ESTRO 2020 Abstract book

S181 ESTRO 2020

gene expression technologies were assessed (Taqman array cards, RNA-seq, Affymetrix Clariom S). Results The 24 prospective samples (age <12 months) yielded higher quality RNA than the retrospective samples (p = 0.008). Success rate of gene expression using Clariom S was achieved in 560 samples (84%). All samples passed QC metric and all 28 genes of the prostate HS were detected and measurable. RNA quality (r=0.03) and yield (r=-0.05) did not correlate with HS. HS did not increase with Gleason grade group (G3 2.40±0.16, G4 2.31±0.30, G5 2.69±0.22). Clariom S consistently outperformed the other platforms studied. There was an inverse correlation between probe amplicon length and gene expression (n=33, r=-0.67) with the Taqman array card. Intratumour heterogeneity based on HS group was demonstrated in 18 samples (45%). No correlation was seen between histopathological adverse features and HS. Conclusion This is the largest prostate radiotherapy cohort with full gene expression data available and hence a valuable resource for research. The Clariom S gene expression platform was superior to Taqman array cards and RNA-seq for validation of a prostate hypoxia gene signature in definitive radiotherapy cohorts using archival FFPE NC. OC-0320 Correlations of tissue and imaging hypoxia biomarkers during chemoradiation of HNSCC patients N.H. Nicolay 1,2 , G. Kayser 3 , N. Wiedenmann 1,2 , M. Mix 2,4 , M. Werner 3 , A. Grosu 1,2 1 Universitätsklinikum Freiburg, Department of Radiation Oncology, Freiburg, Germany ; 2 Deutsches Krebsforschungszentrum, DKTK Partner Site Freiburg, Heidelberg, Germany ; 3 Universitätsklinikum Freiburg, Department of Pathology, Freiburg, Germany ; 4 Universitätsklinikum Freiburg, Department of Nuclear Medicine, Freiburg, Germany Purpose or Objective Tumor hypoxia impairs the response of head-and-neck cancer (HNSCC) patients to radiotherapy and can be detected both by tissue biomarkers and PET imaging. However, the value of hypoxia biomarkers and imaging for predicting HNSCC patient outcomes are incompletely understood, and potential correlations between tissue and PET data remain to be elucidated. Here, we performed exploratory analyses of potential correlations between tissue-based hypoxia biomarkers and longitudinal hypoxia imaging in a prospective trial of HNSCC patients. Material and Methods 49 patients undergoing radiochemotherapy for locally advanced HNSCCs were enrolled in this prospective exploratory trial. They underwent baseline biopsies and [ 18 F]FMISO PET imaging at weeks 0, 2 and 5 during treatment. Immunohistochemical analyses for hypoxia- associated tissue markers HIF1α, CAIX, CD34 as well as biomarkers for other cellular functions influenced by hypoxia (proliferation: Ki67, cancer stem cells: CD44, DNA repair: Ku80) were assessed, and HPV status was investigated by p16 staining and HPV DNA analyses. Biomarker expression was quantified by the H-score and correlated with biological imaging information (Pearson product-moment correlation coefficient) and patient outcome data (Cox regression analysis). Results High HIF1α tumor levels significantly correlated with increased tumor hypoxia at during the first two weeks of treatment as assessed by the difference in the [ 18 F]FMISO tumor-to-background ratios (r=0.35; p<0.05), and high

Conclusion The rate of patients showing no NCF decline 6 and 12 months after early HA-PCI concomitant to CHT does not appear to be better, but rather similar to that observed in patients receiving sequential PCI without HA. 1 Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS. Reference: 1. Wolfson AH, Bae K, Komaki R, et al. Primary Analysis of a Phase II Randomized Trial Radiation Therapy Oncology Group (RTOG) 0212: Impact of Different Total Doses and Schedules of Prophylactic Cranial Irradiation on Chronic Neurotoxicity and Quality of Life for Patients With Limited-Disease Small-Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):77-84. OC-0319 Validation of a companion diagnostic biomarker for prospective use in prostate radiotherapy trials N. Thiruthaneeswaran 1,2 , B.A.S. Bibby 1 , R. Pereira 3 , E. More 1 , R.G. Bristow 3,4 , A. Choudhury 1 , C. West 1 1 University of Manchester, Translational Radiobiology, Manchester, United Kingdom ; 2 University of Sydney, Sydney Medical School, Sydney, Australia ; 3 University of Manchester, Translational Oncogenomics, Manchester, United Kingdom ; 4 Manchester Cancer Research Centre, The Oglesby Cancer Research Building, Manchester, United Kingdom Purpose or Objective A 28-gene hypoxia-associated signature (HS) was derived for prostate cancer. The signature was validated for prognostic significance in eight prostatectomy, a definitive radiotherapy cohort and a salvage radiotherapy cohort. Biomarker validation using scant or minimal formalin-fixed paraffin-embedded (FFPE) tissue from diagnostic biopsies is a challenge due to nucleic acid degradation and low tissue volume. The aim of this study was to technically validate the robustness of the signature for reproducibility, reliability and intratumour heterogeneity. Material and Methods Diagnostic FFPE needle core (NC) biopsies from high-risk prostate cancer patients treated with different radiotherapy regimens were collected (n=663). Intratumour heterogeneity was assessed in 40 patient samples with multiple tumour FFPE NC blocks. Correlation was assessed in matched needle core to macrodissected prostatectomy samples in 12 patients. To assess downstream usability of extracted retrospective RNA three Proffered Papers: Proffered papers 15: Radiation response biomarkers