ESTRO 2023 - Abstract Book

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ESTRO 2023

SARE. 2. It was verified by WB experiments that the symbiotic environment of gut microbiota affected by radiation was activating by the classical NF- κ B pathway, which followed by up-regulation of downstream pro-inflammatory molecules.

PO-2209 Beneficial Effects Of Combining Hypofractionated Radiation Doses With Hyperthermia Temperature

F. Charlemagne Asonganyi 1 , P. M. Sinha 1 , M. K. Sitarz 2 , P. B. Elming 1 , M. R. Horsman 1

1 Aarhus University Hospital, Experimental Clinical Oncology, Aarhus, Denmark; 2 Aarhus University Hospital, Danish Center for Particle Therapy (DCPT), Aarhus, Denmark Purpose or Objective In addition to indirect cell killing through reacting oxygen species (ROS) following stereotactic radiation (SRT) treatment of tumors, the induction of vascular damage also increases the poor microenvironment conditions within tumors. Existing evidence suggests that cells under such conditions are more sensitive to treatment with hyperthermia, thus combining heat with SRT should have greater anti-tumor effects. Objectives: To investigate the potential of combining various hypofractionated schedules with hyperthermia in our C3H mammary carcinoma, which responds to both high radiation doses and heat treatment when injected in the rear leg of our CDF1 mice model. Materials and Methods A C3H mammary carcinoma grown in the right rear foot of CDF1 mice was used when at 200 mm3. SRT (X-rays), involves 1- 5 fractions of 5-25 Gy administered in a one-week period. Hyperthermia entails immersing the tumor-bearing leg in a water bath and heating it at 40.5-42.5OC for 60 minutes starting 30-240 minutes after the final irradiation. Endpoints include tumor growth delay (time to 5x treatment volume; TGT5) or local tumor control at 90 days; 3-days after the final radiation a clamped top-up dose was given to produce a dose-response curve from which the TCD50 value (radiation dose controlling 50% of tumors) was determined. Vascular-mediated effects were estimated using dynamic contrast-enhanced magnetic resonance imaging; the endpoint being the initial area under the uptake curve (IAUC). Statistical analysis involved a Student’s T-test or Chi-squared test (p<0.05 for both). Results The mean (+ 1 S.E.) TGT5 for control tumors was 5 days (+ 0.2) and this significantly increased to 22 days (+ 0.7) following irradiation with 20 Gy. This radiation dose resulted in a small, yet non-significant, 18% (+ 6) decrease in IAUC, Preliminary studies with an SRT treatment of 3 x 15 Gy resulted in a TCD50 value (+ 95% CI) of 30 Gy (+ 8). Heating tumors at 41.5OC 4-hours after the last irradiation significantly decreased this value to 10 Gy (+ 4). Conclusion Conclusions: Our preliminary results with high radiation doses are consistent with some degree of vascular damage and that applying heat after SRT significantly enhanced local tumor control. Additional studies are ongoing to determine the optimal SRT schedule and heat treatment for the greatest anti-tumor response. In addition, the optimal SRT schedules and appropriate temperature would be supplemented with mechanistic studies. 1 Greater Poland Cancer Centre, Radiobiology Laboratory, Pozna ń , Poland; 2 Poznan University of Medical Sciences, Department of Orthopedics and Traumatology, Pozna ń , Poland Purpose or Objective The induction of wound healing response is believed to be one of the reasons for local relapse in breast cancer (BC) patients. In normal tissue, it is necessary for tissue repair. However, induction of adaptive and innate immune response in tumor tissue stimulates cell survival, induction of angiogenesis, and extravasation of circulating tumor cells. Previous studies have shown that surgical wound fluids (SWF) obtained from BC patients after breast-conserving surgery (BCS) stimulated the motility and invasiveness of tumor cells in vitro. Moreover, we have demonstrated that intraoperative radiation therapy (IORT) significantly inhibits the stimulatory effect of SWF on tumor cells in vitro. This effect may be due to both direct cell killing by ionizing radiation and by modulating the tumor microenvironment. Nowadays exosomes are believed to be the most important molecules responsible for cell-to-cell contact and mediate the changes in tumor microenvironment connected to further tumor progression and therapy resistance. We speculate that exosomes are one of the key components of SWF that distinguish BC cells response to BCS and IORT group of SWF. Thus the main aim of this study was to isolate and analyze the exosomes from BCS and IORT patients. Materials and Methods SWF were isolated from BC patients after BCS and BCS followed by IORT. At least 20 SWF were pooled and exosomes were isolated using ultracentrifugation. The electron microscopy, the vesicle range, and the western blot for exosome-specific markers were determined for their validation. In order to determine the miRNA expression profile in exosomes, SWF from 3 BCS and 3 IORT patients were subjected to high-throughput next-generation sequencing. Results We confirmed the presence of exosomes in both SWF from BCS and IORT group. Principal component analysis (PCA) of all differentially expressed miRNAs, revealed that samples from IORT clearly clustered separately from BCS samples. We found 74 miRNA which significantly differentiates both groups of exosomes. Using miRNA databases, we matched miRNA with PO-2210 Exosomal miRNA in postoperative microenvironment of patients with breast cancer treated with IORT K. Kulcenty 1 , M. Lach 2 , I. Piotrowski 1 , W. Suchorska 1