Abstract Book

S1261

ESTRO 37

Purpose or Objective Purpose: NIMRAD is a phase III trial investigating the use of nimorazole hypoxia modification with intensity- modulated radiotherapy in head and neck cancer patients with locally advanced squamous cell carcinoma who are not suitable for concurrent chemotherapy or cetuximab. The translational research aim within NIMRAD is to prospectively validate a hypoxia gene signature biomarker, for use in clinical practise, to personalise treatment by selecting patients with hypoxia tumours for hypoxia modification in combination with radiotherapy. Material and Methods Methods: RNA was extracted from the patients’ diagnostic formalin-fixed paraffin-embedded (FFPE) blocks, a haematoxylin and eosin stained section was also prepared and examined by a pathologist. The 26 genes of the hypoxia gene signature, 5 endogenous control genes and one plate loading control gene were analysed using TaqMan Low Density Array (TLDA) cards. Each FFPE block was assigned a hypoxia score, as a measure of tissue hypoxia. The geometric mean of the endogenous controls was subtracted from the median Ct of the hypoxia signature genes to calculate the ΔCt, which was transformed using the formula 2 - ΔCt to give the hypoxia score. When multiple FFPE blocks were available for individual patients the intratumour heterogeneity of the HS was assessed. The stability and reproducibility of the endogenous controls was also determined using NormFinder and pairwise analysis. Results Results: The expressions of the endogenous control genes GNB2L1, HPRT1, B2M, RPL11 and RPL24 were stable and reproducible between assays and FFPE blocks. The hypoxia scores were more variable when comparing multiple pre-treatment FFPE samples obtained from an individual patient.The percentage of tumour in the FFPE tissue and the RNA yield did not correlate with the intra- tumour hypoxia scores. Conclusion Conclusion: Within the tumour microenvironment hypoxia can be chronic, acute or cycling and the intra-tumour heterogeneity of the hypoxia score reflects this intrinsic variation in tumour hypoxia. The FFPE block selected for measuring the hypoxia gene signature biomarkers and calculating the hypoxia score will be a critical step in the clinical application of the hypoxia gene signature biomarker. EP-2285 Aurora- kinases as predictors of overall survival for oral tongue squamous cell carcinoma P. Nenclares Peña 1 , M. Alonso Riaño 2 , C. Ballestín Carcavilla 2 , A. Ruíz Alonso 1 , J.F. Pérez-Regadera Gómez 1 1 Hospital Universitario 12 de octubre, Radiation Oncology, Madrid, Spain 2 Hospital Universitario 12 de Octubre, Pathology, Madrid, Spain Purpose or Objective Identifying prognostic biomarkers for oral tongue squamous cell carcinoma (OTSCC) is important in order to predict tumour behaviour and to guide treatment. Aurora-kinases play a role in human carcinogenesis and their overexpression is often associated with poor histologic differentiation and poor prognosis. The aim of this study was to determine whether the expression of Aurora-A and Aurora-B is correlated with the prognosis of patients with OTSCC in terms of disease-free survival (DFS) and overall survival (OS) following treatment (surgery or concurrent chemoradiation).

Material and Methods Based on meta-analysis and clinical trial data three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36Gy in18# followed by 36Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84Gy in 70# over 46 days delivered without synchronous chemotherapy.Using the modified linear quadratic equation: BED=D[1+(d/(α/β))]-kT (where BED= biologically effective dose for tumour (Gy α/β ), D= total dose (Gy), d=dose per fraction (Gy), α=linear component of cell kill (Gy -1 ), β=quadratic component cell kill (Gy -2 ), T=overall treatment time (days), k= dose loss per day (Gy α/β day -1 ) (where accelerated population is assumed to occur equally over the overall treatment time)) and the equation E=BED*α ( where E= biological effect), the above isoeffect relationships were expressed algebraically to determine values of α, α/β and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule (α= 0.3Gy -1 , α/β=10 Gy and k=0.42Gy 10 day -1 ). The relative BED loss from accelerated repopulation using the derived parameters in the standard synchronous chemotherapy setting (70Gy in 35# over 46 days with synchronous cisplatin) was then compared with the standard parameters for radiotherapy alone (70Gy in 35# over 46 days). Results The values derived for α, α/β and k were 0.2Gy -1 , 2Gy and 0.7 Gy 2 day -1 . In the setting of radiotherapy alone, modelled loss through repopulation accounted for approximately a quarter of the time uncorrected BED. When applying the derived parameters in the setting of synchronous chemotherapy a similar proportion was lost. Conclusion Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomised trials examining the role of hypofractionated acceleration in SCCHN EP-2284 Prospective validation of a hypoxia gene signature biomarker in the NIMRAD trial J. Irlam 1 , B. Bibby 1 , N. Thiruthaneeswaran 1,2 , A. Williamson 1 , G. Betts 3 , L. Yang 1 , H. Valentine 1 , D. Roberts 1 , A. Choudhury 4 , C. West 1 1 University of Manchester, Translational Radiobiology, Manchester, United Kingdom 2 Sydney Medical School, Clinical Oncology, Sydney, Australia 3 Manchester University Hospitals NHS Foundation Trust, Cellular Pathology, Manchester, United Kingdom 4 Christie Hospital NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom