Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions

Sleurs, Charlotte; Deprez, Sabine; Emsell, Louise; Lemiere, Jurgen; Uyttebroeck, Anne

doi:10.1016/j.critrevonc.2016.05.001

Cited by 33 publications

(43 citation statements)

References 152 publications

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“…They demonstrate the natural tendency of the WM to remyelate after inflammation or vascular damage (Armstrong et al, ). Since chemotherapy could induce such neurotoxic processes (Ahles & Saykin, ; Sleurs et al, a), leading to microstructural changes, recovery processes could arise in childhood cancer patients as well. Furthermore, recently a similar potential recovery was detected in FA values 3 years after treatment in breast cancer patients (Billiet et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Hence, it becomes essential to trace potential neurotoxic mechanisms. For pediatric oncology, it is well‐known that cranial irradiation leads to cognitive deficits in brain tumor patients (Chang et al, ; McDuff et al, ) and leukemia patients (Buizer Buizer, De Sonneville, Van Den Heuvel‐Eibrink, & Veerman, ; Giralt et al, ; Krull et al, ; Sleurs et al, ). Consequently, treatment for leukemia patients was replaced by CNS‐directed chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…In line with these cognitive studies, recent neuroimaging studies have also evidenced white matter (WM; Edelmann et al, ; Elalfy et al, ; Kesler, Gugel, Huston‐Warren, & Watson, ; Schuitema et al, ; Schuitema et al, ) and grey matter changes due to CNS‐directed chemotherapy (Koppelmans, Breteler, Boogerd, Seynaeve, & Schagen, ; Krull et al, ; Tamnes et al, ). In contrast to the large number of reports about late neurocognitive sequelae in leukemia (van der Plas et al, ), only limited research has been conducted on childhood solid non‐CNS tumors (Sleurs et al, a). Recently, a few studies have reported cognitive outcomes of childhood solid non‐CNS tumor survivors.…”

Section: Introductionmentioning

confidence: 99%

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Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

Sleurs

Lemiere

Christiaens

et al. 2018

Human Brain Mapping

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With the increase of survival rates of pediatric cancer patients, the number of children facing potential cognitive sequelae has grown. Previous adult studies suggest that white matter (WM) microstructural changes may contribute to cognitive impairment. This study aims to investigate WM microstructure in childhood bone and soft tissue sarcoma. Differences in (micro-)structure can be investigated using diffusion MRI (dMRI). The typically used diffusion tensor model (DTI) assumes Gaussian diffusion, and lacks information about fiber populations. In this study, we compare WM structure of childhood bone and soft tissue sarcoma survivors (n = 34) and matched controls (n = 34), combining typical and advanced voxel-based models (DTI and NODDI model, respectively), as well as recently developed fixel-based models (for estimations of intra-voxel differences, apparent fiber density [AFD] and fiber cross-section [FC]). Parameters with significant findings were compared between treatments, and correlated with subscales of the WAIS-IV intelligence test, age at diagnosis, age at assessment and time since diagnosis. We encountered extensive regions showing lower fractional anisotropy, overlapping with both significant NODDI parameters and fixel-based parameters. In contrast to these diffuse differences, the fixel-based measure of AFD was reduced in the cingulum and corpus callosum only. Furthermore, AFD of the corpus callosum was significantly predicted by chemotherapy treatment and correlated positively with time since diagnosis, visual puzzles and similarities task scores. This study suggests altered WM structure of childhood bone and soft tissue sarcoma survivors. We conclude global chemotherapy-related changes, with particular vulnerability of centrally located WM bundles. Finally, such differences could potentially recover after treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

Sleurs

Lemiere

Christiaens

et al. 2018

Human Brain Mapping

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“…This primary objective has increasingly been achieved in the last few decades by the introduction of new, more effective treatments, which have substantially improved survival rates especially when treating children and adolescents. However, this success has highlighted the importance of monitoring long-term effects from the cancer and from the treatments used in order to improve the overall quality of life in cancer survivors, particularly for neurodevelopment21. Considering the long time span during which side-effects from chemotherapy may develop, a specific objective of this study was to investigate for impairments in postural control and sensorimotor adaptation in adult survivors of childhood cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Significant work has been carried out to study the long-term effects of chemotherapy in children1521 but no previous studies have considered the effects on adaptive postural control which is fundamental to meet the pressures of physical environments. As chemotherapeutic agents administered in childhood could damage the sensory and motor systems, an improper development of these systems in survivors of childhood cancer may lead to long-term postural instability.…”

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confidence: 99%

Decreased postural control in adult survivors of childhood cancer treated with chemotherapy

Einarsson

Patel

Petersen

et al. 2016

Sci Rep

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The objective of cancer treatment is to secure survival. However, as chemotherapeutic agents can affect the central and peripheral nervous systems, patients must undergo a process of central compensation. We explored the effectiveness of this compensation process by measuring postural behaviour in adult survivors of childhood cancer treated with chemotherapy (CTS). We recruited sixteen adults treated with chemotherapy in childhood for malignant solid (non-CNS) tumours and 25 healthy age-matched controls. Subjects performed posturography with eyes open and closed during quiet and perturbed standing. Repeated balance perturbations through calf vibrations were used to study postural adaptation. Subjects were stratified into two groups (treatment before or from 12 years of age) to determine age at treatment effects. Both quiet (p = 0.040) and perturbed standing (p ≤ 0.009) were significantly poorer in CTS compared to controls, particularly with eyes open and among those treated younger. Moreover, CTS had reduced levels of adaptation compared to controls, both with eyes closed and open. Hence, adults treated with chemotherapy for childhood cancer may suffer late effects of poorer postural control manifested as reduced contribution of vision and as reduced adaptation skills. These findings advocate development of chemotherapeutic agents that cause fewer long-term side effects when used for treating children.

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Processing efficiency in pediatric cancer survivors: A review and operationalization for outcomes research and clinical utility

Trapani

Murdaugh

2022

Brain and Behavior

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Objective Childhood cancer and cancer‐related treatments disrupt brain development and maturation, placing survivors at risk for cognitive late effects. Given that assessment tools vary widely across researchers and clinicians, it has been daunting to identify distinct patterns in outcomes across diverse cancer types and to implement systematic neurocognitive screening tools. This review aims to operationalize processing efficiency skill impairment—or inefficient neural processing as measured by working memory and processing speed abilities—as a worthwhile avenue for continued study within the context of childhood cancer. Methods A comprehensive literature review was conducted to examine the existing research on cognitive late effects and biopsychosocial risk factors in order to conceptualize processing efficiency skill trends in childhood cancer survivors. Results While a frequently reported pattern of neurobiological (white matter) and cognitive (working memory and processing speed) disruption is consistent with processing efficiency skill impairment, these weaknesses have not yet been fully operationalized in this population. We offer a theoretical model that highlights the impacts of a host of biological and environmental factors on the underlying neurobiological substrates of cancer survivors that precede and may even predict long‐term cognitive outcomes and functional abilities following treatment. Conclusion The unified construct of processing efficiency may be useful in assessing and communicating neurocognitive skills in both outcomes research and clinical practice. Deficits in processing efficiency may serve as a possible indicator of cognitive late effects and functional outcomes due to the unique relationship between processing efficiency skills and neurobiological disruption following cancer treatment. Continued research along these lines is crucial for advancing childhood cancer outcomes research and improving quality of life for survivors.

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Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions

Cited by 33 publications

References 152 publications

Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

Decreased postural control in adult survivors of childhood cancer treated with chemotherapy

Processing efficiency in pediatric cancer survivors: A review and operationalization for outcomes research and clinical utility

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