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ESTRO 37

for OS and PFS with a 3-fold increased risk of death (p=.001). If PAI-1 plasma levels were combined with OPN or tumor volume, we determined an additive prognostic impact on OS and PFS with a 2.5 to 3-fold increased risk of death (p=.01). Conclusion Our results suggest that PAI-1 but not uPA and uPAR might add prognostic information in patients with advanced NSCLC undergoing RT. High pre- treatment PAI- 1 plasma levels were found predominantly in M0-stage patients and indicate a favourable prognosis as opposed to OPN plasma levels where high plasma levels are associated with poor survival and metastasis (M1-stage). In combination, PAI-1 and OPN plasma levels successfully predicted outcome and additively correlated with prognosis. These findings support the notion of a differential prognostic impact of OPN and PAI-1 plasma levels in the RT of advanced NSCLC whereas uPA and uPAR plasma levels seem to be of no prognostic relevance in this setting. EP-2308 Inhibition of lipogenesis: a promising approach to optimise the treatment of rectal cancer. P. Bulens 1 , A. Debucquoy 2 , J. Swinnen 2 , K. Haustermans 1 1 University Hospital Leuven, Department of Radiation Oncology, Leuven, Belgium 2 KU Leuven, Department of Oncology, Leuven, Belgium Purpose or Objective For patients with locally advanced rectal cancer, 5-year overall survival after standard preoperative chemoradiation followed by total mesorectal excision surgery is only about 70%. To improve the outcome of these patients, novel strategies to intensify the current chemoradiation regimen are needed. Targeting enhanced lipid metabolism, one of the hallmarks of cancer cells, shows great potential for this treatment intensification. Sterol regulatory element binding protein 1 (SREBP-1), a key transcriptional factor that controls lipogenesis and lipid uptake, has been shown to be stabilised and activated by the PI3K/Akt oncogenic signalling pathway in cancer cells. The SREBP-1 inhibitor Fatostatin inhibits this activation, thereby potentiating cancer cell death in vitro and in vivo. Furthermore, Fatostatin induces a cell cycle arrest in the radiosensitive G2/M phase, which makes it a promising drug to combine with radiotherapy. Therefore, the aim of our research is to explore the radiosensitising potential of the SREBP-1 inhibitor Fatostatin in vitro in colorectal cancer cell lines. Material and Methods Four colorectal tumour cell lines with different molecular characteristics and varying levels of sensitivity to radiotherapy were used for our experiments: HCT116 (sensitive), HT29 and HCA7 (intermediate) and CaCo2 (resistant). By means of a sulforhodamine B assay (SRB), we screened the radiosensitising potential of different doses of Fatostatin (control, 5 µM, 10 µM) in these cell lines. Fatostatin was administrated 24 hours before radiation and removed 24 hours after radiation. Increasing doses of ionising radiation (0 – 2 – 4 – 6 Gy) were delivered using the X-ray generator XSD225kV Baltograph (199 kV, 15 mA). All experiments were repeated in triplicate. Electronic Poster: Radiobiology track: Radiobiology of colorectal cancer

Conclusion Our findings showed significant benefit on survival when prophylactic cranial irradiation is administered. We also found that the TGFB1 rs4803455:CT genotype is associated with worse prognosis in these patients. Therefore, this response marker may be used as a biomarker for future individual therapeutic schemes. EP-2307 Prognostic implications of the urokinase plasminogen activator system and osteopontin in NSCLC C. Ostheimer 1 , C. Evers 1 , T. Reese 1 , M. Bache 1 , D. Vordermark 1 1 Universitaetsklinikum HalleSaale, Radiation Oncology, Halle, Germany Purpose or Objective Components of the urokinase-plasminogen-activator system (uPA, uPAR, PAI-1) are upregulated in malignant cancers where high plasma levels are associated with poor prognosis. Their cooperative interplay with the hypoxia-related protein osteopontin (OPN) which is also significantly overexpressed in malignant tumors, suggests a potential clinical relevance. We previously reported a prognostic relevance of serial OPN measurements and an additive prognostic effect of the biomarkers OPN, carbonic-anhydrase IX and vascular-endothelial-growth- factor in the radical radiotherapy (RT) of non-small-cell lung cancer (NSCLC). However, the clinical relevance of the uPA system, particularly in combination with OPN, has not been comprehensively investigated in the RT of NSCLC so far. Material and Methods Pre-treatment plasma levels of uPA, uPAR, PAI-1 and OPN of 81 patients with locally advanced or metastasized NSCLC were prospectively analysed by ELISA and correlated to clinical patient / tumor data and prognosis after RT. Results uPAR plasma levels were higher in M1 patients, uPA and PAI-1 plasma levels were higher in M0 NSCLC patients. uPAR was significantly correlated with uPA (p<.001) which also correlated with PAI-1 (p<.001). The uPA system was not associated with clinical parameters. The prognostic impact of OPN plasma levels in the RT of NSCLC was previously reported by our group. PAI-I plasma levels significantly impacted overall (OS) and progression- free survival (PFS). Low PAI-1 plasma levels were associated with a significantly reduced OS and PFS with a nearly 2-fold increased risk of death (p=.029) and tumor progression (p=.029). In multivariate analysis, PAI-1 plasma levels remained an independent prognostic factor