Long‐term leukoencephalopathy and neurocognitive functioning in childhood sarcoma patients treated with high‐dose intravenous chemotherapy

Sleurs, Charlotte; Lemiere, Jurgen; Radwan, Ahmed; Verly, Marjolein; Elens, Iris; Renard, Marleen; Jacobs, Sandra; Sunaert, Stefan; Deprez, Sabine; Uyttebroeck, Anne

doi:10.1002/pbc.27893

Cited by 15 publications

(31 citation statements)

References 53 publications

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“…Survivors of childhood bone and soft tissue sarcomas (n=33) who were treated with local treatment (i.e. surgery, radiotherapy) and intravenous chemotherapy only during childhood and adolescence (median 13.32 years old) were recruited in this study (Sleurs et al, 2019). Their treatment consisted of multimodal chemotherapy including high-dose methotrexate either combined with ifosfamide or not (protocols EURAMOS1, RMS2005, NRSTS2005, Euro-Ewing99, MMT95, EORTC2001, IVAD).…”

Section: Participantsmentioning

confidence: 99%

“…Thirty-four healthy control participants, who were recruited via internal hospital announcements, were age-and gender-matched. More detailed characteristics of the participants were described previously (Sleurs et al, 2019) and provided in Table 1. All participants were aged between 16.14-35.28 years (mean=22.51, SD=3.97) at the moment of acquisition.…”

Section: Participantsmentioning

confidence: 99%

“…An extensive neurocognitive test battery covered the domains of intelligence (WAIS), Auditory Verbal Learning Test (AVLT) and Rey Visual Design Learning Test (RVDLT), as well as computerized attention and executive tasks (Amsterdam Neuropsychological Task battery, ANT). Based on previous behavioral group comparisons in this cohort (Sleurs et al, 2019), only significant measures were extracted and analyzed in the current study. These measures included processing speed (based on the 'coding' and 'symbol search' subtests of the WAIS-IV), working memory (based on the 'digit span' and 'arithmetic' subtests of the WAIS-IV), and attentional reaction times (ANT computerized tasks)…”

Section: Data Acquisitionmentioning

confidence: 99%

“…Third, it is known that depression can have an impact on cortical density and thickness (Jaworska et al, 2016;Schmaal et al, 2017;Thompson et al, 2014). In order to account for the effect of depression scores (which were significantly different between the 2 groups, see Supplementary Materials) (Sleurs et al, 2019), these models were expanded including the predictor of depression (BDI) as covariate. Group comparisons were assumed significant if both FWEcorrected p-values at cluster-level reached <.05, and uncorrected p-values at voxel-level reached <.001.…”

Section: Data Preprocessing and Statisticsmentioning

confidence: 99%

“…Pediatric patients with non-CNS solid tumors often receive high doses of intravenous chemotherapy, which was evidenced to result in white matter alterations (Sleurs et al, 2019(Sleurs et al, , 2018, and altered neurocognitive functioning in patients (Mohrmann et al, 2015) or survivors (Edelmann et al, 2016). These studies demonstrated lower intelligence scores in preschool patients (Willard et al, 2017), as well as long-term complaints of affected memory, processing speed (Edelmann et al, 2016), task efficiency (Kadan-Lottick et al, 2010) and difficulties at school in around a third of non-CNS tumor patients (Mohrmann et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma

Sleurs

Blommaert

Batalle

et al. 2020

Brain Imaging and Behavior

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High-dose chemotherapy is increasingly evidenced to be neurotoxic and result in long-term neurocognitive sequelae. However, research investigating grey matter alterations in childhood cancer patients remains limited. As childhood sarcoma patients receive high-dose chemotherapy, we aimed to investigate cortical brain alterations in adult survivors. We analyzed high-resolution structural (T1-weighted) MRI and resting-state functional MRI (rsfMRI), to derive structural and functional cortical information in survivors of childhood sarcoma, treated with high-dose intravenous chemotherapy (n=33). These scans were compared to age-and gender-matched controls (n=34). Cortical volume and thickness were investigated using voxelbased morphometry and vertex-wise surface-based morphometry. Brain regions showing significant group differences in volume or thickness were implemented as seeds of interest to estimate their resting state co-activity with other areas (i.e. functional coherence). We explored whether structural measures were associated with potential risk factors, such as age at diagnosis, and cumulative doses of chemotherapeutic agents (methotrexate, ifosfamide). Finally, we investigated the link between functional regional strength, neurocognitive assessments and daily life complaints. In patients relative to controls we observed lower grey matter volumes in cerebellar and frontal areas, as well as frontal cortical thinning. Cerebellar volume and orbitofrontal thickness appeared dose-and age-related, respectively. Cortical thickness of the parahippocampal area appeared lower, only if the group comparison was not adjusted for depression. This region specifically showed lower functional coherence, which was associated with lower processing speed. This study suggests cortical thinning as well as decreased functional coherence in survivors of childhood sarcoma, which could be important for both long-term attentional functioning and emotional distress in daily life. Frontal areas might be specifically vulnerable during adolescence. Highlights:• Frontal, parahippocampal and cerebellar cortical thinning in childhood cancer survivors • Cortical thinning appear chemotherapy dose-related as well as age-related• Altered functional coherence in patients is associated with lower processing speed

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Section: Participantsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Data Acquisitionmentioning

confidence: 99%

Section: Data Preprocessing and Statisticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma

Sleurs

Blommaert

Batalle

et al. 2020

Brain Imaging and Behavior

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Neurologic morbidity and functional independence in adult survivors of childhood cancer

Vuotto,

Wang,

Okcu

et al. 2023

Ann Clin Transl Neurol

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ObjectiveTo examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)‐directed therapies.MethodsA total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS‐treated]; median age [range] = 25.5 years [18–48]; time since diagnosis = 17.7 years [6.8–30.2]) and 8039 without CNS‐directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver's license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress.ResultsAmong CNS‐treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non‐independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non‐independent (5.7%). In contrast to 50% of non‐CNS‐treated survivors and 60% of siblings, a fourth fully independent class of CNS‐treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70–3.68), seizure (OR = 9.70, 95% CI: 7.37–12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16–3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40–3.88) were associated with non‐independence among CNS‐treated survivors. Non‐independence was associated with emotional distress symptoms.InterpretationCNS‐treated survivors do not attain full independence comparable to non‐CNS‐treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment‐related neurological sequalae.

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Impact of non‐CNS childhood cancer on resting‐state connectivity and its association with cognition

Spitzhüttl

Kronbichler

et al. 2020

Brain and Behavior

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Long‐term leukoencephalopathy and neurocognitive functioning in childhood sarcoma patients treated with high‐dose intravenous chemotherapy

Cited by 15 publications

References 53 publications

Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma

Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma

Neurologic morbidity and functional independence in adult survivors of childhood cancer

Impact of non‐CNS childhood cancer on resting‐state connectivity and its association with cognition

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