ESTRO 2020 Abstract Book

S1011 ESTRO 2020

Results 128 plasma samples were collected from 47 patients (26 SBRT, 21 CRT). 36 proteins showed an altered protein expression which differed at least 50% from baseline; 2 in the SBRT group and 34 in the CRT group. In the SBRT group, NCF2 and NMNAT1 proteins, both involved in superoxide production, were increased at time point 2. In the CRT group, the most notable results were an increase in proteins involved in T-cell immunity (IFN-γ, CCL17, CXCL11) at time point 3 and, according to the KEGG analysis, a decrease of cell adhesion molecules (CD22, CD6) and proteins involved in NK cytotoxicity and graft vs. host reactions (KIR3DL1, FASLG, KLRD1). The variability between patients was small. (Fig. 1: CRT summary)

attained at 10 weeks after IORT (60.20% to 67.10%). A progressive decrease of Treg CD4+CD25+Foxp3+Helios subpopulation, with the lowest values at 3 weeks (38.50% to 27%, p = 0.454) was observed. Changes in MDSCs after IORT were not found (p = 0.11). Conclusion The administration of a single dose of IORT altered the balance of peripheral immune cells by increasing NK cells and cytotoxic T lymphocytes, while decreasing Treg cells without changes in MDSCs. This treatment modality may be an effective approach to improve antitumor immunity, which is a relevant finding for supporting future combinations of IORT with immunotherapy for treating breast cancer patients. PO-1813 Plasma biomarkers of immunogenic cell death during and after SBRT and concurrent chemo-RT for NSCLC. K. Reynders 1,2 , A.D. Garg 3 , E. Van Limbergen 1 , P. Agostinis 3 , J. Vansteenkiste 4 , L. Hendriks 5 , K. Rouschop 6 , Developmental Biology- Maastricht University Medical Centre+, Department of Radiation Oncology, Maastricht, The Netherlands ; 2 KU Leuven, Laboratory of Experimental Radiation Oncology, Leuven, Belgium ; 3 KU Leuven, Laboratory for Cell Death Research and Therapy CDRT- Department of Cellular and Molecular Medicine, Leuven, Belgium ; 4 University Hospitals KU Leuven, Respiratory Oncology Unit, Leuven, Belgium ; 5 GROW School for Oncology and Developmental Biology- Maastricht University Medical Centre+, Department of Pulmonary Diseases, Maastricht, The Netherlands ; 6 MAASTRO- GROW School for Oncology and Developmental Biology- Maastricht University Medical Centre+, Maastricht Radiation Oncology Lab, Maastricht, The Netherlands ; 7 Olink Proteomics, Scientific Advisor, Watertown- MA, USA ; 8 University Hospitals KU Leuven, Department of Radiation Oncology, Leuven, Belgium Purpose or Objective Radiotherapy (RT) is capable of inducing pro-immunogenic cell death (ICD), antigen upregulation and T-cell attraction. To the best of our knowledge, no data are available on the expression and evolution of ICD markers during RT for non-small cell lung cancer (NSCLC). In this exploratory, prospective study, we investigated a set of comprehensive ICD markers at different time points during RT. Material and Methods Patients with newly diagnosed NSCLC scheduled to receive stereotactic body radiotherapy (SBRT) for stage I disease or concurrent radiotherapy (≥ 60 Gy/2Gy) and cisplatin- doublet chemotherapy (CRT) for stage III were included. Excluded were chronic corticosteroid or NSAID use, active auto-immune diseases or immunosuppressive medication. Plasma samples were collected at three time points: immediately before treatment, before the second/third fraction for SBRT or CRT, respectively, and immediately after the last or second last fraction for SBRT or CRT, respectively. Comprehensive proteomic analysis was performed using a multiplex proximity extension assay that enabled detection of more than 1000 proteins simultaneously. A linear mixed model with maximum likelihood estimation for model parameters was used to detect proteins with an average concentration change of at least 50% from baseline to subsequent time points and to analyze differences between treatment groups. Significant differences were determined after Benjamini and Hochberg multiple hypothesis correction. A Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping to look for differences in protein relation networks between the time points was done. The trial was approved by the ethics committees and listed under clinical trial number: NCT02921854. M. Rucevic 7 , M. Lambrecht 8 , D. De Ruysscher 1 1 MAASTRO- GROW School for Oncology and

Conclusion We detected treatment associated differences in multiple proteins involved in the innate and adaptive immune system using a comprehensive proteomics approach. Clear differences emerged between SBRT and CRT. These results are the basis for further studies to unravel the optimal priming of the immune system by RT. PO-1814 RT-induced abscopal effect despite unfavorable pretreatment immune signature E. Firat 1 , T. Watanabe 1 , J. Scholber 1 , R. Luo 1 , N. Ehrat 1 , F. Meiss 2 , G. Niedermann 1 1 Uniklinik Freiburg, Dept. of Radiation Oncology, Freiburg, Germany ; 2 Uniklinik Freiburg, Dept. of Dermatology and Venerology, Freiburg, Germany Purpose or Objective Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB), but clinical trials so far suggest only limited success. We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Material and Methods Pretreatment tumor material obtained a few weeks before ICB and concomittant early SBRT was analyzed by bulk whole-exome sequencing and immunohistochemistry. In addition, PBMCs were analyzed at various time points by flow cytometry. T cell responses to differentiation antigens and to neoepitopes were also characterized. Results Patient 1 had a favorable pretreatment immune signature, indicating the presence of large numbers of exhausted T cells, and immediately showed a complete response (CR), now already lasting for 4 years. Patient 2 had an unfavorable pretreatment immune signature, indicating a prevalence of immunosuppressive myeloid cells. Nonetheless, he showed a metabolically complete systemic response following a second SBRT after progression on long-term anti-PD-1 (> 10 months) and the first SBRT, i.e., a strong RT-induced abscopal effect. However, after 2.5 years, his disease progressed. Upon initiation of ICB and the subsequent first SBRT, patient 1, who rapidly developed a CR, showed a stronger increase in Ki67+ CD8+ T cells compared to the pretreatment levels