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ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial.

4502 Background: In the phase 3 KEYNOTE-564 trial (NCT03142334), adjuvant pembrolizumab (pembro) was superior to placebo (pbo) in participants (pts) with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence post nephrectomy. We report an analysis of pretreatment and on-treatment ctDNA (using 2 versions of a ctDNA assay with different sensitivities) with clinical outcomes in KEYNOTE-564. Methods: Pts with ccRCC at increased risk of recurrence post nephrectomy were randomized 1:1 to pembro or pbo. ctDNA was evaluated using Natera’s Signatera RUO tissue-exome-based 16-plex and 64-plex ctDNA assays. Primary objectives of this analysis were to evaluate the association of baseline ctDNA status and ctDNA status change from baseline to cycle 5 day 1 (C5D1) with disease-free survival (DFS). Significance was prespecified at multiplicity-adjusted α = 0.05. Sensitivity (percentage of ctDNA-positive pts among all pts with a DFS event) and specificity (percentage of ctDNA-negative pts among all pts without a DFS event) to predict DFS were also evaluated. Results: 994 pts were randomized to pembro (n = 496) or pbo (n = 498). ctDNA samples from 736 pts (pembro n = 374; pbo n = 362) were analyzed at baseline and from 641 pts at C5D1 (pembro n = 314; pbo n = 327) using both assays. Median study follow-up was 69.5 mo (range 60.2-86.9). In both treatment arms, ctDNA was detectable at baseline in 40 pts (5.4%) using the 16-plex assay and 60 pts (8.2%) using the 64-plex assay. By risk group, using the 16-plex assay, ctDNA was detectable at baseline in 26 of 642 (4.0%) intermediate-high risk pts, 10 of 53 (18.9%) high-risk pts, and 4 of 38 (10.5%) M1 NED pts; using the 64-plex assay, ctDNA was detectable in 44 of 642 (6.9%) intermediate-high risk pts, 11 of 53 (20.8%) high-risk pts, and 5 of 38 (13.2%) M1 NED pts. For both assays, ctDNA positivity was negatively associated with DFS in both pembro and pbo arms ( P’s < 0.05). ctDNA status at baseline showed low sensitivity and high specificity to predict DFS in both treatment arms (Table). Of pts with detectable ctDNA at baseline and evaluable ctDNA at C5D1, ctDNA clearance at C5D1 occurred in 6 of 10 pts in the pembro arm and 3 of 14 pts in the pbo arm using the 16-plex assay; and 10 of 18 pts in the pembro arm and 9 of 25 pts in the pbo arm using the 64-plex assay. In both assays, ctDNA change from baseline at C5D1 was associated with DFS for both pembro and pbo arms ( P’s < 0.05). Conclusions: While sensitivity was low, ctDNA positivity was associated with worse DFS outcomes irrespective of the ctDNA assay used. ctDNA clearance was higher in the pembro arm than the pbo arm. These data highlight the limitations of these ctDNA assays in ccRCC. Clinical trial information: NCT03142334 . Pembro Pembro Pbo Pbo % (n/N) Sensitivity Specificity Sensitivity Specificity Baseline ctDNA, 16-plex 12 (17/146) 98 (224/228) 10 (18/173) 99 (188/189) Baseline ctDNA,64-plex 15 (22/146) 96 (220/228) 15 (26/173) 98 (185/189)

Safety and efficacy of full-dose apixaban vs rivaroxaban for cancer-associated venous thromboembolism in patients with solid tumors: A real-world study.

e23439 Background: Cancer-associated venous thromboembolism (CA-VTE) is a major cause of morbidity and mortality in patients with active malignancy, and direct oral anticoagulants (DOACs) are increasingly used for the treatment. We evaluated recurrent VTE and bleeding outcomes in patients with active solid tumors treated with apixaban (API) 5 mg or rivaroxaban (RIV) 20 mg. Methods: Using the TriNetX research network, we identified adults with colon, breast, lung, prostate, head and neck, or pancreatic cancer and active disease, defined by receipt of chemotherapy, radiation, or cancer surgery within 6 months of cancer diagnosis. We excluded patients with hematologic malignancies, myelodysplastic syndromes, atrial fibrillation, or pregnancy within 6 months of the cancer index date. Eligible patients had a diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) within 30 days of the cancer index date. They were treated with API 5 mg (excluding any RIV and API 2.5 mg) or RIV 20 mg (excluding any API and RIV 2.5 or 5 mg). Propensity score matching (1:1) was performed on demographics, comorbidities (including CKD and ESRD), hemoglobin, and thrombocytopenia. The primary outcome was recurrent DVT or PE at 1 year. Secondary outcomes included all-cause mortality (ACM), intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, anemia, and blood transfusion (BT). Results: After matching, 5,690 patients were included per cohort. At 1 year, recurrent PE occurred in 4.32% vs 4.38% (hazard ratio [HR] 1.02, 95% CI 0.73–1.43; log-rank p = 0.89), and recurrent DVT occurred in 6.57% vs 5.12% (HR 1.34, 95% CI 1.07–1.68; log-rank p = 0.009) in the API and RIV groups, respectively. ACM was higher with API (30.0% vs 24.5%; HR 1.31, 95% CI 1.22–1.41; log-rank p < 0.0001). Anemia (15.1% vs 13.9%; HR 1.15, 95% CI 1.02–1.30; log-rank p = 0.022) and BT (6.68% vs 5.76%; HR 1.20, 95% CI 1.03–1.41; log-rank p = 0.016) were also more frequent in the API cohort. ICH and GI bleeding rates were similar. Conclusions: In this real-world cohort of patients with active solid tumors and CA-VTE, full-dose API and RIV had similar 1-year risks of recurrent PE, GI bleeding, and ICH. RIV was associated with lower rates of recurrent DVT, all-cause mortality, anemia, and transfusion. Given the observational design and potential residual confounding, these results are hypothesis-generating and highlight the need for prospective head-to-head trials.

Enhanced recovery after surgery in major oncologic head and neck surgery: A systematic review and meta-regression.

e13616 Background: Major oncologic head and neck surgery (OHN) is associated with complex hospitalization and perioperative morbidity. Enhanced Recovery After Surgery (ERAS) pathways aim to standardize multimodal perioperative care and improve recovery; however, evidence in OHN is variable, and the impact of protocolized ERAS bundles has not been comprehensively synthesized. Methods: A systematic review and random-effects meta-analysis were conducted per PRISMA guidelines. MEDLINE, Embase, Emcare, CENTRAL, and trial registries were searched from 2000 to 2026. Randomized controlled trials (RCTs) and observational studies comparing protocolized ERAS with usual care in adults undergoing major OHN were included. Mean differences (MD) were pooled for hospital length of stay (LOS) and risk ratios (RR) for postoperative complications. Meta-regression evaluated associations between LOS & ERAS domains. Sensitivity analyses excluded studies with approximated variance estimates. Results: Twenty-five studies were included overall; 17 studies (1 RCT and 16 nonrandomized studies) contributed to the primary analyses. In sensitivity analyses restricted to studies with reported standard deviations, ERAS was associated with a significant reduction in LOS across all designs (MD −0.77 days; 95%CI −1.50 to −0.04; i 2 = 69.2%). Across all designs, ERAS was associated with fewer postoperative complications (RR 0.74; 0.56 to 1.00; i 2 = 83.6%). No significant association was observed for major complications (RR 1.18; 0.75 to 1.85; i 2 = 0%). Higher ERAS protocol intensity was associated with greater LOS reduction. High-intensity ERAS (≥11 domains) was associated with larger LOS reductions (MD −2.68 days; −4.11 to −1.25) compared with low-intensity ERAS ( < 11 domains; MD −1.05 days; −2.22 to 0.13). In domain-level random-effects meta-regression, select postoperative components were associated with shorter LOS. Standardized flap monitoring was associated with a 2.02-day shorter LOS (95%CI −3.72 to −0.31; p = 0.020). ICU management protocols were associated with a 2.25-day shorter LOS (95%CI −4.19 to −0.31; p = 0.023). Conclusions: ERAS implementation in OHN is associated with shorter hospital LOS, with clinically significant benefits in high-intensity ERAS protocols. Postoperative components, including standardized flap monitoring and ICU management protocols, were associated with shorter LOS. Consistent reporting methodology in ERAS studies is integral to deciphering which domains hold priority and may support refining low- to moderate-intensity protocol bundles that may lead to significant recovery and perioperative optimization with less domain steps to implement.

Advanced perspectives on nanoparticle engineering: Green innovations, and characterization techniques

“Built‐in Electric Field” Design Enables Rapid Li ⁺ Transport in Polymer Electrolyte

ABSTRACT Polymer electrolytes hold great promise for lithium metal batteries owing to their low‐cost, facile processability, and superior electrode compatibility, yet are hindered by intrinsically low ionic conductivity due to their strong Li + −polymer interaction. Inspired by the built‐in electric field (BIEF) concept, we propose a novel strategy of creating a continuous BIEF to uniformly weaken Li +– polymer interactions, thereby achieving a consistently low energy barrier for Li + transport. Specifically, continuous metal Lewis acidic sites (positive side) are introduced along the ether oxygen (−O−) sites (negative side) of the polymer chain, inducing charge redistribution and establishing a directional BIEF. This field reduces the electron density around the −O− groups, significantly attenuating Li + –polymer interactions. The resulting electrolyte achieves an ultrahigh ionic conductivity of 1.14 mS cm −1 and a Li + transference number of 0.78 at 25°C. Remarkably, Li||Li cell shows exceptional cycling stability for over 6000 h. Moreover, Li||LiFePO 4 cell delivers a capacity retention of 84% after 5000 cycles at 2C, and Li||LiNi 0.5 Co 0.2 Mn 0.3 O 2 cell maintains 80% capacity after 500 cycles at 1C. This work pioneers a general BIEF‐based paradigm for designing high‐performance polymer electrolytes, offering a promising avenue toward advanced quasi‐solid‐state batteries.

Real-world clinical utility of liquid biopsy in NSCLC in a community oncology practice: Concordance, discordance, and impact on precision therapy.

e15068 Background: Precision oncology in NSCLC relies on tissue NGS to identify actionable mutations, but in community oncology, tissue limitations—including insufficient samples, technical failures, and delays—often restrict access to targeted therapies. Liquid biopsy (LB), analyzing circulating tumor DNA, provides a minimally invasive complementary approach. Although tissue-LB concordance is well described in clinical trials, real-world data from community oncology practices remain limited. Evaluating feasibility, concordance, and clinical impact of LB in this setting is critical to optimize precision therapy. Methods: We retrospectively analyzed 47 NSCLC patients (median age 65; 18F/29M; 83% smokers) diagnosed in 2024 at a community oncology practice. Tissue NGS was attempted in all patients; 38 returned results, with 5 QNS and 4 missing/uncertain. LB was performed in 14 patients, including 10 with paired tissue results. Actionable alterations assessed included KRAS, MET exon 14 (METex14), ROS1, ERBB2, BRAF, and co-mutations. Endpoints were tissue NGS feasibility, mutational yield, and tissue-LB concordance. Results: Tissue NGS returned evaluable results in 38/47 patients (81%), with 5 QNS (11%) and 4 missing/uncertain (9%), highlighting real-world attrition. Among evaluable tissue, 14 patients (37%) harbored actionable mutations: KRAS (n = 4), KRAS+ROS1 (n = 1), KRAS+METex14 (n = 1), METex14 (n = 3), ROS1 (n = 2), ERBB2 (n = 2), BRAF (n = 1). LB detected actionable mutations in 6/14 patients (43%), including 2 METex14 alterations in patients without tissue NGS, enabling targeted therapy. Among 10 paired tissue-LB cases, concordance was 80% (8/10). Discordances (20%) included one KRAS-positive LB with negative tissue, and one ALK-positive LB versus BRAF-positive tissue, highlighting intra-patient heterogeneity and potential clinical impact on therapy selection. Conclusions: In this community oncology cohort, tissue NGS demonstrated ~19% attrition. LB is a highly effective complementary tool, rescuing actionable mutations in patients without evaluable tissue. Discordances between tissue and LB (20%) underscore the importance of a combined testing approach and multidisciplinary review before initiating targeted therapy. These results highlight the real-world clinical utility of circulating tumor DNA analysis in expanding access to precision therapy in NSCLC outside academic centers. However, there is a need for further larger studies to validate its clinical benefit and optimize precision therapy in community practice.

Feasibility of a novel oncologist-led diagnostic algorithm for Lynch syndrome in colorectal cancer patients: The ItaLynch study.

10618 Background: International guidelines recommend universal Lynch syndrome (LS) screening in colorectal cancer (CRC) using tumor mismatch repair deficiency (dMMR) testing. However, LS remains underdiagnosed worldwide, largely due to inconsistent referral for genetic counseling and germline testing. We report the final feasibility results of a novel, mainstreamed, oncologist-led diagnostic algorithm for LS. Methods: ItaLynch is a prospective, observational, multicenter Italian study on patients with dMMR CRC (May 2021–Dec 2025; 23 high-volume centers). The pathway includes: (1) universal dMMR screening by immunohistochemistry (IHC) in all CRC; (2) reflex testing and “Lynch alert”: MLH1-deficient (dMLH1) tumors undergo BRAFV600E testing and, if wild-type, MLH1 promoter methylation; a Lynch alert is added to all dMMR pathology reports (positive for high LS risk based on reflex testing or non-MLH1 loss; negative for BRAFV600E-mutated or MLH1-hypermethylated cases); (3) oncologist-led mainstream germline testing for patients with positive alert, followed by post-test genetic counseling for carriers of pathogenic variants (PV) or clinically suspicious cases. Results: Up to Dec. 31 2025, we enrolled 1,482 pts with dMMR CRC. Overall, 1,316 were eligible for analysis (14 not eligible; 152 not yet filled out). Excluding 104 cases with incomplete data, 1,212 patients were evaluable from somatic to germline testing. Overall, 1033 (85%) completed the ItaLynch diagnostic pathway, demonstrating the strong feasibility of this this algorithm. Of patients with IHC data, 975 (78%) were dMLH1 and 281 (22%) had non-MLH1 loss. BRAF testing was performed in 904/975 (93%) dMLH1 cases; 386/904 (43%) were BRAFwt. MLH1 methylation testing was done in 329/386 (86%); 146/329 (44%) were not hypermethylated. Germline testing was performed in 108/146 (74%), identifying 21 LS-associated PV (19%). Among non-MLH1 loss, 232/281 (83%) underwent germline testing and 115 (50%) were diagnosed with LS. Overall, germline testing was performed in 361/1,033 adherent patients (35%), identifying 143 PV (40% of tests) and 24 VUS; PV prevalence was 14% (143/1,033). Mainstreaming reduced genetic pre-test counseling visits by 54% (196/361 avoided) and, compared with universal germline testing, avoided 672/1,033 tests (65%). Post-test counseling uptake was 83% among PV carriers. Median turnaround time from somatic to germline diagnosis was 217 days for dMLH1 and 73 days for non-MLH1. Among non-adherent patients, 67 underwent germline testing (14 PV, 3 VUS). In the full cohort, 157 PV were identified (MLH1 37, MSH2 57, MSH6 43, PMS2 20). Conclusions: This oncologist-led, mainstreamed diagnostic pathway for LS is feasible and optimized use of healthcare resources. Analyses of pathway deviations (15%), cost-effectiveness, and clinical/translational outcomes are ongoing.

Helicobacter pylori infection, systemic inflammation, and colorectal cancer: A prospectively enrolled case–control study.

e15668 Background: The association between Helicobacter pylori (H. pylori) infection and colorectal cancer (CRC) remains controversial, with prior studies reporting heterogeneous findings. Systemic inflammation has been implicated in colorectal carcinogenesis and may influence this relationship. We evaluated the independent and combined associations of active H. pylori infection and systemic inflammation with CRC. Methods: From August 2023 to August 2025, we prospectively enrolled 105 treatment-naïve patients with histologically confirmed CRC and 210 age- and sex-matched colonoscopy-negative controls. Active H. pylori infection was assessed using stool antigen testing. Systemic inflammation was evaluated using the pre-treatment neutrophil-to-lymphocyte ratio (NLR), calculated from complete blood counts and dichotomized at the cohort median (2.5). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for CRC after controlling for age, sex, smoking status, diabetes, and body mass index. An interaction term was included to assess effect modification between H. pylori infection and NLR. Results: The median age of participants was 62 years. H. pylori infection was detected in 38.1% (40/105) of CRC cases and 35.7% (75/210) of controls (p = 0.67). Elevated NLR ( > 2.5) was observed more frequently among CRC cases than controls (62.9% vs 28.6%, p < 0.001). In adjusted analyses, H. pylori infection was not associated with CRC (aOR 1.08; 95% CI, 0.65–1.80; p = 0.76). Elevated NLR was strongly associated with CRC (aOR 3.95; 95% CI, 2.38–6.56; p < 0.001). No statistically significant interaction was observed between H. pylori infection and elevated NLR (p for interaction = 0.42). Conclusions: In this prospectively enrolled case–control study, systemic inflammation, as reflected by elevated NLR, was strongly associated with colorectal cancer, whereas active H. pylori infection was not. These findings suggest that inflammatory status may be more relevant to CRC association than H. pylori infection alone and support further investigation of inflammatory biomarkers in colorectal cancer risk stratification.

TAGNOT: A phase 1b/2 tumor-agnostic study of the selective anti-FGFR1 monoclonal antibody OM-RCA-01 in FGFR1-expressing advanced solid tumors.

TPS3166 Background: Fibroblast growth factor receptor 1 (FGFR1) plays a key role in the pathogenesis of multiple malignancies; however, no highly selective FGFR1-targeted therapies for solid tumors are currently approved. OM-RCA-01 is a humanized monoclonal antibody that selectively binds extracellular domains II–IIIc of FGFR1 with high affinity (Kd = 1.59 nM) and has demonstrated promising antitumor activity in preclinical models. In the first-in-human, tumor-agnostic (TAGNOT) study, patients with FGFR1-expressing advanced cancers are being treated with OM-RCA-01. Methods: TAGNOT is a phase 1b/2, multicenter, multicohort, prospective study designed according to the FDA-recommended OPTIMUS approach. Key eligibility criteria include FGFR1 expression by immunohistochemistry (IHC 2+ or 3+ in ≥10% of tumor cells) and metastatic disease progressing after ≥2 prior systemic treatment lines. The primary objective of the phase 1b component is to determine the recommended phase 2 dose (RP2D). Two dose levels of OM-RCA-01 (50 mg and 100 mg administered intravenously every 2 weeks) will be compared for safety (CTCAE v5.0), preliminary efficacy (objective response rate [ORR] per RECIST v1.1), pharmacokinetics, neutralizing antibody formation, and circulating tumor DNA dynamics. The primary endpoint of the phase 2 component is ORR in the ITT population. Five tumor-specific cohorts are planned: clear-cell renal cell carcinoma (n = 11), castration-resistant prostate cancer (n = 11), non-small cell lung cancer without EGFR or ALK alterations (n = 11), breast adenocarcinoma with known receptor status (n = 11), and head and neck squamous cell or salivary gland carcinomas (n = 11). Using Simon’s two-stage design, a total of 55 patients will be enrolled. The null hypothesis of a true ORR of 10% will be tested against a one-sided alternative of 25%. The study will be terminated after the first stage if ≤3 responses are observed among 31 patients. Otherwise, 24 additional patients will be enrolled. The null hypothesis will be rejected if ≥10 responses are observed in 55 patients, yielding a one-sided type I error rate of 0.05 and 90% power. Clinical trial information: NCT07292168 .

Prospective real time clinical validation of a novel circulating tumor–derived blood mRNA Geneverify test for diagnosis of breast cancer.

e15053 Background: Early detection is critical for the effective management of breast cancer. We performed a real-time clinical validation of the plasma cell-free mRNA–based Geneverify test for early breast cancer screening and detection. This next-generation, minimally invasive assay offers rapid and precise molecular insights, with the potential to transform current diagnostic practices by reducing reliance on surgical biopsies. Methods: We evaluated the real-time expression of 30 different breast cancer associated genes in plasma samples collected from 57 subjects (39 cancer cases, 8 benign/ high risk subjects and 10 controls). Eligible participants were selected based on the availability of paired blood and surgical tissue specimens from cases suspected of breast cancer. We validated the diagnostic and prognostic potential of a multi-gene expression panel developed by Geneverify Inc. The log₂-fold change in gene expression was calculated to generate a risk score for each subject. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calibration analysis. Risk scores were compared against biopsy-confirmed diagnoses to calculate sensitivity and specificity. Geneverify scores were evaluated with respect to the patient’s stage, grade, and metastasis. Results: The Geneverify risk score effectively distinguished breast cancer patients from benign controls, demonstrating strong diagnostic discrimination with the ROC curve (AUC: 0.92, P < 0.001, 95% CI = 0.82 – 1.00). Using Youden’s Index a risk score cutoff of 17, the test achieved 100% sensitivity and 75% specificity for breast cancer detection. Spearman’s rank correlation demonstrated a significant positive association between Geneverify Dx scores and both clinical stage and pathological grade. Additionally, patients with metastatic disease exhibited higher risk scores compared with non-metastatic cases. Healthy controls and benign subjects showed markedly reduced gene expression levels and consistently low risk scores. Conclusions: This prospective study represents the first real-time clinical validation of a blood-based, cell-free mRNA Geneverify test for breast cancer. The assay demonstrated high diagnostic accuracy, a strong correlation with breast cancer presence and severity, and the potential to reduce dependence on invasive tissue biopsies. These results support the Geneverify test as a promising tool for early detection, risk stratification, and improved patient management in breast cancer.

Mitochondrial apoptosis markers in the progression of endometrioid adenocarcinoma.

e17625 Background: Endometrial cancer (EC) is one of the most common malignancies of the female reproductive system. The incidence of EC is steadily increasing by approximately 1% annually, accounting for 20–30% of female genital tract tumors. Metabolic reprogramming is recognized as an emerging hallmark of malignant cells. Within these cells, the two critical mitochondrial functions—respiration and apoptosis—are in constant conflict yet intrinsically linked. Apoptosis can function not only as a tumor suppression mechanism but also exhibit pro-oncogenic properties, promoting the emergence and maintenance of aggressive tumors. Currently, research on the mitochondrial apoptotic pathway primarily utilizes human cancer cell lines, while studies examining mitochondria isolated directly from patient tumor tissues remain scarce. The aim of this study was to investigate changes in apoptotic markers within the mitochondria of endometrioid adenocarcinoma (EA) cells in gynecologic oncology patients, depending on the tumor grade. Methods: The study included patients who underwent surgical treatment for stage T1N0M0 EA (n=42) and uterine fibroids (n=14). The EA cohort consisted of 16 patients with well-differentiated (G1), 12 with moderately differentiated (G2), and 14 with poorly differentiated (G3) tumors. The mean age was 60.8±2.9 years for EA patients and 49.4±2.5 years for those with fibroids. Patients did not receive neoadjuvant therapy. Concentrations of cytochrome C (ng/mg protein), AIF (pg/mg protein), Bcl-2 (pg/mg protein), and calcium (μM/mg protein) were determined in the mitochondrial fraction of EA cells, fibroids, and intact uterine tissue using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using parametric and nonparametric tests with correction for multiple comparisons. Results: A decrease in tumor cell differentiation was associated with reduced mitochondrial calcium levels; in G2 and G3 tumors, levels were on average 2.0 times lower than in the mitochondria of intact uterine tissue. Bcl-2 content in G3 tumor mitochondria was significantly higher (1.9 times on average) compared to the respective values in G1 and G2 (p<0.05). Cytochrome C levels in G1 were 2.2 times higher than in G2 and 1.9 times higher than in G3 (p<0.05). Mitochondria of G3 cells exhibited the highest AIF values, which were 2.1 times higher than in intact tissue and 1.9 times higher than in fibroid mitochondria (p<0.05). Conclusions: It is hypothesized that the suppression of apoptosis in endometrioid adenocarcinoma mitochondria is driven by increased Bcl-2 accumulation and decreased calcium levels, accompanied by the retention of cytochrome C and AIF, suggesting metabolic reprogramming necessary for cell survival. The magnitude of biochemical alterations in EA mitochondria increases with the tumor grade, likely contributing to the enhanced aggressiveness of the tumor.

Assessing the true cost of infusion care: Comparing hospital chargemaster, cash, and negotiated prices for infusion CPT codes across top-ranked US hospitals.

e23186 Background: Patients in the United States often lack clear, actionable information about the prices of common outpatient infusion services across hospitals and payers. Recent federal policy, including the No Surprises Act of 2022, require hospitals to publish negotiated prices for all services, creating an opportunity to quantify variation in hospital prices for common infusion services. Despite extensive research documenting price variation across healthcare services, the relationship between hospitals’ prices and Medicare benchmark rates for common infusion services remains poorly characterized. Methods: We extracted publicly available price transparency data from the Turquoise Health aggregate database from 12 top-ranked US hospitals for five common infusion CPT codes. For each code, we captured (1) chargemaster price, (2) discounted cash price, and (3) payer-specific negotiated rates; we summarized inter-facility variation using the median and range across hospitals. We compared median negotiated rates to the 2025 Medicare OPPS benchmark rates for each service. Results: Across 12 top US hospitals, prices for common infusion services varied widely across facilities for all five CPT codes. Median negotiated rates showed especially large inter-facility dispersion, with up to 53-fold variation across hospitals. Three infusion services had median negotiated rates ≥2× the Medicare benchmark rate. Median discounted cash prices exceeded median negotiated rates for all five services, with average cash price 136% of median negotiated rate. Conclusions: Among 12 top US hospitals, there is substantial inter-facility variation in prices for common infusion services, with negotiated rates frequently exceeding Medicare benchmarks. For several infusion codes, median negotiated rates were 2–3× Medicare OPPS benchmark rates. These findings suggest that even routine infusion services expose patients and payers to unpredictable and frequently elevated pricing, underscoring the need for increased transparency for negotiated rates for common infusion services. Hospital prices for 5 common infusion-related cpt codes, as compared to medicare opps benchmark rates. CPT Code Service Medicare OPPS Benchmark ($) Chargemaster Median (Range) Discounted Cash Median (Range) Median Negotiated Rate (Range) Negotiated Price / Medicare Benchmark 96413 Chemo infusion, initial hr $332 $1,181 ($553–$2,091) $743 ($221–$1,608) $670 ($117–$1,286) 2.02 96415 Chemo infusion, additional hr $71 $503 ($118–$843) $367 ($47–$592) $233 ($25–$809) 3.27 96365 Non-chemo infusion, initial hr $211 $643 ($307–$1,324) $408 ($146–$960) $348 ($56–$1,057) 1.65 96366 Non-chemo infusion, additional hr $46 $300 ($95–$545) $230 ($39–$368) $142 ($19–$1,015) 3.07 96360 IV fluid hydration, initial hr $211 $587 ($191–$1,324) $370 ($76–$1,297) $277 ($30–$755) 1.32

Length of stay, costs, and mortality in colon cancer: A regional comparison between the northeast and west.

e13756 Background: Colorectal cancer is a leading cause of cancer-related mortality in the United States, with an estimated 108,860 new colon cancer (CC) cases in 2026. Despite well-documented regional disparities in healthcare resources, their impact on inpatient outcomes among patients with CC remains unclear. This study compares in-hospital and discharge outcomes across U.S. regions to evaluate the influence of geographic variation on inpatient care. Methods: A retrospective cohort study was conducted using the 2019–2023 National Inpatient Sample (NIS) database. Adult patients (≥18 years) hospitalized with CC were identified using ICD-10 codes and stratified into the Northeast (NE) and West (W) regions, with NE as the reference. Baseline characteristics and outcomes were compared between regions using univariate and multivariate logistic regression analyses. Results: Among 1,306,735 CC hospitalizations, 14.7% (n = 192, 090) occurred in the Northeast (NE) and 15.4% (n = 201, 237) in the West (W). Patients in the W were younger (65 vs. 67 years; CoEff −1.4; P < 0.001). Males predominated in both regions (NE 53%, W 54%), with White patients being the largest racial group (NE 72%, W 60%). The second most common race was Black in the NE (11%) and Hispanic in the W (19%). High-income households were more common in the NE (35% vs. 32%), while 17% in both regions were in the lowest-income quartile (P < 0.05), indicating greater income disparity in the NE. Teaching hospitals were more frequent in the NE (87% vs. 75%), while large-bed hospitals were more common in the W (58% vs. 47%; P < 0.001). Patients in the W had a shorter length of stay (6.5 vs. 7.0 days; CoEff −0.6; P < 0.001) but higher costs ($121,110 vs. $94,522; CoEff $26,587; P < 0.001). In-hospital mortality did not differ significantly (OR 0.96; P = 0.410). Conclusions: Significant regional differences were observed among hospitalized patients with CC. Patients in the W were more frequently treated at large-bed hospitals, had shorter lengths of stay, and incurred higher hospitalization costs, potentially reflecting younger demographics and socioeconomic factors. In-hospital mortality, however, was similar between regions. These findings may reflect regional differences in healthcare utilization, hospital resources, and practice patterns, including variations in access to care. Further region-specific prospective studies are needed to elucidate the underlying drivers of these disparities and their impact on long-term outcomes and quality of care.

Plasma cell-free chromatin state kinetics as a predictor of early treatment response in gastric cancer.

e16073 Background: Early and reliable assessment of treatment response across heterogeneous gastric cancer (GC) regimens remains an unmet need. Circulating cell-free chromatin retains tissue-encoded epigenetic information that can be quantified longitudinally. We developed a plasma-based framework to compute cell-free epigenetic clearance rates from serial cell-free chromatin signals (integrating six core histone modifications) and evaluated its value for cross-regimen response assessment, benchmarking against standard clinical evaluation. Methods: We profiled a prospective cohort of 31 GC patients sampled at six longitudinal timepoints across peri-treatment and peri-operative windows, treated with XELOX chemotherapy, RC48 (HER2-targeted antibody–drug conjugate), or JS001 (PD-1 blockade). Using cf-EpiTracing plasma chromatin profiling (≤100 µL plasma; automated workflow), we quantified trajectory-based clearance kinetics and compared regimen-specific response patterns as assessed by (i) routine clinical evaluation (radiographic/clinical assessment and peri-operative pathology including ypTNM where available) and (ii) cf-EpiTracing-derived clearance metrics. Associations with recurrence and prognosis were analyzed during follow-up. Results: Clinical evaluation revealed differential response patterns across regimens in this cohort, and plasma cell-free epigenetic clearance kinetics recapitulated these between-regimen differences, enabling early discrimination of higher- versus lower-benefit treatment courses. Across regimens, clearance kinetics separated respondents from non-respondents at early on-treatment timepoints and provided an orthogonal, quantitative measure consistent with clinical response assessment. In peri-operative settings, clearance-derived metrics supported pre-surgical prediction of pathological outcomes, including identification of ypT0N0M0 status. Clearance trajectories further stratified recurrence risk; 5/31 patients developed recurrence within two-year follow-up. In a small independent pilot validation, the clearance metric showed concordant directionality with clinical outcomes. Conclusions: Longitudinal plasma epigenetic clearance kinetics offer a minimally invasive, quantitative approach for early response monitoring and for comparing treatment effectiveness across GC regimens in a small clinical cohort, while also providing preliminary real-world evidence on outcomes under newer regimens. Clinical trial information: CTR20233553.

HMA plus venetoclax for 7- vs 14- vs 21- vs 28-day cycles in newly-diagnosed acute myeloid leukemia: ELN- and Mayo Genetic Risk–stratified analysis in 540 patients.

6525 Background: Venetoclax plus hypomethylating agent (Ven-HMA) is the standard treatment for unfit patients with newly diagnosed acute myeloid leukemia (ND-AML), with Ven typically administered for 28 days (d) per cycle (DiNardo NEJM 2020) . However, the optimal duration of Ven across risk groups remains unclear. We examined survival outcomes with Ven 7, 14, 21, and 28d in ND-AML, in the context of European LeukemiaNet (ELN) and Mayo Genetic risk models. Methods: ND-AML patients receiving Ven-HMA at the Mayo Clinic were retrospectively studied. Patients were stratified by ELN 2024 (Döhner Blood 2024) and Mayo Genetic risk (Gangat Am J Hematol 2025) , and analyzed using standard statistical methods. Results: 540 patients (median age 75 years, 52% de novo) received HMA with Ven for 7d ( n =33), 14d ( n =117), 21d ( n =96), or 28d ( n =294). ELN and Mayo risk distributions were 22%/35% high, 18%/56% intermediate, 60%/9% low risk, respectively. Baseline characteristics were comparable. CR/CRi rates were comparable across Ven durations, with the exception of lower CR/CRi with 7d vs 21d (p=0.04). Risk-stratified CR/CRi showed variations across Mayo and ELN groups but without significant differences based on Ven duration (Table). Allogeneic transplant rates were 15%, 18%, 18%, 20% for 7, 14, 21, 28d (p=0.86). At a median followup of 37.7 months, median overall survival (OS) differed by ELN risk (6.6, 11.9, 20 months) and Mayo genetic risk (7.8, 17.4 months, not reached (NR)), for high, intermediate, low risk (p<0.01), respectively. Median OS was comparable across Ven 7, 14, 21, 28 d (13, 13, 17, 14 months; p=0.84), with corresponding 1/3/5-year survival rates (Table). 30/60d mortality differed by Ven duration; 7d 10%/20%, 14d 7%/15%, 21d 4%/13%, 28d 4%/6%. Compared with 28d, 30d mortality was higher with 7d and 14d (p=0.07/0.03), and 60d mortality was higher with 7d, 14d, and 21d (p=0.02/0.01/0.05). OS was comparable across Ven durations within ELN intermediate/low risk and all Mayo risk groups, except among ELN high risk, patients receiving 14d Ven had inferior OS compared with 21d and 28d (p<0.01). Cumulative incidence of relapse at 1 year was similar among patients receiving 14, 21, 28d Ven (16%, 18%, 18%;p >0.1). Conclusions: Survival outcomes were comparable across Ven 7, 14, 21, 28 d in ND-AML, with outcomes driven by Mayo Genetic and ELN risk. Despite differences by Ven duration in high-risk groups, higher early mortality with 7d and 14d likely reflects treatment selection. Prospective trials are needed to establish risk adapted Ven dosing strategies. 7 (N=33) 14 (N=117) 21 (N=96) 28 (N=294) P-value CR/CRi (%) 52 63 72 65 0.19 7≠21 Mayo Risk High 33 49 58 55 0.53 - Intermediate 55 69 80 69 0.17 7≠21 Low 100 85 80 84 0.84 - ELN Risk High 33 30 57 53 0.21 - Intermediate 33 59 64 56 0.63 - Low 62 74 80 73 0.46 - Median OS (months) 13 13 17 14 0.84 - 1/3/5-year survival (%)  53/NR/NR     51/25/22  56/23/20  55/27/20  >0.1 -

PREDICT-RD: Postoperative molecular residual disease by ctDNA surveillance in TNBC with residual disease (TBCRC-071).

TPS647 Background: Patients with residual triple-negative breast cancer (TNBC) post-neoadjuvant therapy, particularly those with higher residual cancer burden (RCB II/III), remain at high risk of recurrence despite standard adjuvant therapy. Current post-treatment surveillance relies primarily on clinical follow-up and imaging, which have limited sensitivity to detect disease at a subclinical stage and rarely enable early therapeutic intervention. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) assessment allows detection of tumor-derived DNA in the absence of radiographic disease and offers a framework to identify patients at high risk of recurrence, who may be candidates for early, biomarker-informed treatment escalation prior to overt metastatic recurrence. PREDICT-RD is designed to evaluate the clinical implications of post-surgical ctDNA surveillance in patients with high-risk, early-stage TNBC. We hypothesize that longitudinal monitoring with a tumor-informed, high sensitivity ctDNA assay will identify an MRD-only state in at least 10% of patients, defined by ctDNA positivity in the absence of clinical or radiographic recurrence. A secondary objective is to assess outcomes among patients with ctDNA-detected molecular relapse who undergo adjuvant treatment escalation with datopotamab deruxtecan (Dato-DXd). Dato-DXd is an antibody-drug conjugate composed of a monoclonal antibody targeting TROP2 linked to a topoisomerase I inhibitor payload. In TNBC, Dato-DXd has demonstrated a manageable safety profile and promising efficacy, including an improvement in median PFS of 5.3 months over SoC chemotherapy in the first line setting for patients who are not candidates to receive immunotherapy (TROPION-Breast02). Methods: PREDICT-RD (TBCRC-071) is a prospective phase II, interventional, open-label, single-arm, multi-center study. The trial will enroll 78 patients with Stage II or III TNBC with residual disease (RCB II/III) following neoadjuvant chemo-immunotherapy and surgery. Patients will undergo serial blood sampling for ctDNA assessments using a clinically available tumor-informed personalized assay (Signatera Genome, Natera, Inc.) at predefined intervals during adjuvant therapy and subsequent surveillance. ctDNA test results will be disclosed to both the treating provider and the patient. A positive ctDNA result will prompt consideration of imaging for distant disease. The primary endpoint is the prevalence of MRD-only relapse. Patients meeting these criteria will be considered for treatment escalation with Dato-DXd (up to eight cycles), with ctDNA clearance as a secondary endpoint. Patient-reported fear of recurrence and quality of life will be serially evaluated. Post-treatment surveillance will continue for up to three years following initial consent. Recruitment is anticipated to begin in early 2026 (NCT07069595). Clinical trial information: NCT07069595 .

Clinical and structural factors associated with access to stereotactic body radiation therapy (SBRT) in lung cancer.

e20104 Background: Stereotactic body radiation therapy (SBRT) is an established treatment modality for select patients with non-small cell lung cancer (NSCLC). However, access to SBRT may be influenced not only by clinical disease characteristics but also by structural factors such as insurance coverage. Disentangling age-related eligibility from insurance-mediated access is essential to identifying inequities in treatment allocation and outcomes. Methods: We conducted a retrospective cohort study of 211 patients with lung cancer, stratified by receipt of SBRT to the primary lung lesion. Baseline demographic, clinical, tumor, and treatment characteristics were compared using chi-square or Fisher’s exact tests and Student’s t -tests or Wilcoxon rank-sum tests, as appropriate. Variables significant in bivariate analyses were visualized and entered into a multivariable logistic regression models to identify independent predictors of SBRT receipt, adjusting for age, race, sex, and smoking status. Overall survival (OS) was analyzed using Kaplan–Meier methods with log-rank testing, and multivariable Cox proportional hazards models evaluated the association between SBRT and OS. Survival time was defined from diagnosis to death, with censoring at last follow-up. Statistical significance was defined as p < 0.05. Results: Among 211 patients, 84 (39.8%) received SBRT. Mean age at diagnosis was similar between patients who received SBRT and those who did not (62.9 vs 61.9 years, p = 0.443), suggesting that age alone did not account for treatment differences. Patients receiving SBRT had significantly greater disease burden, including higher rates of stage IV disease (54.8% vs 29.9%, p = 0.003), metastatic disease (82.1% vs 48.0%, p < 0.001), chemotherapy use (94.0% vs 79.5%, p = 0.007), and immunotherapy use (51.2% vs 73.2%, p = 0.002). Body mass index category also differed significantly (p = 0.003), with SBRT recipients more frequently underweight, consistent with increased physiologic vulnerability. Despite comparable age, patients receiving SBRT were significantly less likely to have Medicare insurance (38.1% vs 55.1%, p = 0.023). At last follow up, fewer patients in the SBRT group were alive compared with those who did not receive SBRT (52.4% vs 70.1%, p = 0.014) likely reflecting higher baseline disease staging rather than treatment effect alone. Conclusions: In this cohort, receipt of SBRT was associated with higher disease burden and greater physiologic vulnerability, independent of age. Differences in payer status between treatment groups suggest that. insurance-related factors may influence referral patterns or access to advanced radiation modalities. These findings highlight the need to evaluate how payer status and treatment selection interact to affect survival and equity in lung cancer care.

Integrating genomics, imaging, and clinical data for late-onset cardiomyopathy prediction in pediatric cancer survivors: A multi-modal machine-learning comparison using St. Jude Cloud.

10018 Background: Pediatric cancer survivors face substantial risk of anthracycline- and radiation therapy (RT)-related cardiomyopathy (CM). Current risk stratification using clinical factors alone demonstrates suboptimal discriminative capacity. We hypothesized that integrating multi-modal data (clinical, genomic, and cardiac imaging/electrocardiography) would enhance predictive accuracy for late-onset CM beyond single-modality models. Methods: We analyzed data from 1,217 adult survivors of childhood cancer enrolled in the St. Jude Lifetime Cohort (SJLIFE), accessed via St. Jude Cloud. The primary endpoint was CM, defined as left ventricular ejection fraction (LVEF) <50% or ≥10% absolute decline from baseline. Four progressively complex feature sets were evaluated: (1) Clinical-Only (anthracycline/RT dose, age at diagnosis, sex); (2) Clinical+Genomic (adding 31 protective variants from PeCan); (3) Clinical+ECG/Imaging (adding 86 signal-processed ECG features and global longitudinal strain [GLS]); and (4) Multi-Modal (comprehensive integration). Logistic regression, random forest (RF), and extreme gradient boosting (XGBoost) algorithms were compared using 5-fold stratified cross-validation. Model interpretability was assessed via SHapley Additive exPlanations (SHAP) analysis. Results: Clinical-Only models demonstrated limited discrimination (AUC 0.70; 95% CI, 0.65-0.75). Incremental addition of genomic data (AUC 0.85) or ECG/GLS parameters (AUC 0.89) substantially improved performance. The Multi-Modal XGBoost model achieved superior predictive accuracy (AUC 0.93; 95% CI, 0.90-0.95; sensitivity 0.88; specificity 0.89), marginally outperforming RF (AUC 0.91). SHAP analysis identified GLS as the dominant predictor, followed by cumulative anthracycline dose and protective genomic variants, demonstrating synergistic contribution of multi-modal features. Conclusions: Multi-modal machine learning integration using open-source St. Jude Cloud data enables highly accurate prediction of late-onset CM in pediatric cancer survivors (AUC 0.93). The demonstrated superiority over single-modality approaches supports a paradigm shift toward comprehensive risk stratification. This XGBoost-based model could facilitate precision survivorship care, enabling risk-adapted surveillance intensification and early cardioprotective intervention for high-risk patients. Comparative performance of machine learning models for 10-year cardiomyopathy risk prediction. Model Type Algorithm AUC (95% CI) Sensitivity Specificity Clinical-Only Log. Reg. 0.70 (0.65-0.75) 0.62 0.66 Clinical + Genomic Random Forest 0.85 (0.81-0.89) 0.79 0.82 Clinical + ECG/GLS XGBoost 0.89 (0.86-0.91) 0.78 0.81 Multi-Modal (Full) XGBoost 0.93 (0.90-0.95) 0.88 0.89

Zirconium-engineered nanoplatform to enhance radiotherapy through NOD-like receptor-mediated pyroptosis.

e14595 Background: Radiotherapy faces significant challenges in clinical application due to tumor radioresistance and potential damage to normal tissues. While high-atomic-number nanomaterials show promise as radiosensitizers, their efficacy is often limited to physical dose enhancement without adequately addressing biological mechanisms. Methods: This study develops Zr-ATP nanoparticles through a coordination-driven self-assembly approach between zirconium ions and adenosine triphosphate, creating a biomimetic nanosystem for enhanced radio-immunotherapy. Results: The synthesized nanoparticles exhibit uniform spherical morphology with diameters below 100 nm and demonstrate excellent stability. In vitro studies reveal that Zr-ATP nanoparticles significantly enhance radiation-induced DNA damage and reactive oxygen species generation. Most importantly, the combination of Zr-ATP with radiotherapy simultaneously triggers both immunogenic cell death and pyroptosis, as evidenced by calreticulin exposure, HMGB1 translocation, and caspase-1 activation. Transcriptomic analysis confirms the activation of NOD-like receptor signaling pathway underlying these cell death mechanisms. In vivo evaluation demonstrates that Zr-ATP nanoparticles achieve effective tumor accumulation and, when combined with radiotherapy, significantly inhibit tumor growth while prolonging survival in melanoma-bearing mice. The treatment exhibits a favorable safety profile with minimal systemic toxicity. Conclusions: These findings establish Zr-ATP nanoparticles as a dual-function radiosensitizer that not only enhances physical radiation efficacy but also activates potent antitumor immunity through coordinated induction of immunogenic cell death and pyroptosis, offering a promising strategy for improving radiotherapy outcomes.

Complex segmentectomy versus lobectomy in small-sized peripheral non–small cell lung cancer: A post-hoc supplemental analysis of a multicenter, open-label, phase 3 trial (JCOG0802/WJOG4607L).

8009 Background: JCOG0802/WJOG4607L confirmed the superiority of segmentectomy on overall survival (OS) over lobectomy for small-sized peripheral non-small cell lung cancer (NSCLC). However, it remains unclear whether technically demanding complex segmentectomy offers therapeutic efficacy compared to lobectomy, similar to simple segmentectomy. This study therefore aimed to evaluate the oncological outcomes of complex and simple segmentectomy compared to those of lobectomy using final analysis data from JCOG0802/WJOG4607L. Methods: Simple segmentectomy was defined as resection of the bilateral superior division (S 6 ), left lingular (S 4+5 ), or superior division (S 1-3 ); all other segmentectomies were defined as complex. The primary outcome was OS, and secondary outcomes were respiratory function, relapse-free survival (RFS), cumulative incidence of locoregional relapse, and lung cancer-specific death. To ensure comparability, a location-adjusted analysis was performed, separately comparing lobectomy to simple segmentectomy in patients with tumors in the bilateral S 6 , left S 1-3 , or S 4+5 , and to complex segmentectomy in patients with tumors in the right S 7-10 , S 1-3 , or left S 8-10 , S 1-3 . Results: 1106 patients were assigned to either lobectomy (n = 554) or segmentectomy (n = 552) including 318 complex and 234 simple segmentectomies. At a median follow-up of 10.5 years, the 10-year OS was 83.5% (95% CI: 78.8–87.3%), 83.5% (95% CI: 77.7–87.9%) and 79.8% (95% CI: 76.1–83.0%) for complex, simple segmentectomy, and lobectomy, respectively. In the location-adjusted analysis, the 10-year OS were 83.6% (95% CI: 78.9–87.3%) for complex segmentectomy and 79.2% (95% CI: 74.7–82.9%) for lobectomy (HR 0.839 [95% CI 0.608–1.158]). Similarly, 10-year OS were 82.9% (95% CI: 76.9–87.4%) for simple segmentectomy and 78.0% (95% CI: 72.5–82.6%) for lobectomy (HR 0.791 [95% CI 0.540–1.158]). The reduction of median forced expiratory volume in 1 second at 1 year was less after complex (−7.9%) and simple segmentectomy (−9.0%) than lobectomy (−12.0%; p < 0.001 and p < 0.001, respectively). RFS and lung cancer-specific death were not significantly different among the arms, while the cumulative incidence of locoregional relapse was higher after complex and simple segmentectomy than lobectomy (HR 2.124 [95% CI 1.327–3.339] and HR 1.817 [95% CI 1.071–3.083], respectively). Surgical margins were shorter in complex (median 2.2 cm, p < 0.001) and simple (2.5 cm, p < 0.001) segmentectomy than lobectomy (4.0 cm). Conclusions: Complex segmentectomy showed a trend toward improved OS compared to lobectomy in small-sized peripheral NSCLC similar to simple segmentectomy. However, due to a higher risk of locoregional relapse, complex segmentectomy should be performed with meticulous attention to securing adequate surgical margin. Clinical trial information: UMIN000002317.