Medical Record Level-Evaluation of Impact of Demographic and Socioeconomic Factors on Pediatric Neuro-Oncology Outcomes at Children's Hospital Colorado.

Purpose: A medical record-level cohort study to investigate demographic and socioeconomic factors influencing treatment, timing of care, and survival outcomes in pediatric patients diagnosed with central nervous system (CNS) tumors. Methods: Using electronic health records of patients at Children's Hospital Colorado from 1986-2020, we identified 898 patients treated for CNS tumors. The primary outcomes of interest were 5-year survival, timing of diagnosis, and treatment. Multivariable logistic regression and Cox regression were used to identify covariates associated with our outcomes of interest. Results: We found that age, race, tumor type, diagnosis year, and social concerns influenced receipt and timing of treatment. Age, race, patient rural vs. urban residence, and tumor impacted survival outcomes. Time to presentation and treatment were significantly different between White and minority patients. American Indian/Alaska Native and Black patients were less likely to receive chemo compared to White patients (OR 0.28, 0.93 p = 0.037, < 0.001). Patients with 3 + social concerns were more likely to survive after 5 years than children with no or unknown social concerns (OR 1.84, p = 0.011). However, with an adjusted hazards ratio, children with 2 social concerns were less likely to survive to 5 years than children with no or unknown concerns (OR 0.58, p = 0.066). Conclusions: Demographic and socioeconomic factors influence timing of care and survival outcomes in pediatric patients with CNS tumors. Minority status, age, social factors, rural, and urban patients experience differences in care. This emphasizes the importance of considering these factors and addressing disparities to achieve equitable care.

Identifying patterns of neurocognitive dysfunction through direct comparison of children with leukemia, central nervous system tumors, and sickle cell disease.

PURPOSE: To quantify and compare the magnitude and type of neurocognitive dysfunction in at-risk children with central nervous system (CNS) tumors, acute lymphoblastic leukemia (ALL), and sickle cell disease (SCD) using a common instrument and metric to directly compare these groups with each other. METHODS: Fifty-three participants between the ages of 7 and 12 years (n = 27 ALL, n = 11 CNS tumor, n = 15 SCD) were enrolled and assessed using the NIH Toolbox Cognition Battery (NIHTCB). Participants with ALL or CNS tumor were 0-18 months posttherapy, while participants with SCD possessed the SS or Sß0 genotype, took hydroxyurea, and had no known history of stroke. RESULTS: Independent sample t-tests showed that participants with ALL and CNS tumor experienced greatest deficits in processing speed (ALL d = -0.96; CNS tumor d = -1.2) and inhibitory control and attention (ALL d = -0.53; CNS tumor d = -0.97) when compared with NIHTCB normative data. Participants with SCD experienced deficits in cognitive flexibility only (d = -0.53). Episodic memory was relatively spared in all groups (d = -0.03 to -0.32). There were no significant differences in function when groups were compared directly with each other by analysis of variance. CONCLUSIONS: Use of a common metric to quantify the magnitude and type of neurocognitive dysfunction across at-risk groups of participants by disease shows that participants perform below age-expected norms in multiple domains and experience dysfunction differently than one another. This approach highlights patterns of dysfunction that can inform disease- and domain-specific interventions.

Therapy Selection for Hodgkin Lymphoma in Sickle Cell Disease: balancing risks and benefits.

Advances in treatment have reduced mortality from Hodgkin lymphoma; therefore, greater attention should be focused on minimizing the late effects. A variety of risk-adapted treatment regimens exist that prioritize disease presentation but not patient-specific comorbidities. Herein, we describe a patient with sickle cell disease diagnosed with Hodgkin lymphoma and the considerations made in treatment planning to minimize therapy-related acute toxicity and late effects that overlap with the patient's preexisting sickle cell disease complications.

Mechanisms and Insights for the Development of Heart Failure Associated with Cancer Therapy.

Cardiotoxicity is a well-recognized late effect among childhood cancer survivors. With various pediatric cancers becoming increasingly curable, it is imperative to understand the disease burdens that survivors may face in the future. In order to prevent or mitigate cardiovascular complications, we must first understand the mechanistic underpinnings. This review will examine the underlying mechanisms of cardiotoxicity that arise from traditional antineoplastic chemotherapies, radiation therapy, hematopoietic stem cell transplantation, as well as newer cellular therapies and targeted cancer therapies. We will then propose areas for prevention, primarily drawing from the anthracycline-induced cardiotoxicity literature. Finally, we will explore the role of human induced pluripotent stem cell cardiomyocytes and genetics in advancing the field of cardio-oncology.

Encephalitis in Previously Healthy Children.

Encephalitis is defined as altered mental status for more than 24 hours accompanied by 2 or more findings concerning for inflammation of the brain parenchyma: fever, seizures or other focal neurologic disorders, cerebrospinal fluid pleocytosis, and abnormal neuroimaging and electroencephalographic findings. Herpes simplex virus causes the most severe form of virus-induced encephalitis; the early administration of acyclovir can improve the prognosis of this disease. The rising interest in autoimmune causes of encephalitis, most notably anti-N-methyl-d-aspartate receptor, should prompt the clinician to consider immunomodulatory treatments, which may improve outcomes. A broad testing panel may be necessary to detect the etiologic agent; a few published pediatric cases suggest that infectious and autoimmune causes may occur concurrently in the same patient with encephalitis. More than 40% of children diagnosed as having encephalitis will not return to their previous level of neurologic function after resolution of their disease, although outcomes are highly variable depending on the etiologic agent.

Predictors of cognitive function in pediatric brain tumor patients: Pre-surgery through 24-month follow-up.

The aim of this study was to examine the feasibility of cognitive assessment from pre-surgery through 2-year follow-up in a sample of pediatric brain tumor (BT) patients. We sought to investigate cognitive function over the course of diagnosis and treatment, and as a function of presenting problems, tumor location, treatment type, and tumor severity. Using a prospective, longitudinal design, standardized IQ measures were administered to pediatric BT patients (ages 6-16) prior to surgery (n = 25), 6 months post-diagnosis (n = 24), and 24 months post-diagnosis (n = 23). Group differences emerged based on tumor severity and treatment type at multiple time points, including prior to surgical intervention; children with high grade tumors performed more poorly than children with low grade tumors, and children receiving surgery plus adjuvant therapy performed more poorly than children who received surgery only. When considered together, an analysis of covariance demonstrated that tumor grade significantly accounted for variability in cognitive functioning, while treatment type did not. Although there is overlap clinically between tumor severity and treatment received, results suggest that tumor severity is an important factor contributing to variability in cognitive functioning and should also be considered when monitoring risk for cognitive deficits in children diagnosed with BT.

Parent reports of children's working memory, coping, and emotional/behavioral adjustment in pediatric brain tumor patients: A pilot study.

Neurocognitive problems in childhood survivors of brain tumors are well documented. Further, research has shown that problems in cognitive functioning may be associated with impairment in the use of complex strategies needed to cope with stress, including secondary control coping strategies (e.g., acceptance and cognitive reappraisal) which have been associated with fewer adjustment problems. The present study measured cognitive function, coping strategies, and adjustment in children ages 6-16 years at the time of brain tumor diagnosis and at two follow-up time-points up to 1 year post-diagnosis. In a prospective design, working memory was assessed in a total of 29 pediatric brain tumor patients prior to undergoing surgery, child self-reported coping was assessed at 6 months post-diagnosis, and parent-reported child adjustment was assessed at 12 months post-diagnosis. Significant correlations were found between working memory difficulties and secondary control coping. Secondary control coping was also negatively correlated with child attention and total problems. Regression analyses did not support secondary control coping mediating the association between working memory difficulties and child attention or total problems. These findings represent the first longitudinal assessment of the association between working memory, coping, and adjustment across the first year of a child's brain tumor diagnosis and suggest a possible role for early interventions addressing both working memory difficulties and coping in children with brain tumors.

Presurgical assessment of cognitive function in pediatric brain tumor patients: feasibility and initial findings.

BACKGROUND: Establishing a presurgical baseline of neurocognitive functioning for pediatric brain tumor patients is a high priority to identify level of functioning prior to medical interventions. However, few studies have obtained adequate samples of presurgery assessments. METHODS: This study examines the feasibility of completing tests to assess pre-surgical neurocognitive functioning in 59 identified pediatric brain tumor patients. RESULTS: Eighty-five percent of patients (n = 50) were referred by the neurosurgery team before surgery and 83% of patients (n = 49) enrolled in the study. A full battery, including both performance-based and parent-report measures of neurocognitive function, was completed for 54% (n = 32) of patients. Rates of completion for either parent-report or performance-based measures were 68% (n = 40) and 69% (n = 41), respectively. While the performance-based assessment fell within the average range (M = 95.4, SD = 14.7, 95% CI, 90.7-100.0), 32% of participants had scores one or more standard deviations below the mean, or twice the expected rate. Parent-reports indicated higher level of concern than the general population (M = 55.4, SD = 11.3, 95% CI, 51.8-59.0) and found that 35% fell one or more standard deviations above the mean, or more than twice the expected rate. CONCLUSIONS: Results suggest it is feasible to conduct pre-surgical assessments with a portion of pediatric brain tumor patients upon diagnosis and these results compare favorably with prior research. However, nearly half of identified patients did not receive a full test battery. Identifying barriers to enrollment and participation in research are discussed as well as recommendations for future research.

Neurocognitive late effects of pediatric brain tumors of the posterior fossa: a quantitative review.

Deficits in neurocognitive functioning are an important area of late effects in survivors of pediatric brain tumors; however, a quantitative analysis of the magnitude of these deficits in survivors of brain tumors of the posterior fossa has not been conducted. Despite tumor locations in the posterior regions of the brain, individual studies have documented deficits in a variety of domains, reflective of impairment in other brain regions. The current study provides a comprehensive meta-analysis of literature on neurocognitive late effects found in survivors of posterior fossa tumors. Results indicated significant deficits in both specific and broad indices of neurocognitive functioning, and the overall magnitude of effects across domains ranged from medium to large (g = -0.62 to -1.69) with a large mean overall effect size (g = -1.03). Moderator analyses indicated significantly greater effects for survivors diagnosed at a younger age and those who received radiation therapy. These findings underscore the importance of monitoring neurocognitive late effects in survivors of pediatric brain tumors of the posterior fossa, as well as the need for more consistent consideration of demographic, diagnostic, and treatment-related variables to allow for examination of factors that moderate these deficits.