Brain atrophy in children undergoing systemic chemotherapy for extracranial solid tumors

Abstract

It has been shown that intracthecal chemotherapy may cause brain damage, which can be depicted in neuroimaging studies. The aim of this work was to examine possible morphologic alterations in the brain of children with extracranial solid tumors, without CNS complications, treated with systemic chemotherapy. Brain CT images of 69 children with extracranial malignancies were reviewed and the extent of 12 CSF compartments was measured in 49 CT examinations performed during intravenously given chemotherapy and in 20 after therapy completion. Measurements were compared with corresponding normative data. About half of the children undergoing chemotherapy and half of the patients examined after treatment were found to have diffuse brain atrophy. Focal lesions that might be associated with therapy toxicity were not observed. Chemotherapy, even when administered via the systemic route, may cause brain damage, which is observed long after the end of treatment. Med. Pediatr. Oncol. 28:228–233 © Wiley‐Liss, Inc.

Evidence for acute neurotoxicity after chemotherapy

“…Brain atrophy following chemotherapy had been recognized in the pediatric literature,21, 22 but was thought to be due to a chronic rather than acute effect. Similar arguments have been made with regard to the white matter brain changes observed in women with advanced breast cancer who received high‐dose chemotherapy 23.…”

Neuropsychological outcome in long-term survivors of a childhood extracranial solid tumor who have undergone autologous bone marrow transplantation

“…[5][6][7] Furthermore, systemic chemotherapy may have a deleterious effect on neuropsychological functioning. Some studies have reported diffuse brain atrophy 8 or intellectual declines associated with IV cytotoxic agents [9][10][11] such as cisplatin. 7 Indeed, the potential neurotoxicity of notably busulfan, BCNU, thiotepa melphalan is well known.…”

Late structural alterations of cerebral white matter in long‐term survivors of childhood leukemia

“…SEVERE CONSEQUENCES of brain radiation and/or chemotherapy in survivors of childhood leukemia such as focal necrosis, necrotizing and mineralizing leukoencephalopathy, major arterial occlusion, small vascular malformations, and secondary neoplasms are well described but rare complications (1, 2). During and after chemotherapy alone, transient high T2 signal changes in white matter were observed in 9% of children with acute lymphoblastic leukemia (ALL) (3) as well as generalized brain atrophy in systemic chemotherapy for extracranial tumors (4). However, also in patients without these obvious cerebral lesions, maldevelopment and cognitive deficits during later life have been reported (5).…”