ESTRO 2023 - Abstract Book

S2014

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ESTRO 2023

Results: Median time (days) taken for tumors to reach 1000 mm3 for different treatment groups are shown in the Table 1 below.

Conclusion Conclusions: Our Tumor model is generally unresponsive to Anti-CTLA-4 as a single therapy agent, even though an effect could be observed in the smallest size tumors. An enhanced response was obtained when it was combined with either proton radiation or OXi4503. With increasing the of primary tumor size at treatment, the benefit of combinational therapy decreases, indicating negative co-relation between tumor size at treatment and the resulting efficacy of the combination therapy. There is a possibility of the enhancement being strongly dependent on the extent of damage done prior to anti- CTLA-4 treatment and further investigations are bing carried out to determine the minimum damage for the combination therapy to be effective in smaller size primary tumors. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sk ł odowska-Curie grant agreement No 955625 (Hyperboost; www.Hyperboost-h2020.eu) and a grant from the Danish Cancer Society. Z. Juranyi 1 , Z.S. Kocsis 1 , K. Lumniczky 2 , K. Balázs 2 , P. Ágoston 3 , G. Farkas 1 , G.O. Sándor 1 , G. Székely 1 , T. Major 3 , C. Pesznyák 3 , G. Stelczer 3 , K. Jorgo 3 , L. Gesztesi 3 , C. Polgár 3 , G. Sáfrány 2 1 National Institute of Oncology, Centre of Radiotherapy, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Budapest, Hungary; 2 National Center for Public Health, Dept. of Radiobiology and Radiation Hygiene, Unit of Radiation Medicine, Budapest, Hungary; 3 National Institute of Oncology, Centre of Radiotherapy, Budapest, Hungary Purpose or Objective There is of increasing importance of knowledge of effect of radiotherapy on immune cells due to the advancement of immunotherapies and its combination with conventional therapies. Materials and Methods We recruited prostate cancer patients; 65 Cyberknife therapy (5 x 7.5-8), 55 conventional LINAC teletherapy (28 x 2.5 Gy v. 39 x 2 Gy), 52 high dose rate brachytherapy (HDR, 1 x 19/21 Gy), 69 low dose rate brachytherapy (LDR, 1 x 145 Gy) patients and the median follow up were 36, 48, 48, 60 months, respectively. We performed chromosomal aberration measurements and flow cytometric analysis of the frequency of Treg and NK subsets of immune cells. We compared the side effects between the groups and evaluated the connection between clinical and biological variables. Results The local relapse free survival at 48 months was 95.5 ± 2.5%; 100%; 97.3 ± 2.7 and 93.1 ± 4.7 after LDR, conventional LINAC, cyberknife and HDR therapy, respectively. There were 43.3%; 33.3%; 33.3% and 18.4% late genitourinary ≥ G2 side effects for LDR, conventional LINAC, cyberknife, HDR therapy, respectively. We observed grade 2 late gastrointestinal side effects only after cyberknife (6.7%) and conventional teletherapy (7.2%) and no grade 3 side effects. The dicentrics+rings frequency (/100 cells) at three months after radiotherapy was 5.4 ± 0.6 for cyberknife; 9.1 ± 1.2 for conventional LINAC therapy, 1.1 ± 0.2 for HDR and 2.1 ± 0.2 for LDR therapy. After 12 months, the aberration frequency decreased, but in case LDR and conventional teletherapy, at 48th month, total aberration frequency was still significantly different from baseline. Total aberration frequency baselines were: Cyberknife 4.5 ± 0.5, HDR 3.8 ± 0.6, seed 3.0 ± 0.3, teletherapy 4.1 ± 0.4. Furthermore, we found that chromosome aberrations shortly after radiotherapy correlated significantly with cumulative late side effects. For example, chromatid breaks measured 6 months after LDR therapy, correlated with late genitourinary side effects (r= 0.31, p=0.010). We found that in case of higher radiation induced lymphocyte apoptosis (RILA) value there was less risk of late genitourinary toxicities (p=0.035). We observed long term changes due to radiotherapy in case of LDR patients: For example, CTLA4+ protein saturation (measured by mean fluorescence intensity) on CD4+, Foxp3+ (Treg) cells increased after radiotherapy and it was still significantly different after 36 months from the healthy average. Conclusion We showed that radiotherapy causes damage in the chromosomes of lymphocytes and it changes their immunological properties and distribution of their subpopulations even on a time scale of 3-5 years. PO-2239 Remaining chromosomal and immunological changes years after prostate cancer brachy- and teletherapy

PO-2240 Caspases modulate immunogenic cell death and interferon signaling after radiation and ATR inhibition

A. Eek Mariampillai 1 , S. Hauge 1 , R. Syljuåsen 1