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Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

de Ruiter, Michiel B. ; Reneman, Liesbeth ; Boogerd, Willem ; Veltman, Dick J. ; Caan, Matthan ; Douaud, Gwenaëlle ; Lavini, Cristina ; Linn, Sabine C. ; Boven, Epie ; van Dam, Frits S.A.M. ; Schagen, Sanne B.

Human brain mapping, 2012-12, Vol.33 (12), p.2971-2983 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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Título:
Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging
Autor: de Ruiter, Michiel B. ; Reneman, Liesbeth ; Boogerd, Willem ; Veltman, Dick J. ; Caan, Matthan ; Douaud, Gwenaëlle ; Lavini, Cristina ; Linn, Sabine C. ; Boven, Epie ; van Dam, Frits S.A.M. ; Schagen, Sanne B.
Assuntos: Aged ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Brain - drug effects ; Brain - pathology ; breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Carboplatin - adverse effects ; Carboplatin - pharmacology ; Carboplatin - therapeutic use ; chemotherapy ; Chemotherapy, Adjuvant - adverse effects ; Cognition - drug effects ; cognitive functioning ; Cyclophosphamide - adverse effects ; Cyclophosphamide - pharmacology ; Cyclophosphamide - therapeutic use ; diffusion tensor imaging ; Electrocardiography. Vectocardiography ; Electrodiagnosis. Electric activity recording ; Female ; Health Status ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Medical sciences ; Middle Aged ; multimodal MRI ; Nerve Fibers, Myelinated - drug effects ; Nerve Fibers, Myelinated - pathology ; Nerve Fibers, Unmyelinated - drug effects ; Nerve Fibers, Unmyelinated - pathology ; Nervous system ; Neuropsychological Tests ; proton MR spectroscopy ; Quality of Life ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; side effects ; Survivors ; Thiotepa - adverse effects ; Thiotepa - pharmacology ; Thiotepa - therapeutic use ; Time Factors ; voxel-based morphometry
É parte de: Human brain mapping, 2012-12, Vol.33 (12), p.2971-2983
Notas: The Netherlands Cancer Institute
The department of Radiology (Academic Medical Center of the University of Amsterdam)
istex:33D8FFB26C636062AD1F21C7A2E845A3A05E2762
ArticleID:HBM21422
ark:/67375/WNG-0XBKM2BF-F
Descrição: The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high‐dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract‐based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H‐MRS) in the left centrum semiovale (white matter) showed a reduction of N‐acetylasparate/creatine indicative of axonal injury. Voxel‐based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H‐MRS only in the chemotherapy group. These results converge to suggest that high‐dose adjuvant chemotherapy for breast cancer is associated with long‐term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

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Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

de Ruiter, Michiel B. ; Reneman, Liesbeth ; Boogerd, Willem ; Veltman, Dick J. ; Caan, Matthan ; Douaud, Gwenaëlle ; Lavini, Cristina ; Linn, Sabine C. ; Boven, Epie ; van Dam, Frits S.A.M. ; Schagen, Sanne B.

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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