Biomarkers of Cognitive Impairment in Pediatric Cancer Survivors

Williams, AnnaLynn M.; Cole, Peter D.

doi:10.1200/jco.20.02436

Cited by 11 publications

(4 citation statements)

References 76 publications

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“…Despite wide variability in cognitive outcomes, the most frequently reported deficits are across the domains of attention, processing speed, and working memory skills (Askins & Moore, 2008 ; Williams & Cole, 2021 ; Siegwart et al., 2020 ). Even early research investigating patterns of neurocognitive impairment in pediatric cancer survivors identified measures of working memory and processing speed as unique predictors that accounted for up to 45% of the variance in declining IQ scores among children with ALL treated with cranial radiation therapy (Schatz et al., 2000 ).…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…The ATRT‐Neuropsychology Tool has been implemented in the randomized trial SIOPE ATRT01 (EudraCT 2018‐003335‐29). Analyses should also comprise molecular subgrouping, 53 biomarkers, 54 socioeconomic status, 55 family functioning, 32 neurocognitive profiles, 56 and participation in everyday‐life after treatment 57 …”

Section: Discussionmentioning

confidence: 99%

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies

Traunwieser,

Loos,

Ottensmeier

et al. 2024

Pediatric Blood & Cancer

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BackgroundThe contribution of tumor type, multimodal treatment, and other patient‐related factors upon long‐term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non‐irradiated low‐grade glioma (LGG).Patients and methodsFollowing surgery, patients (0–36 months at diagnosis) had received radio‐chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis.ResultsWe detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001–.019; d = 0.79–1.90). Diagnosis predicted impairments of cognitive outcome, while sex‐ and age‐related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls.ConclusionSurvivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.

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“…With anticipated accrual of 560 children being treated for leukemia at 8 institutions within the DFCI ALL Consortium, this study is powered to describe the relationship between early changes in neurocognitive function detected by LCMM analysis of Cogstate data and neurocognitive impairment one year off therapy on traditional cognitive assessments. In addition, we will be able to identify predictors of treatment-induced neurocognitive impairment, by studying biomarkers in cerebrospinal uid indicative of neurotoxicity [44], genetic variants associated with increased susceptibility, [45] and social determinants of health such as household material hardship. [46,47]…”

Section: Discussionmentioning

confidence: 99%

Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia

Cole

Kim

et al. 2023

Support Care Cancer

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Purpose: Neurocognitive impairment is frequently observed among survivors of childhood acute lymphoblastic leukemia (ALL) within the domains of attention, working memory, processing speed, executive functioning and learning and memory. However, few studies have characterized the trajectory of treatment-induced changes in neurocognitive function beginning in the rst months of treatment, to test whether early changes predict impairment among survivors. If correct, we hypothesize that those children who are most susceptible to early impairment would be ideal subjects for clinical trials testing interventions designed to protect against treatment-related neurocognitive decline.Methods: In this pilot study, we prospectively assessed neurocognitive functioning (attention, working memory, executive function, visual learning, and processing speed), using the Cogstate computerized battery at six time points during the 2 years of chemotherapy and 1 year post treatment enrolled on or as per Dana-Farber Cancer Institute ALL Consortium protocol 11-001; NCT01574274.Results: 43 patients with ALL consented to serial neurocognitive testing. Of the 31 participants who remained on study through the nal time point, one year after completion of chemotherapy, 28 (90%) completed at least ve of six planned Cogstate testing timepoints. Performance and completion checks indicated a high tolerability (≥88%) for all subtests. One year after completion of treatment, 10 of 29 patients (34%) exhibited neurocognitive function more than 2 sd below age-matched norms on one or more Cogstate subtests. Conclusions: Serial collection of neurocognitive data (within a month of diagnosis with ALL, during therapy and one year post treatment) is feasible and informative for evaluating treatment-related neurocognitive impairment.

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Biomarkers of Cognitive Impairment in Pediatric Cancer Survivors

Cited by 11 publications

References 76 publications

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

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

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies

Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia

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