Dorothee Gramatzki1, Philipp Kickingereder2, Bettina Hentschel2, Jörg Felsberg2, Ulrich Herrlinger2, Gabriele Schackert2, Jörg-Christian Tonn2, Manfred Westphal2, Michael Sabel2, Uwe Schlegel2, Wolfgang Wick2, Torsten Pietsch2, Guido Reifenberger2, Markus Loeffler2, Martin Bendszus2, Michael Weller2. 1. From the Department of Neurology and Brain Tumor Center (D.G., M.W.), University Hospital Zurich and University of Zurich, Switzerland; Department of Neuroradiology (P.K., M.B.), University Hospital of Heidelberg; Institute for Medical Informatics, Statistics and Epidemiology (B.H., M.L.), University of Leipzig; Departments of Neuropathology (J.F., G.R.) and Neurosurgery (M.S.), Heinrich-Heine University Düsseldorf; Division of Neurooncology (U.H.), Department of Neurology, University Medical Center Bonn; Department of Neurosurgery (G.S.), University of Dresden; Department of Neurosurgery (J.-C.T.), Ludwig Maximilians University Munich; Department of Neurosurgery (M.W.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Neurology (U.S.), Knappschaftskrankenhaus Bochum-Langendreer, Ruhr-University Bochum; Clinical Cooperation Unit Neurooncology (W.W.), German Cancer Consortium, German Cancer Research Center, and Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg; Department of Neuropathology (T.P.), DGNN Brain Tumor Reference Center, University of Bonn Medical School; and German Cancer Consortium (G.R.), German Cancer Research Center Heidelberg, Partner Site Essen/Düsseldorf, Düsseldorf, Germany. dorothee.gramatzki@usz.ch. 2. From the Department of Neurology and Brain Tumor Center (D.G., M.W.), University Hospital Zurich and University of Zurich, Switzerland; Department of Neuroradiology (P.K., M.B.), University Hospital of Heidelberg; Institute for Medical Informatics, Statistics and Epidemiology (B.H., M.L.), University of Leipzig; Departments of Neuropathology (J.F., G.R.) and Neurosurgery (M.S.), Heinrich-Heine University Düsseldorf; Division of Neurooncology (U.H.), Department of Neurology, University Medical Center Bonn; Department of Neurosurgery (G.S.), University of Dresden; Department of Neurosurgery (J.-C.T.), Ludwig Maximilians University Munich; Department of Neurosurgery (M.W.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Neurology (U.S.), Knappschaftskrankenhaus Bochum-Langendreer, Ruhr-University Bochum; Clinical Cooperation Unit Neurooncology (W.W.), German Cancer Consortium, German Cancer Research Center, and Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg; Department of Neuropathology (T.P.), DGNN Brain Tumor Reference Center, University of Bonn Medical School; and German Cancer Consortium (G.R.), German Cancer Research Center Heidelberg, Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
Abstract
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. RESULTS: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status. CONCLUSION: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. RESULTS: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status. CONCLUSION: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.
Authors: Patrick Y Wen; Michael Weller; Eudocia Quant Lee; Brian M Alexander; Jill S Barnholtz-Sloan; Floris P Barthel; Tracy T Batchelor; Ranjit S Bindra; Susan M Chang; E Antonio Chiocca; Timothy F Cloughesy; John F DeGroot; Evanthia Galanis; Mark R Gilbert; Monika E Hegi; Craig Horbinski; Raymond Y Huang; Andrew B Lassman; Emilie Le Rhun; Michael Lim; Minesh P Mehta; Ingo K Mellinghoff; Giuseppe Minniti; David Nathanson; Michael Platten; Matthias Preusser; Patrick Roth; Marc Sanson; David Schiff; Susan C Short; Martin J B Taphoorn; Joerg-Christian Tonn; Jonathan Tsang; Roel G W Verhaak; Andreas von Deimling; Wolfgang Wick; Gelareh Zadeh; David A Reardon; Kenneth D Aldape; Martin J van den Bent Journal: Neuro Oncol Date: 2020-08-17 Impact factor: 12.300
Authors: Carmen Balana; Maria Angeles Vaz; Juan Manuel Sepúlveda; Carlos Mesia; Sonia Del Barco; Estela Pineda; Jose Muñoz-Langa; Anna Estival; Ramón de Las Peñas; Jose Fuster; Regina Gironés; Luis Miguel Navarro; Miguel Gil-Gil; Miriam Alonso; Ana Herrero; Sergio Peralta; Clara Olier; Pedro Perez-Segura; Maria Covela; Maria Martinez-García; Alfonso Berrocal; Oscar Gallego; Raquel Luque; Franciso Javier Perez-Martín; Anna Esteve; Nuria Munne; Marta Domenech; Salvador Villa; Carolina Sanz; Cristina Carrato Journal: Neuro Oncol Date: 2020-12-18 Impact factor: 12.300