ESTRO 2020 Abstract book

S183 ESTRO 2020

OC-0322 4-miRNA signature and MGMT promoter methylation improve risk stratification in glioblastoma. K. Unger 1,2,3 , D.F. Fleischmann 2,4,5 , V. Ruf 6 , J. Felsberg 7,8 , D. Piehlmaier 1 , D. Samaga 1 , J. Heß 1,2,3 , M. Mittelbronn 9,10,11,12 , K. Lauber 2,3,5 , W. Budach 13 , M. Sabel 14 , C. Rödel 15 , G. Reifenberger 7,8 , J. Herms 6 , J. Tonn 16 , H. Zitzelsberger 1,2,3 , C. Belka 2,3,5 , M. Niyazi 2,5 1 Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Research Unit Radiation Cytogenetics, Neuherberg, Germany ; 2 University Hospital- LMU Munich, Department of Radiation Oncology, Munich, Germany ; 3 Helmholtz Zentrum München- German Research Center for Environmental Health GmbH, Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer”, Neuherberg, Germany ; 4 DKFZ, German Cancer Research Center, Heidelberg, Germany ; 5 German Cancer Consortium DKTK, Partner Site Munich, Munich, Germany ; 6 LMU Munich, Center for Neuropathology and Prion Research, Munich, Germany ; 7 University Hospital Düsseldorf UKD- Heinrich Heine University, Institute for Neuropathology, Düsseldorf, Germany ; 8 German Cancer Consortium DKTK, Partner Site Essen/Düsseldorf, Essen/Düsseldorf, Germany ; 9 Laboratoire National de Santé LNS, National Center of Pathology NCP, Dudelange, Luxembourg ; 10 Luxembourg Institute of Health LIH, Luxembourg Center of Neuropathology LCNP, Luxembourg, Luxembourg ; 11 Luxembourg Institute of Health LIH, Department of Oncology, Luxembourg, Luxembourg ; 12 University of Luxembourg, Luxembourg Centre for Systems Biomedicine LCSB, Esch-sur-Alzette, Luxembourg ; 13 University Hospital Düsseldorf UKD- Heinrich Heine University, Department of Radiotherapy and Radiation Oncology, Düsseldorf, Germany ; 14 University Hospital Düsseldorf UKD- Heinrich Heine University, Department of Neurosurgery, Düsseldorf, Germany ; 15 University Hospital Frankfurt, Department of Radiation Oncology, Frankfurt, Germany ; 16 University Hospital- LMU Munich, Department of Neurosurgery, Munich, Germany Purpose or Objective With a median overall survival (OS) of approx. 14-16 months the prognosis of patients with glioblastoma remains dismal. In a previous study we identified a 4- miRNA signature as prognostic factor for OS in glioblastoma patients who were treated according to the EORTC 26981/22981-NCIC CE3 trial. The signature was independent of known prognostic factors including the MGMT promoter methylation status. In the present study, we validated the signature and assessed the prognostic relevance of the combination of the 4-miRNA signature with MGMT promoter methylation status. Material and Methods The validation cohort (n=106) contained IDH1/2 wildtype tumors with respective treatment and known MGMT promoter methylation status with patients from the LMU Munich (n=37), the University Hospital Düsseldorf (n=33) and The Cancer Genome Atlas (TCGA, n=36). Risk scores were calculated using signature expressions in combination with the signature Cox model coefficients. The combination of miRNA signature with MGMT -promoter methylation defined four risk groups which were used for univariable/multivariable analysis for OS. C-index was used to determine prognostic performance. Results The 4-miRNA signature was independent of sex, age and MGMT promoter methylation status (p> 0.05). 4-miRNA signature-defined high-risk (n=48, med. OS: 16.8 months)

and low-risk (n=58, med. OS: 28.8 months) patients (HR: 2.21, 95%-CI: 1.33-3.69, p=0.0018). 56 patients with methylated MGMT promoter had superior OS (med. OS: 26.4 months) compared to the non-methylated group (med. OS: 16.8 months, p=0.0036, HR: 0.45, 95%-CI: 0.26- 0.78). The four groups resulting from combining miRNA risk signature and MGMT promoter methylation status were associated with OS (p=0.0004): patients with the signature low-risk/ MGMT promoter methylated had a median OS of 37.2 months, the signature low-risk/ MGMT non-methylated and signature high-risk/ MGMT methylated had median OS of 18 and 25.2 months, respectively. The signature high- risk/ MGMT non-methylated group had a median OS of 14.4 months. Compared to the models including the signature and MGMT promoter methylation alone, the C-indices resulting from the Cox model combining the signature and MGMT promoter methylation showed superior prediction performance over the whole observation time. Conclusion We confirmed the 4-miRNA signature as an independent prognostic marker in patients with IDH-wildtype glioblastoma. Survival prediction by combining with MGMT promoter methylation outperformed other established prognostic factors. Yet, and comparable to the detection of the high relevance of IDH1 mutation, it remains to be determined which phenotypic alterations are driving its prognostic value. OC-0323 Serum microRNAs as xerostomia biomarkers in oropharyngeal cancer patients undergoing radiotherapy B. Tomasik 1,2,3 , A. Papis-Ubych 4 , J. Fijuth 3 , P. Kędzierawski 5 , J. Sadowski 5 , R. Stando 5 , R. Bibik 6 , Ł. Graczyk 6 , T. Latusek 7 , T. Rutkowski 8 , P. Widłak 9 , W. Fendler 1,10 1 Medical University of Lodz, Department of Biostatistics and Translational Medicine, Lodz, Poland ; 2 Medical University of Warsaw, Postgraduate School of Molecular Medicine, Warsaw, Poland ; 3 Medical University of Lodz, Department of Radiotherapy, Lodz, Poland ; 4 N. Copernicus Memorial Regional Specialist Hospital, Department of Radiotherapy, Lodz, Poland ; 5 Holycross Cancer Centre, Radiotherapy Department, Kielce, Poland ; 6 Oncology Center of Radom, Department of Radiation Oncology, Radom, Poland ; 7 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - branch in Gliwice, Radiotherapy Department, Gliwice, Poland ; 8 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - branch in Gliwice, I Radiotherapy and Chemotherapy Clinic, Gliwice, Poland ; 9 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - branch in Gliwice, Center for Translational Research and Molecular Biology of Cancer, Gliwice, Poland ; 10 Dana-Farber Cancer Institute, Department of Radiation Oncology, Boston, USA Purpose or Objective Severe xerostomia is noted in up to 75% of patients irradiated for oropharyngeal cancer (OPC). Currently, we do not possess effective tools for measuring radiation sensitivity that would allow tailored therapy. Preliminary literature reports indicate that extracellular microRNAs (miRNAs) may be a new class of biomarkers that will pave the way for further personalization of radiotherapy (RT). Hence, the aim of this study was to analyze temporal changes in expression levels of miRNAs circulating in the serum and to create an efficient test for patient-rated xerostomia 3 months after primary treatment with IMRT with or without chemotherapy for OPC. Material and Methods