Prevalence of leukoencephalopathy and its potential cognitive sequelae in cancer patients

Abstract

Due to the rising use of chemotherapy treatment in cancer patients and growing survival rates, therapy-induced neurotoxic side effects are increasingly reported. Given the ambiguity about the prevalence and severity of leukoencephalopathy, one of such toxic side effects, in non-central nervous system (CNS) cancer patients, we performed a systematic literature search using the PubMed/Medline database to summarize existing literature regarding leukoencephalopathy epidemiology in non-CNS cancer patients and its potential cognitive sequelae. The search was based on the following terms: (‘MRI’ OR ‘T2-weighted MRI’ OR ‘FLAIR’) AND (‘cancer’ OR ‘tumour’ OR ‘leukaemia’ OR ‘neoplasms’) AND (‘chemotherapy’ OR ‘radiotherapy’) AND (‘posterior reversible encephalopathy’ OR ‘leukoencephalopathy’ OR ‘cerebral ischaemia’ OR ‘stroke’). Thirty-two studies discussing the occurrence of leukoencephalopathy in cancer patients were included, of which the majority investigated Acute Lymphoblastic Leukaemia (ALL) patients (n = 22).

Regularly scanned ALL patients showed a prevalence of leukoencephalopathy between 17 − 87%, and 15 − 83% of patients presented with leukoencephalopathy when only scanned after a CNS event. When diagnosed with posterior reversible encephalopathy syndrome, 100% of patients showed leukoencephalopathy because its diagnosis is based in part on observable lesions. An increased prevalence was observed in ALL patients treated with higher doses of methotrexate (5 g/m² MTX, 42 − 87%) when compared to lower doses (< 5 g/m², 32 − 67%). By contrast, in breast cancer patients, white matter lesions were mainly detected in case of neurological symptoms, but not (yet) clearly associated with chemotherapy administration. However, chemotherapy treatment was associated with more infratentorial microbleeds in breast cancer patients . Up to 50% of other (neurologically asymptomatic) solid tumour patients presented white matter lesions, even years after treatment. When cognitive data were investigated, lesioned patients showed lower scores on neurocognitive tests in 50% of studies, years after ending therapy.

In conclusion, leukoencephalopathy is well-documented for ALL patients (with a focus on methotrexate), but there is a lack of knowledge for other intravenous chemotherapeutics, other oncological populations, wider age ranges and possible risk factors (e.g. history of CNS event). Furthermore, the long-term neuropsychological impact and potential risk for neurodegenerative processes due to leukoencephalopathy remains inconclusive. Hence, large international databanks, epidemiological and prospective case-control studies are necessary to stratify risk groups for CNS-related side effects.

Keywords:

• leukoencephalopathy
• cancer
• chemotherapy
• structural
• imaging
• review

Conflict of interest

None.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Notes on contributors

Gwen Schroyen

Gwen Schroyen, PhD student (Master in Biomedical Sciences). Screened articles, performed data extraction and wrote the article. Member of the “Cancer and Cognition” research group, research focus on effects of chemotherapy on the brain via neuroimaging, mainly in breast cancer patients.

Michiel Meylaers

Michiel Meylaers, Medicine student, Screened articles, performed data extraction and wrote the article. Leukoencephalopathy prevalence was research focus as part of master thesis.

Sabine Deprez

Sabine Deprez, Post-doctoral researcher (Master in Engineering), helped write the article. Member of the “Cancer and Cognition” task force, research focus on effects of chemotherapy on the brain via neuroimaging, mainly in breast cancer patients.

Jeroen Blommaert

Jeroen Blommaert, PhD student (Master in Biomedical engineering), helped write the article. Member of the “Cancer and Cognition” task force, research focus on effects of chemotherapy during pregnancy on the brain via neuroimaging.

Ann Smeets

Ann Smeets, Breast cancer surgeon, helped write the article. Member of the “Cancer and Cognition” research group, research focus on effects of chemotherapy on the brain, mainly in breast cancer patients.

Sandra Jacobs

Sandra Jacobs, Paediatric oncologist, helped write the article. Head of paediatric oncology, member of the Leuven Cancer Insitute, research focus on childhood solid and soft tissue tumors and effects on long time survival.

Stefan Sunaert

Stefan Sunaert, Radiologist, helped write the article. Member of the “Cancer and Cognition” research group, research focus on fMRI/ DWI for surgical mapping in brain tumors, effects of chemotherapy on the brain via neuroimaging, strong background on technical processing of radiological sequences.

Charlotte Sleurs

Charlotte Sleurs, Post-doctoral researcher (Master in Psychology). Screened articles, performed data extraction and wrote the article. Member of the “Cancer and Cognition” research group, research focus on effects of chemotherapy on the brain via neuroimaging, in both paediatric and adult survivors of solid or soft tissue tumors.

Anne Uyttebroeck

Anne Uyttebroeck, Paediatric oncologist, helped write the article. Member of the Leuven Cancer Insitute, research focus on effects of chemotherapy, in both paediatric and adult survivors of solid or soft tissue tumors.