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

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 followup 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] . 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. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma ABSTRACTObjective: 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 5 320), WBRT nonsignificantly prolonged progressionfree survival (PFS) (median 18.2 vs 11.9 months, hazard ratio 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. Neurology ® 2015;84:1242-1248 GLOSSARY CHT 5 chemotherapy; CI 5 confidence interval; CR 5 complete response; G-PCNSL-SG 5 German PCNSL Study Group; HD-Ara-C 5 high-dose cytarabine; HDMTX 5 high-dose methotrexate; HR 5 hazard ratio; ITT 5 intent-to-treat; KPS 5 Karnofsky Performance Score; OS 5 overall survival; PCNSL 5 primary CNS lymphoma; PFS 5 progression-free survival; PP 5 per protocol; PR 5 partial remission; WBRT 5 whole-brain radiotherapy.Standards of care have not been well-defined for primary CNS lymphoma (PCNSL). Highdose methotrexate (HDMTX) is the only undisputed standard of care, whereas the addition of whole-brain radiotherapy (WBRT) has been increasingly questioned because of the high frequency of late neurotoxicity ...

Early whole brain radiotherapy in primary CNS lymphoma: negative impact on quality of life in the randomized G-PCNSL-SG1 trial

“…The prolongation of progressionfree survival induced by WBRT in the G-PCNSL-SG-1 trial may be an argument in favor of WBRT in primary therapy. However, the G-PCNSL-SG-1 trial also showed no differences in overall survival between the groups (Thiel et al 2010;Korfel et al 2015). Now, the present data show that some dimensions of quality of life and in particular the cognitive performance in the lifetime remaining are reduced in patients receiving consolidating WBRT.…”

“…1). As the main result, G-PCNSL-SG1 did not find significant differences in overall survival (OS) between the two arms although the non-inferiority of the no early WBRT arm could not be formally proven (Thiel et al 2010;Korfel et al 2015).…”

A focus on pharmacotherapy for primary central nervous system lymphoma

“…The results were confirmed in a long-term analysis including an as-treated evaluation [14]. Although there were some problems with the execution of this study, all detailed in the first publication [1], the question about the role of WBRT could clearly be answered, and as a consequence, WBRT should not routinely be given as a part of initial therapy in PCNSL.…”

Brain Tumor Imaging

“…Whole brain radiotherapy is active in primary CNC lymphomas but is associated with delayed neurotoxicity (Doolittle et al 2013). Therefore, radiotherapy should be reserved for patients who cannot receive chemotherapy or in the recurrent setting (Korfel et al 2015;Thiel et al 2010).…”