title: Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?
abstract: In a previous longitudinal diffusion tensor imaging (DTI) study, we observed cerebral white matter (WM) alterations (reduced fractional anisotropy (FA)) related to decreased cognitive performance 3-5 months after chemotherapy-treatment (t2) when compared to baseline (t1) (Deprez et al. in Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(3), 274-281. doi:10.1200/JCO.2011.36.8571, 2012). The current study investigates the evolution and the nature of these previously observed microstructural changes. Twenty-five young women with early-stage breast cancer who received chemotherapy treatment (C+), 14 who did not receive chemotherapy (C-) and 15 healthy controls (HC) previously studied, underwent reassessment 3-4 years after treatment (t3). We assessed (1) longitudinal changes of cognitive performance and FA and (2) cross-sectional group differences in myelin-water-imaging and multishell diffusion MRI metrics at t3. MRI metrics were assessed on a voxel-by-voxel basis and in regions-of-interest (ROI) in which previous WM injury was detected. Longitudinal results: Mixed-effects modeling revealed significant group-time interactions for verbal memory and processing speed (p < 0.05) reflecting regained performance in the C+ group at t3. Furthermore, in chemotherapy-treated patients, FA returned to baseline levels at t3 in all ROIs (p < 0.002), whereas no FA changes were seen in controls. Additionally, FA increase from t2 to t3 correlated with time since treatment in two of the four regions (r = 0.40, p < 0.05). Cross-sectional results: Advanced diffusion MRI and myelin-water imaging metrics in the ROIs did not differ between groups. Similarly, no whole-brain voxelwise differences were detected. Initial WM alterations and reduced cognitive performance following chemotherapy-treatment were found to recover in a group of young breast cancer survivors three to four years after treatment.
authors.affiliation: Department of Radiology, University Hospitals Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium.|Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Thibo
authors.initials: T
authors.lastname: Billiet
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Department of Old Age Psychiatry, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: Department of Radiology, University Hospitals Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium.|Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Ronald
authors.initials: R
authors.lastname: Peeters
authors.affiliation: Department of Electrical Engineering (ESAT), Processing of Speech and Images (PSI), KU Leuven, Leuven, Belgium.
authors.forename: Daan
authors.initials: D
authors.lastname: Christiaens
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Icometrix, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hecke
authors.affiliation: Leuven Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Smeets
authors.affiliation: Department of Obstetrics and Gynecology, Gynecological Oncology, University Hospitals, Leuven, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.affiliation: Department of Radiology, University Hospitals Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium.|Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
authors.affiliation: Department of Radiology, University Hospitals Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. sabine.deprez@uzleuven.be.|Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. sabine.deprez@uzleuven.be.
authors.forename: Sabine
authors.identifier: http://orcid.org/0000-0001-7451-5355
authors.initials: S
authors.lastname: Deprez
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000073116:Cancer Survivors; D003071:Cognition / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009483:Neuropsychological Tests; D020127:Recovery of Function; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents
keywords: Breast cancer; Chemotherapy; Cognitive impairment; MR diffusion imaging; MR myelin water imaging; White matter