ESTRO 2020 Abstract Book

S1015 ESTRO 2020

(BED) of photon, proton and carbon irradiation, as defined by clonogenic survival, revealed similar effects on leukocyte migration. Carbon ion and photon radiation- induced SASP induced CD4 T cell recruitment towards pancreatic cancer cells and abrogated monocyte recruitment towards melanoma cells. Conclusion Our findings may help to better understand the effects of photon and particle radiation on bystander immune cells, with possible implication for combined immunotherapy applications. PO-1820 Repolarized macrophages, induced by SRS and anti-PD1, mediate long-term survival in murine glioma A. Stessin 1 , M. Clausi 1 , S. Ryu 1 1 Stony Brook University Hospital, Radiation Oncology, Stony Brook- NY, USA Purpose or Objective Glioblastoma multiforme (GBM) is a deadly brain tumor with a short expected median survival, despite current standard-of-care treatment. We explore the combination of high single dose radiation therapy and immune checkpoint inhibitor therapy as a novel treatment strategy for GBM. Material and Methods Mice bearing GL261 intracranial glioma implants were treated with anti-PD1, stereotactic dose RT, or combination thereof, in the presence or absence of T-cell, macrophages, and microglia suppression. MRI was used to monitor tumor growth. Gene expression arrays, immunohistochemistry, and flow cytometry were used to analyze immune cell population dyniamics under conditions of interest. Results We show combined treatment SRS and antiPD1 treatment to be highly effective with a 75% complete pathologic response and dramatically improved survival outcomes in glioma xenograft-bearing mice. We also investigate the roles of different immune cell types. We find both CD8+ T- cells and macrophages to be necessary for the full effect of combined therapy, with T lymphocytes appearing to play a role early on and macrophages mediating a later phase of the combined treatment effect. The combined treatment appears to trigger macrophage repolarization, increasing M1/M2 ratio. Conclusion These findings point to a novel immunologic mechanism underlying the interaction between radiotherapy and immunotherapy. They also provide the basis for clinical investigation of immunogenic dose radiation in combination with immune checkpoint blockade as a potential treatment approach for newly diagnosed high grade gliomas. PO-1821 Investigating immune microenvironment effects of radiotherapy in pre-clinical prostate cancer models Y. Philippou 1 , H. Sjoberg 2 , E.A. Murphy 2 , K. Jones 1 , A. Gordon-Weeks 1 , G. McKenna 1 , G. Uzi 3 , V. Cerundolo 3 , I.G. Mills 2 , F.C. Hamdy 2 , R.J. Muschel 1 , R.J. Bryant 1 1 University of Oxford, Oxford Institute for Radiation Oncology, Oxford, United Kingdom ; 2 University of Oxford, Nuffield Department of Surgical Sciences, Oxford, United Kingdom ; 3 University of Oxford, MRC Human Immunology Unit - Weatherall Institute of Molecular Medicine, Oxford, United Kingdom Purpose or Objective Hypo-fractionated radiotherapy (HF-RT) can enhance anti- tumour immunity, but it is unclear whether this effect can be induced, or harnessed in a multi-modality therapy approach, in the treatment of high-risk locally advanced prostate cancer (PCa). We investigated the temporal

tumour immune microenvironment effects of clinically relevant HF-RT doses delivered to two pre-clinical immunocompetent PCa models. Material and Methods 3x5Gy HF-RT was delivered to 100mm 3 TRAMP-C1 and MyC- CaP subcutaneous flank tumours in syngeneic mice using a Gulmay 320 irradiator (300kV, 10mA) at a dose rate of 2.25Gy/minute. Tumour growth delay and tumour immune microenvironment cellular infiltrates were analysed post- treatment, compared to untreated control tumours, using calliper measurement and flow-cytometry (FACS) analysis respectively. Results 3x5Gy HF-RT caused a significant tumour growth delay in TRAMP-C1 and MyC-CaP tumours compared to untreated control tumours. The mean growth delay to 400mm 3 was greater in TRAMP-C1 than MyC-CaP (27 vs 12 days), suggesting that TRAMP-C1 may be a more radio-sensitive tumour than MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days following initiation of 3x5Gy HF-RT included an increased CD45+ cell infiltrate, comprising primarily tumour-associated macrophages (TAMs) and dendritic cells (DCs) on FACS. At tumour regrowth to 400mm 3 post-3x5Gy HF-RT the tumour immune microenvironment had normalised on FACS compared with control tumours. In contrast, 3x5Gy HF-RT did not cause an increased CD45+ cellular infiltrate in the MyC-CaP tumour immune microenvironment, but resulted in a significantly reduced CD4+helper T-cell infiltrate. Conclusion Clinically relevant 3x5Gy HF-RT resulted in a significant tumour growth delay in both TRAMP-C1 and MyC-CaP pre- clinical PCa allograft models, however this dose of ionising radiation was sublethal with eventual tumour regrowth in both models. 3x5Gy HF-RT resulted in changes within the TRAMP-C1 tumour immune microenvironment at the 7-day time-point, with increased infiltration of TAMS and DCs. However, this effect was not seen in MyC-CaP tumours. Taken together, these results suggest that clinically relevant HF-RT doses can change the immune cellular content of the TRAMP-C1 flank tumour immune microenvironment. Experiments to test the possibility that these immune cell changes may be harnessed in a multi- modality approach to treating high-risk locally advanced PCa in this model are ongoing. PO-1822 PET-CT based metabolic regression velocity following SBRT for spinal oligometstases H. Vyas 1 , S. Vangipuram 1 , A. Bhange 1 , D. Patel 2 , B. Patneedi 1 , K. Ar 1 1 HCG Cancer Centre, Radiation Oncology, Mumbai, India ; 2 Geetanjali Medical College and Hospital, Radiation Oncology, Udaipur, India Purpose or Objective SBRT, predominantly, causes indirect cell kill through (1) Ceramide induced vascular apoptosis which starts few hrs after treatment & peaks around 3rd day (2) immunological alteration in the host tumor microenvironment, a process which starts around 3rd day post-treatment & peaks at 10-12 days. Routine Post SBRT follow up imaging is advocated after 3 months. Present study evaluated the clinicoradiobiolgic response of single or multi-fraction spine SBRT post-treatment for spinal oligometastases with serial FDG PET-CT scans. Material and Methods Five patients with localized spinal metastases with primaries from lung-2, breast - 2, kidney - 1 were included in this proof-of-concept study. Patients were having Poster: Radiobiology track: Radiation and tumour metabolism