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.

The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment.

Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), and potentially inosine triphosphatase (ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) and dihydrofolate reductase (DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1) and thymidylate synthetase (TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.