title: Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study.
abstract: Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests.
authors.affiliation: Department of Neurology, SEIN-Epilepsy Institute in the Netherlands Foundation, Achterweg 5, 2103 SW, Heemstede, The Netherlands, f.froklage@vumc.nl.
authors.forename: F E
authors.initials: FE
authors.lastname: Froklage
authors.forename: L J
authors.initials: LJ
authors.lastname: Oosterbaan
authors.forename: E M
authors.initials: EM
authors.lastname: Sizoo
authors.forename: M
authors.initials: M
authors.lastname: de Groot
authors.forename: I
authors.initials: I
authors.lastname: Bosma
authors.forename: E
authors.initials: E
authors.lastname: Sanchez
authors.forename: L
authors.initials: L
authors.lastname: Douw
authors.forename: J J
authors.initials: JJ
authors.lastname: Heimans
authors.forename: J C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: F J
authors.initials: FJ
authors.lastname: Lagerwaard
authors.forename: J
authors.initials: J
authors.lastname: Buter
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: T J
authors.initials: TJ
authors.lastname: Postma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001284:Atrophy / Q000139:chemically induced; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000139:chemically induced / Q000175:diagnosis; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D056784:Leukoencephalopathies / Q000139:chemically induced* / Q000175:diagnosis; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide