Quantifying Neurological Risk Factors in Childhood Brain Tumor Treatment
Authors:   , McCurdy Mark David , Daly Brian P. 
Published: September 2022

Background: Childhood brain and central nervous system (CNS) tumors are the second most common form of pediatric malignancy. Tumor-directed therapies present a substantial risk to the developing nervous system placing survivors at risk for disruptions across multiple domains of cognitive and behavioral functioning, which are thought to be chronic in nature. Despite these findings, few objective measures have been developed to quantify the extent or intensity of exposure to tumor-related treatments or use this information to predict neuropsychological outcomes. The Neurological Predictor Scale (NPS) is designed to quantify treatment exposures and neurological comorbidities. Preliminary investigations suggested the scale's utility in predicting global cognitive functioning, cognitive efficiency, and adaptive functioning in survivors several years post-treatment. The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) is another clinician-generated scaled used to classify the intensity of pediatric brain tumor treatments. However, no studies to date have examined the utility of this measure in predicting subacute neuropsychological functioning in survivors of childhood brain tumor. Aims: The present study aimed to examine the influence of treatment intensity and treatment-related neurological comorbidities on subacute neuropsychological outcomes in survivors of childhood brain tumor. Specifically, this study sought to establish the utility of the NPS and PNORTI in predicting neuropsychological performance approximately nine months post-treatment conclusion. It was hypothesized that higher scores on each measure would predict worse performance across neuropsychological domains. Neurological sequelae captured by the NPS also were hypothesized to add incrementally to the prediction of subacute neuropsychological functioning when pooled with treatment intensity factors from the PNORTI. Methods: Participants (N = 35) included youth (51.40% female) between the ages of 6 and 15 years (M = 11.00, SD = 2.71). Survivors were recruited from among patients transitioning off tumor-directed treatment for the management of their brain tumor at the Children's Hospital of Philadelphia. Baseline measures were completed by consenting participants within 4-5 months following the cessation of treatment (Baseline) and again 6 (± 2) months later (Follow-up). At each timepoint, participants were administered measures of processing speed and working memory (WISC-IV), executive functioning (TEA-Ch), auditory verbal memory (WRAML-2), and caregiver-reported executive behavior (BRIEF) and adaptive functioning (BASC-2). Hierarchical multiple linear regressions, controlling for Baseline performance, were used to examine the predictive and incremental validity of both treatment-related risk scales. Results: NPS total scores ranged from 1 to 9 (M = 4.69, SD = 2.07) and PNORTI scores ranged from 1 (n = 6; 17.10%) to 2 (n = 29; 82.90%). Interrater reliability coefficients were excellent for the NPS (ICC = 0.97) and PNORTI ([kappa] = .82). Hierarchical multiple regressions revealed that the NPS and PNORTI did not explain an additional amount of variance in processing speed, auditory attention, working memory, executive functioning, verbal memory, or adaptive skills above and beyond Baseline performance on these measures. Additionally, neurological comorbidities and risk factors did not incrementally improve the predictive utility of PNORTI treatment intensity scores for Follow-Up performance across measures. Discussion: The present study provides the first examination of the, interrater reliability, and clinical utility of the NPS and PNORTI for predicting subacute neuropsychological functioning in a sample of childhood brain tumor survivors. The NPS and PNORTI can be readily and reliably generated by providers of differing training backgrounds familiar with neuro-oncology treatments. The subacute period may be premature' for detecting neuropsychological late effects associated with treatment and neurological comorbidities in this population. Future research is needed to determine the predictive utility of these measures in long-term survivors, allowing providers to coordinate early intervention in the survivorship period.