Agnieszka Korfel1, Eckhard Thiel2, Peter Martus2, Robert Möhle2, Frank Griesinger2, Michael Rauch2, Alexander Röth2, Bernd Hertenstein2, Thomas Fischer2, Thomas Hundsberger2, Hans G Mergenthaler2, Christian Junghanß2, Tobias Birnbaum2, Lars Fischer2, Kristoph Jahnke2, Ulrich Herrlinger2, Patrick Roth2, Michael Bamberg2, Torsten Pietsch2, Michael Weller2. 1. From the Department of Hematology, Oncology and Tumor Immunology (A.K., E.T., L.F., K.J.), Charité Berlin; the Departments of Clinical Epidemiology and Applied Biostatistics (P.M.) and Hematology and Oncology (R.M.), University Tübingen; the Department of Radiotherapy and Medical Oncology (F.G.), Pius Hospital Oldenburg; the Department of Neurology (M.R.), Protestant Hospital Bielefeld; the Department of Hematology (A.R.), University Hospital Essen; the Department of Internal Medicine (B.H.), Hospital Bremen Center; the Department of Hematology and Oncology (T.F.), University Hospital Magdeburg; the Department of Neurology (T.H.), University Hospital Mainz; the Department of Hematology and Oncology (H.G.M.), Klinikum Stuttgart; the Department of Hematology and Oncology (C.J.), University Hospital Rostock; the Department of Neurology (T.B.), University Hospital Munich LMU; the Departments of Neurology (U.H., P.R., M.W.) and Radiation Oncology (M.B.), University Hospital Tübingen; the Department of Neurology (U.H.), University Bonn, Germany; the Department of Neurology (P.R., M.W.), University Hospital Zurich, Switzerland; and the Institute of Neuropathology (T.P.), University Hospital Bonn, Germany. agnieszka.korfel@charite.de. 2. From the Department of Hematology, Oncology and Tumor Immunology (A.K., E.T., L.F., K.J.), Charité Berlin; the Departments of Clinical Epidemiology and Applied Biostatistics (P.M.) and Hematology and Oncology (R.M.), University Tübingen; the Department of Radiotherapy and Medical Oncology (F.G.), Pius Hospital Oldenburg; the Department of Neurology (M.R.), Protestant Hospital Bielefeld; the Department of Hematology (A.R.), University Hospital Essen; the Department of Internal Medicine (B.H.), Hospital Bremen Center; the Department of Hematology and Oncology (T.F.), University Hospital Magdeburg; the Department of Neurology (T.H.), University Hospital Mainz; the Department of Hematology and Oncology (H.G.M.), Klinikum Stuttgart; the Department of Hematology and Oncology (C.J.), University Hospital Rostock; the Department of Neurology (T.B.), University Hospital Munich LMU; the Departments of Neurology (U.H., P.R., M.W.) and Radiation Oncology (M.B.), University Hospital Tübingen; the Department of Neurology (U.H.), University Bonn, Germany; the Department of Neurology (P.R., M.W.), University Hospital Zurich, Switzerland; and the Institute of Neuropathology (T.P.), University Hospital Bonn, Germany.
Abstract
OBJECTIVE: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months. METHODS:Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9. RESULTS: In the per-protocol population (n = 320), WBRT nonsignificantly prolonged progression-free survival (PFS) (median 18.2 vs 11.9 months, hazard ratio [HR] 0.83 [95% confidence interval (CI) 0.65-1.06], p = 0.14) and significantly PFS from last HDMTX (25.5 vs 12.0 months, HR 0.65 [95% CI 0.5-0.83], p = 0.001), but without OS prolongation (35.6 vs 37.1 months, HR 1.03 [95% CI 0.79-1.35], p = 0.82). In the intent-to-treat population (n = 410), there was a prolongation by WBRT of both PFS (15.4 vs 9.9 months, HR 0.79 [95% CI 0.64-0.98], p = 0.034) and PFS from last HDMTX (19.4 vs 11.9 months, HR 0.72 [95% CI 0.58-0.89], p = 0.003), but not of OS (32.4 vs 36.1 months, HR 0.98 [95% CI 0.79-1.26], p = 0.98). CONCLUSION: Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT.
RCT Entities:
OBJECTIVE: This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy (WBRT) in primary therapy of primary CNS lymphoma (PCNSL) after a median follow-up of 81.2 months. METHODS:Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate (HDMTX)-based chemotherapy alone or followed by WBRT. We hypothesized that the omission of WBRT would not compromise overall survival (OS; primary endpoint), using a noninferiority design with a margin of 0.9. RESULTS: In the per-protocol population (n = 320), WBRT nonsignificantly prolonged progression-free survival (PFS) (median 18.2 vs 11.9 months, hazard ratio [HR] 0.83 [95% confidence interval (CI) 0.65-1.06], p = 0.14) and significantly PFS from last HDMTX (25.5 vs 12.0 months, HR 0.65 [95% CI 0.5-0.83], p = 0.001), but without OS prolongation (35.6 vs 37.1 months, HR 1.03 [95% CI 0.79-1.35], p = 0.82). In the intent-to-treat population (n = 410), there was a prolongation by WBRT of both PFS (15.4 vs 9.9 months, HR 0.79 [95% CI 0.64-0.98], p = 0.034) and PFS from last HDMTX (19.4 vs 11.9 months, HR 0.72 [95% CI 0.58-0.89], p = 0.003), but not of OS (32.4 vs 36.1 months, HR 0.98 [95% CI 0.79-1.26], p = 0.98). CONCLUSION: Although the statistical proof of noninferiority regarding OS was not given, our results suggest no worsening of OS without WBRT in primary therapy of PCNSL. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in PCNSLHDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone. The study lacked the precision to exclude an important survival benefit or harm from WBRT.
Authors: Ulrich Herrlinger; Niklas Schäfer; Rolf Fimmers; Frank Griesinger; Michael Rauch; Heinz Kirchen; Patrick Roth; Martin Glas; Michael Bamberg; Peter Martus; Eckhard Thiel; Agnieszka Korfel; Michael Weller Journal: J Cancer Res Clin Oncol Date: 2017-04-22 Impact factor: 4.553
Authors: Hyeon Kang Koh; Il Han Kim; Tae Min Kim; Do Hoon Lim; Dongryul Oh; Jae Ho Cho; Woo-Chul Kim; Jin Hee Kim; Woong-Ki Chung; Bae-Kwon Jeong; Ki Mun Kang; Semie Hong; Chang-Ok Suh; In Ah Kim Journal: J Neurooncol Date: 2017-09-22 Impact factor: 4.130