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Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?

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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.

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Acknowledgements

We would like to thank all participants for their time invested in this study and Dr. Frederik Dekeyzer for support with statistical analysis. This work was supported by Research Foundation Flanders (FWO - G.0354.06) and by Stichting tegen Kanker.

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Authors and Affiliations

  1. Department of Radiology, University Hospitals Leuven, UZ Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Thibo Billiet, Ronald Peeters, Stefan Sunaert & Sabine Deprez

  2. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

    Thibo Billiet, Ronald Peeters, Stefan Sunaert & Sabine Deprez

  3. Department of Old Age Psychiatry, University Hospitals Leuven, Leuven, Belgium

    Louise Emsell & Mathieu Vandenbulcke

  4. Department of Electrical Engineering (ESAT), Processing of Speech and Images (PSI), KU Leuven, Leuven, Belgium

    Daan Christiaens

  5. Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands

    Alexander Leemans

  6. Icometrix, Leuven, Belgium

    Wim Van Hecke

  7. Leuven Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium

    Ann Smeets

  8. Department of Obstetrics and Gynecology, Gynecological Oncology, University Hospitals, Leuven, Belgium

    Frederic Amant

Authors
  1. Thibo Billiet
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  2. Louise Emsell
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  3. Mathieu Vandenbulcke
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  4. Ronald Peeters
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  5. Daan Christiaens
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  6. Alexander Leemans
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  7. Wim Van Hecke
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  8. Ann Smeets
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  9. Frederic Amant
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  10. Stefan Sunaert
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  11. Sabine Deprez
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Corresponding author

Correspondence to Sabine Deprez.

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Funding

This work was supported by Research Foundation Flanders (FWO - G.0354.06) and by Stichting tegen Kanker.

Conflict of interest

All authors declare that they have no conflict of interest to report.

Ethical approval

All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Billiet, T., Emsell, L., Vandenbulcke, M. et al. Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?. Brain Imaging and Behavior 12, 64–77 (2018). https://doi.org/10.1007/s11682-016-9665-8

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  • DOI: https://doi.org/10.1007/s11682-016-9665-8

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