ESTRO 36 Abstract Book

S322 ESTRO 36 _______________________________________________________________________________________________

PO-0616 HPV, CSC marker expression and tumor hypoxia as prognosticators for LRC in patients with HNSCC A. Linge 1,2,3,4 , S. Löck 2,3 , C. Krenn 2 , S. Appold 1,3 , F. Lohaus 1,2,3,4 , M. Schneider 2,5,6 , A. Nowak 3,6 , V. Gudziol 3,5 , G.B. Baretton 3,4,7 , F. Buchholz 4,8 , M. Baumann 1,2,3,4,9 , M. Krause 1,2,3,4,9 1 Department of Radiation Oncology, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 2 OncoRay - National Institute for Radiation Research in Oncology, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 3 National Center for Tumor Diseases NCT, partner site Dresden, Dresden, Germany 4 German Cancer Research Center- Heidelberg, DKTK partner site Dresden, Dresden, Germany 5 Department of Otorhinolaryngology, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 6 Department of Oral and Maxillofacial Surgery, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 7 Institute of Pathology, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 8 University Cancer Center- Medical Systems Biology, TU Dresden- Med. Faculty Carl Gustav Carus, Dresden, Germany 9 Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Dresden, Germany Purpose or Objective To validate the prognostic impact of HPV status, cancer stem cell (CSC) expression and tumour hypoxia in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The impact of these biomarkers has been previously reported in an explorative multicentre, retrospective study. Material and Methods In this monocentric validation study, 152 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx were included. Out of them, 40 patients received postoperative radiochemotherapy and 112 patients received radiotherapy only. All patients were treated between 1999 and 2006. Identical methods for biomarker analysis were applied compared to the previous study. HPV DNA status was investigated by PCR-array based genotyping. Gene expression analysis was performed for hypoxia-associated genes and the potential CSC markers CD44, SLC3A2 and MET using nanoString technology. Cox models presented in the previous study were validated using the concordance index as a performance measure. Primary endpoint was loco-regional control. Results were compared to those previously reported. Results Loco-regional control and overall survival were lower as in the cohort reported previously. Despite of this, the prognostic value of the combination of HPV status, CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in univariate analyses using this independent validation cohort. For multivariate models, the concordance index was between 0.58 and 0.69 in validation, which indicates a good prognostic performance of the models. The inclusion of the CSC marker CD44 and the 15-gene hypoxia signature improved the performance of the model, when compared to a baseline model without any CSC markers or hypoxia classifiers. Conclusion The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy. While a lower performance of the prognostic models was expected due to the older validation dataset, the significant validation results indicate the robustness of these markers. A

currently recruiting prospective clinical trial will allow further validation of these results and may help to stratify patients for individualized treatment strategies. In addition, these biomarkers are currently being further explored in patients with early-stage HNSCC, who received surgery only and first results will also be presented. PO-0617 Functional Brain Abnormalities in NPC Patients After Radiotherapy W. Ren 1 , J. Dai 1 , Y. Li 1 , L. Gao 1 , C. Sun 2 1 Cancer Hosp.- Chinese Academy of Med.Sciences, Department of Radiation Oncology, Beijing, China 2 Cancer Hosp.- Chinese Academy of Med.Sciences, Department of Nuclear Medicine, Beijing, China the neurocognitive complications emerge in the survivors of NPC patients who have received RT and greatly affect their quality of life. It is still unclear how the brain functions are affected by radiation and whether these brain functional alterations are related to the radiation dose. This pilot study is aimed at exploring the brain functional alterations by using resting-state functional MRI. Material and Methods 20 NPC patients and 18 normal controls were recruited in this study. All patients were treated with intensity- modulated RT. Resting-state functional MRI scanning and neurocognitive tests including Montreal cognitive assessment (MoCA), Auditory verbal learning test (AVLT), Self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were administered individually during every patient 1 day before initiation of RT and 1 day after completion of RT. The normal controls also accepted the same MRI scanning and the neurocognitive tests. Amplitude of low-frequency (0.01–0.08 Hz) fluctuations (ALFF) during resting-state functional studies were calculated by Data Processing Assistant for Resting-State fMRI (DPARSF) software package to characterize regional cerebral functions. Paired T test was used to compare the cerebral functional alterations before and after treatment while 2-sample T test was used to compare ALFF values before and after treatment separately with healthy controls. Neurocognitive tests comparison of patients before and after radiotherapy and healthy controls were adopted ANOVA analysis. Significance was set at P=0.05. Results Compared with the patients before and after radiotherapy, increased ALFF were observed in inferior temporal gyrus, parahippocampal gyrus, hippocampus; decreased in occipital gyrus, inferior and middle temporal gyrus, lingual gyrus, fusiform gyrus, cuneus gyrus, cingulate gyrus, calcarine. Relative to controls, patients showed significantly increased ALFF in fusiform gyrus and inferior temporal gyrus bilaterally, decreased in left frontal gyrus before radiotherapy. After treatment, ALFF were still showed significantly changes in these regions and also in parahippocampal gyrus, hippocampus, superior and middle frontal gyrus, decreased in lingual gyrus, cingulate gyrus, calcarine. There were no significant results of neurocognitive tests scores. Conclusion Our findings firstly revealed that radiation treatment in NPC patients leads to regional synchronous neural activity changed in a short-term while not only in the regions that involved in the target radiation fields, but also in other low dose functional regions of relative neural pathways which may could explain the cognitive deficits in morphological normal-appearing brain of NPC patients after RT. Additionally, the present study offers promising novel neuroimaging approaches for both investigating mechanism of radiation therapy and tracking clinical dosage effects to optimize and individualize patient’s Purpose or Objective Studies have consistently demonstrated