Abstract Book

S1279

ESTRO 37

exposure of ionizing radiation will provide new insights into the radiotherapy.

resistance has the potential to improve greatly the applicability of radiotherapy, in this disease. This work aims to elucidate mechanisms of resistance of mesothelioma cells to IR and so identify and validate clinically-relevant targets for radiosensitization. Material and Methods The relative expression of proteins involved in the apoptotic pathway was assayed by Western immunoblotting following irradiation of mesothelioma cells. Viability and clonogenic assays were used to describe the radiosensitizing capacity of candidate small molecule inhibitors. Caspase-3/7 activity was measured to assess activation of apoptosis following combination treatment. Results The radioresistance of mesothelioma cells was confirmed in 2D and 3D culture systems. Following exposure to IR, mesothelioma cells were found to upregulate the anti- apoptotic Bcl-2 protein, Bcl-xL. Small molecule BH3- mimetic inhibitors of Bcl-xL, A1331852 and A1155463, exhibited therapeutic activity as single-agents and, crucially, sensitized mesothelioma cells to IR. The observed reduction in survival was associated with increased levels of caspase-3/7 activity and apoptosis. Inhibition of other Bcl-2 proteins had little efficacy, suggesting mesothelioma cells specifically depend on Bcl- xL activity for radioresistance. Furthermore, analysis of the Bcl-2 protein repertoire of mesothelioma cells predicted the radiosensitizing-capacity of Bcl-xL The relative proportion of individual anti-apoptotic Bcl-2 proteins in mesothelioma cells was found to act as a biomarker of the radiosensitizing-potential of BH3- mimetics. Inhibition studies suggested mesothelioma cells exhibit addiction to Bcl-xL, especially in response to IR. Thus, the clinically-problematic radioresistance of mesothelioma cells may be mitigated by therapeutic targeting of anti-apoptotic Bcl-2 proteins. EP-2320 The impact of high and low-LET irradiation on the invasion of glioblastoma cells M. Wank 1 , J. Reindl 2 , J. Gempt 3 , D. Schilling 4 , J. Wilkens 1,4 , T. Schmid 1,4 , S. Combs 1,4 1 Insitute of innovative Radiotherapy, Radiation Oncology, München, Germany 2 Institute for Applied Physics and Metrology, Bundeswehr University Munich, Neubiberg, Germany 3 Department of Neurosurgery, Technical University Munich TUM, Munich, Germany 4 Department of Radiation Oncology, Technical University of Munich TUM, Munich, Germany Purpose or Objective Glioblastoma multiforme (GBM) is the most aggressive and most common primary brain tumour. The standard therapy is a multimodal treatment consisting of surgical resection, fractionated radiotherapy using photons and chemotherapy. Despite this treatment, the prognosis for patients with glioblastoma remains poor (5-year survival below 10%). The major obstacle to a cure is diffuse invasion, which enables tumour cells to escape current cancer therapies. Recent papers are discussing whether ionizing radiation is increasing the invasive potential of human glioblastoma multiforme. Therefore, the aim of this study is to find a better treatment option for GBM. Material and Methods inhibition. Conclusion

EP-2318 Molecular markers associated with pseudoprogression and recurrence pattern in glioblastoma. P. Nenclares Peña 1 , V. Rodríguez González 2 , D. Cantero Montenegro 1 , A. Hernández Laín 1 , J.F. Pérez-Regadera Gómez 2 1 Hospital Universitario 12 de Octubre, Pathology, Madrid, Spain 2 Hospital Universitario 12 de Octubre, Radiation Oncology, Madrid, Spain Purpose or Objective Molecular markers have become an integral part of tumour assessment in modern neuro-oncology and guide clinical decisions in gliomas. This study was conducted to analyse whether isocitrate dehydrogenase (IDH1) mutation, Alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation and O 6 -methyl- guanine methyl transferase (MGMT) gene promoter methylation are associated with pseudoprogression disease (psPD) and pattern of recurrence in GBM patients after concurrent temozolomide (TMZ)-based chemo- radiation. Material and Methods A total of 62 GBM patients were included in this retrospective study. Univariate logistic regression was used to evaluate the association between genetic factors and psPD or pattern of recurrence. Log rang test and Kaplan Meier were performed for the survival analysis. Results Of the 62 GBM patients, MGMT promoter methylation, IDH1 mutation and ATRX mutation were identified in 34 (54.84%), 8 (12.90%) and 10 (16.13%) patients, respectively. We found a significant association between MGMT promoter methylation and psPD (p<0.001), but not between IDH1 or ATRX mutations and psPD. MGMT methylated patients were more likely to show distant recurrence rather than treatment on field or marginal recurrence (p=0.032). GBM patients with psPD had a significant longer median overall survival and progression-free survival (21.8 and 16.14 months) than GBM patients with non-psPD (18.6 and 8.6 months). Conclusion Our results suggest that MGMT promoter methylation is associated with psPD and pattern of distant recurrence in GBM patients after TMZ-based chemoradiation. Additionally, psPD predicts a longer median survival and progression-free survival. EP-2319 Inhibition of anti-apoptotic Bcl-xL mitigates the radioresistance of mesothelioma cells M. Jackson 1 , M. Ashton 1 , A. Chalmers 1 1 Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, Glasgow, United Kingdom Purpose or Objective The incidence of mesothelioma continues to rise, whilst prognosis remains dismal due to a paucity of treatment options. Mesothelioma cells exhibit profound resistance to conventional therapies, including ionizing radiation (IR). Technological improvements in radiotherapy delivery have somewhat assuaged the difficulties associated with complex disease architecture, leading to a resurgence in interest in this modality. However, the intrinsic radioresistance of mesothelioma remains a barrier. Thus, development of a strategy to overcome