Narrative review of primary central nervous system lymphoma: treatment-related neurotoxicity

Abstract

Delayed treatment-related neurotoxicity is a frequent complication among long-term survivors of primary central nervous system lymphoma (PCNSL), and many patients experience cognitive difficulties that interfere with their ability to function at pre-diagnosis levels. This article provides a comprehensive review of cognitive functioning in adult patients with PCNSL according to treatment modality, and it includes articles reporting the results of standardized cognitive assessments. The literature review indicated that cognitive functions were assessed with standardized neuropsychological tests in a relatively limited number of studies. Most studies reported diffuse cognitive impairment at baseline and prior to treatment, likely related to the disease, and improvement following induction high-dose methotrexate (HD-MTX)-based chemotherapy. Studies that assessed cognitive functions systematically months to years after HD-MTXbased chemotherapy and consolidation whole-brain radiotherapy (WBRT) reported cognitive impairment and white matter abnormalities in most patients. The cognitive domains often disrupted by treatment adverse effects include attention, executive functions, graphomotor speed, and memory. Among patients treated with HD-MTX-based chemotherapy or blood brain barrier disruption (BBBD) chemotherapy alone, there was evidence of stable or improved cognitive performance and quality of life (QoL) over time, with subsets of patients showing cognitive decline. Recent prospective randomized longitudinal studies comparing treatment modalities have reported stable or improved cognitive functions over time among most patients treated with HD-MTX-based chemotherapy alone or followed by consolidation with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and cognitive decline in patients treated with consolidation WBRT; although reduced-dose WBRT was associated with less pronounced neurotoxicity. Additional collaborative, randomized, prospective longitudinal studies including standardized assessments of cognitive functions are needed to improve our knowledge and understanding of treatment-related neurotoxicity in this