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e15501 Background: CP is the backbone of first-line therapy for recurrent or metastatic ASCC. In practice, Q3-week CP has been explored as a potential alternative to the standard (d1,8,15 Q28-day cycle) dosing, though its efficacy is not known. This study evaluated CP scheduling and clinical survival associations in metastatic ASCC. Methods: This multicenter retrospective cohort study included patients with metastatic ASCC treated with first-line CP, identified using the Mayo Data Explorer database. Electronic health records were reviewed to collect baseline clinical characteristics, treatment regimens, responses, progression-free survival (PFS), and overall survival (OS). Descriptive statistics were used to summarize patient demographics. Survival was estimated using Kaplan–Meier methods. Multivariable Cox proportional hazards models were used to compare survival by dosing schedule, adjusting for age, ECOG performance status, HPV (p16) status, liver metastasis, and prior chemoradiation. Results: 54 patients treated between 2020-2025 with first-line CP for metastatic ASCC were included. Baseline patient demographics were balanced between dosing groups (Table 1). Median follow-up time was 26.2 months. For Q3-week CP (n = 21), median PFS and OS were 9.8 (95% CI 8.1, NR) and 27.0 (95% CI 15.7, NR) months, respectively, while median PFS was 6.5 (95% CI 4.5,15.3) months with standard CP (n = 33) and median OS was not reached (95% CI 11.2, NR). Response rate was 76% with Q3-week and 60.6% with standard CP (p = 0.23) dosing. Survival outcomes were similar when comparing Q3-week CP relative to standard CP dosing using multivariable analysis (PFS HR 0.68, 95% CI 0.33–1.41; OS HR 1.67, 95% CI 0.67–4.14). Higher ECOG and liver metastasis were independently associated with inferior outcomes, while HPV was associated with improved survival. Subsequent therapy patterns were similar between CP schedule groups. Ten patients (16.9%) received local therapy, and 24 of 28 patients with progression received further systemic therapy, including 21 (87.5%) treated with immunotherapy. Conclusions: Survival outcomes were similar across dosing schedules, suggesting Q3-week CP may be a reasonable alternative to standard CP, with potential to reduce treatment-related burden in metastatic ASCC. Future analysis will compare toxicity profiles between CP dosing schedules, including in combination with PD1 inhibitors given the results of the POD1UM-303 trial. Patient demographics (n=54). Variable Q3-week CP (n=21) Standard CP (n=33) p-value Sex Female 16 (76.2%) 24 (72.7%) 0.77 Male 5 (23.8%) 9 (27.3%) Age Median (Q1, Q3) 62 (50.5, 69) 64 (55.5, 70) 0.57 BMI Median (Q1, Q3) 27.1 (21.9, 34.4) 27.4 (22.5, 31.7) 0.72 ECOG 0 9 (42.9%) 11 (34.4%) 0.53 ≥ 1 12 (57.1%) 21 (65.6%) Confirmed HPV (p16) Positive 16 (76.2%) 24 (72.7%) 0.77 Prior chemoradiation Yes 17 (81.0%) 21 (63.6%) 0.17

e15091 Background: Early identification of patients likely to benefit from immune checkpoint inhibitors (ICIs) remains a major challenge across solid tumors. Circulating tumor DNA (ctDNA) kinetics have emerged as a promising noninvasive biomarker, yet results across studies are heterogeneous. We conducted a systematic review and meta-analysis to evaluate the prognostic and predictive value of early ctDNA reduction in patients receiving ICIs. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception through March 2025 following PRISMA guidelines. Studies evaluating early ctDNA dynamics (≤8 weeks after ICI initiation) in adult patients with solid tumors were included. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR). Random-effects models were used to pool hazard ratios (HRs) and odds ratios (ORs). Heterogeneity was assessed using I² statistics, and publication bias was evaluated with funnel plots and Egger’s test. Results: A total of 27 studies encompassing 3,842 patients across lung, melanoma, breast, gastrointestinal, and genitourinary malignancies met inclusion criteria. Early ctDNA reduction (defined as ≥50–90% decline or complete clearance, study-specific) was associated with significantly improved PFS (pooled HR 0.45; 95% CI 0.38–0.53; I² = 41%) and OS (pooled HR 0.40; 95% CI 0.32–0.49; I² = 36%). Patients demonstrating early ctDNA reduction had a markedly higher ORR (pooled OR 4.92; 95% CI 3.71–6.53; I² = 29%). Subgroup analyses showed consistent benefit across tumor types and ICI regimens. Early ctDNA dynamics outperformed baseline PD-L1 expression and tumor mutational burden in predicting treatment response. No significant publication bias was detected. Conclusions: Early ctDNA kinetics are a robust, tumor-agnostic biomarker associated with improved survival and treatment response in patients receiving ICIs. These findings support the integration of ctDNA monitoring into early treatment assessment and clinical trial design. Prospective trials are warranted to validate ctDNA-guided immunotherapy strategies.

e15060 Background: In metastatic Breast Cancer (mBC) Circulating Tumor Cells (CTCs) are an established prognostic indicator of patients (pts) with highly aggressive disease, poor clinical outcomes, and poor response rates to therapy. However, CTCs are typically found in < 20% of mBC pts and many pts without CTCs also progress. Cancer associated macrophage-like cells (CAMLs) are inflammatory tumor macrophages also found in blood, in > 90% of mBC, and are indicators of poor clinical outcomes independent of CTCs. We conducted a prospective study to model CTC & CAML subtypes from 212 mBC pt blood samples prior to induction of new systemic therapies to optimize and validate risk models based on 2-year outcomes of Progression-free survival (PFS) & Overall survival (OS). Methods: An observational multi-institutional prospective study was conducted on 212 mBC pts prior to induction of a new line of therapy who were progressing on their current therapy. Anonymized (7.5ml) whole blood samples were taken prior to therapy induction and filtered by CellSieve filtration. Quantities and subtypes of CTCs & CAMLs were categorized by their expression of CK+/CD45+/CD14+ for CAMLs and CK+/CD45-/CD14- for CTCs. PFS (RECIST v1.1) and OS hazard ratios (HRs) were calculated by censored univariate & multivariate analysis at 2 years. Results: Pt median age was 51 years (range 25-92); TNBC (44%), ER/PR+ (30%), HER2+ (15%). Pts were treated with chemotherapy alone (18%), immune checkpoint inhibitor (46%), targeted (40%), hormone (8%) and unknown (5%). 38% (81/212) pts had ≥1 CTCs which correlated with significantly poorer PFS (HR = 1.9; 95%CI 1.3-2.7; p = 0.0016) and OS (HR = 2.0; 95%CI, 1.3-3.0; p = 00025), with the most significant risk at ≥8 CTCs (14% pts), PFS (HR = 3.8; 95%CI, 2.1-6.9; p < 0.0001) and OS (HR = 7.2; 95% CI, 3.4-14.9; p < 0.0001). Independently, 93% (n = 196/212) of pts had ≥1 CAML, with a threshold of >40um size (84% pts) had significantly poorer PFS (HR = 2.0; 95% CI, 1.2-3.1; p = 0.0032), but not OS (HR = 1.5; 95%CI, 0.9-2.7; p = 0.1169). However, a threshold of >125um size CAML (43% pts) also had significantly poorer PFS (HR = 1.8; 95% CI, 1.2-2.7; p = 0.0013) and OS (HR = 1.6; 95% CI, 1.0-2.5; p = 0.0233). By combining models, the best outcomes were seen in pts with 0 CTCs & 0 CAMLs (mPFS = 12.6 & mOS = 21.3), followed by 0 CTCs & ≥40um CAMLs (mPFS = 5.2 & mOS = 17.5) and 0 CTCs & ≥125um CAMLs (mPFS = 4.9 & mOS = 15.2). Poorer outcomes were seen with ≥1 CTCs (mPFS = 3.3 & mOS = 13.5) and the worst outcomes with ≥8 CTCs (mPFS = 2.5 & mOS = 4.8). Conclusions: CTCs were uncommon in mBC pts but correlated with very poor clinical outcomes. In parallel analysis, CAMLs were common with CAML size correlating with increasingly poorer outcomes. By combining CTC & CAML subtypes, mBC pts were more accurately stratified by risk of progression and death. Additional multivariate studies correlating treatment class and tumor response rates are ongoing.

e14545 Background: Durable antitumor immunity depends on the maintenance of stem-like CD8⁺ T cells capable of sustaining long-term effector responses. Oncolytic viruses (OVs) are potent immunomodulatory agents that reshape the tumor microenvironment and augment antitumor immunity. We hypothesized that platinum-based chemotherapy alters tumor-intrinsic type I interferon (IFN-I) signaling in a manner that can be functionally restored by OV therapy, thereby promoting the generation and persistence of stem-like CD8⁺ T cells. Methods: Tumor cells treated with platinum chemotherapy were evaluated in vitro for changes in IFN-I pathway activity, OV replication, and markers of immunogenic cell death (ICD). Syngeneic mouse tumor models were used to assess antitumor efficacy and immune remodeling following combination therapy. Tumor-infiltrating lymphocytes were analyzed by single-cell RNA sequencing and multiparameter flow cytometry to define CD8⁺ T-cell states and functional programs. Guided by these preclinical findings, a clinical trial combining XELOX, PD-1 blockade, and OV therapy was initiated (ChiCTR2500107607). Results: Platinum chemotherapy significantly suppressed tumor-intrinsic IFN-I signaling, while OV therapy restored antiviral responses, enhanced viral replication, and increased ICD in vitro. In vivo, the combination strategy resulted in superior tumor control and profound remodeling of the tumor immune microenvironment. The most pronounced immunologic effect was observed within the stem-like CD8⁺ T-cell compartment. Combination therapy induced a distinct population of TCF7⁺ ISG15^high NFATC1^low AP-1^low CD8⁺ T cells, characterized by restrained activation, enhanced persistence, and reduced propensity toward terminal exhaustion. In IRF7-deficient tumors, this stem-like CD8⁺ T-cell population failed to emerge and antitumor efficacy was significantly diminished, indicating that moderate tumor-intrinsic IFN-I signaling is required for this immune state. Conclusions: Tumor-intrinsic type I interferon signaling is a critical determinant of synergy between platinum chemotherapy and oncolytic virotherapy, enabling the maintenance of durable stem-like CD8⁺ T-cell immunity. These findings establish a mechanistic rationale for combining platinum chemotherapy, oncolytic viruses, and immune checkpoint blockade and support ongoing clinical translation. Clinical trial information: ChiCTR2500107607.

e14535 Background: Anti-programmed cell death ligand PD-L1/PD-1 immune checkpoint inhibitors (ICIs) are approved for metastatic breast cancer (mBC) patients (pts) with a tumor combined positive score (CPS) ≥10% in their tissue. However, many pts with < 10% CPS may also respond to ICIs. Recent studies in lung cancer have shown that circulating tumor cells (CTCs) and tumor-macrophage fusion cells (TMFCs) both express, and may upregulate, PD-L1 which is predictive for ICI responses. We initiated a prospective study to monitor PD-L1 in CTCs & TMFCs in mBC pts prior to receiving systemic ICIs to correlate their PD-L1 expression to progression free survival (PFS) and overall survival (OS) at 24 months. Methods: We conducted a multi-institutional prospective pilot study of n = 102 pts with pathologically confirmed mBC, having failed ≥1 prior lines of therapy, prior to receiving ICIs (n = 52 Pembrolizumab, n = 39 Retifanlimab, n = 5 Atezolizumab, and n = 1 Nivolumab). Anonymized blinded peripheral blood samples (7.5ml) were procured prior to ICI induction (T0) and (~40 days after ICI induction (T1). TMFCs & CTCs were isolated using Cellsieve microfilters with average PD-L1 expressions measured then categorized as negative/low or high. Tumor CPS was categorized as negative/low (< 10%) or high (> 10%). We compared TMFC PD-L1 to tissue CPS by linear regression. TMFC/CTC PD-L1 expression and tissue PD-L1 CPS were compared to pts’ PFS and OS by Cox proportional univariate and multivariate analysis over 24 months. Results: Of n = 102 pts, median age = 59 years (range 32-77); 42% (43/102) were ER+, 33% (33/102) were PR+, 5% (5/102) were HER2+, and 56% (57/102) were triple-negative. 32% (32/102) had an ECOG score of 0, 25% (26/102) had ECOG 1, and 43% of scores were unavailable. N = 42 pts had available tumor CPS data, which did not correlate to TMFC/CTC PD-L1 at T0 or T1. Pts with high CPS did not significantly predict for PFS (HR = 0.78; 95% CI, 0.3-1.9; P = 0.7627) nor OS (HR = 0.54; 95% CI, 0.2-1.7; P = 0.4471). Pts with high TMFC/CTC PD-L1 at T0 also did not significantly predict for PFS (HR = 0.74; 95% CI, 0.5-1.2; P = 0.2799) nor OS (HR = 0.84; 95% CI, 0.4-1.6; P = 0.7220). However, of the n = 82 pts who provided T1 samples, high CTC/TMFC PD-L1 at T1 was significant for better PFS (HR = 2.55; 95% CI, 1.6-4.2; P = 0.0004) and better OS (HR = 2.06; 95%CI, 1.1-3.8; P = 0.0309). Conclusions: In this study of mBC pts treated with PD-L1 ICIs, tissue CPS did not correlate with PD-L1 expression in CTCs or TMFCs. Further, neither CPS nor baseline PD-L1 in CTC/TMFCs predicted for clinical outcomes in ICI therapies. However, PD-L1 in CTC/TMFCs ~40 days post-induction of ICI did predict for better response rates. While this study suggests predictive value of monitoring PD-L1 in blood during ICI therapies, further studies are required to refine and validate these findings.

e14524 Background: Immune checkpoint inhibition has demonstrated meaningful clinical benefit in microsatellite instability–high (MSI-H) colorectal cancer (CRC); however, outcomes remain heterogeneous. The interaction between tumor immune microenvironment features, tumor mutational burden (TMB), and survival outcomes has not been fully characterized. We conducted an integrative analysis of publicly available genomic data to evaluate the prognostic impact of immune infiltration stratified by MSI status and TMB in CRC. Methods: Transcriptomic, somatic mutation, and clinical data for primary colorectal adenocarcinoma were obtained from TCGA-COAD and TCGA-READ. About 600 patients with overall survival data were analyzed. MSI status was taken from TCGA molecular subtype annotations. TMB was defined as the number of nonsynonymous somatic mutations per tumor and dichotomized at the median.Immune infiltration (CD8⁺ and CD4⁺ T cells, macrophages, neutrophils, dendritic cells) was estimated using TIMER. Patients were classified as high or low infiltration by the median. Overall survival was assessed using Kaplan–Meier analysis and Cox models adjusted for age, sex, and tumor stage., and tumor stage. Results: The cohort included approximately 15% MSI-H tumors, which demonstrated significantly higher TMB compared with microsatellite-stable (MSS) tumors. MSI-H tumors exhibited an inflamed immune phenotype, with approximately twofold higher CD8⁺ T-cell infiltration relative to MSS tumors. Across the overall cohort, high CD8⁺ T-cell infiltration was associated with improved OS compared with low infiltration (median OS not reached vs approximately 60–70 months). In contrast, increased macrophage infiltration was associated with inferior survival outcomes. When stratified by genomic features, the favorable prognostic association of CD8⁺ T-cell infiltration was most pronounced in MSI-H and TMB-high tumors, corresponding to an estimated 30–40% relative reduction in mortality risk compared with MSI-H/TMB-high tumors with low immune infiltration. Immune infiltration demonstrated weaker and less consistent associations with OS in MSS/TMB-low tumors. In multivariable analyses, CD8⁺ T-cell infiltration remained independently associated with improved OS after adjustment for clinical covariates, whereas macrophage infiltration remained independently associated with worse outcomes. Findings were consistent across colon and rectal cancer subgroups. Conclusions: In this integrative analysis of TCGA colorectal cancer datasets, features of the tumor immune microenvironment, together with MSI status and TMB, were associated with survival. These results support immune-genomic stratification and suggest that combining immune and molecular biomarkers may improve prognostic assessment and immunotherapy trial design in colorectal cancer.

e14111 Background: Primary CNSL (PCNSL) is a rare, aggressive B-cell non-Hodgkin lymphoma limited to the CNS, while secondary CNSL (SCNSL) represents CNS involvement from systemic lymphoma. Previous observations focused on CNSL have limited data clinically comparing PSNSL and SCNSL. We aimed to evaluate overall survival and associated factors in patients with PCNSL vs SCNSL using a large population database. Methods: We conducted a retrospective cohort study using the SEER-22 database to identify patients diagnosed with CNSL between 2020-2022. Group comparisons used t-tests or ANOVA for continuous variables, chi-square tests for categorical variables, and Kaplan–Meier survival analysis, with all analyses performed in RStudio 4.1.1 and significance deemed as p<0.05. Results: 14,964 patients with CNS lymphoma were identified, with 84.6% PCNSL and 15.4% SCNSL cases. The overall median age was 65 years (IQR 20), with 52% male, 66% White patients, residing in urban areas (90%) and median household income of $50,000–$75,000 (52%). Compared with PCNSL, patients with SCNSL were significantly older (72 vs 64 years, p<0.0001). SCNSL more frequently involved the cerebrum (39% vs 34%) and cerebellum (5.5% vs 4.5%), but less commonly affected the nerves (12.0% vs 12.5%) and spinal cord (4.2% vs 5.1%) (p<0.05). Disease was predominantly unilateral (95.8%) in both groups. Chemotherapy (55% vs 56%) and radiotherapy (19% vs 18%) utilization did not differ significantly, with external beam radiation comprising 94.3% of radiated cases. PCNSL patients were more likely to undergo surgical intervention than SCNSL patients (31.8% vs 28.7%; p=0.0027). Diffuse large B-cell lymphoma was the most common histologic subtype in both PCNSL (70.1%) and SCNSL (74.3%). Median overall survival was shorter in SCNSL (1.64 years) than PCNSL (1.99 years). Survival improved significantly across diagnostic eras (2000–2005 to 2016–2020; log-rank p<0.001), while lower income (<$50,000) and rural residence were associated with inferior outcomes (p=0.028 and p=0.033). Conclusions: Survival in CNS lymphoma remains poor, with SCNSL associated with worse outcomes compared with PCNSL. Greater understanding of treatment variation and disease differences is needed to optimize therapy and improve patient outcomes. Characteristic PCNSL SCNSL Total p-Value N 12667 2297 14964 Population Distribution 0.033 Urban 11426 2038 13464 Rural 1241 259 1500 Surgery 0.0027 Yes 3630 730 4360 No 9037 1567 10604 Months from Diagnosis to Rx(Mean, SD) 0.31 (0.86) 0.27 (0.65) 0.30 (0.83) 0.0077 Death Status <0.0001 Dead 8603 1772 10375 Alive 4064 525 4589 Overall Survival (in years, Mean, SD) 1.99 (2.85) 1.64 (2.31) 1.93 (2.77) <0.0001

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.