ESTRO 2020 Abstract Book

S1014 ESTRO 2020

level on CD4 + Foxp3 + cells increased after implantation then it showed a decreasing tendency. The fraction of MDSCs showed a significant decrease at all time points up to 24 months. The level of NK cells increased significantly and remained elevated even 36 months after therapy completion. Subpopulations of dendritic cells (DCs, CD123 + , CD11c + ) were elevated before RT, remained elevated up to 6 months after seed implantation and started to decrease to control levels thereafter. HDR RT patients experienced the less urinary inconveniences, IPSS and QoL was the worst directly after teletherapy (16.8 ± 1.4 and 3.0 ± 1.3 in average, respectively). ≥ G2 acute GU side effects (69.9%)and ≥ G2 late GU toxicity (50.0%) were the most frequent after seed therapy. Conclusion These data indicate a radiation effect on the homeostasis of CD4 + cells, persistently elevated Treg levels as a result of seed brachytherapy, temporarily increased fraction of CTLA4 + CD4 + cells with inhibitory phenotype, a persistent effect of radiation on MDSCs, long-lasting increase in the fraction of NK cells even after the end of RT, a direct effect of therapeutic dose accumulation in the normalisation of DC levels. HDR RT caused the less ≥G2 GU and GI acute and late side effects. These values changed in parallel with cytogenetic parameters, suggesting their use as predictive indicator of toxicity. The follow-up period is 5 years, data processing regarding immunological values in the other arms is still in progress. PO-1819 Leukocyte migration towards particle radiation-induced senescence-associated secretory phenotypes T. Walle 1 , T. Beikert 2 , J. Kraske 2 , T. Trinh 2 , A. Tietz 2 , J. Debus 3 , P. Huber 2 1 dkfz/University Hospital/NCT, Oncology/Molecular and Radiation Oncology, Heidelberg, Germany ; 2 dkfz/University Hospital, Molecular and Radiation Oncology, Heidelberg, Germany ; 3 dkfz/University Hospital/HIT, Radiation Oncology, Heidelberg, Germany Purpose or Objective Cytotoxic therapies, such as radiation therapy (RT), induce cellular senescence and subsequent secretion of soluble mediators from tumor cells, which are collectively called the senescence-associated secretory phenotype (SASP). SASP can affect both tumor cells and bystander cells, such as leukocytes and affect their migratory behavior. Here, we comprehensively assessed the effects of photon and particle radiation induced SASP on leukocyte migration. Material and Methods Human tumor cell lines of different tumor type were irradiated using an X-ray machine (Faxitron, Multirad) or with protons or carbon ions using a cyclotron (Heidelberg Ion Therapy Center). Biologically effective doses were determined by clonogenic assays for photon, proton and carbon ion radiation. Cellular senescence was determined by β-galactosidase staining and automated quantification of microscopy images. Tumor cell apoptosis was assessed by Annexin V and 7AAD flow cytometric staining. Chemokine release was analyzed by flow-cytometry based multiplex bead arrays and subsequent leukocyte migration was determined by modified Boyden chamber assays. Results High single-dose photon irradiation induced cellular senescence and SASP with release of different chemokines and growth factors in solid tumor cell lines of different tumor type. SASP limited proliferation and reinforced radiation-induced apoptosis of tumor cells. We observed general and cell line specific effects of SASP on leukocyte migration: SASP triggered migration of NK cells and abrogated migration of monocytes towards different solid tumor cell lines. Higher migration of CD4+ T cells was observed towards pancreatic cancer cells. Comparison of SASPs induced by physical and biological equivalent doses

Conclusion Radiation has a selective, negatively persistent and clinically significant effect on the lymphocytes, whereas the decline of platelets and neutrophils after radiotherapy quickly recovers. The effect on lymphocytes is partly driven by the volume of the body exposed to a given dose of radiation. PO-1818 Cytogenetic and immunological markers to predict side effects and tumour control in cancer patients Z. Juranyi 1 , Z. Kocsis S. 1 , K. Lumniczky 2 , K. Balázs 2 , P. Ágoston 3 , G. Farkas 1 , M. Kun-Gazda 1 , G. Székely 1 , T. Major 3 , C. Pesznyák 3 , G. Stelczer 3 , K. Jorgo 3 , L. Gesztesi 3 , C. Polgár 4 , G. Sáfrány 2 1 National Institute of Oncology, Centre of Radiotherapy- Department of Radiobiology and Diagnostic Onco- Cytogenetics, Budapest, Hungary ; 2 National Public Health Center, Department of Radiation Medicine- Division of Radiobiology and Radiohygiene, Budapest, Hungary ; 3 National Institute of Oncology, Centre of Radiotherapy, Budapest, Hungary ; 4 National Institute of Oncology- Semmelweis University, NIO Centre of Radiotherapy- SE Department of Oncology, Budapest, Hungary Purpose or Objective Biomarkers would be beneficial for predicting individual radiosensitivity and to follow immunological responses due to radiotherapy. Analysis of chromosome aberrations is an established biomarker for absorbed dose and might offer predictive value for late side effects. Recent data provided evidences that radiotherapy might stimulate antitumor immune responses, which may also be important in future immunotherapeutic aspects. Material and Methods Blood samples from 113 prostate cancer patients were collected. According to the type of radiotherapy (RT) patients were divided in four arms: Cyberknife, LINAC, LDR and HDR brachytherapy. Changes in cytogenetic and immune parameters were investigated before, right after then 3, 6, 9, 12, 24, 36 months after therapy. Clinical data were recorded using RTOG/EORTC genitourinary (GU) and gastrointestinal (GI) grade, IPSS (International Prostate Symptom Score) and QoL (Quality of life) questionnaires. Results LINAC and Cyberknife therapy markedly increased the frequency of chromosome aberrations in peripheral blood lymphocytes (4.1 ± 0.4 to16.1 ± 1.8 and 4.1 ± 1.5 to 10.8 ± 4.4 total aberration/100 cells at three months), LDR and HDR therapy caused moderate increase (2.7 ± 0.4 to 6.4 ± 0.6 and 2.5 ± 0.3 to 4.2 ± 0.3), which decreased to baseline at 24 months after RT, except for LINAC. The fraction of CD4 + cells decreased after seed implantation. LDR brachytherapy led to a progressive elevation in the proportion of Treg cells. Proliferation of CD4 + cells was significantly higher before treatment, after brachytherapy the Ki67 expression decreased. CTLA-4