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Radiogenomic biomarkers for identifying surgery-sparing candidates in locally advanced gastric or gastro-esophageal junction cancer treated with perioperative immunochemotherapy: A discovery and validation study.

4058 Background: Perioperative immunochemotherapy has markedly increased pathologic complete remission (pCR) rates in patients with locally advanced gastric cancer or gastroesophageal junction cancer (LAGC/GEJC), raising the possibility of surgery-sparing strategies in selected patients. However, reliable non-invasive tools to identify pCR preoperatively are lacking. This study aimed to develop and validate a radiogenomic model integrating CT radiomics and peripheral blood single nucleotide polymorphism (SNP) data to predict pCR. Methods: This retrospective multicenter study included 642 patients with LAGC/GEJC from 14 institutions who received perioperative immunochemotherapy. Patients were assigned to a primary cohort (n = 442; training n = 309, internal validation n = 133) and an external validation cohort (n = 200). Radiomic features were extracted from preoperative CT images, and SNPs were genotyped from peripheral blood. Feature selection was performed using LASSO, generating radiomic (Rad-score) and genomic (Gen-score) signatures. A combined radiogenomic model incorporating Rad-score, Gen-score, and clinical variables was developed using multivariable logistic regression. Model performance was evaluated using AUC and decision curve analysis (DCA). Results: Fourteen radiomic features and eight SNPs were selected. The radiogenomic model consistently outperformed single-modality models across cohorts. In the training set, the combined model achieved an AUC of 0.915 (95% CI 0.880–0.950), exceeding Rad-score (AUC 0.832) and Gen-score (AUC 0.798; both P < 0.001). In the internal validation set, the AUC was 0.882 (95% CI 0.825–0.939), and in the external validation set, 0.852 (95% CI 0.795–0.909), remaining superior to either modality alone. DCA demonstrated greater net clinical benefit of the combined model. At the optimal cutoff, 91.5% of true pCR cases were correctly identified in the validation cohort. Conclusions: A radiogenomic model integrating CT radiomics and peripheral blood SNP signatures enables accurate, non-invasive prediction of pCR in LAGC/GEJC patients undergoing perioperative immunochemotherapy and may support identification of candidates for surgery-sparing management.

A meta-analysis on outcomes of zanidatamab plus chemotherapy in patients with advanced HER2-gastroesophageal adenocarcinoma.

e16076 Background: Zanidatamab is a novel HER2-targeted antibody that binds to two non-overlapping extracellular domains of the HER2 receptor (EC2 and EC4). Early-phase trials have shown clinical benefit of first-line zanidatamab in patients with advanced HER2-positive gastroesophageal adenocarcinoma (GEA). We performed a meta-analysis to evaluate the efficacy and safety of zanidatamab in this patient population. Methods: We searched PubMed, Embase, Cochrane, ASCO, and ESMO databases for studies examining zanidatamab as first-line treatment in patients with HER2-positive advanced GEA. Outcomes of interest included progression-free survival (PFS); objective response rate (ORR); disease control rate (DCR); duration of response (DOR); and incidence of adverse events (AEs). Analyses were presented as median or proportions in percentages with 95% confidence intervals (CIs). Random-effect models were used for analysis. Results: Three clinical trials (HERIZON-GEA-01, Elimova et al [2025], Lee et al [2025]) involving 685 patients with advanced HER2-positive GEA treated with zanidatamab plus chemotherapy and/or anti-PD1 were included. These comprised: a phase 2 single-arm trial (Elimova et al) of zanidatamab plus chemotherapy (capecitabine/oxaliplatin, fluorouracil/cisplatin, or mFOLFOX6) in 46 patients (non-randomized); a phase 1b/2 single-arm trial (Lee et al) of zanidatamab plus tislelizumab plus capecitabine/oxaliplatin in 33 patients (cohorts A/B with different dosing, non-randomized); and the phase 3 HERIZON-GEA-01 trial, randomizing patients to zanidatamab plus chemotherapy plus tislelizumab (cohort B, n = 302), zanidatamab plus chemotherapy plus placebo (cohort C, n = 304), or trastuzumab plus chemotherapy plus placebo (not in meta-analysis). Overall, 70% (95% CI, 67%-74%) achieved an ORR, and 96% (95% CI, 78%-100%) a DCR. Median PFS was 12.6 months (95% CI, 10.9-14.7), and median DOR 17.1 months (95% CI, 13.1-22.4). AEs led to dose reductions from treatment-related diarrhea in 16% (95% CI, 1%-75%). Treatment discontinuation rate was 20% (95% CI, 3%-44%): 6% (95% CI, 1%-15%) due to zanidatamab. Serious treatment-emergent AEs occurred in 66% (95% CI, 50%-81%). Grade ≥3 TRAEs affected 65% (95% CI, 58%-71%), with grade ≥3 diarrhea in 26% (95% CI, 19%-34%) and nausea in 5% (95% CI, 2%-13%). Other important AEs: immune-mediated (25%), left ventricular dysfunction (6%), non-infectious pulmonary toxicity (4%). Conclusions: Zanidatamab shows meaningful activity as first-line treatment for advanced HER2-positive GEA, but with notable toxicity, mainly diarrhea. Future randomized studies will refine its profile. Main outcomes of this meta-analysis. Pooled proportion/median (95% CI) ORR 70% (67-74%) DCR 96% (78-100%) mPFS 12.6 months (10.9-14.7) mDOR 17.1 months (13.1-22.4) All-grade diarrhea 89% (75-98%) High-grade diarrhea 26% (19-34%)

Delayed time to treatment initiation among patients with HPV-associated oropharyngeal squamous cell carcinoma, 2011–2024.

e18091 Background: Delays in time to treatment initiation (TTI) has been shown to have a negative impact on cancer outcomes. We evaluated factors associated with delayed TTI among patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), a population with generally favorable outcomes with appropriate and timely treatment. Methods: Study data was derived from the Hutchinson Institute for Cancer Outcomes Research (HICOR) data repository, which links Western Washington (WA) SEER records, WA State Cancer Registry, and insurance claims data from the major payers in WA state (Regence, Premera, Medicare, Medicaid). We identified patients diagnosed with OPSCC between 2011 and 2024 who were positive for p16 or high-risk HPV by ISH. Eligible patients were adults 18 years and older, with primary cancer site involving the oropharynx, and continuous insurance enrollment from diagnosis through 6 months after diagnosis or death. Patients with tumors outside the oropharynx based on ICD 10 codes and those with HPV negative disease were excluded. TTI, defined as days elapsed between diagnosis and date of first treatment (radiation, chemotherapy, or surgery), was determined for all patients who received treatment; patients who had TTI > 60 days were considered to have delayed TTI. Descriptive statistics were used to characterize the study population. A multivariable logistic regression was used to identify factors associated with delayed TTI (>60 days). Results: Among HPV-positive patients (n=1019), the majority were male (87.3%), White (90.3%), aged 65 years and older (53.6%), on Medicare coverage (40.9%), with the tonsils as the most common primary tumor site (46%). Overall, 20.9% of patients with HPV positive OPSCC experienced delayed TTI. Among patients with delayed TTI, about 34.3% were Medicaid enrollees compared with commercial (17.7%), Medicare (20.1%), and those with multiple payers (17.9%) (p<0.001). Despite a disproportionately large White population, delayed TTI was higher among other races (31.2%) compared to White patients (19.9%) (p=0.011). In the multivariable model, Medicaid coverage remained independently associated with delayed TTI compared to patients on commercial insurance (adjusted OR 2.47, 95% CI 1.52–4.00, p<0.001). Other covariates including sex, age, cancer stage, area deprivation index, and rural/urban residence were not statistically significant. Conclusions: In this HPV-associated OPSCC cohort (2011–2024), approximately 1 in 5 patients experienced TTI >60 days. Insurance type—particularly Medicaid coverage—was the dominant predictor of delayed TTI after adjustment, suggesting persistent access barriers. This disparity in TTI uncovered in our study – impacting Medicaid patients – presents a unique opportunity for targeted interventions to improve care quality and outcomes among HPV OPSCC patients.

Hidden advanced physiology in non-metastatic gastrointestinal cancer: Malnutrition/cachexia and in-patient failure-to-rescue.

11102 Background: Cancer stage is often used as a proxy for inpatient risk, yet physiologic reserve may better determine outcomes. It was hypothesized that among gastrointestinal (GI) cancer hospitalizations without coded metastasis, malnutrition/cachexia identifies a vulnerable subgroup with complication burden, ICU escalation, and post-complication mortality approaching that of metastatic disease. Methods: A survey-weighted analysis of the National Inpatient Sample (NIS), 2016–2023, was conducted. Adult hospitalizations with any GI malignancy (ICD-10-CM C15–C20, C22–C25) were included; encounters with palliative care coding (Z51.5) were excluded. Metastatic disease was defined by C77–C79. Vulnerability was defined as malnutrition/cachexia (E43, E44, E46, R64). Major complications included sepsis, bleeding/transfusion, venous thromboembolism, acute kidney injury (AKI), bowel injury/peritonitis, and respiratory failure. ICU escalation proxies included mechanical ventilation and/or shock. Outcomes were compared across three groups: non-metastatic/no vulnerability, non-metastatic/vulnerable, and metastatic. Failure-to-rescue was defined among non-metastatic surgical hospitalizations as death following ≥1 major complication. Results: The cohort included 748,734 weighted hospitalizations; 39.6% had coded metastasis. Among non-metastatic admissions, vulnerability prevalence increased from 15.6% in 2016 to 21.9% in 2023. In-hospital mortality in the non-metastatic/vulnerable group (4.14% [95% CI, 4.00–4.29]) approximated metastatic mortality (3.96%) and exceeded non-metastatic/no vulnerability mortality (1.86% [95% CI, 1.81–1.91]). Compared with non-metastatic/no vulnerability, vulnerable admissions demonstrated higher ICU escalation (7.75% [95% CI, 7.56–7.94] vs 3.54%), AKI (27.30% [95% CI, 26.98–27.62] vs 17.25%), and any major complication (59.31% [95% CI, 58.95–59.67] vs 42.93%). Resource utilization was higher in the vulnerable group (LOS 9.33 vs 5.49 days; cost $33,156 vs $22,879). Among non-metastatic admissions with complications, mortality was higher with vulnerability (6.46% [95% CI, 6.24–6.69] vs 3.88%). In the non-metastatic surgical subcohort, failure-to-rescue mortality was 5.90% (95% CI, 5.59–6.22) with vulnerability versus 2.65%. Conclusions: Among U.S. GI cancer hospitalizations without coded metastasis, malnutrition/cachexia identifies a high-risk inpatient phenotype with complication burden, ICU escalation, and post-complication mortality closely resembling metastatic disease. These findings suggest physiologic vulnerability, rather than stage alone, drives inpatient risk and failure-to-rescue, supporting targeted inpatient risk stratification and earlier supportive interventions.

Comparison of immediate and delayed autologous breast reconstruction methods: A retrospective cohort study.

e12739 Background: Breast reconstruction using autologous flaps is currently the gold standard in breast reconstructive plastic surgery. Anterior abdominal wall flaps yield the most natural aesthetic result due to the similar textures of the tissues of the anterior abdominal wall and breast. When choosing this type of breast reconstruction, one should take into account a number of factors, such as age, body mass index, comorbidities, the anatomical features of blood supply to the donor and recipient zones, a history of operations on the anterior abdominal wall and cicatricial deformity. The number of postoperative complications is larger in patients having risk factors. Studies aimed at reducing the incidence of complications from autologous breast reconstruction are now in progress. A retrospective study was conducted to assess the impact of complex treatment during autologous breast reconstruction using anterior abdominal wall flaps in patients with breast cancer. Methods: The study included 116 patients with stage 0-IIIC breast cancer with immediate or delayed autologous breast reconstruction (Group I [64 patients] underwent immediate and delayed breast reconstruction using a DIEP flap and Group II [52 patients] underwent immediate and delayed breast reconstruction using a TRAM flap. Results: The frequency of weakness of the anterior abdominal wall in the TRAM-flap group was significantly higher (p < 0.001). Partial flap necrosis occurred more frequently in the delayed TRAM flap group (p < 0.001), total flap necrosis occurred more frequently in the immediate DIEP flap group (p = 0.025). Complications in patients with obesity was significantly higher (p = 0.002). The duration of delayed autologous breast reconstruction does not correlate with the incidence of complications in patients who received radiation therapy and chemotherapy before surgery (p = 0.84, p = 0.131 respectively). During radiation therapy after autologous breast reconstruction, flap liponecrosis occurred significantly more often (p = 0.021), and the incidence of flap liponecrosis was significantly higher in the group of immediate operations than in delayed ones (p = 0.004). According to the results of the Breast-Q questionnaire, the indicators of psychosocial, sexual well-being, satisfaction with the reconstructed breast were significantly higher in the group of DIEP flaps (p = 0.002, p = 0.004, p = 0.046, respectively). Also, in the DIEP-flap group, physical well-being (p < 0.05) and postoperative satisfaction with the abdomen (p = 0.003) were rated higher. Conclusions: The results of the clinical study demonstrate that autologous reconstruction is promising method, but requires careful planning of the operation and selection of candidates. This operation is a necessary step for a full-fledged psycho-emotional, functional and aesthetic rehabilitation of the patient after mastectomy.

Prognostic impact of MRD positivity at ultra-sensitive ctDNA levels using a WGS-based personalized assay: A pan-cancer analysis from MONSTAR-SCREEN-3.

3044 Background: While circulating tumor DNA (ctDNA) demonstrates promise as a molecular residual disease (MRD) biomarker, its clinical implementation has been primarily limited to tumors with favorable ctDNA shedding characteristics. The MONSTAR-SCREEN-3 evaluates a whole-genome sequencing (WGS)-based MRD assay to assess MRD positivity at ultra-sensitive level beyond conventional WES-based MRD, including traditionally low-shedding tumors. Methods: MONSTAR-SCREEN-3 is a prospective multicenter study targeting 1,100 patients with solid tumors undergoing curative-intent treatment. Personalized panels were constructed using Precise MRD (Myriad Genetics), incorporating up to 1,000 tumor-specific alterations identified through WGS of matched tumor tissue. Serial plasma samples were collected at baseline, post-neoadjuvant treatment (NAT) (when applicable), 1-month (1M) post-surgery, every 3 months in year 1, and every 6 months thereafter up to 2 years. Assay performance was evaluated across multiple cancer types for ctDNA detection and recurrence monitoring. Results: Between May 2024 and November 2025, 1,088 patients across over 20 cancer types were enrolled, including colorectal (n=250), breast (n=156), cervical (n=95), gastric (n=88), and pancreatic (n=69) cancers. Treatment strategies included upfront surgery (n=704), NAT (n=296), and definitive chemoradiotherapy (n=96). Median follow-up was 5.3 months (range, 0–18.1). Baseline ctDNA detection was achieved in 96.2% (684/711), with 16.4% at ultra-sensitive levels (tumor fraction <100 parts per million [ppm]). Post-operative MRD positivity was 26.4% (163/617) at 1M and 23.8% (120/504) at 3M, with 46.0% and 41.7% detected at ultra-sensitive levels, respectively. Among 91 patients who received NAT and underwent pathological assessment, post-NAT MRD status demonstrated a sensitivity of 74.3% (55/74) and a specificity of 100% (17/17) for predicting pathological complete response (P<0.01). Among patients with available survival data, post-1M MRD positivity was associated with significantly worse disease-free survival (DFS) compared with MRD negativity (HR, 16.9; 95% CI, 8.2–34.8; P < 0.001). Furthermore, post-1M MRD positivity at levels below 100 ppm was associated with significantly inferior DFS compared with MRD negativity (HR, 8.2; 95% CI, 3.4–19.4; P < 0.001), whereas post-1M MRD positivity at levels ≥100 ppm was associated with significantly worse DFS compared with MRD positivity below 100 ppm (HR, 3.4; 95% CI, 1.7–6.7; P < 0.001). Conclusions: The WGS-based MRD assay demonstrated high baseline detection sensitivity and robust ultra-sensitive detection across diverse cancer types. Our findings show that post-1M MRD positivity below 100 ppm at ultra-sensitive level is prognostic for recurrence risk. Updated molecular and clinical outcome data will be presented. Clinical trial information: UMIN000053975.

Stage-dependent metabolic reprogramming in treatment-naïve lung adenocarcinoma: From oxidative flexibility to glycolytic entrapment.

e20566 Background: Lung adenocarcinoma demonstrates metabolic reprogramming during progression, frequently shifting from mitochondrial oxidative phosphorylation (OXPHOS) toward aerobic glycolysis (Warburg phenotype). We evaluated stage-associated systemic metabolic, inflammatory, and oxidative stress signatures in treatment-naïve patients. Methods: In a prospective cohort, 150 patients with histologically confirmed lung adenocarcinoma were analyzed: stage IV (n = 75) versus early stage I–II (n = 75). Fasting plasma and 24-hour urine were collected. Glycolysis markers (glucose, lactate, pyruvate), OXPHOS-associated metabolites (β-hydroxybutyrate, acetoacetate, glutamine, alanine), cytokines (IL-6, IL-1β, TNF-α), oxidative stress–related markers (melatonin, dopamine), and LDH isoenzymes (LDH-1 to LDH-5) were assessed using enzymatic assays, HPLC/GC-MS, ELISA, and electrophoresis. Group comparisons used ANOVA; significance threshold p < 0.05. Results: Compared with stage I–II, stage IV disease showed significantly increased glycolysis markers (relative levels): glucose 160 vs 100, lactate 150 vs 80, and pyruvate 130 vs 70 (all p < 0.01). OXPHOS-associated metabolites were reduced: β-hydroxybutyrate 40 vs 100, acetoacetate 50 vs 95, glutamine 45 vs 90, and alanine 35 vs 85 (all p < 0.01). Pro-inflammatory cytokines were elevated in stage IV: IL-6 80 vs 30, IL-1β 70 vs 25, and TNF-α 65 vs 20 (all p < 0.01). LDH-5 increased (80 vs 25; p < 0.01), consistent with enhanced glycolytic flux. Oxidative stress–related markers decreased: melatonin 35 vs 90 and dopamine 40 vs 85 (both p < 0.01). Conclusions: Advanced (stage IV) lung adenocarcinoma is characterized by a systemic pattern consistent with “glycolytic entrapment,” accompanied by inflammatory cytokine elevation, LDH-5 upregulation, and depletion of OXPHOS-linked metabolites and antioxidant markers. These findings support stage-informed biomarker strategies and provide a rationale for therapeutically targeting the glycolysis–lactate axis and inflammatory pathways in advanced disease.

Real-world outcomes of systemic therapy sequencing after earlier-generation EGFR TKI failure in NSCLC with brain metastases.

2028 Background: Patients with EGFR-mutated non–small cell lung cancer (NSCLC) frequently develop BM, and CNS progression is a common mode of failure on earlier-generation EGFR tyrosine kinase inhibitors (TKIs). After TKI failure in the setting of BM, optimal next-line systemic therapy remains uncertain, particularly regarding the comparative effectiveness of targeted escalation, immunotherapy (IO)-based regimens, and chemotherapy. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. We identified EGFR-mutated NSCLC patients treated with first- or second-generation EGFR TKIs who subsequently developed metachronous BM and initiated next-line systemic therapy between 2015 and 2025. Patients with leptomeningeal disease prior to earlier-generation TKI exposure were excluded. Treatment strategies were categorized as targeted escalation with osimertinib, IO-based therapy (immune checkpoint inhibitor with or without chemotherapy), or chemotherapy alone. The index date was defined as initiation of next-line systemic therapy. Propensity score matching was performed for pairwise comparisons. The primary endpoint was overall survival (OS) at 180 days. Restricted mean survival time (RMST) through 181 days was evaluated as a sensitivity analysis. Baseline covariate balance after matching was assessed using standardized mean differences, with values <0.10 indicating adequate balance. Results: After propensity score matching with adequate baseline balance, osimertinib was associated with significantly lower 180-day mortality compared with chemotherapy (24.5% vs 33.2%; hazard ratio [HR] 0.69, 95% CI 0.47–1.00). Comparisons between osimertinib and IO-based therapy showed numerically lower 180-day mortality with osimertinib (26.0% vs 32.6%; HR 0.79, 95% CI 0.54–1.15), but this difference did not reach statistical significance. Similarly, IO-based therapy was not associated with a statistically significant survival advantage compared with chemotherapy alone (31.7% vs 37.5%; HR 0.78, 95% CI 0.58–1.06). RMST analyses for death over 181 days were directionally consistent with hazard ratio–based results, with modest, non-significant differences in mean survival time. Conclusions: In EGFR-mutated NSCLC patients with metachronous brain metastases after earlier-generation TKI failure, targeted escalation with osimertinib was associated with significantly lower 180-day mortality compared with chemotherapy. IO-based approaches demonstrated intermediate, directionally favorable but non-significant outcomes relative to both osimertinib and chemotherapy. These real-world findings support guideline recommendations prioritizing next-generation TKIs and help inform systemic treatment sequencing in a CNS-enriched population where prospective data remain limited.

Association of facility type and metastatic burden with survival in gastric adenocarcinoma: A National Cancer Database study.

11065 Background: While we know metastatic burden dictates survival in gastric adenocarcinoma (GA), how this intersects with where a patient receives care remains less clear. Academic centers (AC) often report better outcomes, but we haven't fully determined if this "academic advantage" holds true once you account for the sheer extent of disease at the time of diagnosis. We set out to test whether AC care offers a survival benefit that persists regardless of a patient's baseline metastatic burden. Methods: We retrospectively analyzed the National Cancer Database (2016–2023), identifying 102,869 patients with GA. We grouped patients by facility type (AC vs. community). We mapped metastatic burden at diagnosis across six specific sites: bone, brain, liver, lung, distant lymph nodes, and other. After comparing baseline characteristics, we estimated 3-year overall survival (OS) using Kaplan–Meier methods. Our primary tool was a multivariable Cox model, adjusting for age, Charlson–Deyo score, clinical stage, and metastatic burden to isolate the link between facility type and mortality. Results: Of the 102,869 patients, 58.4% (n = 60,064) were treated at ACs and 41.6% (n = 42,805) at community sites. Interestingly, community patients arrived with a higher burden of disease (33.8% vs. 30.4%; p < 0.001), and 11.7% of the total cohort had multi-site metastasis (≥2 sites). The liver was the most frequent site of spread, appearing more often in community settings (18.4% vs 15.4%; p < 0.001). Three-year OS was significantly higher at ACs (45.2% vs 35.8%; p < 0.001). After adjusting for site count, comorbidity, age, and stage, AC treatment remained independently associated with lower mortality (HR 0.81; 95% CI 0.80–0.83; p < 0.001). Notably, this academic survival advantage was not driven by any single metastatic site; the benefit persisted across all individual sites of involvement, including brain and lung, with no site showing a loss of AC advantage. Conclusions: Survival differed by treatment facility even after accounting for metastatic burden. Patients treated at academic centers had better outcomes across metastatic sites, including those with extensive disease. These findings point to differences in care delivery and access to specialized expertise. Expanding academic practices, such as multidisciplinary tumor boards and referral pathways, into community settings may help reduce these gaps.

National trends and disparities in esophageal cancer and respiratory failure mortality among adults aged ≥45 years in the United States, 1999–2024: A CDC WONDER analysis.

e16021 Background: Esophageal cancer (EC) remains highly lethal in the United States, with approximately 22,370 new cases in 2024. Respiratory failure (RF) frequently complicates advanced disease, and deaths involving both conditions have risen substantially since 1999, necessitating population-based mortality analysis. This study aimed to characterize national mortality trends involving EC and RF, with a focus on demographic, geographic, and urban–rural disparities. Methods: We conducted a retrospective analysis of U.S. deaths associated with EC (C15) and RF (J96) among adults aged ≥45 years using data from the Centers for Disease Control and Prevention WONDER database. Age-adjusted mortality rates (AAMRs) per 1 million were computed and stratified by year of death, sex, race, census region, and urbanization. Joinpoint regression estimated Average Annual Percent Changes (AAPC) with 95% confidence intervals (CI). Results: Between 1999 and 2024, 32,348 deaths were attributed to EC and RF. National AAMRs increased during this period from 8.2 to 13.7 (AAPC: 2.18*; 95% CI: 1.70 to 2.67). Males bore a higher mortality burden than females (AAPC: 2.23*; 95% CI: 1.7 to 2.7). Mortality was elevated in both examined age groups (45-64 and 64-85+), with the most significant impact observed among individuals aged 65-85+ years (AAPC: 2.52*; 95% CI: 2.02 to 3.02). Race-stratified analysis revealed non-Hispanic (NH) White individuals demonstrated the most pronounced increase across the study period (AAPC: 2.72*; 95% CI: 2.19 to 3.25). Geographically, the Midwestern census region showed the steepest rise in mortality, with rural counties nationwide exhibiting a similar increase(In Table). Conclusions: Mortality due to EC and RF has increased insidiously over the past two decades, while the literature on the combined effects of diseases remains limited. The burden is disproportionately higher among males, adults aged ≥65 years, and NH White individuals, particularly in Midwestern and rural regions. These disparities highlight a growing public health burden and emphasize the need for targeted prevention, early detection, optimized respiratory and oncologic care, and region-specific policies to mitigate inequities. Variable AAMR 1999 AAMR 2024 AAPC (95% CI) Overall 8.2 13.7 2.18*(1.70-2.67) Gender:FemaleMale 3.714 5.123.8 1.73*(0.89-2.56)2.23*(1.71-2.75) Census region:NortheastMidwestSouthWest 8.277.510.8 15.513.412.214.9 2.43 *(2.05-2.82)3.22 *(2.38-4.07)1.91*(1.06-2.77)1.30 (-0.16-2.80) Age:45-64years65-85+years 415.5 5.727.7 1.37(-0.01-2.78)2.52*(2.02-3.02) Race:HispanicNH WhiteNH Black 5.27.712.8 9.514.411.2 2.54*(1.76-3.33)2.72*(2.19-3.25)-0.41(-1.33-0.52) Urbanization: (1999-2020)MetroNon-Metro 1999 8.56.9 2020 11.313.8 1.34*(0.83-1.85)3.47*(2.25-4.71) *Indicates p<0.05.

Comparative effectiveness of antibody-drug conjugates and targeted therapies in acute myeloid leukemia: A network meta-analysis of 15,412 patients.

e18535 Background: Front-line AML treatment now includes antibody–drug conjugates and targeted therapies. However, relative effectiveness across fitness and molecular subgroups has not been systematically compared. We conducted a network meta-analysis to evaluate comparative outcomes among novel approaches in newly diagnosed AML. Methods: This Bayesian random effects NMA followed PRISMA 2020 and Cochrane guidelines. PubMed, Scopus, Embase and Cochrane were searched through January 2026 for randomized studies evaluating antibody–drug conjugates, FLT3 inhibitors, IDH inhibitors, BCL-2 inhibitors, and other targeted agents. OS and CR were analyzed for intensive-eligible and ineligible patients using log-hazard ratios and odds ratios with 95% credible intervals. Treatments were ranked using SUCRA. Results: Forty-five trials enrolling 15,412 patients were included. Among intensive-eligible patients, FLT3 inhibitor regimens and gemtuzumab ozogamicin ranked highest for OS (SUCRA 69–79%), with quizartinib plus chemotherapy showing most favorable estimate (HR 0.77, 95% CrI 0.58–1.01). In intensive-ineligible patients, ivosidenib plus azacitidine showed greatest OS benefit (HR 0.44, 95% CrI 0.20–0.99; SUCRA 92%), followed by venetoclax plus azacitidine (HR 0.62). Pairwise analyses confirmed OS improvement with FLT3 inhibitors, GO, and venetoclax combinations. No increase in 30-day mortality was observed. Conclusions: ADCs and targeted treatments enhance survival in newly diagnosed AML without raising early mortality. Treatment benefit varies by molecular profile and fitness, supporting individualized selection. Key OS results. Population Treatment HR (95% CrI) Intensive-eligible FLT3i+chemo 0.74 Intensive-eligible GO+chemo 0.86 Intensive-ineligible Ivo+aza 0.44 (0.20–0.99) Intensive-ineligible Ven+aza 0.62 (0.38–1.04) Maintenance FLT3i 0.53

Synergistic Cu mesh-CuO supported Ag nanoparticles for enhanced 2-nitrophenol reduction

Correction to “Photosynthetic Nanobacteria Drive Metabolic–Immune Synergy for Hypoxia‐Resistant Cancer Therapy”

SHR-A2102, a Nectin-4 targeted antibody-drug conjugate, combined with HRS-4642 in previously treated pancreatic ductal adenocarcinoma harboring KRAS G12D mutation.

4191 Background: Patients (pts) with previously treated advanced pancreatic ductal adenocarcinoma (PDAC) have limited options. The high prevalence of Nectin-4 expression (~71%) and KRAS G12D mutations in PDAC provides a rationale for dual targeting. Here we report results from a molecularly defined cohort in a phase 2 platform trial evaluating the combination of SHR-A2102 and HRS-4642, a KRAS G12D inhibitor. Methods: Eligible pts with Nectin-4 expression and KRAS G12D mutation who had failed standard therapy were enrolled. During the safety run-in, 2 dose levels of SHR-A2102 were evaluated in combination with HRS-4642 (500mg Day 1/1200mg Day 8, iv, q3w) to determine the recommended expansion dose (RED). The Bayesian Optimal Phase II (BOP2) design was applied for efficacy expansion, with a planned enrollment of 10 to 30 pts. The primary endpoints were safety and RED (safety run-in), and objective response rate (ORR; efficacy expansion). The key secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DoR), and disease control rate (DCR). Results: As of Dec. 31, 2025, 36 pts were enrolled and treated (median age, 61 years; ECOG PS 1, 86.1%; ≥2 lines of prior therapy, 88.9%; median Nectin-4 H-score, 10). No dose-limiting toxicity (DLT) occurred, and the RED was established as SHR-A2102 (8mg/kg iv, q3w) plus HRS-4642. Treatment-related adverse events (TRAEs) occurred in all pts (100%), with no grade 5 TRAEs. 13 pts (36.1%) experienced grade 3/4 TRAEs, the most common including neutrophil count decreased and gamma-glutamyl transpeptidase increased (each 11.1%), and anemia (8.3%). In the RED group (n=30), the confirmed ORR was 36.7% (11PR) and the DCR was 86.7%, meeting the primary endpoint. ORR showed no apparent correlation with Nectin-4 H-score. The median DoR was 6.3 months (range: 4.4-NR); the median PFS was 4.1 months (range: 2.7-5.7), and the median OS was not reached. Conclusions: SHR-A2102 combined with HRS-4642 showed a tolerable safety profile and promising preliminary anti-tumor activity in advanced PDAC harboring KRAS G12D mutation, irrespective of Nectin-4 expression. Clinical trial information: NCT06547736 .

Effects of resorcinol isoprenyl benzene derivative IPI201 on natural killer cell cytotoxicity and tumor cell viability in human colorectal adenocarcinoma cells.

2545 Background: Natural killer (NK) cells play a critical role in anti-tumor immunity, yet their cytotoxic efficacy can be limited by tumor resistance. Resorcinyl isoprenyl benzene derivatives have previously shown anti-tumor activity, but effects on NK cell-mediated cytotoxicity remain unclear. IPI201 is a synthetic resorcinyl isoprenyl benzene derivative. We evaluated whether IP201 augments NK cell cytotoxicity and explored potential mechanisms. Methods: Cytotoxicity assays were performed using HT-29 colorectal carcinoma cells co-cultured with either standard NK cells or activated NK cells genetically modified to produce soluble IL-15 (sIL15 NK) under conditions of IPI201 pre-treatment or co-treatment. Cancer cell lysis was quantified over time to assess total cytolysis (AUC), maximum rate of killing (V max ), and time to 50% maximal cytolysis (T 50 ). NK activation markers were assessed by flow cytometry. NK cell survival following IPI201 exposure was assessed over 7 days using cell density quantification. Results: IPI201 enhanced NK cell-mediated cytotoxicity against colorectal cancer cells. Pre-treatment increased overall cytolysis and killing rates by 625% in standard NK cells and 50% in sIL15 NK cells ( P <0.05). Co-treatment similarly increased tumor cell lysis (P<0.05). IPI201 alone induced rapid tumor cell death, outperforming standard NK cells alone in overall cytolysis, killing rate, and time to peak effect ( P <0.05). Enhanced cytotoxicity was not associated with changes in NK activation markers. Instead, IPI201 increased NK cell survival across doses, with the highest dose increasing Day 7 density by 117% in standard NK cells and 214% in sIL15 NK cells ( P <0.05). Further, IPI201 sensitized tumor cells to NK-mediated killing following tumor cell pre-treatment (+130% in both NK cell types; P <0.05). Conclusions: IPI201 induces tumor cell death independent of NK cells and enhances NK cell-associated cytotoxicity during pre- or -co-treatment. These effects may arise from increased NK cell survival and/or heightened tumor cell susceptibility to immune-mediated killing. To our knowledge, IPI201 is now the third known molecule alongside IL-2 and IL-15, that is independently sufficient to support NK cell survival. These findings support further investigation of IPI201 as a multifunctional immunomodulatory and cytotoxic agent in combination cell-based cancer therapies.

Electrolyte abnormalities and severity, mortality, and resource utilization in U.S. cancer hospitalizations: National Inpatient Sample, 2018–2022.

e23190 Background: Electrolyte abnormalities are common during cancer hospitalizations and are often managed as isolated disturbances. National data describing their association with inpatient physiologic severity, mortality, and resource utilization in oncology hospitalizations remain limited. Methods: A serial cross-sectional, hospitalization-level analysis of the 2018 to 2022 Healthcare Cost and Utilization Project National Inpatient Sample (NIS) was performed using discharge-level survey weighting with hospital clustering and stratification to generate nationally representative estimates. Adult hospitalizations with a principal diagnosis of malignancy were identified using ICD-10-CM codes C00 to C97 and D45 to D47. ICD-defined electrolyte abnormality phenotypes included hyponatremia (E87.1), hypercalcemia (E83.52), hypokalemia (E87.6), and hyperkalemia (E87.5), with a composite exposure capturing any electrolyte abnormality. Primary outcomes were All Patient Refined Diagnosis Related Group (APR-DRG) severity of illness subclass, with extreme inpatient severity defined as APR-DRG level 4. Secondary outcomes included in-hospital mortality, length of stay (LOS), and hospitalization cost. Survey-weighted multivariable models adjusted for demographics, payer, socioeconomic status, admission characteristics, cancer type, and hospital characteristics. Results: Among 961,848 unweighted cancer hospitalizations representing 4,809,239 hospitalizations nationally, any electrolyte abnormality occurred in 24.07%. Hyponatremia occurred in 11.12%, hypercalcemia in 2.85%, hypokalemia in 10.97%, and hyperkalemia in 4.13%. Hospitalizations with any electrolyte abnormality had higher mean APR-DRG severity than those without (3.13 vs 2.40), longer LOS (9.79 vs 5.77 days), and higher mean cost ($28,812 vs $21,146). Extreme inpatient severity occurred more frequently in hospitalizations with electrolyte abnormalities than without (5.88% vs. 2.69%). After adjustment, any electrolyte abnormality remained independently associated with higher inpatient severity (beta 0.51, 95% CI 0.50-0.52), increased odds of extreme severity (OR 2.37, 95% CI 2.29-2.45), and higher mortality (OR 1.91, 95% CI 1.86-1.96). Hyperkalemia showed the strongest associations with inpatient severity (beta 0.59, 95% CI 0.56-0.62), extreme severity (OR 3.01, 95% CI 2.79-3.25), and mortality (OR 3.29, 95% CI 3.02-3.58). Conclusions: Electrolyte abnormality phenotypes are common in U.S. cancer hospitalizations and are independently associated with substantially higher inpatient physiologic severity, mortality, and resource utilization. These findings support electrolyte abnormalities as markers of inpatient vulnerability that may inform risk stratification and operational planning in hospitalized oncology populations.

Economic value of romiplostim for management of chemotherapy-induced thrombocytopenia in gastrointestinal cancers in the United States.

e23153 Background: Chemotherapy-induced thrombocytopenia (CIT) is a common complication of multiagent chemotherapy that may lead to dose reductions, treatment delays, or discontinuation, potentially compromising cancer outcomes and increasing healthcare utilization. In the phase 3 RECITE trial, romiplostim improved platelet counts and reduced CIT-related chemotherapy modifications in patients with gastrointestinal (GI) cancers. We evaluated the cost-effectiveness of romiplostim versus usual care in GI cancer patients receiving chemotherapy in the US. Methods: A Markov model with time-dependent transitions was developed from the US health system perspective. A hypothetical cohort of adults with GI cancers and baseline thrombocytopenia receiving oxaliplatin-based chemotherapy received romiplostim plus usual care or usual care alone. Patients transitioned among five health states: full-dose chemotherapy, modified chemotherapy, major bleeding, disease progression, and death. The model included a 6-month chemotherapy phase followed by a post-chemotherapy phase, using 3-week cycles and 1- and 5-year horizons. Romiplostim (2 mcg/kg) was initiated after two chemotherapy cycles upon development of CIT and administered weekly during chemotherapy. Transition probabilities, costs, and utilities were derived from published literature and clinical trial data. Outcomes included total costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), chemotherapy modifications avoided, and major bleeding events avoided. Cost-effectiveness was assessed against US willingness-to-pay thresholds of $100,000 and $150,000 per QALY gained. One-way sensitivity analyses evaluated parameter uncertainty. Results: Over a 5-year horizon, romiplostim was associated with a gain of 0.4 QALYs (≈ 5 months) and increased costs by $32,079 versus usual care, resulting in an ICER of $77,591 per QALY gained which indicated romiplostim cost-effectiveness at the prespecified thresholds. Over a 1-year horizon, the ICER was $482,090 per QALY gained, suggesting romiplostim was not cost-effective in the short term. Romiplostim reduced chemotherapy modifications at a cost of $64,179 per modification avoided. During chemotherapy, major bleeding events were reduced by about 15 events per 100 patients, corresponding to $213,460 per bleeding episode avoided. Results were most sensitive to time horizon, romiplostim dose and price, vial size/drug-wastage, chemotherapy duration, and transition probabilities. Conclusions: In patients with GI cancers who develop CIT, romiplostim may provide long-term economic value by preserving chemotherapy delivery, reducing bleeding complications, and improving quality-adjusted survival. These findings support the targeted use of romiplostim as a value-based supportive care strategy in oncology.

Improving timeliness of radiology imaging scheduling at a comprehensive cancer center: A quality improvement initiative.

e23283 Background: Timely radiologic imaging is essential for diagnosis, staging, and treatment monitoring in oncology care. At the University of New Mexico Comprehensive Cancer Center, the average time to schedule radiologic examinations was 11 days, contributing to delays in care and reduced patient satisfaction. A quality improvement initiative was implemented to reduce imaging scheduling time by 50% (to ≤5.5 days), with a long-term goal of near–real-time scheduling. Methods: In 2025, a multidisciplinary team evaluated radiology scheduling workflows and identified key drivers of delay, including off-site scheduling, protocolization of repeat oncologic studies, and staffing limitations. Interventions included stationing a dedicated radiology scheduler at the cancer center and exempting previously performed standard cancer imaging from repeat protocolization. Computed tomography (CT) was prioritized due to high utilization. Scheduling times from June 1 to December 11, 2025, were compared with the pre-intervention period (May 2024–May 2025). Average days to order completion, which was time from order entered till radiology report was complete and available, was also tracked. Patient experience was assessed using post-scheduling surveys. Results: Post-intervention, the overall mean scheduling time for all exams, including CT scans, decreased as shown in below table. Run-chart analysis demonstrated pre intervention steady state, a sustained improvement over time, and all post-intervention months meeting the target of ≤5.5 days except for a single outlier in October. With the new process, 90% of patients scheduled their imaging before leaving the cancer center. Patient surveys showed a 98% satisfaction rate with the new process and 86% of patients felt it was convenient to schedule their exams on site at the cancer center. Conclusions: Embedding radiology scheduling within a cancer center resulted in substantial and sustained reductions in imaging scheduling delays. This cost neutral, scalable intervention improved access to high-volume oncologic imaging and may Imaging scheduling and completion times pre- and post-intervention. Modality Avg Days to Schedule Imaging (Pre) Avg Days to Schedule Imaging (Post) Absolute Change (Days) Percent Change Avg Days to Order Completion (Pre) Avg Days to Order Completion (Post) Absolute Change (Days) PercentChange PET/CT 9.09 4.04 −5.05 −56% 37.90 15.18 −22.72 −60% MRI 13.32 6.62 −6.70 −50% 41.58 16.27 −25.31 −61% CT 15.39 9.58 −5.81 −38% 51.95 24.58 −27.37 −53% IR Biopsy 2.36 2.77 +0.41 +17% 11.60 8.96 −2.64 −23% Mammogram 1.95 0.75 −1.20 −62% 31.53 9.62 −21.91 −69% Ultrasound 3.88 1.17 −2.71 −70% 19.54 10.18 −9.36 −48%

Segment-level molecular characterization of the proximal colon in TCGA colon adenocarcinoma.

e15737 Background: Colon adenocarcinoma is biologically heterogeneous and is commonly summarized using binary tumor sidedness. While clinically convenient, this framework may obscure more granular anatomic variation, particularly within the proximal colon. We examined whether key molecular phenotypes vary across specific proximal colonic segments using uniformly annotated phenotype data from The Cancer Genome Atlas (TCGA). Methods: Colon adenocarcinoma cases from the TCGA-COAD cohort with annotated anatomic tumor location were evaluated. Analyses were restricted to proximal colonic segments (cecum, ascending colon, hepatic flexure, transverse colon). To ensure uniform comparability across molecular features, analyses were limited to tumors with complete annotation for all evaluated phenotypes, including hypermutation status, mismatch repair (MMR) protein loss by immunohistochemistry, MLH1 silencing, and CpG island methylator phenotype (CIMP). Differences in age at diagnosis across segments were assessed using one-way analysis of variance (ANOVA). Segment-level differences in molecular phenotypes were assessed using chi-square testing. Age- and stage-adjusted analyses were performed using regression models to evaluate whether observed segment-level differences persisted after adjustment. Results: The final analytic cohort included 68 proximal colon tumors with complete molecular phenotype annotation. Age at diagnosis did not differ significantly across proximal colonic segments (one-way ANOVA, p = 0.15), and pathologic stage distribution was similar across segments (χ² = 5.25, p = 0.81). In unadjusted analyses, segment-level heterogeneity was observed for hypermutation (χ² = 9.34, p = 0.025) and MLH1 silencing (χ² = 8.10, p = 0.044), with prevalence increasing from the cecum to the ascending colon and peaking at the hepatic flexure, followed by lower prevalence in the transverse colon. CIMP-high status (χ² = 5.69, p = 0.13) and MMR protein loss (χ² = 2.47, p = 0.48) did not demonstrate statistically significant segment-level differences. After adjustment for age, the association between segment and hypermutation was attenuated to trend level (p = 0.059). In contrast, after adjustment for pathologic stage, segment-level differences in hypermutation (p = 0.041) and MLH1 silencing (p = 0.039) remained statistically significant. Conclusions: Colon adenocarcinoma exhibits clinically relevant molecular heterogeneity within the proximal colon that is not captured by binary sidedness classifications. Hypermutation status and MLH1 silencing vary significantly across proximal colonic segments independent of tumor stage, with enrichment at the hepatic flexure. These findings support a more granular, segment-based model of colon cancer biology and suggest that anatomic factors unique to specific proximal segments may contribute to observed molecular heterogeneity.

Prognostic factors for survival outcomes in stage III cervical cancer patients receiving definitive (chemo)radiotherapy in Indonesia: A retrospective study.

e17501 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC). However, the adoption of CCRT is often hindered by financial barriers, limited healthcare capacity, and heightened concerns about adverse events, leading to the reluctance in administering CCRT. This study aimed to decipher factors associated with the clinical outcomes of stage III cervical cancer patients treated with (chemo)radiotherapy in Indonesia. Methods: This retrospective cohort study included patients with stage III cervical cancer receiving definitive external beam radiotherapy (EBRT) and brachytherapy at Dr. Cipto Mangunkusumo Hospital, Indonesia, between 2019 and 2022. Demographic, clinical, tumor, and treatment-related characteristics were extracted from medical records. Bivariate and multivariate analyses were performed to identify factors associated with 2-year overall survival (OS) and progression-free survival (PFS) estimated using the Kaplan-Meier method. Results: A total of 218 patients were eligible for this study. Most patients were diagnosed with stage IIIC1r (70.2%) cervical squamous cell carcinoma (82.6%). Most of them received CCRT (65.6%) with a median total EQD2 dose of 80 Gy and overall treatment time (OTT) of 97 days. With a median follow-up was 21 months, the 2-year OS and PFS were 70.6% and 71.6%, respectively. On multivariate analysis, tumor size (hazard ratio [HR]: 2.47; p = 0.013), hemoglobin level (HR: 0.50; p = 0.010), and CCRT (HR: 2.38, p = 0.001) were significant predictors for OS. Furthermore, tumor size (HR: 2.14, p = 0.032), nodal involvement (HR: 0.44, p = 0.015), and CCRT (HR: 1.75, p = 0.037) were significant predictors for PFS. Conclusions: Smaller tumor size and administering CCRT were independent prognostic factors for improved OS and PFS. In addition, anemia was significantly associated with poorer OS, whereas nodal involvement was significantly associated with poorer PFS. Expanding access for CCRT must be prioritized to improve clinical outcomes for patients with LACC. Multivariate analysis of prognostic factors for 2-year OS and PFS. Variables Reference/Median HR (95% CI) for OS P value HR (95% CI) for PFS P value Age (years) < 50 vs > 50 0.92 (0.56 – 1.51) 0.731 1.10 (0.66 – 1.82) 0.716 Histology SCC vs other 1.15 (0.59 – 2.25) 0.685 1.19 (0.61 – 2.35) 0.609 Tumor size (cm) < 4 vs > 4 2.47 (1.21 – 5.01) 0.013* 2.14 (1.07 – 4.26) 0.032* Nodal involvement – vs + 1.24 (0.52 – 2.93) 0.632 0.44 (0.23 – 0.85) 0.015* Hemoglobin (g/dL) < 10 vs > 10 0.50 (0.29 – 0.85) 0.010* 0.58 (0.33 – 1.00) 0.051 Treatment CCRT vs RT 2.38 (1.42 – 3.98) 0.001* 1.75 (1.04 – 2.97) 0.037* Total EQD2 (Gy) < 80 vs > 80 0.58 (0.30 – 1.12) 0.105 0.89 (0.39 – 2.02) 0.771 OTT (days) < 97 vs > 97 1.22 (0.73 – 2.05) 0.455 1.01 (0.60 – 1.67) 0.967 *Cox regression test: p<0.05.