Kumar, Harendra

e24201 Background: Anthracyclines remain curative in many pediatric and adolescent/young adult (AYA) cancers but confer dose-dependent cardiotoxicity. Dexrazoxane reduces cardiac injury; however, concerns persist regarding potential impact on oncologic outcomes. Methods: We conducted a PRISMA-compliant systematic review and meta-analysis of studies comparing anthracycline therapy with versus without dexrazoxane in pediatric/AYA populations. Databases included MEDLINE, Embase, and CENTRAL. Outcomes included cardiac function (LVEF decline, clinical heart failure), event-free survival (EFS), overall survival (OS), relapse, and second malignant neoplasms (SMN). Random-effects meta-analysis pooled hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for binary endpoints. Results: Twelve studies with 1,384 patients were included. Dexrazoxane significantly reduced risk of clinical heart failure (RR 0.34, 95% CI 0.21–0.55) and preserved LVEF compared with controls. No significant differences were observed in EFS (HR 0.97, 95% CI 0.84–1.12), OS (HR 0.95, 95% CI 0.81–1.11), relapse (RR 1.02, 95% CI 0.87–1.19), or SMN incidence (RR 1.05, 95% CI 0.78–1.41). Benefits were consistent across cancer types, cumulative anthracycline doses, and follow-up durations. Conclusions: Dexrazoxane provides substantial cardio protection in pediatric and AYA patients receiving anthracyclines without compromising oncologic outcomes or increasing risk of SMNs. Clinical Takeaway: Routine incorporation of dexrazoxane in high-risk anthracycline regimens can prevent cardiotoxicity while maintaining curative potential.

e24198 Background: Even when radiotherapy is delivered outpatient, treatment-related nausea, vomiting, and dehydration can precipitate hospitalization, driving cost and morbidity. National estimates of this burden are limited. Methods: We analyzed the HCUP National Inpatient Sample (NIS) for 2016–2022 to identify hospitalizations with radiotherapy encounters (Z51.0) and concurrent diagnoses of nausea, vomiting, or dehydration using ICD-10 codes. Outcomes included length of stay (LOS), total charges, ICU use proxies, in-hospital mortality, and non-home discharge. Survey-weighted national estimates were calculated, and multivariable regression assessed predictors including cancer site proxies, age, comorbidity burden, insurance status, income quartile, and hospital characteristics. Results: Across 7,842 weighted admissions, mean LOS was 4.6 days (SD 2.1), mean total charges $23,400 (SD $8,700), and ICU-level care proxies were required in 12% of admissions. In-hospital mortality was 0.9%, and 21% of patients required non-home discharge. Older age, higher comorbidity burden, lower income quartile, and rural hospital location were independently associated with longer LOS, higher charges, and greater risk of non-home discharge (p < 0.01). Admissions for gastrointestinal or head/neck malignancies had the highest rates of RINV-related hospitalization. Temporal trends showed stable rates over the 7-year period. Conclusions: Hospitalizations for RINV and dehydration during radiotherapy represent a measurable national burden with disparities by socioeconomic status, tumor site, and hospital location. Clinical Takeaway: Targeted outpatient supportive interventions, particularly for high-risk patients, may reduce hospitalization, costs, and morbidity during radiotherapy.

e24087 Background: Radiotherapy-induced nausea and vomiting (RINV) negatively impacts adherence and quality of life. Multiple antiemetic strategies exist, but comparative effectiveness and ranking across regimens remain unclear, particularly regarding olanzapine-containing combinations. Methods: We conducted a systematic review and network meta-analysis of randomized and comparative studies evaluating antiemetic prophylaxis for RINV. Databases included MEDLINE, Embase, CENTRAL, and clinical trial registries. Interventions were categorized into clinically interpretable nodes (e.g., 5-HT3 antagonist ± dexamethasone, NK1-based combinations, olanzapine-containing regimens). The primary outcome was complete response (no emesis, no rescue therapy) during acute and delayed phases. Secondary outcomes included no nausea, severity, sedation, and discontinuation. Random-effects network meta-analysis was performed with treatment ranking using SUCRA probabilities. Results: Twenty-two studies encompassing 3,145 patients were included. Olanzapine-containing regimens ranked highest for complete response during both acute (SUCRA 92%) and delayed phases (SUCRA 89%), outperforming standard 5-HT3 + dexamethasone (SUCRA 64%). NK1-based triple therapy showed intermediate efficacy (SUCRA 78%). Olanzapine regimens had modest increases in sedation (RR 1.14, 95% CI 1.01–1.29) but no significant differences in discontinuation rates. Subgroup analyses indicated consistent benefits across radiation sites, fractionation schedules, and emetogenic risk. Conclusions: Olanzapine-based antiemetic regimens provide superior prevention of RINV compared with standard therapies, with acceptable tolerability across radiotherapy settings. Clinical Takeaway: Incorporating olanzapine into prophylactic antiemetic strategies can optimize symptom control, improve patient adherence, and enhance quality of life during radiotherapy.

e22007 Background: Long-term neurocognitive impairment is a major source of disability in survivors of pediatric CNS tumors. Proton radiotherapy may reduce dose to developing brain structures, potentially preserving cognition compared with conventional photon therapy. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, PsycINFO, and CENTRAL. Eligible studies included pediatric CNS tumor patients treated with proton or photon radiotherapy reporting neurocognitive outcomes (full-scale IQ, attention, processing speed, executive function) over time. Standardized mean differences (SMD) were pooled using random-effects models, and slope analyses assessed longitudinal IQ change. Subgroups included age at radiotherapy, craniospinal vs focal fields, tumor type, chemotherapy exposure, and follow-up duration. Certainty of evidence was graded using GRADE. Results: Eleven studies encompassing 624 patients were included. Proton therapy was associated with significantly less decline in full-scale IQ compared with photon therapy (SMD 0.43, 95% CI 0.21–0.65, p < 0.001). Domain-specific analyses showed preservation of attention (SMD 0.36, 95% CI 0.10–0.61) and processing speed (SMD 0.41, 95% CI 0.18–0.64). Longitudinal slope analysis indicated an average IQ decline of 0.7 points/year after proton therapy versus 2.4 points/year after photon therapy. Benefits were greatest in younger children (<8 years) and those receiving craniospinal irradiation. Attrition and missing data were similar across groups. Conclusions: Proton radiotherapy in pediatric CNS tumors is associated with clinically meaningful preservation of neurocognitive function compared with photon therapy, particularly in younger patients and those receiving extensive fields. Clinical Takeaway: When available, proton therapy should be considered for children at high risk of cognitive decline to optimize long-term functional outcomes.

e14101 Background: Pediatric and adolescent/young adult (AYA) malignant brain tumors remain a leading cause of cancer-related death. Population-level geographic and rural–urban disparities may reflect differences in access to specialized care and supportive services. Methods: Using CDC WONDER mortality data (1999–2023), we identified deaths from malignant brain tumors using ICD-10 codes. Pediatric (0–14 years) and AYA (15–39 years) populations were analyzed separately. Age-adjusted mortality rates (AAMR) per 100,000 were calculated by state, region, and urban–rural classification. Joinpoint regression assessed temporal trends, and interactions evaluated differential trends by rurality and geography. Results: A total of 14,532 deaths were analyzed. National AAMR declined modestly in pediatric patients (AAPC −1.1%, p < 0.01) but remained relatively stable in AYA patients (AAPC −0.3%, p = 0.12). Rural areas consistently showed higher mortality than urban areas in both age groups (p < 0.01). Regional disparities were evident, with highest pediatric and AYA mortality in the Southeast and Midwest. Inflection points indicated modest improvements following 2007 and 2015, likely reflecting advances in treatment and supportive care, but rural–urban gaps persisted. Rolling averages confirmed stability of these trends despite small-area data suppression. Conclusions: Geographic and rural–urban disparities in pediatric and AYA malignant brain tumor mortality persist despite modest national improvements, highlighting populations at greatest risk. Clinical takeaway: Targeted resource allocation and improved access to specialized neuro-oncology care in high-burden and rural regions are needed to reduce mortality and close disparities.