ESTRO 36 Abstract Book

S862 ESTRO 36 _______________________________________________________________________________________________

radiation also affects the release of tumor antigens, the dendritic cell activity and antigen presentation, the presence of immunosuppressive cells in the tumor microenvironment and tumor infiltrating lymphocytes, the regulation of immunogenic cell surface receptors, and immunogenic cell death. However, the balance between pro-tumor and anti-tumor effects is delicate, and the application of immunotherapy in combination with radiotherapy has to be designed very carefully in order to tip the immunomodulatory effect of radiation in the right direction. There are many parameters that can be varied in this equation, including time, dose and fractionation. Therefore, in order to better understand the immunomodulatory effect of radiation, and to be able to optimize the combined treatment, there is a great need for mathematical models. Material and Methods In this work, a mathematical model based on the work by Serre et al. 1 was developed to describe the synergistic effect of immunotherapy and radiotherapy observed in a previous pre-clinical study in glioma carrying rats. 2 Animals with intracranial tumors were given indoleamine 2,3-dioxygenase (IDO) inhibitory treatments with intraperitoneal injections of 1-methyl tryptophan (1-MT), in combination with radiotherapy given as single fractions of 8 Gy. 1 Serre R, et al. Mathematical model of cancer immunotherapy and its synergy with radiotherapy. Cancer Res 76(17):4931–40, 2016. 2 Ahlstedt J, et al. Effect of Blockade of Indoleamine 2, 3- dioxygenase in Conjunction with Single Fraction Irradiation in Rat Glioma. J J Rad Oncol 2(3):022, 2015. Results Using the mathematical model tumor growth and survival curves were simulated, and the parameters of the model were fit to the experimental data. Good agreement for median survival time was achieved both for the two modalities given separately as monotherapies, as well as for the combined treatment, see Figure. Conclusion Conclusion: The simplified mathematical model presented in this work captures the general features of the synergistic combination of IDO-inhibitory immunotherapy and single fraction radiotherapy. The model can be used to explore possible alternative time, dose and fractionation, in order to gain improved insight into the effects of these parameters, and to generate plausible hypotheses for further pre-clinical studies. EP-1600 Delta radiomics of NSCLC using weekly cone- beam CT imaging: a feasibility study J. Van Timmeren 1 , R. Leijenaar 1 , W. Van Elmpt 1 , S. Walsh 1 , A. Jochems 1 , P. Lambin 1 1 Department of Radiation Oncology - MAASTRO, GROW School for Oncology and Developmental Biology - Maastricht University Medical Centre MUMC, Maastricht, The Netherlands Purpose or Objective Currently, prognostic information is commonly derived using radiomics features from medical images acquired prior to treatment. However, the potential of delta

Results A total of 315 simulations were performed. Figure 2 shows the total doses necessary to kill 50% to 99.9% of the tumor cells, depending on the fractionation. The mean (SD) doses (Gy) to kill 99% of the tumor cells were therefore 72 (±14), 68 (±13) and 65 (±12) for fractionations (Gy) of 2, 2.5 and 3, respectively. The mean (SD) doses (Gy) to kill 99.9% of the tumor cells were therefore 107 (±17), 101(±16) and 94 (±15) for fractionations (Gy) of 2, 2.5 and 3, respectively. The foci with GS 7: 4+3 needed significantly higher doses than the foci with GS 7: 3+4 to destroy the tumor cells from 50% to 99.9%, at all fractionations (Mann-Whitney test).

Conclusion Our histopathological specimen based simulations allowed to estimate the total doses necessary to kill the tumor cells, depending on the fractionation. GS: 4+3 tissue appears more radioresistant than GS:3+4 tissue. EP-1599 Mathematical modeling of the synergistic combination of cancer immunotherapy and radiotherapy C. Ceberg 1 , J. Ahlstedt 2 , H. Redebrant Nittby 3 1 Ceberg Crister, Medical Radiation Physic- Lund University, Lund, Sweden 2 Lund University, The Rausing Laboratory, Lund, Sweden 3 Skåne University Hospital, Department of Neurosurgery, Lund, Sweden Purpose or Objective Cancer immunotherapy is a promising treatment modality that is currently under strong development with a large number of ongoing pre-clinical and clinical studies. In an attempt to improve the treatment efficacy combinatorial strategies are explored, and the combination of immunotherapy and radiotherapy is of particular interest, since more than half of all cancer patients already receive radiotherapy as part of their treatment. It is well known that radiation has immunomodulatory effects. In addition to killing off tumor cells as well as immune effector cells,