Abstract Book

S1272

ESTRO 37

Sciences, Department of Radiation Medicine, Lanzhou, China

improvement of quality of life in these patients. We investigated the association between clinical, therapeutic, tumor-related and genetic variables (single nucleotide polymorphisms [SNPs] in the Transforming Growth Factor B1 [TGFß1] and Heat Shock Protein B1 [HSPB1] genes) and overall survival in patients with small Prospective multicenter study of one-hundred and twenty-five patients with available genomic DNA samples, diagnosed of SCLC and treated between June 2012 and October 2016. There were 103 men (82%) and 22 women, with a median age of 63 years old (range, 43- 84 years). Most of patients (78%) had a Karnoffsky performance status ≥ 80. Forty-three percent of patients smoked more than 40 daily cigarettes and 80% presented with limited stage at diagnosis. 78% received a dose of radiotherapy ≥45 Gy being bid in 46% of cases. 84% received concomitant chemotherapy based on cisplatin. Additionally, 57% received prophylactic cranial irradiation. The follow-up was 11.4 months (range, 1.6 to 47.5 months). We genotyped fifteenth SNPs of the TGFß and six SNPs of HSPB1 genes by the polymerase chain reaction restriction fragment polymorphism method. An univariate and multivariate Cox regression analyses were performed. The Kaplan–Meier analysis was used to estimate the cumulative overall survival (OS) probability. Results In the univariate analysis, the history of previous cancer (HR:1.87; P=0.05), extended stage (HR:2.27; P=0.003), normofractionated thoracic radiotherapy (vs bid; HR:1.81; P=0.033) were associated with lower OS. In contrast, the radiation total dose ≥45 Gy (HR:0.18; P<0.001), prophylactic cranial irradiation (HR:0.20; P=0.05) and concurrent chemoradiation based on cisplatin (HR:0.42; P=0.041) were associated with better OS. The prophylactic cranial irradiation was the only feature mentioned above that retained significance in multivariate analysis (2-years OS: 54.2% vs 0.1%; HR 0.20;CI:0.09-0-44; P<0.001). In addition, the TGFB1 rs4803455 SNP also associated with OS not only in the univariate analysis (P=0.004) but also in the multivariate analyses (P=0.017). Specifically, the CT genotype of TGFB1 rs4803455 was associated with a statistically significant worse OS (OS at 2 years: CT 17.3% [HR:2.47; CI:1.18-5.20; P=0.017] vs CC 53.3% vs TT 58.4%). cell lung cancer (SCLC). Material and Methods

Purpose or Objective F1Fo-ATP synthase (F1Fo-ATPase) is a reversibly rotary molecular machine whose dual functions of synthesizing or hydrolyzing ATP switch upon the condition of cell physiology. The robust ATP-hydrolyzing activity occurs in ischemia for maintaining the transmembrane proton motive force of mitochondria inner membrane, but the effect of F1Fo-ATPase on X-ray response of non-small-cell lung cancer (NSCLC) cells is unknown. We assume that ATP-hydrolyzing activity of F1Fo-ATP synthase contributes to radioresistant in NSCLC cells. Material and Methods NSCLC cells (A549) were preincubated with BTB (at a final concentration of 10 µM) for 2 hours before radiation ensuring absorption of drug. Radiation exposures were performed using an X-ray machine (Faxitron RX-650, USA) with 100 kVp. Cell proliferation was analyzed using Cell Counting Kit-8. The change in the mitochondrial membrane potential (ΔΨm) was assessed using JC-10 mitochondrial membrane potential assay kit. Colony formation assay was performed to identify the change in radioresistant. Real-time quantitative PCR analysis of ATP5α1 was carried out to detect the change of mRNA expression. Results NSCLC cells (A549) were pretreated with BTB06584 (BTB), an elective ATP hydrolysis inhibitor, followed by X-ray radiation. Cell viability and clonogenic survival were markedly decreased, clear indications of enhanced radiosensitivity through BTB incubation. Additionally, ATP5α1 was upregulated in parallel with elevated ATP hydrolytic activity after X-ray radiation, showing an increased mitochondrial membrane potential (ΔΨm). ATP hydrolysis inhibition led to collapse of ΔΨm suggesting ATP hydrolytic activity could enhance ΔΨm after X-ray radiation. Furthermore, we also demonstrated that apoptosis was pronounced with the prolonged collapse of ΔΨm due to hydrolysis inhibition by BTB incubation. Conclusion Overall, these findings supported that ATP hydrolysis inhibition could enhance the radiosensitivity in NSCLC cells (A549) after X-ray radiation, which was due to the collapse of ΔΨm. EP-2306 Prognostic value of PCI and single nucleotide polymorphism rs4803455 of TGFß1 gene in SCLC P. Ayala 1 , J. Cacicedo 2 , D. Delgado 3 , J.M. Nieto- Guerrero 3 , D. Herrero 4 , J.M. Praena 5 , L. Quintana 1 , P. Borrega 1 , M.J. Ortiz 3 , J.L. López-Guerra 3 1 San Pedro de Alcántara University Hospital, Clinical Oncology, Cáceres, Spain 2 Cruces Hospital, Radiation Oncology, Bilbao, Spain 3 Virgen del Rocío University Hospital, Radiation Oncology, Seville, Spain 4 Virgen del Rocío University Hospital, Clinical Oncology, Seville, Spain 5 Virgen del Rocío University Hospital, Mehodology Unit, Seville, Spain Purpose or Objective Small cell lung cancer is one of the greatest therapeutic challenges of modern oncology, due to modest improvement of survival with classical treatments and absent of new drugs. There are currently under investigation possible prognostics factors that would allow a more individual therapeutic approach and an