Ulrich Herrlinger1,2, Niklas Schäfer3, Rolf Fimmers4, Frank Griesinger5, Michael Rauch6, Heinz Kirchen7, Patrick Roth8, Martin Glas3,9, Michael Bamberg10, Peter Martus11, Eckhard Thiel12, Agnieszka Korfel12, Michael Weller13,8. 1. Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. ulrich.herrlinger@ukbonn.de. 2. Department of General Neurology, University Hospital Tuebingen, Geissweg 3, 72076, Tübingen, Germany. ulrich.herrlinger@ukbonn.de. 3. Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 4. Institute of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 5. Department of Hematology and Oncology, Pius Hospital Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany. 6. Department of Neurology, Protestant Hospital Bielefeld, Burgsteig 13, 33617, Bielefeld, Germany. 7. Department of Internal Medicine I, Krankenhaus der Barmherzigen Brüder Trier, Nordallee 1, 54292, Trier, Germany. 8. Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland. 9. Division of Clinical Neueroncology, Department of Neurology, University of Essen Medical Center, 45147, Essen, Germany. 10. Department of Radiation Oncology, University Hospital Tuebingen, Geissweg 3, 72076, Tübingen, Germany. 11. Institute for Medical Biostatistics, University Hospital Tuebingen, Geissweg 3, 72076, Tübingen, Germany. 12. Department of Hematology and Oncology, Charité Berlin, Hindenburgdamm 30, 12203, Berlin, Germany. 13. Department of General Neurology, University Hospital Tuebingen, Geissweg 3, 72076, Tübingen, Germany.
Abstract
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.
RCT Entities:
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.
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