Publikation
Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma
Wissenschaftlicher Artikel/Review - 25.02.2015
Korfel Agnieszka, Junghanß Christian, Birnbaum Tobias, Fischer Lars, Jahnke Kristoph, Herrlinger Ulrich, Roth Patrick, Bamberg Michael, Pietsch Torsten, Mergenthaler Hans G, Hundsberger Thomas, Thiel Eckhard, Martus Peter, Möhle Robert, Griesinger Frank, Rauch Michael, Röth Alexander, Hertenstein Bernd, Fischer Thomas, Weller Michael
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Kurzbeschreibung/Zielsetzung
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.