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Beyond KIT and PDGFRA: Molecular landscape and outcomes of wild-type GIST.
e23518 Background: Gastrointestinal Stromal Tumors (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract. Most GISTs harbor activating mutations in KIT or PDGFRA. In contrast, GISTs that are negative for KIT/PDGFRA mutations on next generation sequencing (NGS) are defined as wild-type (WT) GIST. While KIT/PDGFRA-mutant GISTs often respond to TKIs, the biology, treatment responsiveness, and outcomes of WT GIST are not well defined. We present a single institution retrospective review of WT GIST. Methods: 370 patients were screened for pathologically confirmed GIST with an absence of both KIT and PDGFRA mutations on NGS. Demographic information, primary site, molecular genomic profiles, therapeutic regimens, and survival data were included. Results: 365 patients were confirmed on pathology to have GIST. 184 patients had NGS completed; 18 patients met WT criteria (9.8% of 184). The most frequent primary locations were stomach (n = 12, 66.7%) and small intestine (n = 3, 16.7%). SDH-deficient GIST were most common (n = 9, 50%), followed by “quadruple WT” (n = 4, 22.2%), and RAS pathway mutations (n = 3, 16.7%); 2 patients did not have SDH testing (16.7%). At time of diagnosis, most of the cohort had stage IV disease (n = 10, 55.5%), followed by stage III (n = 4, 22.2%), then stage II (n = 2, 11.1%) and stage I disease (n = 2, 11.1%). 17 patients underwent surgical resection; 1 surgery was aborted due to disease burden. Imatinib was the most used systemic therapy (n = 14, 77.8%) and first-line in 13 cases; median imatinib duration was 415 days. It was most often discontinued for disease progression (n = 5, 35.7.5%) or treatment related toxicity (n = 2, 14.3%). Subsequent TKIs (sunitinib, regorafenib, ripretinib) and immune checkpoint inhibitors were used in a subset of later-line settings. Across all WT GIST patients, 5-year overall survival (OS) was 88.9% (95% CI 75.5–100%) with median OS of 129 months; 5-year progression-free survival was 55.6% (95% CI 36.8–84.0%) with median time to first progression of 73 months. Conclusions: KIT/PDGFRA WT GIST represents a rare but clinically important subset at our institution, with pronounced molecular heterogeneity driven predominantly by SDH-deficient and RAS pathway–altered tumors and a distinct minority of quadruple WT cases. In this series, long-term survival was unexpectedly favorable despite a high proportion of patients with advanced-stage disease, highlighting the critical role of comprehensive genomic profiling to correctly classify WT GIST. Robust, multi-institutional cohorts are urgently needed to refine prognostic estimates and to develop and test tailored treatment strategies for SDH-deficient and quadruple WT GIST.
Survival with Bria-IMT + CPI in advanced metastatic breast cancer at 12 and 24 months.
1108 Background: Metastatic breast cancer (MBC) remains limited by resistance and cumulative toxicity in heavily pretreated patients. Bria-IMT combines a whole-cell vaccine (SV-BR-1-GM) with anti-PD-1 (CPI) to enhance tumor antigen presentation and overcome immune exhaustion. SV-BR-1-GM is an irradiated breast cancer cell line engineered to secrete GM-CSF, promoting HLA class I and II antigen presentation and T-cell activation. We identified a subset with durable clinical benefit and biologic correlates. Methods: Phase I/II evaluating the Bria-IMT regimen (SV-BR-1-GM with CPI (pembrolizumab or retifanlimab). In the phase II portion, pts were randomized 1:1 to CPI initiation at cycle 1 (C1) or delayed start at cycle 2 (C2). Two SV-BR-1-GM formulations were administered: IFNγ-stimulated (IFγ) or unstimulated (≠IFγ). Baseline circulating tumor cells (CTCs) and delayed-type hypersensitivity (DTH) responses to SV-BR-1-GM were assessed as biomarkers. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan Meier (KM). Subgroup comparisons (CPI sequencing, IP formulation, DTH status, and baseline CTC status) are exploratory. Results: 32 phase 2 pts were randomized: median age 61 (range 41-80); median prior lines 6 (range 2-13); PFS 3.5 mo (95% CI 3.0 - 4.2); OS 9.5 mo (95% CI 7.0 - 17.4). Among CPI C1 vs C2 starts: median OS 13.3 v 7.4mo (HR 0.8; 95% CI 0.4-1.9, p = 0.6); OS KM probability at 12 mo 47% v 58%. Median OS w ≠IFγ v IFNγ IP =16.6 v 9.1 mo (HR 0.58; 95% CI 0.2-1.4, p = 0.23); OS KM at 12 mo 52.4% v 27.3%. DTH+ v DTH- median OS 11.9 v 4.7 mo (HR 0.0009; p = <0.001), OS KM @12 mo 48% v 0%. CTCs <5 v > 5 at baseline had median OS 16.6 v 5.5 mo (HR 0.005; 95% CI 0.0003-0.09, p < 0.001), OS at 12 mo 49% vs 33%. Among long term survivors @12mo, OS probability 44.0% (95% CI 26.2-59.7%) and @24 mo 26% (95% CI 12.1-42.4%). Median follow up 25.8 with PFS 5.4 mo. 5 received ≠IFγ formulation v 1 w IFNγ. All 6 (3 with CPI @C1, 3@C2) experienced delayed type hypersensitivity reaction to inoculation. 67% of long responders matched HLA at >1 allele, 33% no match. Grade ≥3 AEs in 47% of pts, most common injection site rxn, nausea, fatigue; no tx related D/C; no unexpected safety signals. Conclusions: In heavily pretreated MBC, Bria-IMT demonstrated a tolerable safety profile and the emergence of a long-term survivor cohort. Durable survival was observed beyond 12 and 24 months. Differential survival favoring Ph3 formulation, DTH positivity, lower baseline CTC burden, and early CPI sequencing was observed. These findings support prospective validation of DTH and CTC as predictive biomarkers and the continued use of the Ph3 IP formulation in the ongoing phase 3 study Bria-ABC (NCT06072612). Clinical trial information: NCT06072612 .
Denosumab versus zoledronic acid in patients with breast cancer: A propensity-matched real-world time-to-event analysis.
12079 Background: Bone-modifying agents are routinely used in patients with breast cancer to reduce skeletal-related complications and metabolic disturbances. Denosumab and zoledronic acid are commonly prescribed; however, comparative real-world data evaluating their relative safety and effectiveness remain limited. We compared time-to-event outcomes associated with denosumab versus zoledronic acid in a large real-world cohort of patients with breast cancer. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, comprising electronic health records from 70 healthcare organizations. Adult patients with breast cancer who received either denosumab or zoledronic acid were identified, excluding those with underlying osteoporosis. Patients were propensity score–matched 1:1 based on demographics, comorbidities, concomitant oncologic therapies, and baseline laboratory parameters, yielding 15,147 patients per cohort. Outcomes assessed over a 5-year follow-up period included time to hypercalcemia, severe hypercalcemia (serum calcium ≥14.0 mg/dL), hypocalcemia, pathological fracture in neoplastic disease, and bone pain. Time-to-event analyses were performed using Kaplan–Meier methods and compared with log-rank testing; hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: After propensity score matching, 15,147 patients were included in each cohort with well-balanced baseline characteristics. Over 5 years of follow-up, hypercalcemia did not differ between patients treated with zoledronic acid and denosumab (hazard ratio [HR] 0.99, 95% CI 0.88–1.10; log-rank p = 0.831). Severe hypercalcemia (serum calcium ≥14.0 mg/dL) was uncommon, with no significant difference between groups (HR 1.25, 95% CI 0.94–1.68; log-rank p = 0.129). Pathological fracture in neoplastic disease occurred less frequently in the zoledronic acid cohort, although this difference did not reach statistical significance (HR 0.88, 95% CI 0.76–1.01; log-rank p = 0.060). Hypocalcemia was significantly less frequent among patients receiving zoledronic acid compared with denosumab (HR 0.44, 95% CI 0.40–0.49; log-rank p < 0.001). Bone pain did not differ significantly between treatment groups (HR 0.95, 95% CI 0.89–1.02; log-rank p = 0.186). Conclusions: In this real-world analysis of patients with breast cancer, denosumab and zoledronic acid demonstrated similar time-to-event outcomes for hypercalcemia, severe hypercalcemia, pathological fracture, and bone pain, while zoledronic acid was associated with a significantly lower risk of hypocalcemia. These findings highlight important distinctions in toxicity profiles between agents and may inform individualized selection of bone-modifying therapy. Prospective studies are warranted to further define optimal agent selection in specific clinical subgroups.
Standardizing patient-initiated electronic messaging in a high-volume breast center.
e13557 Background: Patient-initiated electronic messaging volume has risen nationally, with a 30% annual increase in medical advice requests, 11% yearly rise in telephone messages, and a 157% increase in patient messages following the COVID-19 pandemic. At our large academic Breast Center, MyChart message volume exceeded 100,000 messages annually for three consecutive fiscal years, with over 90% requesting medical advice. High message volume, coupled with inconsistent workflows and unclear patient expectations, negatively impacted care delivery efficiency, staff workload, and patient experience. Methods: We conducted a quality improvement initiative to optimize patient education and standardize InBasket message handling for clinical care messages; non-clinical messages (e.g., scheduling) were excluded. Two objectives were targeted: (1) improving patient MyChart education and expectations and (2) standardizing InBasket message handling workflows. Interventions included updated patient-facing team sheets, standardized MyChart communication guidelines, SmartPhrases reinforcing message expectations, and staff-facing triage guidelines, escalation pathways, standardized response templates, and InBasket handling procedures. Nurses, as frontline managers of InBasket messages, were selected as the survey population. Pre- and post-intervention surveys assessed nursing staff comfort, effectiveness, and workflow clarity. Results: For Objective 1 (nursing satisfaction and ease with patient MyChart education and expectation-setting), survey scores increased from 64% pre-intervention to 72% post-intervention, exceeding the target improvement of 6 percentage points. For Objective 2 (nursing satisfaction and ease with InBasket message handling standardization), scores improved from 88% to 94%, meeting the predefined goal. Staff reported improved clarity regarding appropriate message use, standardized escalation pathways, and reduced unnecessary message back-and-forth. Conclusions: Standardized patient education and structured InBasket workflows improved care delivery efficiency, staff confidence, and satisfaction with electronic message management in a high-volume Breast Center. Clear patient expectations and defined escalation pathways enhanced communication safety and predictability. This scalable care delivery model is applicable to other subspecialty oncology clinics managing high electronic communication burden. Nursing survey: satisfaction and ease pre- and post-intervention. Objective Measure Pre-Intervention Post-Intervention Objective 1 Patient MyChart Education & Setting Expectations 64% 72% Objective 2 InBasket Message Handling Standardization 88% 94%
RISE trial: A novel virtually delivered supervised exercise intervention targeting cognitive impairment and gut microbiome in adolescent and young adult (AYA) brain tumor survivors.
TPS12167 Background: Up to 45% of AYA brain tumor survivors experience cancer-related cognitive impairment (CRCI) affecting processing speed, attention, working memory, and executive function—domains critically impacting quality of life (QOL). Moderate-intensity exercise can improve cognitive function by enhancing gut microbiome composition and function. However, only 50% of AYA cancer survivors receive any exercise information from medical providers, with 42% actually meeting physical activity recommendations. Considering developmental milestones and the unique needs of AYA brain tumor survivors, tailoring virtually delivered exercise interventions paired with behavioral coaching and supportive care navigation to promote the adoption of a physically active lifestyle may be a promising approach to reducing CRCI through modulation of gut microbiome health. Few randomized controlled trials (RCTs) have examined this type of exercise intervention for AYA brain tumor survivors. Additionally, the influence of the gut microbiome on the relationship between exercise and cognitive function in AYA brain tumor survivors has not yet been studied. To address these gaps, we developed the Remote Implementation of Supervised Exercise (RISE) intervention, a 12-week personalized aerobic and strength training exercise intervention with behavior coaching and supportive care navigation. The RISE trial aims to evaluate feasibility (primary), cognitive and physical activity (secondary), and gut microbial composition changes (exploratory). Methods: RISE is a two-arm 1:1 pilot RCT (NCT06799481) of 40 AYA brain tumor survivors (aged 18-39) with CRCI enrolled at Emory University and MD Anderson Cancer Center. Controls receive an activity tracker and 18 wellness calls from a trainer inquiring about adverse events and survivorship topics. Intervention participants participate in 18 virtual exercise sessions with an exercise coach, consisting of progressive aerobic and strength training exercises with active lifestyle behavior coaching. Intervention participants also receive an activity tracker and participate in self-led exercise sessions via the Physitrack telehealth app for 12 weeks. Assessments at baseline, 6, 12, and 18 weeks measure cognitive function, physical activity levels, gut microbiome, physical function, diet, and QOL. Descriptive analysis will be used to assess feasibility, defined as enrollment of 50% eligible AYAs, 75% adherence to intervention, and 80% retention at the end of the 12-week intervention. As of January 2026, 17 of 40 patients have been enrolled, and accrual is expected to be complete within 1 year. Clinical trial information: NCT06799481 .
Adjuvant pembrolizumab in clear cell renal cell carcinoma with high recurrence risk: A multicenter real-world study.
e16538 Background: Pembrolizumab has demonstrated efficacy in improving disease-free survival (DFS) and overall survival (OS) as adjuvant therapy in clear cell renal cell carcinoma (ccRCC) at high risk of recurrence. However, real-world evidence supporting its use in Chinese patients remains limited. This study evaluated the real-world effectiveness and safety of adjuvant pembrolizumab in a multicenter cohort. Methods: This multicenter retrospective study recruited 18–80-year-old patients with high-risk clear cell renal cell carcinoma (ccRCC). High-risk status was defined as either M0 disease with adverse pathological features (pT2 with grade 4/sarcomatoid differentiation, any pT3/T4, or any pT with N1) or M1 oligometastatic disease achieving no evidence of disease (NED) after complete resection. The treatment cohort included patients who received at least one cycle of adjuvant pembrolizumab and was 1:2 matched to an observation cohort via propensity score matching to achieve baseline balance. The primary endpoint was DFS; secondary endpoints included OS and treatment-related adverse events (TRAEs). Results: Between January 2023 and December 2025, 396 patients were enrolled, including 114 who received pembrolizumab and 282 managed with observation. Baseline imbalances in age, M stage, and nuclear grade were observed before matching. After matching, 90 patients in the pembrolizumab group and 161 in the observation group were analyzed, with well-balanced baseline characteristics. At the data cutoff (December 31, 2025), median follow-up was 13.1 months in the pembrolizumab group and 24.6 months in the observation group. Disease recurrence occurred in 6.7% (6/90) of patients receiving pembrolizumab compared with 22.4% (36/161) in the observation cohort. Median DFS was not reached in either group (HR 0.56, 95% CI 0.23–1.00). The 24-month DFS rate was 90.5% in the pembrolizumab group versus 73.2% in the observation group. TRAEs were reported in 50.8% of treated patients, predominantly grade 1-2. Grade 3 TRAEs occurred in 13.3% of patients, and grade 4 events were limited to two cases of immune-related myocarditis. The most common TRAEs included rash (21.3%), proteinuria (12.2%) and thyroid dysfunction (10.2%). Severe adverse events (SAEs) led to treatment discontinuation in 10.5% of patients, with hypothyroidism (3.5%), colitis (2.6%) and hypertransaminasemia (2.6%) as the most frequent events, and no treatment-related deaths were noted. Retrospective study design and short follow-up limit long-term outcome assessment. Conclusions: In this multicenter real-world Chinese cohort, adjuvant pembrolizumab was associated with improved DFS and a manageable safety profile in patients with high-risk ccRCC. Larger studies with longer follow-up are warranted to further validate these findings.
Outcomes of a feasibility and safety trial of tile-based radiation therapy with cesium-131 followed by external beam radiation therapy with concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma (NCT05342883).
2011 Background: Standard of care (SOC) of Glioblastoma (GBM) includes maximal safe resection followed by external beam radiation therapy (EBRT) with concomitant temozolomide (TMZ). This typically begins 4-6 weeks after surgery, during which rapid early progression (REP) occurs in ~50% of patients and is associated with worse survival, especially in unmethylated GBM (median OS ~13 months as per BN007). SOC treatment in BN007 showed ~38% ≥grade 3 treatment-related adverse events (TRAEs). GammaTile (GT Medical Technologies, Inc., Tempe, AZ), a tile-based radiation therapy (TBRT) with cesium-131 sources, immediately initiates radiation at resection, eliminating the 4-6-week delay. Methods: This is a prospective, single arm, open-label feasibility study across 15 US centers with a primary aim of assessing the safety and feasibility of combining resection + TBRT with an abbreviated course of EBRT with concurrent and adjuvant TMZ for newly diagnosed molecular GBM. Eligible patients were ≥18 years old; only patients with IDH-wildtype were included in survival analysis. MGMT and IDH underwent central lab review. Feasibility was defined as percent of patients who started EBRT+TMZ between 21-35 days post-surgery. Safety was assessed by incidence of ≥grade 3 TRAEs. REP was centrally reviewed. Additional aims included PFS and OS estimated using Kaplan-Meier. A planned sample size of 61 was chosen to ensure feasibility could be estimated with a ±10% degree of precision. Results are presented based on the modified intent to treat (mITT) population (enrolled patients who had surgery and confirmed GBM). Results: From 8/2022-8/2025, 70 patients were enrolled and had surgery; 67 of whom had confirmed GBM. Table 1 presents baseline characteristics. Median follow-up was 12.4 months. 93% started EBRT+TMZ; 74% started 21-35 days post-surgery. The median (range) of days from surgery to EBRT+TMZ was 29 (23-70) days. There were no delays due to EBRT planning. 39% of patients experienced a ≥grade 3 TRAE: 22% of patients were related to surgery only, 18% to radiation only, and 13% to surgery and radiation. 6.0% of patients showed REP. Median OS for patients with unmethylated MGMT was 16.5 months vs. 28.0 months for patients with methylated MGMT. The median PFS for patients with unmethylated MGMT was 9.3 months vs. not yet met for patients with methylated MGMT. Conclusions: Feasibility and safety are in line with SOC. REP had a notable reduction compared to literature. OS is encouraging. These data provide the basis for a phase 3 randomized trial (NCT07195591). Clinical trial information: NCT05342883 . Baseline characteristics. Parameter Detail n 67 Age, median 66 Male:Female, n 42:25 Ethnicity (Non-Hispanic), n 61 Race (White), n 56 EOR – GTR:not GTR, % 66:34 IDH-wildtype:mutated, n 66:1 MGMT promoter methylated:unmethylated, n 28:39
Recurrence modeling with electronic health records through natural language processing and machine learning techniques.
e18004 Background: Head and neck cancer patients with locally advanced disease requiring free flap reconstruction are at high risk for locoregional and distant recurrence yet early identification of recurrence is challenging. Unstructured clinical notes contain rich longitudinal information that may capture early signals of disease progression. We evaluated whether natural language processing (NLP)-based large language models (LLM) applied to electronic health record (EHR) notes could predict recurrence in this high-risk population. Methods: 789 patients with head and neck cancers treated with free flap reconstruction from 1997-2023 at a single institution were retrospectively analyzed. EHR pathology, radiology, and clinical notes from diagnosis through five months post-diagnosis were collected. Notes were either combined into a single aggregated document per patient or as individual notes. Any notes post-recurrence were censored. Text was vectorized using term frequency-inverse document frequency (TfidfVectorizer) and a domain-adapted contextual language model trained on clinical notes (clinicalBERT). Patients were split into training and testing cohorts prior to feature extraction. Logistic regression models were trained to predict recurrence. For per-note analyses, the note with the highest recurrence probability was used for lead-time estimation. Results: The median follow-up in the entire cohort was 39.43 months (IQR 18.53-78.23). 13.05% (103/789) patients experienced disease recurrence at a median of 8.82 months since initial diagnosis (IQR 5.83-17.67). Overall discriminative performance was modest across all models. The best performing model was the combined note TfidfVectorizer, with an AUC of 0.585. Per-note TfidfVectorizer, combined note clinicalBERT, and per-note clinicalBERT had declining AUCs of 0.580, 0.525, and 0.514 respectively. Models showed relatively high specificity but limited sensitivity for recurrent cases with a maximum F1-score of 0.28 for the combined note TfidfVectorizer. Among true-positive recurrence predictions in per-note analysis, the median lead time of predicted recurrence was 194 days (IQR 100-728) for TfidfVectorizer and 187 days (IQR 86-748) for clinicalBERT. Conclusions: NLP models applied to unstructured EHR notes demonstrated limited discrimination for recurrence prediction in head and neck cancer patients undergoing free flap reconstruction. While recurrence-associated signals were detectable months to years before diagnosis in a subset of patients, overall predictive performance was modest. Predictive performance may be improved by incorporating temporal modeling, restriction to oncology-relevant note types, aggregation of notes by date of encounter, and integration of structured clinical variables.
Environmental co-benefits of WISDOM risk-based breast cancer screening: A multi-institutional pathway-based life cycle assessment.
e23224 Background: The WISDOM randomized clinical trial demonstrated that risk-based breast cancer screening incorporating population-based genetic testing safely stratified screening intensity and was noninferior to annual screening for stage ≥IIB cancers while reducing mammography utilization. Breast cancer screening also represents a substantial national expenditure, estimated at approximately US$11B annually in recent years.The environmental consequences of screening guideline intensity and downstream diagnostic cascades—relevant to population health and environmental justice—remain under-characterized. Methods: We conducted a pathway-based life cycle assessment (LCA) to quantify environmental impacts of hypothetical breast cancer screening–diagnostic cascades under (1) population-based annual screening and (2) WISDOM-aligned risk-stratified screening pathways. The modeled clinical sequence included screening mammography, recall, diagnostic imaging, biopsy, and pathology. Pathways were parameterized for four clinically defined risk groups (low, average, elevated, high), with procedure volumes and intensities informed by WISDOM trial screening assignments and supporting empirical evidence. A cradle-to-grave boundary captured energy use, consumables, equipment manufacturing, and waste. Primary data inputs were derived from audit and process inventories across three US academic centers. Environmental outcomes were expressed as kg CO₂-equivalents (CO₂e) per patient pathway and summarized across risk strata. Results: Compared with population-based annual screening, risk-stratified pathways were associated with an approximate 30% reduction in total greenhouse gas emissions. Emissions were dominated by routine mammography (approximately 65% of total pathway emissions) and downstream diagnostic imaging and biopsy (approximately 20%). Per-patient emissions increased with escalating risk intensity: +30%, +163%, and +400% for average-, elevated-, and high-risk pathways, respectively, relative to low-risk pathways. The average-risk group accounted for approximately 52% of total pathway emissions due to its prevalence. Conclusions: WISDOM-aligned risk-based screening may offer clinically safe screening intensity while reducing the environmental footprint of breast cancer screening pathways by approximately 30%, largely through decreased routine mammography volume and associated downstream diagnostic cascades. Incorporating environmental impact metrics into screening policy evaluations could strengthen value-based, equitable guideline modernization by jointly considering outcomes, costs, and environmental externalities.
The economic and clinical impact of lung cancer patient support programs (LC-PSP) using real-world (RW) clinical outcomes.
e23026 Background: Timely access to precision therapies is critical to improving lung cancer outcomes. Canada’s universal healthcare system supports access to essential oncology drugs, but complex and lengthy approval and funding processes often delay access to novel therapies. PSPs provide access to novel therapies in the pre-funding period. This study assesses the clinical and economic impact of LC-PSPs over the past decade. Methods: Clinical outcomes (PFS, OS, and treatment duration) for individuals receiving drugs via an LC-PSP were obtained from a provincial lung cancer database in Alberta, Canada. Clinical trial data, health-utility indices (HUI), cost-effectiveness data (ICER), unsubsidized drug costs from Canada’s Drug Agency (CDA), and approval and funding dates from Health Canada & Alberta Health Services informed estimates of person life years gained (PLYG) on LC-PSP drugs, the economic value of quality-adjusted life years (QALY) gained, total value of drugs provided, and the median interval between drug approval and funding in Alberta, respectively. PLGY and QALY were calculated as: 1) PLYG: The difference between observed and estimated PFS or OS. Estimates were calculated by multiplying the pivotal clinical trial hazard ratio by observed PFS or OS. 2)cQALY: PLGY multiplied by the drug-specific HUI to adjust for quality of life. 3) Economic value of QALY (in Canadian dollars): QALY multiplied by drug-specific ICER. Results: 146 patients received novel therapies via 14 different LC-PSPs between 2015 and 2025. 66% were female and median at age diagnosis was 60 years. 67% of LC-PSP drugs provided were targeted oral inhibitors for actionable alterations [ ALK (crizotinib, alectinib, lorlatinib) , EGFR (afatinib, dacomitinib, osimertinib) , RET (selpercatinib) , and ROS1 (crizotinib)], 17% immune checkpoint inhibitors (neoadjuvant nivolumab), 12% other monoclonal antibody (amivantamab), and 3% T-cell engagers (tarlatamab). Median delay between HC approval and funding was 843 days (range: 260 – 1338). Median PLYG (months) for PFS and OS were 9.1 (QALY value: $119,730.60 CAD) and 14.5 (QALY value: $185,917.87 CAD), respectively. Total value of drugs provided through these 14 LC-PSP was $2.4 million CAD. Conclusions: This RW study shows that LC-PSPs provide substantial financial value and critically bridge the > 2-yr gap between HC approval and provincial funding for novel lung cancer therapies. Our findings reflect meaningful patient benefit through inferred survival gains and improved quality of life from extended disease control and underscore the need to reform regulatory processes to ensure equitable access to effective new therapies. Opportunities, including navigation support, to strengthen interim access through efficient identification of eligible patients and streamlining PSP applications will further enhance access to unfunded yet clinically meaningful therapies.
Global trends in incidence and mortality of liver cancer by etiology and sociodemographic index among adolescents and young adults, 1990–2023.
e22583 Background: Liver cancer in adolescents and young adults (AYA) is an emerging global challenge with evolving etiologic drivers and persistent disparities in prevention and treatment. Long-term, etiology-specific global data focused on AYAs remain limited. Using Global Burden of Disease (GBD) 2023 data, we assessed trends in liver cancer incidence and mortality by etiology and country-level sociodemographic index (SDI). Methods: We conducted a population-based observational analysis using GBD 2023 data. Age-standardized incidence (ASIR) and death rates (ASDR) for liver cancer among AYAs (15–39 years) were evaluated globally from 1990–2023, stratified by etiology (hepatitis B virus [HBV], hepatitis C virus [HCV], alcohol use, and nonalcoholic steatohepatitis [NASH]) and SDI. Percent change was calculated across predefined periods (1990–1999, 2000–2009, 2010–2019, and 2020–2023). Results: In 2023, an estimated 33,736 incident cases and 24,754 deaths from liver cancer occurred among AYAs globally. From 1990–2023, ASDR declined by 8.9% and ASIR by 3.8%, with a parallel reduction in disability-adjusted life-years (−5.5%). HBV remained the leading etiology yet demonstrated the largest long-term mortality decline (ASDR −18.3%), with pronounced reductions in high-middle SDI (−34.5%) and high SDI (−29.5%) regions. In contrast, mortality increased for NASH (+30.4% globally; +51.4% in middle SDI) and alcohol-related liver cancer (+35.9%). HBV-related mortality remained highest in low-SDI regions in 2023 (ASDR 0.777 per 100,000), while HCV mortality increased substantially in low-middle SDI regions (+45.9%), contrasting with continued declines in high-SDI settings (−16.6% to −18.7%). Mortality trends followed a biphasic pattern, with increases in 1990–1999 (ASDR +8.6%), declines in 2000–2009 (−17.9%) and 2010–2019 (−10.9%), and a concerning reversal in 2020–2023 (ASDR +17.5%; ASIR +17.6%) across etiologies. Conclusions: As the largest global analysis of AYA liver cancer, this study demonstrates a recent re-acceleration in incidence and mortality driven by metabolic, alcohol-related, and HCV etiologies, with widening SDI-based disparities. These findings highlight liver cancer as an emerging early-onset malignancy and underscore the need for AYA-focused prevention strategies addressing metabolic risk, alcohol use, and viral hepatitis, particularly in regions undergoing epidemiologic transition. Period-specific percent change in liver cancer mortality among adolescents and young adults by etiology, 1990–2023. Death Rate Change (%): 1990-1999 2000-2009 2010-2019 2020-2023 Liver cancer 8.6% -17.9% -10.9% 17.5% Liver cancer due to HBV 10.7% -20.8% -16.7% 16.1% Liver cancer due to alcohol 9.3% -5.1% 6.9% 19.3% Liver cancer due to HCV 1.6% -5.1% 4.9% 21.4% Liver cancer due to NASH 4.9% -7.0% 8.3% 22.2%
Safety and efficacy of ZN-A-1041, a highly blood-brain barrier (BBB)–permeable HER2 tyrosine kinase inhibitor (TKI), + trastuzumab deruxtecan (T-DXd) or pertuzumab-trastuzumab (PH) in HER2-positive metastatic breast cancer (HER2+ mBC): Phase Ic expansion results from the ZN-A-1041-101-US trial.
1055 Background: Brain metastases (BMs) are a common site of progression in HER2+ mBC due to limited BBB penetration of systemic therapies. ZN-A-1041 is an oral, selective HER2 TKI designed for high intact BBB permeability. We report ZN-A-1041-101-US (NCT05593094) Phase Ic expansion results of ZN-A-1041 + T-DXd in patients (pts) with HER2+ mBC refractory to prior treatments (txs), or + PH as maintenance therapy after first-line taxane + H ± P induction. Phase Ia and Ib (dose-escalation as single agent or in combination therapies) results have been reported (Anders ASCO 2023). Methods: The study enrolled pts with HER2+ mBC, with or without BMs (including leptomeningeal disease). Pts in Phase Ic received ZN-A-1041 800 mg twice daily (BID) + PH (Arm C), or were randomized to ZN-A-1041 800 mg or 600 mg BID, + T-DXd 5.4 mg/kg every 3 weeks (Arms A and B, respectively). Primary objectives: safety and tolerability. Secondary objectives included systemic objective response rate (ORR) and disease control rate (DCR) per Response Evaluation Criteria in Solid Tumours version 1.1. Results: As of July 31, 2025 (last pt in), enrollment in Arms A, B, and C was 24, 23, and 20 pts, respectively; median age was 57, 54, and 46 years; 50, 36, and 70% had de novo stage IV disease. Baseline central nervous system (CNS) metastases were present in 58, 59, and 16% of pts. Median prior lines of therapy for metastatic disease was 1, 1, and 0. Median ZN-A-1041 tx duration was 23.0, 24.6, and 42.9 weeks. The most frequent all-grade tx-emergent adverse events (TEAEs) across Arms A, B, and C, respectively, were nausea (83, 96, and 47%), diarrhea (62, 77, and 68%), and vomiting (46, 64, and 47%); diarrhea (17, 9, and 5%) was the most frequent Grade ≥3 TEAE. Preliminary systemic efficacy is summarized in the Table. Intracranial lesion shrinkage was observed in pts with BMs across all tx arms. Conclusions: ZN-A-1041 showed manageable safety profiles and promising clinical activity when combined with standard anti-HER2 therapies in pts with HER2+ mBC, both with or without CNS metastases. High disease control in pts pretreated with T-DXd and notable continued responses in the PH maintenance setting support further clinical evaluation of these combinations. Clinical trial information: NCT05593094 . Arm n ORR, % (95% CI) Complete response, % of pts DCR, % (95% CI) A: ZN-A-1041 800mg + T-DXd 20 65.0 (40.8, 84.6) 10.0 95.0 (75.1, 99.9) B: ZN-A-1041 600mg + T-DXd 21 76.2 (52.8, 91.8) 9.5 90.5 (69.6, 98.8) C: ZN-A-1041 800mg + PH 13* 30.8 (9.1, 61.4) 5.6 100 (75.3, 100.0) *Efficacy reported for 13 pts with measurable disease receiving maintenance therapy with ZN-A-1041 + PH after taxane + H ± P induction. CI, confidence interval.
Glucagon-like peptide-1 receptor agonist use in lung cancer patients receiving immune checkpoint inhibitors: A real-world study.
8598 Background: Immune checkpoint inhibitors (ICI) have become a cornerstone of treatment for lung cancer. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have been associated with improved outcomes in cancer patients in prior studies; however, their impact on outcomes among lung cancer patients receiving immunotherapy remains limited. Methods: We conducted a retrospective cohort study using the TriNetX real-world data platform. Adult patients with lung cancer treated with ICIs, including PD-1, PD-L1, or CTLA-4 inhibitors, were included. Patients were stratified based on exposure to GLP-1 RA. Propensity score matching (1:1) was performed to balance baseline demographics and comorbidities, including type 2 diabetes mellitus and body mass index. Primary outcomes included all-cause mortality, intensive care unit (ICU) admission, and hospitalization. Secondary outcomes included immune-related pneumonitis, colitis/enteritis, cachexia, and major adverse cardiovascular events (MACE). Results: After matching, 2,013 patients were included in each group, with a median follow-up of 372 days in the GLP-1 RA group and 383 days in the non-GLP-1 RA group. Mean age was 66.8 and 67.2 years, respectively, and approximately 50% of patients were male. Most patients were White (77.2% vs 71.8%), followed by Black (14.1% vs 14.0%) and Asian (2.1% vs 1.8%). GLP-1 RA use was associated with a significantly lower all-cause mortality rate compared with non-use (35.7% vs. 53.4%; p < 0.0001), with a hazard ratio of 0.65 (95% CI, 0.59–0.71). Significant reductions were also observed in ICU admissions (22.8% vs 29.0%; p = 0.0001), hospitalizations (64.1% vs 71.8%; p = 0.0001), pneumonitis (5.2% vs 6.8%; p = 0.0457), and MACE (19.9% vs 25.3%; p = 0.0026). No significant differences were observed in colitis/enteritis (9.3% vs 9.4%; p = 0.9704) or cachexia (8.0% vs 9.8%; p = 0.0650). In a subgroup analysis of lung cancer patients not receiving ICI, GLP-1 RA use was similarly associated with lower mortality, ICU admission, hospitalization, and MACE, without differences in immune-related toxicities. Conclusions: GLP-1 RA use among lung cancer patients was associated with improved survival, reduced healthcare utilization, and fewer selected adverse events in patients receiving ICI therapy. These associations likely reflect established metabolic and cardiovascular benefits of GLP-1 RA and may also involve antitumor mechanisms suggested in prior studies. Residual confounding related to healthcare access and socioeconomic factors cannot be fully excluded and should be considered when interpreting these findings. Prospective studies are warranted to validate these observations and clarify underlying biological mechanisms.
K-ACCELERATE: A multi-center prospective trial to evaluate the utility of a ctDNA-based assay for accelerating multi-cancer diagnosis among high-risk symptomatic participants.
10555 Background: In low- and middle-income countries, most cancers are diagnosed after symptom onset, where non-specific symptoms complicate referral and delay diagnosis. We previously developed SPOT-MAS, a multi-cancer early detection test integrating epigenetic, genetic, and fragmentomic features of circulating tumor DNA (ctDNA). Here, we report results from K-ACCELERATE (NCT06391749), a prospective multi-center study evaluating SPOT-MAS as a diagnostic aid in symptomatic individuals. Methods: Adults (≥18 years) with symptoms suggestive of colorectal, gastric, breast, liver, or lung cancer were recruited across 13 hospitals in Vietnam from July 2024. All participants underwent SPOT-MAS testing alongside standard-of-care diagnostics and were followed for up to 12 months. Primary endpoints included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and tissue-of-origin (TOO) accuracy, using imaging and/or biopsy as the reference standard, analyzed overall and by symptomatic pathway. Results: Of 972 eligible participants, 862 achieved diagnostic resolution and completed follow-up, including 130 cancer cases and 732 non-cancer cases. Overall sensitivity and specificity of SPOT-MAS were 65.4% (95% CI: 56.9–73.0) and 92.1% (95% CI: 89.9–93.8), respectively. Pathway-specific sensitivity was 58.7% for breast cancer, 62.1% for lung cancer, 64.3% for gastrointestinal cancers, 80.0% for liver cancer, and 100% for multiple-pathway presentations. Among confirmed cancer cases, ctDNA-based tissue-of-origin prediction achieved 82.4% accuracy. Incorporation of ctDNA testing into clinical triage increased PPV from 15.1% to 59.4%, representing a nearly four-fold improvement over symptom-based assessment, while maintaining a high NPV of 93.7%. Conclusions: This study provides clinical evidence supporting the feasibility of SPOT-MAS as a non-invasive adjunct diagnostic tool for individuals presenting with cancer-related symptoms in low-resource settings. These findings lay the foundation for future prospective interventional studies to evaluate the clinical impact of ctDNA-guided diagnostic pathways in high-risk symptomatic populations. Clinical trial information: NCT06391749 .
Examining the relationship between social support and inflammatory markers among patients with gynecologic cancer.
5626 Background: Social support has been associated with improved health outcomes. Little research on the association between social support and inflammatory markers has been done among patients with gynecological cancer. The aim of this study is to examine whether there is an association between social support and inflammatory markers in patients currently receiving treatment for gynecologic cancer. Methods: These data were collected from a prospective cohort study designed to investigate the potential associations between cardiometabolic health and cancer treatment among women with gynecological cancer. As a secondary outcome, social support was assessed using the social provision scale (SPS), with higher scores indicating greater perceived social support. Fasting venous blood was collected for inflammatory marker analysis (Interleukin-6: IL-6, Tumor Necrosis Factor-alpha: TNF-α, C-reactive protein: CRP). Descriptive statistics included means for continuous variables and frequencies for categorical variables. Correlation analyses were used to assess the degree of relationship between variables. Partial correlations were used to adjust for potential confounders. Study protocol was approved by IRB at the University of Tennessee Graduate School of Medicine. Results: A total of 43 women with gynecological cancer (primary site: uterus = 16, ovary = 24, cervix = 1, vulva/vagina = 2) completed study measures. The mean age was 63.5 years (SD=10.5). Regarding participants characteristics, 91% identified as White, 99% identified as non-Hispanic, 35% reported being high school graduate or GED, 45% were unemployed, 66% were married, 51.2% had newly diagnosed cancer, 49% had metastatic disease, 74% received chemotherapy only, 14% immunotherapy, 12% combination of both immunotherapy and chemotherapy. SPS scores were negatively correlated with IL-6 (ρ = –0.362, p = 0.038), indicating that higher perceived social support was associated with lower IL-6 levels. SPS scores were not significantly correlated with CRP (ρ = –0.09, p = 0.62) and TNF-α (ρ = –0.295, p = 0.096). After adjusting for BMI, SPS score showed significant associations with IL-6 (ρ = –0.406, p = 0.021) and TNF-α (ρ = –0.360, p = 0.043), but its relationship with CRP (ρ = –0.029, p = 0.874) remained non-significant. Conclusions: The results of this study suggest a negative association between social support and inflammation among patients with gynecologic cancer. Future research may consider exploring the pathways to explain this relationship and identify possible interventions focused on social support to decrease inflammatory processes among patients with gynecologic cancer.
A randomized, double-blind, two-arm, single-dose, parallel study to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Bmab 1000 and originator denosumab in healthy male participants.
e15001 Background: Bmab 1000 has been approved as a biosimilar to originator denosumab (DENO). This study compared the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of Bmab 1000 and DENO in healthy male participants. Methods: This randomized, double–blind, two–arm, single–dose, Phase 1, parallel study randomized Indian participants 1:1 to a single subcutaneous dose of 35 mg (0.5 mL) Bmab 100 (n=109) or DENO (n=111). A healthy, male–only population ensured a homogenous and sensitive population to detect any product differences. The study included a 3–day in–house stay and 36–week follow–up post dosing. Blood samples were collected at predefined time points for PK, PD, immunogenicity, and safety assessments. Calcium (≥1000 mg/day) and Vitamin D (≥400 IU/day, <1000 IU/day) supplementation was provided throughout to minimize the risk of hypocalcemia. The primary PK parameters were maximum observed serum denosumab concentration (C max ), area under the serum concentration–time curve from time zero to the last quantifiable concentration (AUC 0–t ), and area under the curve extrapolated to infinity (AUC 0–inf ). Bioequivalence was concluded if the 90% confidence intervals for the test/reference geometric least squares mean ratios of the primary PK parameters fell within the predefined acceptance range of 80.00–125.00%. PD and safety were analyzed descriptively. Results: Overall, 220 participants, mean age 40 years, were randomized in the study, of whom 218 received treatment (Bmab 1000, n=107; DENO, n=111). Following treatment, the PK profiles of Bmab 1000 (n=104) and DENO (n=108) were found to be comparable and met bioequivalence (Table). Assessment of the secondary PK endpoints demonstrated similarity between the groups. PD assessments (based on serum C–terminal telopeptide of Type 1 collagen) and immunogenicity evaluations (incidence and titers of anti–drug antibodies) were comparable between treatments. The safety profile of Bmab 1000 was similar to that of DENO. A single fatal event attributed to gastrointestinal symptoms, unrelated to the drug, was reported post dosing with DENO. Conclusions: This study demonstrated PK bioequivalence and comparable PD, safety, and immunogenicity between Bmab 1000 and DENO in healthy male participants. Clinical trial information: CTRI/2024/02/063265. Statistical results of the denosumab primary pharmacokinetics parameters. PK Parameter Geometric Least Squares Means Ratio (Bmab 1000/DENO) 90% Confidence Intervals C max (ng/mL) 105.77 99.30, 112.66 AUC 0–t (ng/mL.h) 106.65 99.51, 114.29 AUC 0–inf (ng/mL.h) 106.71 99.60, 114.32
Natural language processing–assisted chart review to assess documented cannabis use in electronic medical records (EMR) of adults undergoing cancer infusion therapy.
11125 Background: Patients’ consumption of cannabis for symptom management is well-documented, yet prevalence of cannabis use, and its documentation among patients undergoing active cancer treatment is understudied. Our goal was to assess the prevalence of documented cannabis use in the EMR of patients undergoing infusion cancer therapy. Methods: We conducted a cross-sectional analysis of adult members of Kaiser Permanente Southern California undergoing infusion therapy between February 16 to 28, 2025. Natural language processing (NLP) of search terms indicative of cannabis use was used to identify any EMR documentation of such use in unstructured clinical notes in the past year. Each matched query included 15-20 words before and after the keyword and was manually reviewed for clinical context and confirm cannabis use. Results: We identified N = 690 cancer survivors undergoing infusion therapy during the two-week period. Of these, N = 354 (51%) had a cannabis notation in their EMR after applying the NLP program. Half were female. Altogether 1,010 snippets from N = 354 patients were output into a spreadsheet for manual review; each snippet required about 30 seconds to determine cannabis use status. Of the N = 354 patients, overall prevalence of cannabis use was 29% (N = 101). The highest prevalence was in patients undergoing first line palliative treatment (38%); followed by palliative after first line (25%); adjuvant (16%); then curative first line therapy (13%). Cannabis use was lower in among those undergoing curative after first line therapy (6%) and neoadjuvant therapy (3%). Highest cannabis use was observed in those with cancer of the breast (15%); lung (14%); prostate (10%); colorectal (10%) and gynecologic (8%). Regarding demographics, odds of cannabis use was greater in males (OR = 1.34, 95% CI: 0.82-2.21) vs. females (ref). Compared with Asians (ref), odds of cannabis use was about two-fold greater in Hispanic (OR = 1.95, 95% CI: 0.78-5.35), Black (OR = 2.47, 95% CI: 0.80-7.87), and White (OR = 2.30, 95% CI: 0.95-6.15) patients. Odds of cannabis use was 24% greater in younger individuals ( < 50 years, OR = 1.76, 95% CI: 0.84-3.61), but all confidence intervals crossed the null. Conclusions: NLP-assisted manual review of chart notes is a time-efficient method to collect information on unstructured data. This methodology determined prevalence of cannabis use in patients undergoing cancer infusion therapy is 29%. Cannabis use was greater among patients being treated in palliative settings compared to adjuvant/curative settings. A limitation of this study is that cannabis use may be underestimated because we assume that not all discussions were recorded in the EMR. Information garnered from this cross-sectional data exploration will be used to plan a prospective study of cancer survivors to examine the risks and benefits of cannabis use.
An integrated population pharmacokinetic/pharmacodynamic (popPK/PD) model to select the linvoseltamab (LINVO) dosing regimen in patients with high-risk smoldering multiple myeloma (HR-SMM).
7525 Background: LINVO is a BCMA×CD3 bispecific antibody approved for triple-class exposed relapsed/refractory (RR) multiple myeloma (MM) after ≥3 therapies (EU) or ≥4 prior lines of therapy (USA). LINVO 200 mg was approved based on the deep and durable responses and manageable safety profile observed in the LINKER-MM1 study (objective response rate [ORR] 71%; NCT03761108). LINVO 200 mg demonstrated promising efficacy and a generally manageable safety profile as an early intervention in HR-SMM (ORR 100%; Phase [Ph] 2 LINKER-SMM1 NCT05955508; IMS 2025 OA-68) and as frontline therapy in newly diagnosed (ND) MM (ORR 86%; Ph 1/2 LINKER-MM4 NCT05828511; ASH 2025 #697). We present results from a semi-mechanistic popPK/PD model of LINVO integrating data from pts with RRMM, NDMM, and HR-SMM, to support full dose selection for a Ph 3 HR-SMM study. Methods: A popPK/PD model was developed from LINKER-MM1 RRMM data to predict LINVO concentration (conc) and disease burden dynamics (soluble BCMA, total [involved + uninvolved] free light chain [FLC] conc). Free LINVO conc was a strong predictor of ORR and progression-free survival in the LINKER-MM1 model. The model was updated with data from LINVO administration in pts with NDMM and HR-SMM. Based on baseline disease characteristics in pts with HR-SMM, the model was used to predict free and total LINVO conc for regimens with full doses of 50, 100, and 200 mg in a clinical trial simulation setting. The model assumed that T-cell–mediated tumor killing was dependent on free LINVO forming the T-cell + drug + MM cell complex. The variability in observed response rates across studies was presumed to arise due to differences in disease burden, MM plasma cell proliferation, and T-cell fitness, with the killing rate expected to be more similar between HR-SMM and NDMM than between HR-SMM and RRMM. Results: The dose regimen chosen for evaluation in a Ph 3 HR-SMM study comprised a 200 mg dose given weekly in cycle (C) 1 with the frequency decreasing to every 2 weeks after C1, every 4 weeks after C6, and every 8 weeks after C13. Following initial weekly dosing in this regimen, the free LINVO conc predicted in HR-SMM matched the free LINVO conc predicted in the higher efficacy arm of LINKER-MM4 and the higher efficacy arm in Ph 2 of LINKER-MM1. The model predicted that the 200 mg dose regimen would achieve deep responses (measured by substantial reduction in FLC conc) as rapidly as Week 8, and continue through Week 30, despite the reduced dosing frequency. Conclusions: The totality of evidence, including efficacy and safety data in pts with SMM, dose-ranging data (PK/PD, safety, and efficacy) in pts with NDMM and RRMM, and exploratory analyses integrating exposure and response markers across studies, supports selection of the less intensive LINVO 200 mg dose regimen (compared with NDMM and RRMM) in the Ph 3 HR-SMM study. Clinical trial information: NCT03761108 ; NCT05828511 ; NCT05955508 .
An NCDB analysis on the demographic, treatment, and survival of seromucinous carcinoma.
e17538 Background: Seromucinous carcinoma (SMC) is a rare subtype of ovarian cancer composed predominantly of serous and endocervical-type mucinous epithelium. Fewer than 40 cases have been reported in the literature, with no stage IV cases to date. Documented cases of ovarian SMC showed a 5-year survival rate of less than 60%. Given the rarity of SMC, an investigation of socioeconomic and demographic factors using the National Cancer Database (NCDB) may provide an important perspective on its epidemiology. Methods: Data from the NCDB, between 2018 - 2020, was used for a retrospective cohort analysis of 247 patients with a histologically confirmed diagnosis of SMC identified using the ICD-O-3 code 8474. Demographic characteristics such as age, sex, race, Hispanic status, educational attainment, and Charleson-Deyo score were assessed using descriptive statistics. Incidence trends were interpreted via regression analysis. Results: 247 patients were identified in the database with a confirmed diagnosis of SMC, with a strong increasing incidence of patients diagnosed per year (R^2 = 0.860). Most individuals were non-Hispanic and White (83.0%). All patients were female (100.0%) with the mean age at diagnosis being 55.5 years old (SD = 15.4). The largest portion of patients fell into the lowest income quartile quartile of adults without a high school degree (27.5%). Over half of patients were diagnosed at stage I (54.3%) with the ovary as the primary site (98.0%). Most individuals had Charlson-Deyo co-morbidity scores of 0 (81.4%). Surgical resection of the primary site was performed in 99.2% of patients with negative margins being achieved in 60.7% of cases. The mean tumor size was 122.9 mm (SD = 80.7). The majority of patients did not receive palliative care (99.6%). The percent of patients that received chemotherapy, radiation, hormone therapy, and immunotherapy is 45.7%, 0.8%, 6.5%, and 1.6% respectively. The 30-day mortality rate was 0.8% with a 90-day mortality rate of 1.6%. The 2-year survival rate was 92.9% (SE = 0.02) with the mean survival at 42.9 months (SD = 0.91). Conclusions: This study represents the first NCDB analysis of SMC. Our results indicate that most cases of SMC were diagnosed at an early stage in majority non-Hispanic White female patients that were in their middle adulthood, with prior studies demonstrating a wider age range. Our results also exhibit SMC associated with a larger tumor size compared to other cancer types. These findings highlight the need for further investigation into SMC to better understand the impact of demographic and socioeconomic factors on the diagnosis, treatment, and overall survival of patients.
Enhanced recovery after surgery (ERAS) pathways in gynecologic oncology: A systematic review and meta-regression of perioperative domains.
e17537 Background: Enhanced Recovery After Surgery (ERAS) pathways are multimodal perioperative care programs designed to reduce surgical stress and accelerate postoperative recovery. While ERAS implementation in gynecologic oncology (GynOnc) has been associated with improved outcomes, domain-specific effects are unclear, and limited data exists on its impact in marginalized populations of social risk. Methods: We conducted a systematic review and meta-analysis of ERAS pathways versus usual care in adults undergoing GynOnc surgery. Eligible studies included randomized controlled trials (RCTs) and nonrandomized studies (NRS) reporting perioperative outcomes. ERAS exposure was defined as multi-stage, evidence-based domains per ACOG and ERAS Society guidelines. Primary outcomes were length of stay (LOS), postoperative complications (overall and Clavien-Dindo ≥III), 30-day readmission, reoperation, and mortality. Random-effects meta-analyses were conducted, with meta-regression to display the impact of different ERAS domains on primary outcomes. Risk of bias and all stages were completed by individual reviewers. The protocol is registered on OSF. Results: Inclusion criteria were met in 46 studies, with 31 studies providing data for meta-analysis. There were 5823 ERAS patients (EG) vs. 5119 controls (CG). Weighted mean age was 58.58 in EG and 58.19 in CG. Mean difference in hospital LOS was 2.21 [95%CI 1.28-3.14; i2=97%] days shorter in RCTs and 1.2 [0.88-1.43; i2=98%] in NRS compared to usual care. Complications were reduced by 40% [RR 0.60, (0.41-0.87); i2=49%] in RCTs and 21% [RR 0.79, (0.69-0.90); i2=73%] in NRS, compared to usual care. Multivariable meta-regression in RCTs showed early diet prolonged LOS by 3.63 days (34% of between-study variability), while 8 other domains independently shortened LOS by up to 1.62 days. There was no dose-response relationship between number of ERAS domains and LOS. Conclusions: ERAS displayed significant improvements in patient outcomes and is associated with reduced LOS regardless of implementation intensity. This supports framing ERAS as a threshold intervention rather than a linear “more is better” exposure. Protocol harmonization via structured ERAS protocols may optimize the perioperative care of GynOnc patients. Further understanding of the interaction of domains in such analysis is warranted. Consistent reporting methodology in ERAS studies is integral to deciphering which domains hold priority, while limited equity data is available to assess if ERAS implementation holds similar weight in different patient groups.