by Gwen Schroyen, Charlotte Sleurs, Emilie Bartsoen, Dirk
Smeets, Donatienne van Weehaeghe, Koen Van Laere, Ann Smeets, Sabine Deprez,
Stefan Sunaert
The Breast: Published:February 02, 2022
Background
Although chemotherapy-induced leukoencephalopathy has been
described in case and cohort studies, literature remains inconclusive about its
prevalence and mechanisms. Therefore, we investigated the presence of
leukoencephalopathy after multiagent chemotherapy in women treated for breast
cancer and potential underlying neuroinflammatory processes.
Methods
In this exploratory study, 15 chemotherapy-treated and 15
age-matched chemotherapy-naïve patients with early-stage breast cancer, as well
as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including
T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA
translocator protein (TSPO) radioligand [18F]DPA-714. Total and regional
(juxtacortical, periventricular, deep white matter and infratentorial) lesion
burden were compared between the groups with one-way ANOVA. With paired
t-tests, [18F]DPA-714 volume of distribution [VT, including partial volume
correction (PVC)] in lesioned and normal appearing white matter (NAWM) were
compared within subjects, to investigate inflammation. Finally, two general
linear models were used to examine the predictive values of neurofilament
light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [18F]DPA-714
VT of lesions showing elevated inflammation.
Results
No significant differences were found in total or localized
lesion burden. However, significantly higher (20–45%) TSPO uptake was observed
in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90)
compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated
patients after PVC (p = 0.005, t = 4.30). NfL serum
levels were not associated with total lesion volume or tracer uptake in
juxtacortical lesions.
Conclusion
This multimodal neuroimaging study suggests that
neuroinflammatory processes could be involved in the development of
juxtacortical, but not periventricular or deep white matter,
leukoencephalopathy shortly after chemotherapy for early-stage breast cancer.
