ESTRO 2022 - Abstract Book

S115

Abstract book

ESTRO 2022

17 Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 18 Heidelberg Ion Therapy Center (HIT), Department of Radiation Oncology, University of Heidelberg Medical School, Heidelberg, Germany; 19 National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 20 Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 21 Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 22 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Munich, Munich, Germany; 23 Department of Radiotherapy and Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany; 24 Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 25 Department of RadioOncology, Technische Universität München, Munich, Germany; 26 Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 27 German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Tübingen, Tübingen, Germany; 28 Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Germany Purpose or Objective The aim of this matched-pair study including patients with locally advanced head and neck squamous cell carcinoma (HNSCC) was to develop a novel gene signature in order to identify patients amongst those who are at intermediate risk according to clinical risk factors but biologically at high risk for the development of loco-regional recurrences after surgery and postoperative radiotherapy (PORT). Materials and Methods Gene expression analysis was performed using GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients that were treated with PORT alone within the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Propensity score matching (PSM) analysis was performed to identify matched patient pairs from the PORT and PORT-C cohorts using the matchIt R package. The nearest method was used on the logit of the propensity score using a caliper of width equal to 0.2 times the standard deviation. The clinical parameters T-stage, tumour localization (oral cavity vs others), N-stage and tumour grade were used for matching as they were expected to differ between the cohorts. Differential gene expression (DGE) analysis was performed between the resulting matched cohorts. The genes with a fold-change (FC) of ≥ 1.5 and an FDR adjusted p-value of ≤ 0.05 in Cox regression analysis on the PORT cohort were selected to develop a gene signature. Results 124 patient pairs treated with PORT-C or PORT were generated with low standardized mean differences in the matched clinical parameters. We identified a 2-gene signature consisting of MIR548A1 and MIR3186 , that was used to stratify patients into risk groups for loco-regional recurrence in the PORT cohort (p<0.001) but not in the PORT-C cohort (p=0.32). High risk was related to down-regulation of the two genes. The comparison of the high-risk patients between the two types of treatment showed better LRC after treatment with PORT-C (p=0.011). While 94% of patients were recurrence-free after two years in the high-risk group of the PORT-C cohort, this was true for only 63% in the corresponding group of the PORT cohort. A multivariable Cox model including the 2-gene signature, treatment type and their interaction showed a significant interaction term (p=0.039), i.e. the 2-gene signature was indicative for the type of treatment. Conclusion We have identified a novel 2-gene signature for LRC that may be used to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and thus often treated with PORT, who can benefit from additional concurrent chemotherapy. Independent prospective validation of this retrospective result is required before potential application in a clinical trial. 1 OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany, Institute of Radiooncology – OncoRay, Helmholtz-Zentrum Dresden-Rossendorf (HZDR) Dresden, Germany, Dresden, Germany Purpose or Objective We have previously shown that the radioresistant prostate cancer (PCa) and PCa stem cells (CSCs) had increased glutamine (Gln) requirement (1). Gln conduces to energy production in the TCA cycle to sustain the redox state and tumor epigenetic resetting. Inhibition of the glutaminase-driven Gln catabolism set the ground for CSC depletion and tumor radiosensitization (1). Moreover, we demonstrated that autophagy is utilized by hormone-naive cells like LNCaP as a prosurvival strategy to cope with the Gln depletion (1, 2). Despite our previous study aiming to decipher mechanisms that link Gln metabolism and PCa radioresistance, we sought to explain the role of Gln transporters (GTs) in PCa development and radioresistance as it is not well understood and warrant further investigation. Understanding the role of GTs may provide better approaches for individualized treatment regimens to overcome PCa radioresistance (3). Thus, we hypothesized that targeting GTs may yield novel and efficient strategies for PCa radiosensitization. As a result of in-silico analyses, we focused on the solute carrier (SLC) group of membrane GTs, namely SLC1A5 , SLC7A5 , and SLC38A1 . Materials and Methods Differential expression of GTs in previously established parental and radioresistant DU145 and LNCaP PCa sublines is determined using global gene expression profiling and qRT-PCR (4). Mining of publicly available patient datasets validated MO-0140 Glutamine transporters as regulators of prostate cancer radioresistance U. Kahya 1