ESTRO 38 Abstract book

S592 ESTRO 38

is evidence that local treatment in short-course radiotherapy is effective and should be considered amongst the therapeutic options for these patients; however this should be evaluated prospectively in a larger patients cohort. PO-1064 Reducing dysphagia with palliative 2D HDR brachytherapy improves survival in esophageal cancer W. Burchardt 1 , A. Chyrek 1 , J. Skowronek 1 1 Greater Poland Cancer Centre, Department of Brachytherapy, Poznan, Poland Purpose or Objective The goal of this study was to assess the effectiveness of dysphagia relief and overall survival in patients with advanced esophageal cancer treated with palliative high- dose-rate (HDR) 2D brachytherapy (BT). Material and Methods The study was conducted using data from medical reports of Cancer Center from January 2010 to December 2016. 133 patients with advanced or incurable esophageal cancer were treated with palliative purpose with 2D HDR BT. Median dose was 22,5 Gy in 3 fractions as primary treatment. The dysphagia was assessed in 93 patients and these patients were further analyzed. Median age was 65 years (45-88). 17,2 % of patients were female and 82,8 % male. Squamous cell carcinoma was diagnosed in 59,4 %, adenocarcinoma in 22,6% and other tumors in 6,7% cases. In 11,3 % of patients, the histopathological report was unknown. 19 patients were treated with chemotherapy and 4 with external beam radiotherapy after BT. Results Median follow up was 2,8 months (range 0,2-42,7). Median tumor length was 7,5 cm. Patients before treatment present following grades of dysphagia: I – 57 %, II – 33,3 %, III – 6,5 %, IV – 3,2 %; grades dysphagia after BT were significantly lower: 0– 38,7 %, I - 31,2 %, II – 20,4 %, IV – 1,1 % (p<0,001, Wilcoxon test). Mean time of dysphagia relief was 4,6 months and was achieved in 55 %, stabilization occurred in 31 %, and worsening of symptom was reported in 14% of cases. The patients with dysphagia relief (4,2 vs 2,2 months, p<0,01) or age <= 65 lived longer (3,7 vs 2,0 months p<0,01). The length of the tumor, primary localization, and primary grade of the dysphagia weren’t factors which influenced the survival of patients. The logistic regression model didn’t find any predictors for treatment response. Conclusion HDR 2D BT reduces dysphagia and prolongs survival especially in younger patients who response the treatment. HDR 2D BT meets the assumption of palliative treatment for advanced esophageal cancer. PO-1065 Multiparametric radiobiological parameters implementation to predict radiation-induced side effects M. Ben Kacem 1 , M. Benadjaoud 2 , F. Soysouvanh 1 , M. Dos Santos 3 , G. Tarlet 1 , V. Buard 1 , A. François 1 , O. Guipaud 1 , F. Milliat 1 , V. Paget 1 1 National Insitute for Radiobiological Protection and Nuclear Safety IRSN, Radiobiology of Medical Exposure Laboratory LRMed, Fontenay aux Roses, France ; 2 National Insitute for Radiobiological Protection and Nuclear Safety IRSN, Radiobiology and Regenerative Medicine Research Service SERAMED, Fontenay aux Roses, France ; 3 National Insitute for Radiobiological Protection and Nuclear Safety IRSN, Radiobiology of Accidental Exposure Laboratory LRAcc, Fontenay aux Roses, France Poster: Radiobiology track: Radiobiology of normal tissues

Purpose or Objective Radiotherapy (RT) is used to treat more than half of cancers. Despite the development of practices and devices that precisely deliver radiation dose to tumor with high dose rate, the biological effects on healthy tissue remain poorly studied. To predict radiation-induced biological effects, radiobiologists use the Relative Biological Effectiveness (RBE) concept to compare doses between two ionizing radiations given the same biological effect. RBE is essentially based on clonogenic assay to determine the impact of a defined ionizing radiation. Survival clonogenic curves are modelled by the linear quadratic model, and, according to several studies, this assay is insufficient to predict effects on healthy tissues after radiation. Based on the various effects known after irradiation, it is necessary to develop multiparametric RBE measures to predict the biological effects of emerging radiation therapy protocols. Material and Methods Human Umbilical Vein Endothelial Cells (HUVECs) were irradiated with a linear accelerator using two different dose rates (0.63 and 2.5 Gy/min). Endothelial cells (EC) were chosen for their involvement in radiation induced damages on healthy tissue. To predict accurately the adverse effects on healthy tissues, we have measured multiple in vitro biological readouts (clonogenic assay, viability, cell cycle, senescence and gene expression) at 3, 7, 14 and 21 days post-irradiation. The biological measures are already modelled on Matlab for each assay and will be integrated all together in a unique predictive model. Finally, total body irradiations and localized irradiations were conducted on preclinical mice models (C57BL/6J) to validate the in vitro data. Results Our in vitro results show a significant dose rate effect on cellular morphology of HUVECs. After irradiation at the lowest dose rate, clonogenic survival (RBE ≈ 0.8) and cell viability (RBE < 1) are higher. Furthermore, we have measured less Β-galactosidase activity (related to radio- induced senescence) after irradiation at 0.63 Gy/min compared to 2.5 Gy/min (RBE = 0.5). Moreover, the proportions of cells in the cell cycle phases and a 44 genes expression involved in senescence process were found modified according to the dose rate. In vivo , after the irradiation of an exteriorized segment of small intestine (19 Gy) on mice, a significant higher loss of weight was measured at the higher dose rate. Conclusion These data show a deleterious effect of the highest dose rate. The mathematical model will be consolidated by supplemental in vitro measures on Human Lung Microvascular Endothelial Cells (HMVEC-L) to validate the impact of the dose rate. To complete this study, we also focus our work on biological effects of different fractionated irradiation protocols both in vitro (on HUVECs) and in vivo (whole thorax irradiations on a preclinical mice model). These biological measures will be modelled and integrated within the predictive model in the future.

Poster: Radiobiology track: Radiobiology of stem cells (cancer and normal tissue)

PO-1066 The unique DDR mechanisms of human induced pluripotent stem cells (hiPSC)-derived chondrocytes E. Stelcer 1,2,3 , K. Katarzyna 1,2 , S. Wiktoria M. 1,2 1 Poznan University of Medical Sciences, Department of Electroradiology, Poznan, Poland ; 2 Greater Poland Cancer Centre, Radiobiology Lab, Poznan, Poland ; 3 Medical University of Warsaw, Postgraduate School of Molecular Medicine, Warsaw, Poland