Abstract Book

ESTRO 37

S584

Conclusion Analysis of published clinical cohort dose-volume data with toxicity outcomes provides evidence for a significant dose-volume-toxicity response effect for a range of clinically-relevant doses in the treatment of rectal cancer. The largest absolute differences in irradiated volume are seen at low doses, but the largest relative differences at high doses. Significant correlations of volume with toxicity risk are seen at both low dose (V 10Gy ) and high dose (V 30Gy , V 35Gy , and V 40Gy ), which has important implications for minimising risk of toxicity in these patients. PO-1040 Comprehensive bioinformatics analysis about the radiosensitivity in esophageal carcinoma M. Li 1 , B. Li 1 1 Shandong Cancer Hospital, radiation department, Jinan, China Purpose or Objective Esophageal carcinoma (EC) is a common malignancy and radiotherapy plays an important role in its treatment, while few biomarker could predict the radiotherapy response in current clinical practice. To explore the radiation response associated genomic characterizations, we performed a comprehensive bioinformatics analysis using the TCGA EC data with radiation records. Material and Methods All the clinical and genomic data of TCGA esophageal carcinoma were obtained from GDC Data Portal. To avoid confounding factor, we firstly used correlation test or χ 2 test to assess the interdependency of clinical information. The survival time related to radiation therapy were defined from the start of radiation therapy to the last follow up or death, and log rank test and Cox model were adopted for survival analysis. The level 3 MAF files and genome wide segmented SNP chips were used for demonstrate mutation and copy number variations profiles. For mRNA-seq counts data, DESeq2 were used for differential expression analysis, while we adopted CIBERSORT tool to estimate the infiltrating immune cells. We used minfi to handle the methylation data and limma was employed for normalization and comparation for other expression profiles. PCA and MDS were used for exploration of high dimension genomic profiles, while co- expression analysis and hierarchical cluster were used to demonstrate the genomic internal connectivity. We further performed gene set enrichment analysis and biological network analysis for mechanism exploration. Results Fifty TCGA EC patients received radiotherapy, among whom 35 categorized to radio-sensitive and 14 radio- resistant group according to their radiation response. For clinical variables, the radiation response strongly associated with chemo-resistant status. In survival analysis adjusted by clinical parameters, despite the relative low statistic power due to small proportion 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.

Poster: Radiobiology track: Normal tissue radiobiology (others)

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 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