ESTRO 2023 - Abstract Book

S2000

Digital Posters

ESTRO 2023

HMGB1 was measured after in vitro irradiation by ELISA. CD276 as a possible target for immunotherapy was measured by flow cytometry. Results Of the eleven collected samples, stem-cell enriched cultures could be established in six cases (one dedifferentiated liposarcoma, two myxoid liposarcoma, one alveolar soft tissue sarcoma, two NOS sarcoma). For one cell line, tu-mor cell content was confirmed by MDM2 amplification also detected by pathology in the tumor tissue of a dedif-ferentiated liposarcoma. Stem cell marker profiles differed between the cell lines. NGFR was detected in all tested cell lines, ALDH1A3 in three cell lines. HMGB1 concentrations was higher in supernatant of primary stem cell en-riched cell lines compared to ATCC cell lines. After irradiation with 16 Gy three of four cell lines showed a signifi-cant increase of HMGB1 in supernatant compared to unirradiated controls, one cell line showed a non-significant increase. CD276 surface abundance was evaluated in SWS872 and showed the highest increase 48h after irradia-tion. Increase was radiation-dose dependent reaching statistical significance after irradiation with 16 Gy. Conclusion Stem-cell enriched cell lines could be established for six of eleven tumor samples of different histologic subtypes. The cell lines differed in their mRNA abundances of stem cell markers. All tested cell lines showed signs of immu-nogenic cell death (HMGB1 in supernatant) after high doses of in vitro irradiation and CD276 expression. As CD276 has been described as an immunotherapy target in pediatric sarcomas and might also be a candidate in adult type soft tissue sarcoma. As the surface abundance was increased after irradiation, combination therapies might be worth investigating. 1 Queens University , Patrick G. Johnston Centre for Cancer Research, Belfast , United Kingdom; 2 Queens University, Patrick G. Johnston Centre for Cancer Research, Belfast, United Kingdom Purpose or Objective Abiraterone acetate and Enzalutamide are novel anti-androgens shown to be one of the few treatments to improve both progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. However, many questions exist regarding the optimal combination and scheduling with radiation, the degree of additivity or synergism, and the underlying mechanisms governing any potential synergy. This study attests to the biological rationale for selecting Abiraterone or Enzalutamide as, currently, the choice of therapy is a clinical decision based on experience and side effect profiles. As well as combinations with external beam radiotherapy, a key unexplored area of interest are the combination of these inhibitors with the α -emitter radium-223, which targets bone metastases, with preliminary studies, such as the ERA-223 study, highlighting the need for further studies to mechanistically determine if these combinations are effective and safe. Materials and Methods To better understand this, we conducted a detailed analysis of the effects of Abiraterone (10 µ M), Enzalutamide (10 µ M) or DMSO (Control) alone or in combination with a dose range of X-rays and radium-223 exposure on cell cycle, DNA damage, DNA repair, cell proliferation and cell viability across a panel of androgen-insensitive (PC3) and androgen-sensitive (LNCaP) prostate models and osteoblastic bone models (SJSA-1, SAOS-2). Results We showed AR suppression in an AR-sensitive setting led to radiosensitivity to X-rays and radium-223, resulting from the downregulation of crucial DSB DNA repair proteins such as RAD51 (HR) and DNA-PK (NHEJ), with reductions in HR at least partially due to cell cycle distribution shifts away from S and G2. This downregulation leads to increased levels of DNA damage and, ultimately, cell death, as observed through increases in sub-G1, which was supported through increased PARP- cleavage expression highlighting increased levels of apoptosis. Conclusion In conclusion, comparisons of Abiraterone versus Enzalutamide have shown Abiraterone to be significantly more effective in inhibiting DNA repair and increased cell death than Enzalutamide, providing a rationale for its selection over Enzalutamide in a clinical setting should side effect profiles not be a consideration. Our results also support using Abiraterone and Enzalutamide in combination with X-rays and radium-223 to enhance tumour response. PO-2224 Abiraterone and Enzalutamide sensitise response to radium-223 by suppressing key DNA repair proteins T. Wright 1 , K. Prise 2 , A. Cole 2 , V. Dunne 2

PO-2225 Characterization of the RBE of various photon radiation qualities on human cancer cell lines

N. Chabaytah 1,2 , J. Babik 2 , J. Li 3,7 , B. Behmand 2 , T. Connell 3 , M. Evans 3 , R. Ruo 3 , H. Bekerat 3,6 , S. A. Enger 3,4,5 , T. Vuong 3,6

1 McGill University, Biological and Biomedical Engineering, Montreal, Canada; 2 Research Institute of the McGill University Health Centre, MPU, Montreal, Canada; 3 Medical Physics Unit, McGill University, Oncology, Montreal, Canada; 4 Research Institute of the McGill University Health Centre, Oncology, Montreal, Canada; 5 Lady Davis Institute for Medical Research, Jewish General Hospital , Oncology, Montreal, Canada; 6 Jewish General Hospital, Oncology, Montreal, Canada; 7 Lady Davis Institute for Medical Research, Jewish General Hospital, -, Montreal, Canada Purpose or Objective To investigate the relative biological effectiveness of different photon-based radiation qualities, on various human cancer cell lines: HeLa (cervix), PC-3 (prostate) and HCT116 (rectal).