6533b85cfe1ef96bd12bd574

RESEARCH PRODUCT

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

Agnieszka KorfelFrank GriesingerMichael BambergPeter MartusRobert MöhleTobias BirnbaumTorsten PietschKristoph JahnkeChristian JunghanßThomas HundsbergerHans G. MergenthalerPatrick RothBernd HertensteinLars FischerThomas FischerEckhard ThielMichael RauchMichael WellerUlrich HerrlingerAlexander Röth

subject

MaleOncologyAntimetabolites Antineoplasticmedicine.medical_specialtyLymphomamedicine.medical_treatmentPopulationMedizin610 Medicine & healthDisease-Free Survivallaw.inventionCentral Nervous System NeoplasmsRandomized controlled triallawInternal medicinemedicineClinical endpointHumanseducationAgededucation.field_of_studyChemotherapybusiness.industryHazard ratioAntineoplastic ProtocolsMiddle AgedCombined Modality TherapyConfidence interval10040 Clinic for NeurologyRadiation therapyMethotrexateTreatment Outcome2728 Neurology (clinical)MethotrexateNeurology (clinical)Cranial Irradiationbusinessmedicine.drug

description

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.

10.5167/uzh-110459https://doi.org/10.5167/uzh-110459