Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial
Neuro-Oncology, vol. 23, pp. 1315–1326
Abstract
BACKGROUND: To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL). METHODS: One hundred and ninety-nine patients from a phase III trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients ≤60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated. RESULTS: 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774). CONCLUSIONS: Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients ≤60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition.
Authors 18
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Matthijs van der Meulen corresponding
Erasmus MC · Erasmus MC Cancer Institute
Affiliation as printed
Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Leiden University Medical Center · Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum
Affiliation as printed
Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
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Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum
Affiliation as printed
Department of Medical Psychology, Haaglanden Medical Center, The Hague, The Netherlands
Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
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Affiliation as printed
HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Affiliation as printed
Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands
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The University of Western Australia · Sir Charles Gairdner Hospital · Pathwest Laboratory Medicine
Affiliation as printed
Haematology Department, Sir Charles Gairdner Hospital and PathWest Laboratory Medicine, Nedlands, Western Australia, Australia
University of Western Australia, Crawley, Western Australia, Australia
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Maastricht University Medical Centre
Affiliation as printed
Department of Hematology, University Medical Center, Maastricht, The Netherlands
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Amsterdam University Medical Centers · Cancer Center Amsterdam · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Hematology, Amsterdam UMC-Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
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The Netherlands Cancer Institute
Affiliation as printed
Department of Neuro-oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Radiotherapy, University Medical Center Groningen, Groningen, The Netherlands
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Leiden University Medical Center · Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum
Affiliation as printed
Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
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Erasmus MC · Erasmus MC Cancer Institute
Affiliation as printed
Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Hematology, Middlemore Hospital, Auckland, New Zealand
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Erasmus MC · Erasmus MC Cancer Institute
Affiliation as printed
Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Cancer Institute
Affiliation as printed
Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
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