ESTRO 37 Abstract book

ESTRO 37

S585

reached end point ,some genes (eg. FZD1, CCDC152) showed relationship with prognosis. In mutation profile analysis, the mutations of tumor suppressor gene NFE2L2 were only observed in radio-sensitive group. As for expression profile, many different expressed genes were related to development (eg. WNT11, DNER ) and immune functions (eg. IL-24, ADAM8 ). The inferred infiltrating macrophages and T cells varied in different radiation response, and the enrichment analysis also confirmed enriched pathways associated with leukocyte infiltration. The profiles of microRNA and methylation provide some insight of the regulation of radiation resistance related pathways. Conclusion Here, we performed a comprehensive bioinformatics analysis and our results provide a genomic landscapes of the intrinsic difference of EC heterogeneous radiation response, which indicates the role of cancer immunity in the radiotherapy of EC. Considering the limitation of relative small number of the involved patients, further works are needed to validate detected potential predictive biomarkers. PO-1041 A novel oral selenocystine prevents pneumonitis in a mouse model exposed to whole lung radiation J. Goda 1 , A. Kunwar 2 , V. Gota 3 , V. Jain 4 , K.I. Priyadarshini 4 1 Advanced Centre for Treatment- Research and Education in Cancer- Mumbai, RADIATION ONCOLOGY, Mumbai, India 2 Bhabha Atomic research Centre, radiation and photo chemistry division, Mumbai, India 3 Advanced Centre for Treatment- Research and Education in Cancer- Mumbai, Clinical Pharmacology, Mumbai, India 4 Bhabha Atomic research Centre, chemistry division, Mumbai, India Purpose or Objective We investigated the lung radioprotective efficacy of a novel oral selenocystiene derivative (DRUG-X) in irradiated mice. Material and Methods The study was approved by the institutional animal ethics committee. C3H/HeJ (pneumonitis responding) mice received single 18 Gy (0.6 Gy/min), thoracic radiation (RT) and a subset of these were treated with the drug formulation orally (2.5 & 10 mg/kg) thrice weekly 2 hours post-RT and monitored till respiratory distress symptoms appeared. The pneumonitis progression in the irradiated mice was monitored by acquiring CT scans at regular intervals. Further, to study the effect of the drug on tumor radiosensitivity, human lung carcinoma(A 549) cells were irradiated to a dose of 2 Gy followed by treatment with increasing concentrations of the drug for determining the survival fraction by clonogenic assay. Results To study the efficacy of oral selenocystine derivative as a lung radioprotector, we established the oral dosage equivalent to that of an Intraperitoneal (IP) dose of 2mg/kg. Bio-equivalence analysis of IP formulation of the drug (2mg/kg) and oral formulation was done by monitoring the level of selenium by atomic absorption Poster: Radiobiology track: Normal tissue radiobiology (others)

spectroscopy in the lung homogenates prepared at various time points starting from 5min to 24h post therapy. Comparing previously available pharmacokinetic data of oral administration (50 mg/kg), oral formulation had similar pharmacokinetic patterns as IP formulation in the lungs. We found that lung availability (C max =0.32 ± 0.05 µg/g) was comparable irrespective of the mode of administration. Lung radioprotection studies were carried out at a doses of 2 and 10 mg/kg. Thoracic CT scans performed on biweekly intervals indicated that the pneumonitis started ~ 80 days post-RT and within a week of onset got consolidated in the entire lung. This drug at a dose of 2 mg/kg significantly delayed the progression of pneumonitis (P<0.05) and improved the asymptomatic survival compared to radiation control. 10 mg/kg dose was found to be too toxic. We evaluated the effect of this drug with radiation on A549 through clonogenic assay. Results indicated that radiation dose of 2 Gy led to significant decrease in survival fraction of A549 cells. Drug treatment induced concentration dependent toxicity in the lung cancer cells. The IC 50 of the drug was estimated to be 7µM. When used concurrently with RT showed higher cytotoxicity with an IC 50 of 1µM. suggesting that it does not protect but sensitizes tumor cells to radiation. Further work on this drug is in progress and the final results will be presented. Conclusion The oral formulation of this novel selenocystine derivative not only prevents radiation induced pneumonitis but also reversed the grade of pneumonitis in some of the mice. Initial studies revealed that it also has anti-tumor effects on lung cancer cell. Future studies will focus on further evaluating its effect on lung radioprotection, toxicological effects, in-vivo lung tumor response and mechanistic studies . Phosphorylation of SMC1 Protein S. Park 1 1 Asan Medical Center, Radiation oncology, Seoul, Korea Republic of Purpose or Objective Biodosimetry has the potential to quantify individual exposures for triage for dose-appropriate medical intervention in the event of a large-scale nuclear event. Structural maintenance of chromosomes 1 (SMC1) protein is a member of the highly conserved cohesin complex that is phosphorylated in response to ionizing radiation. This study was aimed developing a biodosimetry method using SMC1 phosphorylation as a measure of exposure to low-dose ionizing radiation. Material and Methods Firstly, to investigate if phosphorylation of SMC1 shows a dose-dependent accumulation in normal cell lines, the WI-38VA-13 (SV40-transformed human fibroblasts) and PO-1042 Biodosimetry Using Radiation-induced