ESTRO 2022 - Abstract Book

S1621

Abstract book

ESTRO 2022

Ultra-high dose rate irradiation (FLASH) is a novel therapeutic modality that has been reported to spare tissues compared to conventional dose rate. We aimed to investigate the effect of FLASH on head and neck (H&N) cancer cells and salivary gland dysfunction caused by radiotherapy. Materials and Methods H&N cancer cells (HSG and FaDu) were irradiated with 10 MeV electron beam at a dose rate of 132.2Gy/s (FLASH) or 0.1Gy/s (CONV), by a modified clinic linear accelerator. The irradiated dose was confirmed with EBT-XD film, and 3, 7, and 11 Gy were irradiated. We evaluated the cell cycle and the surviving fraction of cells with clonogenic assays. We administered single dose head and neck irradiation to mice with a 6 MeV electron beam at dose rate of 105.6-126 Gy/s (FLASH) or 0.03Gy/s (CONV), using a modified linear accelerator. The irradiated dose was confirmed with EBT3 film, and 9-76 Gy and 10-30 Gy were irradiated for FLASH and CONV, respectively. Parotid and submandibular glands were obtained from mice at 3 and 30 days after irradiation. Immunohistological examination and apoptotic assays were conducted to assess the radiation response. Results The proportion of sub G0/G1 was higher in the FLASH group, and the surviving fraction was significantly decreased in FLASH through every dose range. At three days post-irradiation, both 10 Gy and 30 Gy irradiated groups showed a greater number of salivary cells and increased expression of AQP5 in FLASH compared to conventional irradiated mice. As a late toxicity (30 days of irradiation), fibrosis did not show any significant difference, although FLASH group received much higher radiation dose. There was no difference in apoptosis between groups on post 3 days, but FLASH showed significantly less degree of apoptosis on 30 days after irradiation. Conclusion This study demonstrates that FLASH irradiation strengthens the therapeutic effect for H&N cancers and attenuates radiation-induced salivary gland damage. Further research is needed on the biological mechanisms involved. 1 Institute for Oncology and Radiology of Serbia, Department of Experimental Oncology, Belgrade, Serbia; 2 Vinca Institute of Nuclear Sciences, University of Belgrade, Department of Radiobiology and Molecular Genetics, Belgrade, Serbia; 3 Institute for Oncology and Radiology of Serbia, Department of Radiation Oncology, Belgrade, Serbia Purpose or Objective About half of all prostate cancer (PCa) patients receive radiotherapy (RT) either as single curative treatment or as adjuvant/salvage treatment after radical prostatectomy. However, RT is associated with a spectrum of side effects (toxicity) in the surrounding normal tissues. Acute toxicity occurs within 90 days of treatment, is usually transient and affects skin and mucosa of bladder and intestine resulting in dermatitis, cystitis or diarrhea. XRCC3 gene encodes for protein that is involved in homologous recombination repair of double-strand breaks created by ionizing radiation. Disruption of these pathways has the potential to affect the normal tissue response to RT. The T variant of XRCC3 Thr241Met single nucleotide polymorphisms (SNP) in exon 7 (C>T, rs861539) was reported to be associated with elevated levels of DNA adducts, chromosomal deletions, sensitivity to ionizing radiation and cross-linking agents. The aim of this study was to examine association between this SNP and RT-induced normal tissue toxicity in PCa patients. Materials and Methods Eighty one patients who had a histologically confirmed localized or locally advanced PCa were included in the study. Patients were treated with 3DC RT (n=70) or ARC RT (n=11) with radical (72 Gy)(47 patients) or postoperative/salvage (66 Gy)(34 patients) RT without previous hormonal therapy. DNA from peripheral blood mononuclear cells was extracted by salting out method. XRCC3 Thr241Met SNP was determined by PCR-RFLP analysis. The restriction fragments were separated on 2100 Bioanalyzer using DNA 1000 kit. The differences in the distribution of genotypes of XRCC3 Thr241Met between patients with or without acute RT-induced genitourinary (GU) or gastrointestinal (GI) toxicity were tested by χ 2 and Fisher’s exact test. P values ≤ 0.05 were considered statistically significant, while p values between 0.1 and 0.05 were pointed out as a statistical trend. Data were analyzed by SigmaStat 3.5. Results The acute GI toxicity appeared in 100%, 94.6% and 81.8% of ThrThr, ThrMet and MetMet PCa patients, raspectivelly. There was the statistical trend towards higher acute GU toxicity in carriers of Thr variant (ThrThr plus ThrMet) vs . MetMet (p=0.087) as well as ThrThr vs . MetMet (p=0.058). For acute GI toxicity, there was a similar distribution in genotypes: 90.9%, 91.9%, 90.9% for ThrThr, ThrMet, MetMet, respectively. PCa patients with ThrThr genotype had higher rate of acute GU toxicity grade ≥ 2 (45.5%) than ThrMet (28.6%) and MetMet (22.2%) while in GI toxicity MetMet had higher rate of grade ≥ 2 (40%) than ThrThr (23.3%) and ThrMet (23.5%) but without statistical significance. Conclusion The obtained data indicate that Thr variant of XRCC3 Thr241Met SNP is related to acute GU toxicity. Grade ≥ 2 acute GU toxicity could be associated with ThrThr while GI toxicity with MetMet genotype. Further study on larger group is necessary to confirm this date and to clarify mechanism underlying this observation. PO-1823 XRCC3 Thr241Met gene polymorphism and acute radiotherapy induced toxicity for prostate cancer E. Mali š i ć 1 , N. Petrovi ć 2 , M. Nikitovi ć 3

Poster (digital): Tumour radiobiology