Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning

Deprez, Sabine; Amant, Frédéric; Smeets, Ann; Peeters, Ronald; Leemans, Alexander; Hecke, Wim Van; Verhoeven, Judith; Christiaens, Marie-Rose; Vandenberghe, Joris; Vandenbulcke, Mathieu; Sunaert, Stefan

doi:10.1200/jco.2011.36.8571

Cited by 341 publications

(303 citation statements)

References 51 publications

Supporting

Mentioning

257

Contrasting

Unclassified

Order By: Relevance

“…Magnetic resonance imaging studies have demonstrated lower integrity of cerebral white matter (location of myelinated axons) rather than gray matter (location of neuronal cell bodies) in patients with CICI than in healthy subjects (10)(11)(12). However, these findings do not directly indicate whether the decreased integrity of the cerebral white matter is caused by damage to axons themselves, which are the main components of white matter, or by Wallerian axonal degeneration following neuronal damage.…”

Section: Introductioncontrasting

confidence: 43%

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Natori

Ogata

Sumitani

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. Experimental Design: Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ2 and Mann–Whitney tests were used for statistical analysis. Results: Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H–positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups. Conclusions: The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy. Clin Cancer Res; 21(6); 1348–52. ©2015 AACR.

show abstract

Section: Introductioncontrasting

confidence: 43%

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Natori

Ogata

Sumitani

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Taken together, these findings suggest that this injury may begin quite early in the disease course but is more affected chronically and/or by adjuvant treatments. Regional clustering and Hurst exponent results indicate a widespread effect, consistent with previous studies (Deprez et al., 2012; Kesler et al., 2015). Frontal, parietal, and temporal areas were altered in the breast cancer group compared to controls, consistent with deficits in memory, executive function, and verbal fluency.…”

Section: Discussionmentioning

confidence: 99%

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

et al. 2017

View full text Add to dashboard Cite

IntroductionSeveral previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non‐CNS cancers.MethodsUsing a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29–65 and 50 frequency‐matched healthy female controls who underwent anatomic and resting‐state functional MRI as well as cognitive testing.ResultsCompared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p = .03). This hyper‐correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p = .005).ConclusionsOur findings could not be accounted for by psychological distress and suggest that non‐CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor‐induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

show abstract

“…Neither the biological basis for this syndrome, nor the predictors, nor any interventions, are well understood although recent investigations suggest a relationship with structural changes occurring in cerebral white matter and several investigations are underway. 135,136 While much of the prior work has focused on the effects of chemotherapy, ET may also adversely affect cognition, [137][138][139][140] although few specific investigations have been conducted and none in young women. In the ZIPP trial (6 cycles of CMF ± 2 years of goserelin, goserelin plus tamoxifen, or tamoxifen), no effect of treatment on patients' selfevaluation of memory and concentration was shown.…”

Section: Brca Mutation Carriers (Table 8)mentioning

confidence: 99%

Second international consensus guidelines for breast cancer in young women (BCY2)

et al. 2016

View full text Add to dashboard Cite

Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning

Abstract: We report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.

Cited by 341 publications

References 51 publications

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

Second international consensus guidelines for breast cancer in young women (BCY2)

Contact Info

Product

Resources

About