. 2018.[14]Tagliaferri L et al. J ContempBrachytherapy. 2017 [16]Massaccesi M et al. Acta Oncol. 2015

Symposium: Mouse models: Animal models the next step for RT

SP-0013 Linking radiation-induced damage to systemic effects: what can we learn from preclinical models of normal tissue complications V. Jendrossek 1 1 University Hospital Essen, Institute of Cell Biology Cancer Research- Department of Molecular Cell Biology, Essen, Germany Abstract text Radiotherapy (RT) is part of standard treatment for lung cancer patients but disease progression is common. Herein biological factors such as high intrinsic or microenvironment-mediated radiation resistance of the cancer cells and potentially tumour immune escape limit successful RT or combined radiochemotherapy (RCT). Moreover, adverse late effects in the highly radiosensitive normal lung preclude the use of curative doses leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. Historically, RT has been introduced as a highly efficient and spatially accurate local therapy. But under certain conditions RT can also elicit systemic effects that impact treatment outcome in normal and tumor tissues locally and occasionally at non-irradiated tumour sites outside the radiation field (abscopal effects). Elegant work in preclinical models in mice has demonstrated that the systemic effects of ionizing radiation are immune mediated. Further experimental work has helped to substantially advance our understanding of the contribution of radiation-induced immune changes in the pathogenesis of radiation-induced adverse late effects e.g. in the lung. The presentation will introduce the molecular and cellular processes that link radiation- induced DNA-damage to activation of cells from the innate and adaptive immune system, highlight the dual face of radiation-induced acute and chronic immune changes in normal and tumour tissues, and discuss the importance of dose and fractionation for RT-induced immune changes. Finally, the presentation will discuss the use of radiation- induced immunoregulatory mechanisms as therapeutic targets that may allow to limit RT-induced adverse late effects and to increase the therapeutic gain of RT. Such compounds may be of future clinical relevance in view of the increasing interest in combining RT with immune checkpoint blockade or other immune modulators to enhance the immune response against the tumour. SP-0014 New developments in small animal image guided radiotherapy: Bladder cancer A. Kiltie 1 1 CRUK/MRC Oxford Institute for Radiation Oncology, Dept. of Oncology, Oxford, United Kingdom Abstract text Muscle-invasive bladder cancer can be treated clinically by bladder removal (cystectomy) or bladder preservation, where the patient keeps their native bladder. Trimodality therapy, with complete transurethral resection of the tumour followed by concurrent chemoradiation, with or without neoadjuvant chemotherapy is the current standard of care, although many elderly patients receive only radiotherapy alone, due to the toxicity of current radiosensitising agents. There is therefore an urgent need