ESTRO 2023 - Abstract Book

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ESTRO 2023

With fractionated irradiation, SCC viability was significantly reduced in the 5:1 group compared with the TR146 alone group at both 6Gy and 15Gy (p<0.0001). There was no significant difference in cell viability between the TR146 groups irradiated with 6Gy or 15Gy. There was significantly reduced SCC viability in the 5:1 group at 6Gy over 3 fractions compared with 15Gy over 3 fractions (p=0.008). Conclusion We demonstrate that NK cells increase radiation-mediated cell death of radioresistant HN-SCCs. Furthermore, our findings suggest that NK cells present in the tumour microenvironment prior to irradiation are more integral to radiation-mediated SCC cell death than NK cells recruited to the tumour post-irradiation. This co-culture model will also enable the study of interactions between cancer, NK cells and the wider tumour micro-environment.

PO-2214 Dose Rate in External Beam Radiotherapy: Missing Piece of the Puzzle?

M.T. Yilmaz 1 , M.E. Gedik 2 , A. Gok 3 , A. Caglayan 4 , F.Y. Yedekci 1 , S. Aydin Dilsiz 5 , G. Gunaydin 6 , A. Akyol 7 , P. Hurmuz 1

1 Hacettepe University Faculty of Medicine, Radiation Oncology, Ankara, Turkey; 2 Hacettepe University, Basic Oncology, Ankara, Turkey; 3 Hacettepe University, Stem Cell Research and Application Center, Ankara, Turkey; 4 Hacettepe University Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey; 5 Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey; 6 Hacettepe University Faculty of Medicine, Basic Oncology, Ankara, Turkey; 7 Hacettepe University Faculty of Medicine, Pathology, Ankara, Turkey Purpose or Objective The fact that treatment can be given at a limited dose rate range in external radiotherapy (ERT) applications with crude delivery techniques and devices have caused the dose rate to be ignored for a long time. Recently dose delivery technology has been rapidly evolving and the biological effects of high dose rates are a matter of interest. It is also known that interactions within the tumor microenvironment (TME) play a vital role in tumor response and treatment resistance. Herein we aimed to investigate the effect of three frequently used dose rates on TME. Materials and Methods To establish the tumor model, 1 million (cell count optimized by pilot experiments) B16-F10 malign melanoma cells were injected subcutaneously into the right flank of C57BL/6 mice. The ERT time of the tumor was determined as 0.5 cm in diameter. Fifty-four mice were randomized to 2 different doses (2 Gy and 10 Gy) and 3 different dose rates (1 Gy/min, 6 Gy/min, 14 Gy/min) and the control group. The tumor of the mice was followed by daily vernier scale measurements. Sacrification was performed on the 7th day after ERT. Intracardiac blood was collected for comet assay, and tumor & metastatic organs were harvested and examined histomorphological and immunohistochemically. Results After irradiation, the mean tumor size in the 10 Gy arm was smaller than the 2 Gy and control arms (p<0.01 and p=0.007). There was no significant difference between the 2 Gy and control arms in tumor size (p=0.53). Additionally, there was no significant difference in tumor sizes at different dose rates for low and high doses (p=0.12, p=0.21). DNA damage to blood mononuclear cells in the control arm was less than in the 10 Gy arm (p=0.04). No DNA damage difference was observed between the 2 Gy and 10 Gy arms (p=0.65). Each dose arm was evaluated in terms of dose rates and no significant difference was found (p= 0.79, p=0.24). The number of mitosis per 10 HPF was assessed in the histopathological evaluation. The number of mitoses in the 10 Gy arm was less than in the 2 Gy arm (p=0.001). There was no significant difference at different dose rates in the 2 Gy and 10 Gy arms (p=0.28, p=0.97). The pleomorphism score was evaluated as mild-moderate and severe (score 1-2-3). The pleomorphism score in the 10 Gy arm was higher than the 2 Gy and control arm (p<0.01) (Figure). There was no difference between the 2 Gy arm and the control arm (p=0.04). Pleomorphism scores were similar at different dose rates at low and high doses (p=0.35, p=0.58). There was no difference in the staining pattern with aSMA and SOX-10 between different dose rates.

Conclusion In our study involving the B16-F10 syngenic tumor model, we could not find a significant effect of three different dose rates on TME. However, it is possible to reach higher dose rates with continuously developing treatment techniques. For this reason, dose rate should be stated as a treatment variable in protocols. "This project was supported by the TÜB İ TAK, Short Term R&D Funding Program."