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.

Systematic review of longitudinal studies on chemotherapy‐associated subjective cognitive impairment in cancer patients

“…In one study, group differences in longitudinal changes in SCI were unconfirmed in a multivariate model . Five studies reported no differences in longitudinal changes in SCI between the CTX group and non‐CTX patients or healthy controls . No differences emerged in three non–breast‐cancer studies and in two studies with a follow‐up at least 1 year posttreatment .…”

“…Patients' ages varied. To avoid age‐related cognitive impairment, nine studies selected patients younger than 75 . Three studies specifically targeted elders .…”

“…Most studies (n = 12) collected follow‐up data at least twice. Follow‐up occurred during the post‐CTX period with five studies having a long‐term follow‐up at least 1 year post‐CTX …”

Assessment and management of cognitive changes in patients with cancer

“…In patients who have no cognitive impairments, reassurance and observation may be helpful and should be accompanied by recommendations to address the patient’s cognitive concerns with compensatory strategies and lifestyle interventions relevant to brain health. Some studies have demonstrated an improvement in cognitive function and brain imaging abnormalities over time after chemotherapy is completed, suggesting that transient and potentially reversible effects are at play. However, others have shown persistent or even progressive declines, and in patients who demonstrate significant impairments or are reporting worsening of symptoms long after treatment, more active approaches are called for.…”

Brain white matter fibre tracts: a review of functional neuro-oncological relevance

“…Longitudinal diffusion MRI studies in non-CNS cancers have identified widespread changes in WM microstructure suggestive of demyelination and axonal damage pre-to-post chemotherapy 57. Interestingly, these WM changes tend to normalise within a few (3–5) years following treatment 58. A direct role for DT is not currently proposed for guiding systemic treatments.…”