ESTRO 38 Abstract book

S72 ESTRO 38

returned to baseline function. Late grade 4 GU toxicity (long-term urinary catheter) was observed in 1 patient. Conclusion MR-guided salvage brachytherapy appears to have a favourable therapeutic index in the post-RT local recurrence setting with minimal long-term toxicity. Focal brachytherapy alone may have comparable outcomes to whole gland treatment. Further study is needed to improve patient selection, and to determine optimal target volumes and dose schedules.

OC-0151 Radiation and PI3K-αδ inhibitor enhanced anti-tumor effect of PD-1 blockade in syngeneic tumor model I.A. Kim 1,2,3 , J.M. Park 3 , J.H. Lee 1 , D. Kim 1 , Y. Lim 1 1 Seoul National Univ. Bundang Hospital, Radiation Oncology and Medical Science Research Institute, Seongnam- Gyeonggi-Do, Korea Republic of; 2 Seoul National University College of Medicine, Radiation Oncology, Seoul, Korea Republic of; 3 Seoul National University Graduate School of Medicine, Tumor Biology and Cancer Research Institute, Seoul, Korea Republic of Purpose or Objective Breast cancer has been showing relatively poor response to immune checkpoint blockades potentially due to low immunogenicity of tumor and immunosuppressive tumor microenvironment. Radiation (RT) has been showing immune stimulatory effect and PI3Kδhas immune suppressive effect via modulation of regulatory T cell (Treg). Therefore, we hypothesize that in situ tumor vaccination via RT and suppression of immune tolerance via PI3Kδ inhibition could enhance the clinical efficacy of immune checkpoint blockade. As PI3KA controls a key oncogenic signaling pathway, we evaluated whether RT or novel PI3Kaδ inhibitor or both could enhance the efficacy of antitumor effect of a PD-1 blockade in immune competent syngenic triple negative breast cancer (TNBC) model. Material and Methods 4T1 murine breast cancer cells were grown subcutaneously in the hind limb of BALB/c mice. The mice were grouped as following seven groups: control, RT, PI3Kαδ inhibitor, PI3Kαδ inhibitor+ RT, PD-1 blockade, PD-1 blockade + RT, and triple combination group. Tumors were irradiated using 24 Gy/3 fractions. PD-1 blockade (10 mg/kg) and PI3Kαδ inhibitor (4 mg/kg) were administered every other day for two weeks, respectively. Tumor size was measured periodically using a Vernier caliper and bioluminescence imaging to evaluate efficacy of each modality and combination therapy. Immune-modulatory function was evaluated using FACS, Elispot assay and immunohistochemical (IHC) staining. Results Triple combination of RT, PD-1 blockade, and PI3Kαδ inhibitor significantly delayed tumor regrowth whereas PD-1 inhibitor alone showed only modest effect in 4T1 syngenic TNBC model. FACS and IHC study for immune repertoire using tumor samples showed that RT and PD-1 blockade modestly increased the proportion of cytotoxic CD8+ T cells and PI3Kαδ inhibitor led to decrease the proportion of Treg. Triple combination showed remarkable increase of cytotoxic CD8+ T cells suggesting synergistic immune modulatory effect of RT, PD-1 blockade and PI3Kαδ inhibitor. Triple combination led to significant upregulation of c-GAS/STING pathway in tumor and increased IFN-g level in blood compared to each modality alone. Conclusion Taken together, combination of RT and PI3Kαδ inhibitors maximized immune stimulatory effect in immune competent syngenic TNBC model and enhanced the response of PD-1 inhibitor via non-redundant synergistic immune modulatory effect. This study provides a preclinical rationale for the combination of PI3Kαδ inhibitor and RT with PD-1 blockade to overcome the immune tolerance of breast cancer. (Work supported by the grants from Korean Ministry of Science, Technology, Information & Communication, NRF#2017R1A2B4002710 & #2017M2A2A7A01018438 to In Ah Kim) OC-0152 IDO inhibition strongly enhances effects of combined hRT and PD1/PD-L1 checkpoint blockade T. Watanabe 1,2 , G. Niedermann 1,3 1 University of Freiburg, Department of Radiation Oncology- Faculty of Medicine, Freiburg, Germany;

Joint Symposium: ESTRO-CARO: Functional imaging in RT: from biology to guidance

SP-0148 Developments in techniques and processing tools for functional imaging in radiotherapy Sara Leibfarth 1 , René M. Winter 1 , Simon Böke 1,2,3 , Daniela Thorwarth 1,3 1 university Hospital Tübingen, Section for Biomedical Physics, Tübingen, Germany 2 University Hospital Tübingen, Department of Radiation Oncology, Tübingen, Germany 3 German Cancer Consortium Dktk- Partner Site Tübingen, and German Research Center Dkfz- Heidelberg,Tübingen, Germany Abstract text Functional imaging may be highly beneficial for radiotherapy (RT) planning, response monitoring, and follow-up. In magnetic resonance (MR) imaging, diffusion weighted MR (DW-MR) and dynamic contrast enhanced MR (DCE-MR), are promising functional imaging methods. PET tracers with potential benefit for RT are FDG and dedicated hypoxia tracers such as FMISO. Combined PET/MRI represents a technology allowing for simultaneous, intrinsically registered PET and MR data. In this talk, one focus will be on deriving quantitative parameter maps from functional imaging, discussing models for parameter extraction from DWI, DCE and dynamic FMISO acquisitions. In addition model-free, data- driven approaches such as principal component analysis will be discussed as an alternative approach for parameter map generation. Another focus will be on approaches to combine single functional parameter maps into multiparameteric models for specific tasks, such as the distinction between tumor- and non-tumor tissue, the characterization of local tumor biology, and response evaluation. Such models might in the future allow for individually adapted treatment approaches based on multiparametric functional imaging. SP-0149 Functional imaging in preclinical models for exploring new radiotherapy strategies S. Stapleton 1 1 Massachusetts General Hospital, Massachusetts, USA

Abstract not received

SP-0150 Using functional imaging as a guidance and decision tool in radiotherapy M.Milosevic 1 1 Princess Margaret Cancer Centre Department of Radiation Oncology

Abstract not received

Proffered Papers: RB 2: How to exploit immunogenic cell death mechanisms in radiotherapy