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  1. Article: Changes in leukoencephalopathy and serum neurofilament after (neo)adjuvant chemotherapy for breast cancer.

    Schroyen, Gwen / Sleurs, Charlotte / Ottenbourgs, Tine / Leenaerts, Nicolas / Nevelsteen, Ines / Melis, Michelle / Smeets, Ann / Deprez, Sabine / Sunaert, Stefan

    Translational oncology

    2023  Volume 37, Page(s) 101769

    Abstract: Background: Previous case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and ... ...

    Abstract Background: Previous case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker.
    Methods: This prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31-64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression.
    Results: Stronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ß
    Conclusion: These results underscore the possibility of chemotherapy-induced leukoencephalopathy months post-treatment, as well as the added value of serum-NfL as a prognostic marker for peripheral/central neurotoxicity.
    Translational relevance: Previous case studies have provided evidence of chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective studies to estimate longitudinal changes are currently missing. In this study, we used longitudinal fluid-attenuated inversion-recovery magnetic resonance imaging to assess white matter lesion volumes in patients treated for non-metastatic breast cancer and healthy women. Our findings demonstrate that chemotherapy-treated patients exhibit stronger increases in lesion volumes compared with healthy women, specifically in deep white matter, at three months post-chemotherapy. Increases could mainly be attributed to enlargement of existing lesions, rather than development of new lesions. Last, serum concentrations of neurofilament light chain, a neuroaxonal damage marker, increased shortly after chemotherapy and long-term post-chemotherapy levels were associated with lesion volumes. These findings highlight the potential of this non-invasive serum marker as a prognostic marker for peripheral and/or central neurotoxicity. Implementation in clinical practice could aid in therapeutic decisions, assessing disease activity, or monitoring treatment response.
    Language English
    Publishing date 2023-08-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233
    ISSN 1936-5233
    DOI 10.1016/j.tranon.2023.101769
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  2. Article ; Online: The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

    Melis, Michelle / Schroyen, Gwen / Leenaerts, Nicolas / Smeets, Ann / Sunaert, Stefan / Van der Gucht, Katleen / Deprez, Sabine

    Cancer

    2023  Volume 129, Issue 7, Page(s) 1105–1116

    Abstract: Background: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, ... ...

    Abstract Background: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated.
    Methods: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values.
    Results: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training.
    Conclusion: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.
    MeSH term(s) Female ; Humans ; Breast Neoplasms/complications ; Breast Neoplasms/therapy ; Breast Neoplasms/psychology ; Cancer Survivors/psychology ; Cognition ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/therapy ; Mindfulness ; Quality of Life
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.34640
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  3. Article: The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints.

    Melis, Michelle / Schroyen, Gwen / Blommaert, Jeroen / Leenaerts, Nicolas / Smeets, Ann / Van Der Gucht, Katleen / Sunaert, Stefan / Deprez, Sabine

    Cancers

    2023  Volume 15, Issue 14

    Abstract: Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a ... ...

    Abstract Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI.
    Methods: Female breast cancer survivors reporting cognitive complaints (
    Results: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1β, and IL-8).
    Conclusion: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.
    Language English
    Publishing date 2023-07-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15143632
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  4. Article: A Systematic Review on the Potential Acceleration of Neurocognitive Aging in Older Cancer Survivors.

    Kerstens, Charlotte / Wildiers, Hans P M W / Schroyen, Gwen / Almela, Mercedes / Mark, Ruth E / Lambrecht, Maarten / Deprez, Sabine / Sleurs, Charlotte

    Cancers

    2023  Volume 15, Issue 4

    Abstract: As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, ... ...

    Abstract As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer's disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies.
    Language English
    Publishing date 2023-02-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15041215
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  5. Article ; Online: Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients: A cross-sectional PET-MRI study.

    Schroyen, Gwen / Sleurs, Charlotte / Bartsoen, Emilie / Smeets, Dirk / van Weehaeghe, Donatienne / Van Laere, Koen / Smeets, Ann / Deprez, Sabine / Sunaert, Stefan

    Breast (Edinburgh, Scotland)

    2022  Volume 62, Page(s) 61–68

    Abstract: 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 ... ...

    Abstract 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 [
    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.
    MeSH term(s) Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Cross-Sectional Studies ; Female ; Humans ; Leukoencephalopathies ; Magnetic Resonance Imaging/methods ; Neuroinflammatory Diseases ; Positron-Emission Tomography/methods ; Receptors, GABA/metabolism
    Chemical Substances Receptors, GABA ; TSPO protein, human
    Language English
    Publishing date 2022-02-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1143210-x
    ISSN 1532-3080 ; 0960-9776
    ISSN (online) 1532-3080
    ISSN 0960-9776
    DOI 10.1016/j.breast.2022.02.001
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  6. Article ; Online: Correction to: Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [

    de Laat, Bart / Klingl, Yvonne E / Schroyen, Gwen / Ooms, Maarten / Hooker, Jacob M / Bormans, Guy / Van Laere, Koen / Ceccarini, Jenny

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 9, Page(s) 3303

    Language English
    Publishing date 2022-02-08
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-022-05802-z
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  7. Article: Correction: Schroyen et al. Neuroinflammation and Its Association with Cognition, Neuronal Markers and Peripheral Inflammation after Chemotherapy for Breast Cancer.

    Schroyen, Gwen / Blommaert, Jeroen / van Weehaeghe, Donatienne / Sleurs, Charlotte / Vandenbulcke, Mathieu / Dedoncker, Nina / Hatse, Sigrid / Goris, An / Koole, Michel / Smeets, Ann / van Laere, Koen / Sunaert, Stefan / Deprez, Sabine

    Cancers

    2023  Volume 15, Issue 12

    Abstract: In the original publication [ ... ]. ...

    Abstract In the original publication [...].
    Language English
    Publishing date 2023-06-07
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15123091
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  8. Article: Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review.

    Schroyen, Gwen / Vissers, Julie / Smeets, Ann / Gillebert, Céline R / Lemiere, Jurgen / Sunaert, Stefan / Deprez, Sabine / Sleurs, Charlotte

    Translational oncology

    2021  Volume 16, Page(s) 101297

    Abstract: Breast cancer treatment can induce alterations in blood- and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors. This systematic review summarized studies of the ... ...

    Abstract Breast cancer treatment can induce alterations in blood- and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors. This systematic review summarized studies of the last decade, using the PubMed database, evaluating blood markers, and the association between blood- or structural neuroimaging markers and cognition across the chemotherapy trajectory for primary breast cancer, following PRISMA guidelines. Forty-four studies were included. Differences were observed in all blood marker categories, from on-therapy until years post-chemotherapy. Associations were found between cognitive functioning and (1) blood markers (mainly inflammation-related) during, shortly-, or years post-chemotherapy and (2) white and gray matter metrics in frontal, temporal and parietal brain regions months up until years post-chemotherapy. Preliminary evidence exists for epigenetic and metabolic changes being associated with cognition, only after chemotherapy. This review demonstrated time-dependent associations between specific blood-based and structural neuroimaging markers with cognitive impairment in patients with breast cancer. Future studies are encouraged to include both neuroimaging- and blood markers (e.g. of neuronal integrity, epigenetics and metabolism) to predict long-term cognitive effects of chemotherapy.
    Language English
    Publishing date 2021-12-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2443840-6
    ISSN 1936-5233
    ISSN 1936-5233
    DOI 10.1016/j.tranon.2021.101297
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  9. Article ; Online: Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [

    de Laat, Bart / Kling, Yvonne E / Schroyen, Gwen / Ooms, Maarten / Hooker, Jacob M / Bormans, Guy / Van Laere, Koen / Ceccarini, Jenny

    European journal of nuclear medicine and molecular imaging

    2021  Volume 49, Issue 2, Page(s) 492–502

    Abstract: Purpose: Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest ...

    Abstract Purpose: Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety.
    Methods: We performed a longitudinal [
    Results: We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2 weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A-binding potential after 2 versus 4 weeks of exposure showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens (p
    Conclusion: This study shows that chronic voluntary alcohol consumption induces a reversible increased PDE10A enzymatic availability in the striatum, which is related to the amount of alcohol preference. Thus, PDE10A-mediated signaling plays an important role in modulating the reinforcing effects of alcohol, and the data suggest that PDE10A inhibition may have beneficial behavioral effects on alcohol intake.
    MeSH term(s) Alcohol Drinking/adverse effects ; Alcoholism/diagnostic imaging ; Alcoholism/metabolism ; Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Phosphoric Diester Hydrolases/metabolism ; Positron-Emission Tomography/methods ; Pyrazoles ; Pyridines ; Rats
    Chemical Substances 2-((4-(1-(2-fluoroethyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl)phenoxy)methyl)-3,5-dimethylpyridine ; Pyrazoles ; Pyridines ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
    Language English
    Publishing date 2021-06-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-021-05448-3
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  10. Article ; Online: Brain gray matter reduction and premature brain aging after breast cancer chemotherapy: a longitudinal multicenter data pooling analysis.

    de Ruiter, Michiel B / Deardorff, Rachael L / Blommaert, Jeroen / Chen, Bihong T / Dumas, Julie A / Schagen, Sanne B / Sunaert, Stefan / Wang, Lei / Cimprich, Bernadine / Peltier, Scott / Dittus, Kim / Newhouse, Paul A / Silverman, Daniel H / Schroyen, Gwen / Deprez, Sabine / Saykin, Andrew J / McDonald, Brenna C

    Brain imaging and behavior

    2023  Volume 17, Issue 5, Page(s) 507–518

    Abstract: Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as ... ...

    Abstract Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies.
    MeSH term(s) Humans ; Female ; Gray Matter/diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Cross-Sectional Studies ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Aging
    Language English
    Publishing date 2023-05-31
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2377165-3
    ISSN 1931-7565 ; 1931-7557
    ISSN (online) 1931-7565
    ISSN 1931-7557
    DOI 10.1007/s11682-023-00781-7
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