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      Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study

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          Abstract

          Background

          Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy.

          Methods

          Women aged ≥ 60 years with stage I–III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models.

          Results

          A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy ( p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = − 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = − 6.94) compared to the non-TC group (change = − 1.21, p for interaction = 0.07) and healthy controls (change = 0.09, p for interaction = 0.02).

          Conclusions

          There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings.

          Trial registration

          ClinicalTrials.gov, NCT01992432. Registered on 25 November 2013. Retrospectively registered.

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          Most cited references21

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          One-year brain atrophy evident in healthy aging.

          An accurate description of changes in the brain in healthy aging is needed to understand the basis of age-related changes in cognitive function. Cross-sectional magnetic resonance imaging (MRI) studies suggest thinning of the cerebral cortex, volumetric reductions of most subcortical structures, and ventricular expansion. However, there is a paucity of detailed longitudinal studies to support the cross-sectional findings. In the present study, 142 healthy elderly participants (60-91 years of age) were followed with repeated MRI, and were compared with 122 patients with mild to moderate Alzheimer's disease (AD). Volume changes were measured across the entire cortex and in 48 regions of interest. Cortical reductions in the healthy elderly were extensive after only 1 year, especially evident in temporal and prefrontal cortices, where annual decline was approximately 0.5%. All subcortical and ventricular regions except caudate nucleus and the fourth ventricle changed significantly over 1 year. Some of the atrophy occurred in areas vulnerable to AD, while other changes were observed in areas less characteristic of the disease in early stages. This suggests that the changes are not primarily driven by degenerative processes associated with AD, although it is likely that preclinical changes associated with AD are superposed on changes due to normal aging in some subjects, especially in the temporal lobes. Finally, atrophy was found to accelerate with increasing age, and this was especially prominent in areas vulnerable to AD. Thus, it is possible that the accelerating atrophy with increasing age is due to preclinical AD.
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            Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer.

            Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250).
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              Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies.

              There is consistent evidence that brain volume changes in early and late life. Most longitudinal studies usually only span a few years and include a limited number of participants. In this review, we integrate findings from 56 longitudinal magnetic resonance imaging (MRI) studies on whole brain volume change in healthy individuals. The individual longitudinal MRI studies describe only the development in a limited age range. In total, 2,211 participants were included. Age at first measurement varied between 4 and 88 years of age. The studies included in this review were performed using a large range of methods (e.g., different scanner protocols and different acquisition parameters). We applied a weighted regression analysis to estimate the age dependency of the rate of relative annual brain volume change across studies. The results indicate that whole brain volume changes throughout the life span. A wave of growth occurs during childhood/adolescence, where around 9 years of age a 1% annual brain growth is found which levels off until at age 13 a gradual volume decrease sets in. During young adulthood, between ∼18 and 35 years of age, possibly another wave of growth occurs or at least a period of no brain tissue loss. After age 35 years, a steady volume loss is found of 0.2% per year, which accelerates gradually to an annual brain volume loss of 0.5% at age 60. The brains of people over 60 years of age show a steady volume loss of more than 0.5%. Understanding the mechanisms underlying these plastic brain changes may contribute to distinguishing progressive brain changes in psychiatric and neurological diseases from healthy aging processes. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. Copyright © 2011 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                626-301-8396 , Bechen@coh.org
                Sethisea@gmail.com
                Tjin@coh.org
                Spatel@coh.org
                Nye2@coh.org
                Casun@coh.org
                Rrockne@coh.org
                Nmrimaging@gamil.com
                Rootj@mskcc.org
                Asaykin@iupui.edu
                Ahlest@mskcc.org
                Holodnya@mskcc.org
                Nprakash@coh.org
                Jmortimer@coh.org
                Jwaisman@coh.org
                Yuyuan@coh.org
                Gsomlo@coh.org
                Danli@coh.org
                Riyang@coh.org
                Hetan@coh.org
                Vkatheria@coh.org
                Rmorrison@coh.org
                Ahurria@coh.org
                Journal
                Breast Cancer Res
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central (London )
                1465-5411
                1465-542X
                2 May 2018
                2 May 2018
                2018
                : 20
                : 38
                Affiliations
                [1 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Department of Diagnostic Radiology, , City of Hope National Medical Center, ; Duarte, CA 91010 USA
                [2 ]The MRI Institute for Biomedical Research, Magnetic Resonance Innovations, Inc., Detroit, MI USA
                [3 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Department of Population Science, , City of Hope National Medical Center, ; Duarte, CA 91010 USA
                [4 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Center for Cancer and Aging, City of Hope National Medical Center, ; Duarte, CA 91010 USA
                [5 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Division of Mathematical Oncology, , City of Hope National Medical Center, ; Duarte, CA 91010 USA
                [6 ]ISNI 0000 0001 1456 7807, GRID grid.254444.7, Department of Biomedical Engineering, , Wayne State University, ; Detroit, MI 48202 USA
                [7 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Neurocognitive Research Lab, , Memorial Sloan Kettering Cancer Center, ; 641 Lexington Avenue, 7th Floor, New York, NY 10022 USA
                [8 ]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Center for Neuroimaging, Indiana University School of Medicine, ; 355 West 16th Street, Indianapolis, IN 46202 USA
                [9 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Department of Radiology, , Memorial Sloan-Kettering Cancer Center, ; 641 Lexington Avenue, 7th Floor, New York, NY 10022 USA
                [10 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Division of Neurology, , City of Hope National Medical Center, ; Duarte, CA 91010 USA
                [11 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, Department of Medical Oncology, , City of Hope National Medical Center, ; Duarte, CA 91010 USA
                Author information
                http://orcid.org/0000-0002-1557-159X
                Article
                965
                10.1186/s13058-018-0965-3
                5932862
                29720224
                b917eb29-3a36-413f-912c-e0de9d33d53c
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 October 2017
                : 31 March 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: R03 AG045090
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01 AG037037
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                brain mri,brain volume,chemotherapy,cancer-related cognitive impairment,breast cancer

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