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Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation

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Abstract

Introduction

The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT.

Methods

PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals.

Results

Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL.

Conclusions

Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.

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Acknowledgements

This study was supported in part by MSKCC Department of Neurology Research and Development Funds, and the National Cancer Institute P30 CA008748 core grant.

Author information

Author notes

  1. Maria Kryza-Lacombe

    Present address: San Diego Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA

  2. Lauren E. Abrey

    Present address: Novartis Oncology, Basel, Switzerland

  3. Antonio Omuro

    Present address: Yale Cancer Center and Department of Neurology, Yale School of Medicine, New Haven, CT, USA

Authors and Affiliations

  1. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Denise D. Correa, Erica Braun, Maria Kryza-Lacombe, Ka-Wai Ho, Lauren E. Abrey, Lisa M. DeAngelis & Antonio Omuro

  2. Department of Neurology, Weill Cornell Medical College, New York, NY, USA

    Denise D. Correa & Lisa M. DeAngelis

  3. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Anne S. Reiner & Katherine S. Panageas

  4. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Joachim Yahalom

  5. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Craig S. Sauter

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  1. Denise D. Correa
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Corresponding author

Correspondence to Denise D. Correa.

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Conflict of interest

Dr. Correa serves on the Editorial Board of Neuro-Oncology Practice. Ms. Reiner serves on the Editorial Board of Journal of the National Cancer Institute, Journal of the National Cancer Institute Cancer Spectrum. Dr. Panageas serves on the Editorial Board of Clinical Cancer Research, Journal National of the Cancer Institute, Journal of the National Cancer Institute Cancer Spectrum. She holds stock ownership in Johnson and Johnson, Pfizer, Viking Therapeutics, Catalyst Biotech. Dr. DeAngelis serves on the Editorial Board of Neurology, Journal of Neuro-Oncology, The Open Clinical Cancer Journal, CNS Oncology, Neuro-Oncology, and Neuro-Oncology Practice, and Scientific, and on the Advisory Board of Sapience Therapeutics. Dr. Omuro serves on the Editorial Board of Journal of Neuro-Oncology and Neuro-Oncology Practice, and has consulted for BTG. Dr. Sauter has served as a paid consultant on Advisory Boards for: Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite, a Gilead Company and GSK. He has received research funds for investigator-initiated trials from Juno Therapeutics and Sanofi-Genzyme. Dr. Abrey is a full-time employee and shareholder in Novartis. The following co-authors have no conflicts of interest: Ms. Braun, Ms. Kryza-Lacombe, Dr. Yahalom, and Dr. Ka-Wai Ho.

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Correa, D.D., Braun, E., Kryza-Lacombe, M. et al. Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation. J Neurooncol 144, 553–562 (2019). https://doi.org/10.1007/s11060-019-03257-1

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