Christina Schaub1, Sied Kebir1,2,3, Nina Junold1, Elke Hattingen4, Niklas Schäfer1,2, Joachim P Steinbach5, Astrid Weyerbrock6, Peter Hau7, Roland Goldbrunner8, Michael Niessen1, Frederic Mack1, Moritz Stuplich1, Theophilos Tzaridis1, Oliver Bähr5, Rolf-Dieter Kortmann9, Uwe Schlegel10, Friederike Schmidt-Graf11, Veit Rohde12, Christian Braun13, Mathias Hänel14, Michael Sabel15, Rüdiger Gerlach16, Dietmar Krex17, Claus Belka18, Hartmut Vatter19, Martin Proescholdt20, Ulrich Herrlinger1, Martin Glas21,22,23. 1. Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany. 2. West German Cancer Center (WTZ), University Hospital Essen and German Cancer Consortium, Partner Site University Hospital Essen, University Duisburg-Essen, Essen, Germany. 3. Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 4. Neuroradiology; Department of Radiology, University of Bonn Medical Center, Bonn, Germany. 5. Dr. Senckenberg Institute of Neurooncology, University of Frankfurt, Frankfurt, Germany. 6. Department of Neurosurgery, University of Freiburg, Freiburg, Germany. 7. Department of Neurology and Wilhelm Sander NeuroOncology Unit, University of Regensburg, Regensburg, Germany. 8. Department of Neurosurgery, University of Cologne, Cologne, Germany. 9. Department of Radiation Oncology, University of Leipzig, Leipzig, Germany. 10. Department of Neurology, Knappschaftskrankenhaus Klinikum der Ruhr-Universität Bochum, Bochum, Germany. 11. Department of Neurology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany. 12. Department of Neurosurgery, Georg-August-University, Göttingen, Germany. 13. Department of Neurology, University Hospital Tübingen, Tübingen, Germany. 14. Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany. 15. Department of Neurosurgery, Medizinische Fakultät, Heinrich-Heine-Universität, Düsseldorf, Germany. 16. Department of Neurosurgery, HELIOS Klinikum Erfurt, Erfurt, Germany. 17. Department of Neurosurgery, Technical University Dresden, Dresden, Germany. 18. Department of Radiation Oncology, LMU Munich, Munich, Germany. 19. Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany. 20. Department of Neurosurgery, University of Regensburg, Regensburg, Germany. 21. Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany. martin.glas@uk-essen.de. 22. West German Cancer Center (WTZ), University Hospital Essen and German Cancer Consortium, Partner Site University Hospital Essen, University Duisburg-Essen, Essen, Germany. martin.glas@uk-essen.de. 23. Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. martin.glas@uk-essen.de.
Abstract
BACKGROUND: We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergoradiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. METHODS: In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness. Tumor growth patterns were classified as either multifocal or local at baseline and recurrence; at first recurrence, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations with treatment arms were calculated using Fisher's exact test. RESULTS: At baseline, 115 of 142 evaluable patients (81%) had a locally confined tumor. Between treatment arms, there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern (12 and 13%, p = 0.55). Distant lesions appeared in 17% (BEV/IRI) and 13% (TMZ) of patients (p = 0.69). 15% of patients in the BEV/IRI arm and 8% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.42). CONCLUSIONS: The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastoma patients in the GLARIUS trial. BEV/IRI was not associated with an increased rate of multifocal, distant, or highly invasive tumors at the time of recurrence.
RCT Entities:
BACKGROUND: We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. METHODS: In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness. Tumor growth patterns were classified as either multifocal or local at baseline and recurrence; at first recurrence, we additionally assessed whether distant lesions appeared. Invasiveness was determined as either diffuse or non-diffuse. Associations with treatment arms were calculated using Fisher's exact test. RESULTS: At baseline, 115 of 142 evaluable patients (81%) had a locally confined tumor. Between treatment arms, there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern (12 and 13%, p = 0.55). Distant lesions appeared in 17% (BEV/IRI) and 13% (TMZ) of patients (p = 0.69). 15% of patients in the BEV/IRI arm and 8% in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern (p = 0.42). CONCLUSIONS: The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastomapatients in the GLARIUS trial. BEV/IRI was not associated with an increased rate of multifocal, distant, or highly invasive tumors at the time of recurrence.
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