Late effects of high‐dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

Ruiter, Michiel B. de; Reneman, Liesbeth; Boogerd, Willem; Veltman, Dick J.; Caan, Matthan W.A.; Douaud, Gwenaëlle; Lavini, Cristina; Linn, Sabine C.; Boven, Epie; Dam, F.S.A.M. van; Schagen, Sanne B.

doi:10.1002/hbm.21422

Cited by 236 publications

(245 citation statements)

References 57 publications

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“…The only other study that investigated the association between hippocampal volume and chemotherapy did also not observe a relationship between the two [8]. Of all studies that investigated the effect of chemotherapy on brain structure, none examined total tissue volumes after cytotoxic treatment [2][3][4][7][8][9][10]. We found significant effects of chemotherapy on TBV and gray matter volume.…”

Section: Discussionmentioning

confidence: 73%

“…Up till now three studies have reported adverse effects of chemotherapy on white matter as measured with diffusion tensor imaging (DTI) [4][5][6]. Therefore, it might be that the small effects of chemotherapy on total gray matter volume may be accompanied by microstructural whitematter changes.…”

Section: Discussionmentioning

confidence: 99%

“…A study that strictly examined hippocampal volume did not find differences between cancer patients who received chemotherapy 3 years before and those who did not [8]. We recently showed that breast cancer survivors who completed high-dose chemotherapy almost 10 years before had less focal gray matter than survivors who never received chemotherapy [4]. A prospective study observed focal gray matter volume decrease 1 month after cessation of chemotherapy, which recovered in some, but not all regions at 1 year post-treatment [9].…”

Section: Introductionmentioning

confidence: 92%

“…White-matter pathology has been observed within months up to 10 years post-treatment. Compared to healthy controls and breast cancer patients who never received cytotoxic treatment, chemotherapy-exposed patients had more white matter hyperintensities [2,3] and decreased integrity of major white matter tracts in frontal and temporal regions of the brain [4,5]. The integrity of the genu of the corpus callosum also was lower in chemotherapy-exposed patients [6].…”

Section: Introductionmentioning

confidence: 99%

“…Their sample sizes were relatively small: the number of chemotherapy-exposed patients ranged from 5 to73 (Table 1) [ [2][3][4][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

Koppelmans

Ruiter

Lijn

et al. 2011

Breast Cancer Res Treat

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152

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A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it is unclear if non-CNS chemotherapy is associated with long-term structural brain changes. We compared focal and total brain volume (TBV) of a large set of non-CNS directed chemotherapy-exposed breast cancer survivors, on average 21 years post-treatment, to that of a population-based sample of women without a history of cancer. Structural MRI (1.5T) was performed in 184 chemotherapy-exposed breast cancer patients, mean age 64.0 (SD = 6.5) years, who had been diagnosed with cancer on average 21.1 (SD = 4.4) years before, and 368 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were: TBV and total gray and white matter volume, and hippocampal volume. In addition, voxel based morphometry was performed to analyze differences in focal gray matter. The chemotherapy-exposed breast cancer survivors had significantly smaller TBV (-3.5 ml, P = 0.019) and gray matter volume (-2.9 ml, P = 0.003) than the reference subjects. No significant differences were observed in white matter volume, hippocampal volume, or local gray matter volume. This study shows that adjuvant chemotherapy for breast cancer is associated with long-term reductions in TBV and overall gray matter volume in the absence of focal reductions. The observed smaller gray matter volume in chemotherapy- 123Breast Cancer Res Treat (2012) 132:1099-1106 DOI 10.1007/s10549-011-1888-1 exposed survivors was comparable to the effect of almost 4 years of age on gray matter volume reduction. These volume differences might be associated with the slightly worse cognitive performance that we observed previously in this group of breast cancer survivors.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

“…Their sample sizes were relatively small: the number of chemotherapy-exposed patients ranged from 5 to73 (Table 1) [ [2][3][4][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

Koppelmans

Ruiter

Lijn

et al. 2011

Breast Cancer Res Treat

Self Cite

152

113

View full text Add to dashboard Cite

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Systemic chemotherapy decreases brain glucose metabolism

Horky

Gerbaudo

Zaitsev

et al. 2014

Ann Clin Transl Neurol

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ObjectiveCancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients.MethodsUsing sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer.ResultsSignificant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts.InterpretationOur data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients.

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Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Thebault

Lee

Bose

et al. 2020

Ann Clin Transl Neurol

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Objective: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods: Sera were collected from 22 MS patients pre-and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. Results: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

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Late effects of high‐dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

Cited by 236 publications

References 57 publications

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

Systemic chemotherapy decreases brain glucose metabolism

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

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