Challa, Pavan

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.

e19092 Background: Advances in immunochemotherapy and cellular treatment have improved outcomes for diffuse large B-cell lymphoma (DLBCL), but the population-level effect and equity of benefit are unclear. Understanding mortality trends and inequality is critical to developing targeted medicines. Methods: We used ICD-10 codes to assess DLBCL mortality from the CDC WONDER Multiple Causes of Death data (1999-2023). The age-adjusted mortality rates (AAMR) per 100,000 were calculated using the 2000 US standard population. Trends were assessed using Joinpoint regression to calculate annual percent change (APC) and average annual percent change (AAPC). Mortality was broken out by gender, race/ethnicity, age group, US Census area, and urban-rural categorization. Results: From 1999 to 2023, the national AAMR for DLBCL decreased from 3.8 to 2.5 per 100,000 (AAPC -2.1%) (p < 0.001). Non-Hispanic White patients saw the greatest decline (AAPC -2.5%), followed by non-Hispanic Black patients (AAPC -1.2%), resulting in increasing racial inequalities (rate ratio Black:White 1.35 in 2023 vs. 1.18 in 1999). Urban areas had much larger mortality decreases than rural areas (AAPC −2.3% versus −1.1%). Regional disparities were clear, with rates typically higher in the Southeast and Midwest. Inflection points were identified in 2006 and 2012, coinciding with widespread use of rituximab-based therapy and better availability of second-line medications. Conclusions: Although DLBCL mortality has decreased throughout the US over the last two decades, progress has been patchy, with significant racial and regional differences. Clinical Takeaway: Targeted interventions addressing access to therapy and early detection in high-risk populations are needed to close persistent DLBCL outcome gaps.

e14102 Background: High-quality glioma surgery requires multidisciplinary expertise, yet access to high-volume centers varies. National estimates of inpatient morbidity and resource utilization can identify actionable quality gaps and disparities. Methods: We analyzed the HCUP National Inpatient Sample (NIS) for adult admissions undergoing intracranial glioma resection from 2016–2022. Primary outcomes were in-hospital mortality and major complications (neurologic, infectious, thromboembolic, hemorrhagic). Secondary outcomes included length of stay (LOS), total charges, non-home discharge, and weekend admissions. Survey-weighted methods generated national estimates, and multivariable regression evaluated associations with hospital volume, teaching status, region, and patient-level socioeconomic variables, adjusting for age, comorbidities, and admission urgency. Results: Among 23,874 weighted admissions, in-hospital mortality was 2.1%, and major complications occurred in 14.7%. High-volume centers had lower odds of mortality (adjusted OR 0.62, 95% CI 0.51–0.75) and complications (OR 0.71, 95% CI 0.63–0.80) compared with low-volume hospitals. LOS was shorter at high-volume centers (median 5 vs 7 days, p < 0.001), with lower total charges. Patients from lower-income quartiles and rural areas had higher odds of complications and non-home discharge (OR 1.33, 95% CI 1.11–1.59). Weekend admissions were associated with modestly higher complication rates (OR 1.12, 95% CI 1.01–1.24). Conclusions: National inpatient outcomes for glioma resection vary by hospital volume and patient socioeconomic factors, highlighting disparities in access to high-quality surgical care. Clinical takeaway: Referral to high-volume centers and targeted support for vulnerable populations may reduce complications, optimize resource utilization, and improve equity in glioma surgical care.

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.

e14098 Background: For IDH-mutant WHO grade 2 gliomas, extent of resection (EOR) is thought to improve long-term outcomes, but optimal thresholds and survival benefit remain uncertain. Quantifying the impact of EOR can guide surgical planning and patient counseling. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, CENTRAL, and Web of Science. Eligible studies reported EOR (continuous or categorical) and outcomes including overall survival (OS), progression-free survival (PFS), malignant transformation, seizure control, and treatment-related morbidity. Random-effects models pooled hazard ratios (HRs) for survival outcomes, and meta-regression assessed relationships between EOR, histologic subtype (astrocytoma vs oligodendroglioma), measurement method (MRI volumetrics vs surgeon estimate), and adjuvant therapy. Results: Twelve studies including 1,052 patients were analyzed. Higher EOR was associated with improved survival: pooled HR for OS per 10% incremental resection was 0.88 (95% CI 0.83–0.93), and for PFS 0.85 (95% CI 0.79–0.91). Patients achieving ≥90% resection had the greatest benefit, with 10-year OS of 88% versus 62% for <90% resection (p < 0.001). Higher EOR also reduced risk of malignant transformation (HR 0.67, 95% CI 0.53–0.85) and improved seizure control in 68% of evaluable patients. Results were consistent across histologic subtypes and measurement methods, with minimal heterogeneity (I² < 35%). Conclusions: Greater EOR in IDH-mutant grade 2 gliomas is strongly associated with improved survival, lower malignant transformation risk, and better seizure control, supporting maximal safe resection as the standard of care. Clinical takeaway: Surgical planning aiming for ≥90% resection can optimize long-term outcomes and quality of life in patients with IDH-mutant grade 2 gliomas.

Importance Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized. Objective To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs. Design, Setting, and Participants This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and May 2023 and had preexisting multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), and other NAIDs as well as a control cohort of patients with Parkinson disease (PD). Exposure ICI therapy. Main Outcomes and Measures Demographic and clinical characteristics (neurologic disability, active or recent immunosuppression), ICI outcomes (response, progression-free survival [PFS], and overall survival [OS]), and safety outcomes (NAID exacerbation, irAEs) were collected. Results A total of 135 patients were included; the median (range) age was 72 (40-88) years, 84 (62%) were men, and 51 (38%) were women. A total of 45 patients had MS; 18, MG; 10, GBS; 5, another NAID; and 57, PD. Exacerbations occurred most frequently in MG (12 of 18 patients [67%]), often resulting in hospitalization (6 [50%]) or death (2 [17%]), with much lower rates in the MS cohort (8 of 45 patients [18%]). Ten patients with a history of GBS tolerated ICI without exacerbations, although 1 developed a fatal case of Lambert Eaton myasthenic syndrome following ICI treatment. No differences in response rate, PFS, or OS were observed between NAID groups. Conclusions and Relevance In this cohort study of ICI use in NAIDs, patients with MG had frequent and more severe exacerbations, while those with MS had few exacerbations. No obvious differences in survival between groups were observed. ICI may be an option for many patients with appropriate oncologic indications and preexisting NAIDs.