Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial

Matthijs van der Meulen; Linda Dirven; Esther J J Habets; Katerina Bakunina; Marion Smits; Hakim C Achterberg; Tatjana Seute; Gavin Cull; Harry Schouten; Josée M Zijlstra; Dieta Brandsma; Roelien H Enting; Max Beijert; Martin J B Taphoorn; Martin J van den Bent; Samar Issa; Jeanette K Doorduijn; Jacoline E C Bromberg

doi:10.1093/neuonc/noab021

Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial

Neuro Oncol. 2021 Aug 2;23(8):1315-1326. doi: 10.1093/neuonc/noab021.

Authors

Matthijs van der Meulen¹, Linda Dirven^{2

3}, Esther J J Habets^{3

4}, Katerina Bakunina⁵, Marion Smits⁶, Hakim C Achterberg⁶, Tatjana Seute⁷, Gavin Cull^{8

9}, Harry Schouten¹⁰, Josée M Zijlstra¹¹, Dieta Brandsma¹², Roelien H Enting¹³, Max Beijert¹⁴, Martin J B Taphoorn^{2

3}, Martin J van den Bent¹, Samar Issa¹⁵, Jeanette K Doorduijn¹⁶, Jacoline E C Bromberg¹

Affiliations

¹ Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
³ Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands.
⁴ Department of Medical Psychology, Haaglanden Medical Center, The Hague, The Netherlands.
⁵ HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
⁶ Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁷ Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁸ Haematology Department, Sir Charles Gairdner Hospital and PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
⁹ University of Western Australia, Crawley, Western Australia, Australia.
¹⁰ Department of Hematology, University Medical Center, Maastricht, The Netherlands.
¹¹ Department of Hematology, Amsterdam UMC-Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹² Department of Neuro-oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
¹³ Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁴ Department of Radiotherapy, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Department of Hematology, Middlemore Hospital, Auckland, New Zealand.
¹⁶ Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.

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.

Keywords: atrophy; cognition; radiation; rituximab; white matter lesions.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System Neoplasms*
Humans
Lymphoma*
Lymphoma, Non-Hodgkin* / complications
Lymphoma, Non-Hodgkin* / drug therapy
Middle Aged
Neuropsychological Tests
Rituximab / therapeutic use

Substances

Rituximab

Abstract

Publication types

MeSH terms

Substances

Grants and funding