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

Purpose In the randomized G-PCNSL-SG-1 trial, the addition of whole brain radiotherapy (45 Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients. To determine whether WBRT might lead to quality of life (QoL)-relevant late neurotoxicity, this trial prospectively monitored QoL. Methods QoL measurements were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with repeated Mini Mental State Examinations (MMSE). Exploratory data analysis included the 318 patients in the per-protocol population. Results In year 2 after randomization, cognitive functioning and global health status were reduced in the early WBRT arm as compared to the no early WBRT arm ( p = 0.004 and p = 0.022, respectively). Also, fatigue ( p = 0.037), appetite loss ( p = 0.006) and hair loss ( p = 0.002) were more intense in the early WBRT arm. MMSE testing revealed lower values ( p = 0.002) in the early WBRT arm. A mixed model analysis of longitudinal data additionally showed differences favoring the no early WBRT arm in 15 of 26 dimensions of QoL. Conclusions The analysis of subjective QoL questionnaires and objective MMSE testing revealed that QoL and cognition were conserved in the arm without early WBRT. Thus, even though it was an exploratory analysis, the results of G-PCNSL-SG1 challenge the place of WBRT in the primary therapy of PCNSL.