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Neurology. 2015 Mar 24;84(12):1242-8. doi: 10.1212/WNL.0000000000001395. Epub 2015 Feb 25.

Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma.

Author information

  • 1From 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.
  • 2From 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.

© 2015 American Academy of Neurology.

PMID:
25716362
[PubMed - indexed for MEDLINE]
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