Apostolos Menegakis1, Chiara De Colle2, Ala Yaromina3, Joerg Hennenlotter4, Arnulf Stenzl4, Marcus Scharpf5, Falko Fend5, Susan Noell6, Marcos Tatagiba6, Sara Brucker7, Diethelm Wallwiener7, Simon Boeke8, Umberto Ricardi2, Michael Baumann9, Daniel Zips8. 1. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Tübingen, Germany. Electronic address: apostolos.menegakis@uni-tuebingen.de. 2. Department of Oncology, Radiation Oncology, University of Turin, Italy. 3. Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 4. Department of Urology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. 5. Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. 6. Department of Neurosurgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. 7. Department of and Research Institute for Women's Health, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. 8. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Tübingen, Germany. 9. German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Germany.
Abstract
PURPOSE: To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. MATERIALS AND METHODS: Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. RESULTS: Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. CONCLUSION: Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted.
PURPOSE: To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. MATERIALS AND METHODS: Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. RESULTS: Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. CONCLUSION: Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted.
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