Browse Articles

Evaluating the impact of a statewide intervention on multiple myeloma bispecific T-cell engaging antibody (BsAb) therapy uptake in Florida (FL).

7532 Background: BsAbs are highly effective, off-the-shelf T-cell engagers recently approved for relapsed/refractory multiple myeloma (MM) but remain underutilized in real-world settings. In partnership with the Florida Society of Clinical Oncology (FLASCO), a statewide initiative was launched to expand BsAb access through peer-led regional discussions focused on operational barriers, care transitions, and therapy management strategies. This study assessed the real-world impact of these interventions on BsAb utilization in FL. Methods: Multidisciplinary discussion forums were held in 4 FL metropolitan areas (Jan-Apr 2024). We conducted single and controlled interrupted time series (ITS) analyses using IQVIA eLAAD claims data (Apr 2023 - Sep 2025) including adult patients with a diagnosis of MM, evidence of claim activity, and provider state information. Fifth line or later (5L+) status was estimated as 3.3% of MM prevalence (Nikolaou et al.) BsAb utilization (% of MM 5L+ patients receiving a BsAb) was evaluated using segmented regression to estimate pre- and post-intervention trends, excluding the intervention period. We reported BsAb utilization by comparing FL with all other states, between community versus academic settings, and assessing the number of sites administering BsAb. Results: Before the intervention, BsAb utilization among MM 5L+ patients in FL rose from 8.2% (Apr 2023) to 11.2% (Dec 2023) (0.3 pp/mo; p=0.23), compared with a rise from 6.7% to 16.3% (1.3 pp/mo; p<0.0001) across all other states over the same time period. Post-intervention, BsAb utilization in FL increased from 22.8% (May 2024) to 35.9% (Sep 2025), reflecting a 7.0% immediate increase and 0.8 pp/mo sustained growth, exceeding the post-intervention trend observed across all other states (23.5% to 30.3%; 0.5 pp/mo). Overall, although pre-intervention BsAb utilization in FL was lower than all other states, FL demonstrated a 1.2 pp/month higher post-intervention utilization trend (p<0.001; Table). Post-intervention, FL community sites showed a 0.13 pp/mo higher BsAb utilization trend than academic sites, and the number of community sites administrating BsAb increased from 5 to 9, with no change among academic sites. Conclusions: This study suggests that the FLASCO-led, collaborative model increased BsAb utilization in FL community oncology sites and offers a framework for broader community adoption across other states. Parameter estimates from ITS model(s). FL (%) p-value Other US States (%) p-value Difference CITS:FL - Other US States (%) p-value Intercept (Apr 2023) 8.6 <.0001 7.7 <.0001 0.9 0.52 Monthly change pre-intervention 0.3 0.23 1.3 <.0001 -0.9 0.002 (Apr - Dec 2023) Immediate change post-intervention 7 0.01 0.2 0.87 6.8 0.01 (May 2024) Monthly change post-intervention 0.8 <.0001 0.5 <.0001 1.2 0.0003 (May 2024 – Sep 2025)

Correction: Retraction: Unleashing the role of e-word of mouth on purchase intention in select Facebook fan pages of smart phone users

Multifunctional CuFe₂O₄/rGO nanocomposites: Green synthesis, photocatalytic degradation of methyl violet, and electrochemical detection of Pb²⁺/Cd²⁺

Pressure‐Independent Acoustic‐Vortex Communication With Enhanced‐Capacity and Cryptographic Information by Free‐Flooded Metasurfaces (Adv. Mater. 34/2026)

Dual‐Site Synergistic Ultrathin Pt‐Based High‐Entropy Alloy Nanosheets Enabling High‐Performance Industrial Alkaline HER

ABSTRACT Two‐dimensional (2D) Pt‐based high‐entropy alloys (HEAs) are promising electrocatalysts due to fully exposed active surfaces and tunable multi‐element synergy. However, synthesizing such ultrathin, homogeneous nanostructures remains a formidable challenge, as conventional methods struggle to overcome the intrinsic anisotropic growth tendencies of Pt‐based systems. Herein, we develop a nucleation‐controlled strategy using Pd as structural template to achieve ultrathin PtPdRuNiInSn HEA nanosheets with atomic homogeneity. This structure combines maximized surface accessibility with multi‐element synergy, delivering exceptional alkaline hydrogen evolution activity of 16.5 A mg −1 at −70 mV versus RHE, a 19.6‐fold enhancement over Pt/C. Operando spectroscopy and DFT calculations reveal that Pt/Pd/Ru sites optimize H* adsorption while Ni/In/Sn sites facilitate OH* activation, synergistically lowering the reaction barriers. The entropy‐stabilized configuration demonstrates outstanding durability (negligible activity loss after 50000 cycles) and industrial viability, enabling anion‐exchange membrane electrolyzers to operate steadily for 2500 hours at 1 A cm −2 . This work establishes a general paradigm for designing advanced Pt‐based 2D high‐entropy electrocatalysts.

COPD prescription patterns after the 2018 Japan floods: analysis of national data

Abstract Climate change has led to an increase in flood disasters worldwide, raising concerns about their potential impact on respiratory health. This study investigated the impact of the 2018 Japan Floods, one of the largest flood disasters in Japan’s history, on prescription rates for chronic obstructive pulmonary disease (COPD). To examine the impact of the disaster on COPD-related prescriptions, we analysed anonymised health insurance claims data from the Japanese National Database. The study focused on residents of three prefectures that included the most severely affected areas during the 2018 Japan Floods, covering a 2-year observation period—1 year before and 1 year after the disaster. First, we compared new prescriptions of long-acting inhaled COPD medications after the disaster between victims and non-victims among individuals who had not received such prescriptions during the previous year (n = 3,674,535). Second, we examined prescriptions for antibiotics or systemic steroids after the disaster among individuals already receiving long-acting inhaled COPD medications before the disaster (n = 18,059), as indicators of COPD exacerbations. Cox proportional hazards models showed that new prescriptions for long-acting inhaled COPD medications were significantly higher among disaster victims than among non-victims in the year following the 2018 Japan Floods (aHR: 1.56; 95% CI [1.25–1.95]). Difference-in-differences analysis showed that exacerbation-related prescriptions significantly increased among disaster victims compared with non-victims (aROR: 1.50; 95% CI [1.06–2.11]). New prescriptions for COPD controller medications and exacerbation-related prescriptions significantly increased in populations affected by the 2018 Japan Floods.

Longitudinal analysis of human milk oligosaccharides and mucin-2-glycans in infants reveals enrichment of sulfated and glucuronic acid-bearing HMOs

Shifting drivers of hospitalization in endometrial cancer: Toxicity-like organ failure phenotypes in the modern treatment era.

11066 Background: Frontline endometrial cancer care has rapidly shifted toward immune-based regimens. Whether inpatient admissions have concurrently shifted toward toxicity-like organ failure syndromes, with changing ICU use and rescue outcomes, remains unknown. Methods: We performed a survey-weighted analysis of the National Inpatient Sample (NIS) 2016–2023. Adult hospitalizations with endometrial cancer in any diagnosis position (C54/C55) were included; admissions with palliative care coding (Z51.5) were excluded. Eras were defined as 2016–2017 versus 2018–2023. Toxicity-like organ failure phenotypes were identified using ICD-10-CM proxies including pneumonitis or respiratory toxicity, colitis or diarrhea, myocarditis or pericarditis, hepatitis or liver failure, neutropenic sepsis, acute kidney injury, and electrolyte collapse. A broader sensitivity phenotype additionally included endocrine crises. ICU escalation was proxied by mechanical ventilation or shock. Major complications were defined using a composite bundle, and failure-to-rescue was defined as death among complication admissions. Outcomes included in-hospital mortality, ICU escalation, complications, length of stay (LOS), cost, and routine discharge. Results: Among 74,895 unweighted endometrial cancer hospitalizations, 25.8% occurred in 2016–2017 and 74.2% in 2018–2023. Overall inpatient mortality was 1.86% (95% CI 1.66%–2.07%) in 2016–2017 and 2.09% (95% CI 1.96%–2.22%) in 2018–2023. Hospitalizations involving any toxicity-like organ failure phenotype increased from 34.3% (95% CI 33.4%–35.1%) in 2016–2017 to 45.2% (95% CI 44.7%–45.7%) in 2018–2023. Pneumonitis or respiratory toxicity increased from 6.23% to 9.91%, acute kidney injury from 14.9% to 21.0%, and electrolyte collapse from 23.7% to 31.7%. ICU proxy use increased from 2.50% (95% CI 2.27%–2.73%) to 3.30% (95% CI 3.15%–3.45%), driven by higher shock coding (0.82% to 1.61%). Major complications increased from 36.1% (95% CI 35.3%–36.9%) to 46.5% (95% CI 46.0%–47.1%). Mortality among admissions with toxicity-like organ failure decreased modestly from 4.75% (95% CI 4.25%–5.30%) to 4.25% (95% CI 4.00%–4.52%), while mortality among ICU-level admissions remained high and unchanged (29.7% vs 29.2%). Routine discharge declined from 66.6% (95% CI 65.6%–67.6%) to 62.2% (95% CI 61.7%–62.7%), and LOS increased in the modern era (mean 5.22 days, 95% CI 5.16–5.28). Conclusions: From 2016–2023, endometrial cancer hospitalizations increasingly involved toxicity-like organ failure phenotypes with rising ICU escalation and complication burden, while inpatient mortality changed minimally. These findings highlight a growing disconnect between outpatient therapeutic advances and inpatient recognition and rescue capacity.

Tumor treating fields therapy in patients with newly diagnosed glioblastoma and poor performance status: Real-world analysis of patients treated in the US.

2044 Background: TTFields therapy is an FDA-approved treatment for patients with newly diagnosed glioblastoma, showing benefit in overall survival (OS) when added to maintenance temozolomide (TMZ). While device effectiveness was demonstrated regardless of performance status (PS) in the EF-14 study, only patients with Karnofsky Performance Status (KPS) of ≥70 were eligible for the study. This study investigates real-world outcomes of patients with newly diagnosed glioblastoma and poor PS who were treated with TTFields. Methods: Electronic medical records of patients initiating treatment with TTFields in the US commercial setting between January 1, 2019 and December 31, 2021 were accessed via the xCures real-world data platform and Novocure systems, from which clinical data were extracted. To be included in the analysis, patients needed to have a documented new diagnosis of glioblastoma occurring within 180 days of initiating TTFields and have KPS ≤60 or ECOG PS ≥2 within 3 weeks of treatment initiation. IDH status was ascertained where data were available. Device usage was calculated as the average percentage of time the device was used within the first 3 months of therapy, as recorded by the device log files. Patients were divided into high and low usage groups. High usage was defined as usage ≥50% and treatment duration ≥30 days, and low usage as usage <50% or treatment duration <30 days, excluding patients with a death event within 30 days of initiating TTFields. Demographics, disease characteristics, and survival outcomes were evaluated. Data cutoff for analysis was Jan 7, 2026. Results: The study included 306 patients, of whom 198 (65%) were high users and 108 (35%) low users. Baseline characteristics were balanced between the two groups. Although most patients had KPS of 60 or ECOG PS of 2 (n=204, 67%), the study included 102 patients (33%) who had KPS ≤50 or ECOG PS ≥3. The entire cohort had median OS from diagnosis of 13.3 months (95% CI, 12.4–14.5). Median OS was 14.1 months (95% CI, 12.8–15.9) in the high-use group compared with 11.9 months (95% CI, 9.6–13.3) in the low-use group (HR, 0.69 [95% CI, 0.53–0.89]; P=0.005). Similar results were observed regardless of the performance scale utilized. Further subgroup analysis showed a consistent usage effect for patients ≥65 and <65 years of age (HR, 0.71 [0.49–1.02], P=0.067 and HR, 0.69 [0.47–1.00], P=0.049, respectively). Conclusions: Patients with newly diagnosed glioblastoma and poor performance status receiving TTFields therapy in the real-world setting appear to have favorable survival when compared with historical data. Usage is associated with improved survival in this population, including among elderly patients for whom treatment options are limited. Additional studies examining TTFields in this high-need population with limited trial options are warranted.

LUCID: Turning clinical noise into signal, structuring oncology data at scale.

e15507 Background: Most clinically meaningful oncology information is recorded in unstructured formats, limiting its consistent use. Northwell Health diagnoses approximately 26,000 new cancer patients annually and operates a data lake in which all patient-level digital information is accessible. LUCID was developed to convert unstructured oncology data into structured representations in order to enable reliable downstream clinical, research, and operational use. Methods: LUCID is a platform deployed within a secure, HIPAA compliant environment designed to convert unstructured oncology data into clinically meaningful variables. The architecture combines natural language processing pipelines with modular large language model agents using GPT-5-mini. The modules described here characterize cancer presence, pathologic features, surgical resection events, staging, and follow longitudinal radiographic disease status. Each module was evaluated against clinician-validated ground truth, with cases reviewed by at least two clinicians and disagreements adjudicated by a third reviewer. Performance was assessed using accuracy, precision, recall, and F1 score. Time per patient abstraction and computational cost were measured. Results: 30 patient records were randomly select amongst patients who had undergone a biopsy at Northwell Health within the last decade and had a GI malignancy-associated ICD code; 20 of these cases had malignancy identified and were then assessed for staging and radiographic changes over time. These cases represented real-world heterogeneity including >6 histologies, a range of TNM stages (I-IV), and a breadth of longitudinal imaging assessments (average 13 per patient). Across evaluated domains, LUCID achieved accuracy ranging from 93.0% to 100.0%, with F1 scores from 0.96 to 1 (Table 1). False positives (FP) describe identification of events such as progression or response, whereas false negatives (FN) represent no call detected for an event. Errors were typically attributed to clinical edge-cases such as pseudo-malignant cysts. Abstraction required a total of 85 seconds per patient and 3 cents in processing cost. Conclusions: This proof- of- principle shows that structured oncology information can be extracted efficiently and at scale from unstructured clinical data within a health-system data lake. Although LUCID is capable of generating longitudinal patient timelines, this evaluation focused on module-level performance to enable objective measurements. Ongoing work applies this architecture to expand clinical and research capabilities system-wide. LUCID Module performance. Domain N Accuracy Precision Recall F1 Error profile Cancer Presence 30 100% 100% 100% 100% Valid Resection 30 93% 100% 82% 90% 2 FN Histology and Differentiation 30 97% 95% 100% 98% 1 FP T stage 20 100% 100% 100% 100% N stage 20 100% 100% 100% 100% M stage 20 95% 95% 100% 97% 1 FP Radiographic Changes 106 96% 95% 98% 96% 3 FP

Updated results of a single-arm phase II clinical trial of gemcitabine, cisplatin, and nab-paclitaxel as neoadjuvant therapy for pancreatic ductal adenocarcinoma.

e16468 Background: Neoadjuvant chemo approach is favored in resectable/borderline resectable (R/BR) pancreatic ductal adenocarcinoma (PDAC) to increase the proportion of patients receiving systemic therapy. Current standard regimens, modified Folinic acid, Fluorouracil, Irinotecan, Oxaliplatin (mFOLFIRINOX) and gemcitabine nab-paclitaxel (GN), yield a 33% major pathologic response rate [SWOG S1505]. The regimen of capecitabine, cisplatin, nab-paclitaxel and gemcitabine (PAXG) improved median event free survival compared to mFOLFIRINOX but was equally toxic. The addition of cisplatin to GN(GCN) achieved a clinical response in 71% of patients with metastatic PDAC in a phase Ib/II trial. We evaluated the efficacy and safety of a biweekly neoadjuvant GCN regimen in R/BR PDAC patients. Methods: This ongoing single-arm phase II trial (NCT06423326) aims to evaluate biweekly neoadjuvant GCN in 36 patients with biopsy-proven R/BR PDAC (ECOG 0-1, no prior therapy, adequate organ function). GCN (G 800 mg/m², C 25 mg/m², N 100 mg/m²) is administered IV on days 1 and 15 of 28-day cycle for 4 cycles. CT scans were repeated every 2 weeks, and surgery occurred within 21-42 days after last chemo dose. The primary endpoint is clinical response including biochemical ( > 50% decrease in CA19-9), radiographic, pathologic responses or stable disease leading to surgical resection. Secondary endpoints include R0 resection rates, pathological response, chemotherapy completion, and recurrence free survival. Results: Between Aug 2024 and Dec 2025, 14 patients were enrolled and 12 were analyzed. The median age was 70.5 years; 50% males, 50% ECOG PS of 0 and 75% resectable disease. Median CA 19-9 was 192 (range 2–1542) before the first cycle and 67 (range 2–848) after the fourth cycle of GCN. Of 12 patients, 11 completed the 4 cycles and 4 (25%) required a dose reduction. 75% had biochemical response, all had stable radiographic disease (83%) or partial response (17%). 9 (75%) completed surgery, 89% of those had R0 resection and 33% node-negative. Any pathologic response was observed in 66% and 33% had a major pathologic response. Most resected patients completed adjuvant chemotherapy (8,89%) and 4/9 (45%) recurred. Grade 3 adverse events occurred in 75% (9/12), and included constipation (18%), neutropenia (18%), thromboembolic events (18%), anemia (9%), skin rash (9%), muscle pain (9%) and surgical wound infection (9%); no grade 3 neuropathy, grade 4 toxicities or treatment-related deaths occurred. Conclusions: Neoadjuvant biweekly gemcitabine, cisplatin and nab-paclitaxel is safe with favorable tolerability and manageable toxicity in patients with R/BR PDAC. The regimen demonstrates promising clinical response and high rates of surgical resection with the potential to outperform the current standard regimens, supporting the ongoing trial and further research. Clinical trial information: NCT06423326 .

Age-vulnerability interaction and real-world treatment outcomes in <i>EGFR</i> -mutant non–small cell lung cancer.

e20685 Background: Older adults with EGFR-mutant metastatic non-small cell lung cancer (NSCLC) are underrepresented in clinical trials, and treatment decisions often rely on chronological age rather than biologic reserve. Whether vulnerability modifies the relationship between age and real-world treatment outcomes remains unknown. Methods: We conducted a retrospective cohort study of patients with EGFR-mutant metastatic NSCLC treated with first-line EGFR TKI from 2012-2025 at Northwell Health. Baseline vulnerability was defined using a composite score incorporating 5 established risk factors: high comorbidity burden, performance status (ECOG≥2), hypoalbuminemia ( &lt; 3.5 g/dL), polypharmacy (≥5 medications), and recent hospitalization within prior 6 months. Patients were classified as non-vulnerable (0-1) vs vulnerable (≥2). Outcomes included time to treatment discontinuation (TTD) and progression-free survival (PFS). Multivariable Cox proportional hazards models adjusted for diagnosis era, EGFR mutation subtype, and baseline brain metastases. Effect modification between age (≥75 vs &lt; 75) and vulnerability was tested using interaction terms. Results: Among 112 patients (median age 72, range 40-90), 37% (n = 41) were aged ≥75. Vulnerability (score≥2) was present in 50% of younger and older patients (p = 0.3). Patients received osimertinib (52%), erlotinib/gefitinib (33%), or afatinib (14%). In adjusted models, age ≥75 alone was not associated with TTD (HR 0.88, 95% CI 0.49-1.56, p = 0.65). However, a significant age-vulnerability interaction was noted (p = 0.03). Among non-vulnerable patients (n = 51), age ≥75 was associated with longer TTD (HR 0.43, 95% CI 0.20-0.95) while among vulnerable patients (n = 39), age ≥75 predicted shorter TTD (HR 2.60, 95% CI 1.07-6.22). A similar interaction was observed for PFS (p = 0.04). Among non-vulnerable patients, age ≥75 was not associated with PFS, whereas among vulnerable patients, age ≥75 predicted a shorter PFS (HR 2.1, 95% CI 0.5-10). Diagnosis era, EGFR subtype, and baseline brain metastases remained significant predictors in multivariable models. Conclusions: Chronological age alone does not explain treatment outcomes in EGFR-mutant NSCLC. Vulnerability metric, derived from 5 readily available clinical factors, modifies how age translates into attrition and progression, identifying a high-risk subgroup of older vulnerable patients. Fit older adults achieve outcomes comparable to younger patients. These findings advance precision geriatric oncology by moving beyond one-size-fits-all age cutoff and support vulnerability-informed treatment sequencing and warrant prospective validation.

NALIRIFOX plus targeted therapy as first-line treatment for metastatic colorectal cancer: A phase I study.

3564 Background: FOLFOXIRI combined with targeted therapy is recommended for metastatic colorectal cancer (mCRC) patients suitable for intensive treatment or conversion surgery. However, the combination of irinotecan liposome, oxaliplatin, fluorouracil (NALIRIFOX) in mCRC remains uninvestigated. This Phase I study aimed to determine the maximum tolerated dose (MTD) of irinotecan liposome in this combined therapy for mCRC. Methods: Patients with histologically confirmed and initially unresectable mCRC were enrolled. In the dose-escalation phase (Phase Ia), a 3+3 design was utilized. Eligible patients received fixed doses of oxaliplatin (85mg/m 2 ), fluorouracil (2400mg/m 2 ) and bevacizumab (5mg/kg), while the dose of irinotecan liposome was escalated starting from 60mg/m 2 . If a dose-limiting toxicity (DLT) occurs at 60mg/m 2 , the dose can be reduced to 50mg/m 2 . Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE5.0). In the dose-expansion phase (Phase Ib), irinotecan liposome was administered at the recommended dose from Phase Ia. Based on the RAS/BRAF gene status, either bevacizumab or cetuximab was combined with NALIRIFOX. The safety and efficacy of the combination were further assessed in Phase Ib. Results: From March 2024 to March 2025, 9 patients in the dose-escalation phase and 64 patients in the dose-expansion phase were enrolled, included 48 males and 25 females with a median age of 57 years. The MTD of irinotecan liposome was determined to be 50mg/m². Identified DLTs included grade 3 diarrhea and febrile neutropenia. As of January 15, 2026, 65 patients had at least one tumor assessment. The objective response rate (ORR) was 81.5% and the disease control rate (DCR) was 100.0%. The median PFS was 12.3 months (95% CI 9.8-14.7). The rate of R0 resection was 12.3%. The most common ≥grade 3 treatment-related adverse events (TRAEs) were diarrhea (18.4%) and neutropenia (14.5%). Conclusions: Irinotecan liposome at a dose of 50 mg/m² in the NALIRIFOX regimen showed manageable safety and promising efficacy as first-line treatment for mCRC. Clinical trial information: NCT06225622 .

CDH17 expression and tumor microenvironment composition in gastric cancer.

4033 Background: Cadherin 17 (CDH17), commonly referred to as liver-intestine cadherin, is a calcium-dependent cell adhesion molecule, is overexpressed across multiple gastrointestinal epithelial malignancies and is implicated in tumorigenesis and aggressive tumor phenotypes through diverse signaling pathways. Preclinical studies have demonstrated the therapeutic potential of anti-CDH17 approaches across multiple therapeutic modalities. However, the relationship between CDH17 and cellular characteristics within the gastric cancer tumor microenvironment (TME) is yet to be sufficiently characterized. Methods: To systematically investigate the association between CDH17 expression and TME composition in gastric cancer, we conducted a comprehensive multi-cohort analysis of clinically annotated gastric cancer samples with RNA sequencing data. Within each cohort, CDH17 expression levels were quantified and dichotomized into high and low expression groups based on cohort-specific median transcripts per million (TPM) values. We applied the xCell immune deconvolution algorithm to estimate the relative immune and stromal cell populations enrichment across all samples. Results: In total, we studied 1,811 samples within ten datasets. CDH17 high-expressing gastric cancers demonstrated a distinctive TME signature characterized by selective cellular depletion rather than generalized immune suppression. Natural killer (NK) cell enrichment was identified in three cohorts; however, this pattern lacked pan-cohort consistency. Notably, CDH17 high expression was associated with significant depletion in multiple critical effector populations, including CD8+ cytotoxic T lymphocytes (CD8+ T-cells: 6/10 cohorts p &lt; 0.05), myeloid dendritic cells and cancer-associated fibroblasts (8/10 cohorts, p &lt; 0.05), and hematopoietic stem cells (5/10 cohorts, p &lt; 0.05). In contrast, other immune and stromal cell populations demonstrated heterogeneous patterns of association with CDH17 expression, with no clear or uniform enrichment or depletion across cohorts. Conclusions: CDH17 high-expressing gastric cancers harbor an immunologically "cold" tumor microenvironment characterized by selective depletion of critical effector immune and stromal cell populations.

The landscape of MET alterations in non-small cell lung cancer in Southeast China: A real-world study.

e20686 Background: MET alterations are critical oncogenic drivers in NSCLC. However, real-world data regarding the distribution, clinical characteristics, treatment and outcomes remain limited. Methods: We retrospectively analyzed 574 MET-altered NSCLC patients treated at a comprehensive hospital in southeastern China(July 2021-December 2023). MET alterations were categorized into MET Overexpression, MET Amplification, MET Exon14 Skipping, and MET Other Mutation, identified via PCR, IHC, NGS or FISH. MET-OE-high was defined as IHC 2+/3+. Baseline, pathological, co-mutation, treatment, and survival data were collected. With a minimum follow-up of 2 years, we analyzed 24-month survival and evaluated the prognostic impact of MET-TKIs. Results: Of 574 patients: MET-OE(81.4%), MET-amp(11.0%), MET-ex14(4.70%), and Others(2.96%). Subgroups were predominantly middle-aged/elderly males, &gt; 40% had smoking history and &gt; 35% hypertension. Specimens were mainly from bronchoscopic or percutaneous biopsies. Pathologically, adenocarcinoma predominated across subtypes; in MET-OE, its prevalence increased with IHC intensity (p &lt; 0.05). MET-amp exhibited the highest rates of advanced stage (87.3%), bone metastases (36.5%), and brain metastases (17.5%). TP53 was the top co-mutation(20.7%–25.0%). Targeted therapy predominated (First-line 54.6%, Second-line 38.9%), followed by chemo-immunotherapy, whereas specific MET-TKI utilization was only 10.5%. 24-month overall survival was lower in MET-amp (44.4%) and MET-ex14(48.1%) compared to MET-OE(57.2%) and Others(58.8%). MET-TKIs showed survival benefit trends in MET-OE-high, MET-ex14 and MET-amp. Post-PSM 24-month OS (treated vs untreated): 69.2% vs. 38.5% (MET-OE-high), 71.4% vs. 25.0% (MET-ex14) and 47.4% vs. 42.9% (MET-amp). Conclusions: Despite demographic similarities, MET subtypes exhibit significant pathological, co-mutational, therapeutic and prognostic heterogeneity. MET-TKIs show potential benefits for MET-OE and MET-ex14, warranting large-scale validation.

Tracking genomic evolution in <i>ERBB2</i> -altered biliary tract cancer through longitudinal tumor profiling.

4137 Background: HER2, encoded by ERBB2 (HER2), is overexpressed and clinically actionable in a subset of patients with biliary tract cancers (BTC). Zanidatamab and trastuzumab deruxtecan are now approved for patients with HER2 overexpressed tumors, though all patients ultimately progress on treatment and acquired resistance mechanisms are poorly defined. We aimed to characterize the genomic evolution in patients with ERBB2 altered advanced BTC via serial tumor and cfDNA sampling during systemic therapy. Methods: Patients with ERBB2 altered BTC were extracted of Memorial Sloan Kettering Cancer Center (MSK)’s prospectively maintained institutional genomic profiling protocol (NCT01775072). Eligibility required ≥2 molecular profiles obtained during systemic therapy. Tumor sequencing was performed using MSK-IMPACT (tissue-based NGS) and/or MSK-ACCESS (ctDNA NGS). Paired samples could include tissue and/or ctDNA. Clinical data were annotated, and longitudinal molecular profiles were analysed to assess temporal changes in ERBB2 status. Results: Among 1628 patients with BTC in the institutional database, 122 (7.5%) had ERBB2 altered tumors. Of these, 26 patients had ≥2 molecular samples available for longitudinal analysis. Five were excluded due to incomplete clinical and/or molecular data, leaving 21 eligible patients [Median age at diagnosis, 63 years (range 38–76), gallbladder cancer (n = 12, 57%), intrahepatic cholangiocarcinoma (n = 6, 29%), and extrahepatic cholangiocarcinoma (n = 3, 14%)]. At baseline, ERBB2 alteration patterns included ERBB2 amplification in 15 patients (71.4%), single nucleotide variants (SNV) in 2 patients (9.5%), and concurrent amplification and SNVs in 3 patients (14.3%). The most common co-occurring alterations involved TP53 (67%), SMAD4 (19%), CDKN2A (19%), and SMAD4 (19%). Over the course of systemic treatment [Median number of treatment lines, 3.5 (range 1-6), 71% patients received HER2 directed therapy (n = 15) at any line], loss of ERBB2 amplification at last available molecular sampling was observed in 7 patients (46%) and gain in 1 patient. Longitudinal profiling also demonstrated acquisition of additional alterations in receptor tyrosine kinase (RTK) pathways, including MAPK genes in 19% patients and MET alterations in 4.7%. Among the 15 patients who received HER2-directed therapy, MAPK alterations were observed in 4 (25%) and MET alterations in 1 (6%) at progression. Conclusions: ERBB2 alterations in BTC evolve over time with frequent loss of amplification and emergence of RTK pathway alterations during systemic therapy. Acknowledging limitations of small sample size as well utilization of both cfDNA and tumor profiling, these findings highlight the genomic heterogeneity of ERBB2 altered BTC and support the potential value of longitudinal profiling to better understand mechanisms of resistance and help inform treatment sequencing.

Real world outcomes of neoadjuvant immune checkpoint blockade (ICB) for resectable stage III melanoma: Pathologic response and FDG PET/CT correlates.

9569 Background: Neoadjuvant (NA) ICB is standard of care for resectable stage III melanoma, with major pathological (p) response (R) (MPR, ≤10% viable tumor) strongly predicting relapse free survival (RFS). Imaging biomarkers to predict MPR are lacking. We evaluated the outcomes of patients (pts) treated with NA pembrolizumab (Pem) or nivolumab (NIVO) + ipilimumab (IPI) therapy, focusing on pR and FDG PET/CT metabolic changes. Methods: We retrospectively analyzed pts with resectable stage IIIB-D melanoma treated with NA Pem or NIVO + IPI at Peter Mac from March 2022 to Dec 2025. Clinical characteristics, pR, RFS, and treatment-related adverse events (TRAEs) were analyzed. RFS was calculated from date of surgery until day of death, recurrence or last follow up. Maximum standardized uptake value (SUVmax) of the most avid lesion (lymph node (LN) or in-transit metastases (ITM)) at baseline and post NA ICB on FDG PET/CT scans were recorded. Results: Of the 130 pts, 100 had LN metastasis only, 19 ITM only and 11 LN + ITM. 77 (59.2%) received Pem and 53 (40.8%) received NIVO + IPI. 117 pts (90.0%) underwent surgery: LN dissection in 40, index LN (ILN) excision in 58, ITM excision in 18 and excision of ITM + ILN in 1. 13 pts did not have surgery, 10 due to progressive disease on FDG PET/CT, complete resolution of ITM in 2, and toxicity in 1. MPR was seen in 74 (63.2%), partial response (pPR) in 7 (6.0%) and pathological non-response (pNR) in 36 (30.8%) pts. A ∆SUVmax decline ≥50% post NA ICB was strongly predictive of MPR, whereas pts without significant metabolic response were more likely to have pNR (sensitivity 93.2%, specificity 60.0%, positive predictive value 71.9%, negative predictive value 88.9% and accuracy 77.4% p =0.005). In ILN disease, 40/43 pts (93.0%) with ≥50% drop in ∆SUVmax achieved MPR (p&lt;0.0001). In ITMs, a decline in ∆SUVmax ≥50% resulted in MPR in all 10 pts (table 1). At 12 months (m) median follow up, 14 pts recurred including 4 after MPR. The estimated 12m RFS was 89.0% for Pem and 79.3% for NIVO + IPI. 12m RFS in pts with ∆SUVmax decline ≥50% for Pem was 97% and 82% for NIVO + IPI ( p =0.045). Grade ≥3 TRAEs occurred in 12 pts (7.5%), more frequently with NIVO + IPI. Conclusions: NA ICB yields high MPR rates in stage III melanoma. Early metabolic response on FDG PET/CT, defined as a ΔSUVmax ≥50% decline is a strong, readily implementable imaging biomarker for predicting MPR following NA ICB, enabling early treatment adaptation and personalized surgical decision-making. Pem (n=77) NIVO + IPI (n=53) Median age [range] 67 [41-92] 67 [20-82] BRAF mutant, n (%) 23 (29.9) 27 (50.9) Stage III B/C/D, n 26/50/1 20/33/0 Site of disease, neck/axilla/groin/ITM, n 23/28/13/13 18/20/12/6 MPR, n (%) 45 (65.2) 29 (60.4) MPR ∆SUVmax decline ≥50% 33/35 13/14 MPR ∆SUVmax decline &lt;50% 12/34 7/22 12m RFS ∆SUVmax decline ≥50% (95% CI) 96% (89%-100%) 100% 12m RFS ∆SUVmax decline &lt;50% (95% CI) 82% (67%-100%) 80% (59%-100%)

Safety and efficacy of nesuparib (JPI-547) with gemcitabine-nab-paclitaxel (GemAbraxane) or modified FOLFIRINOX (mFOLFIRINOX) in patients with locally advanced or metastatic PDAC: Results from an ongoing phase Ib/II study.

4193 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with poor outcomes in advanced disease. Nesuparib is a dual tankyrase (TNKS) and poly(ADP-ribose) polymerase (PARP) inhibitor that induces a “BRCAness” phenotype via WNT and Hippo signaling. This Phase Ib study evaluated the safety, tolerability, and preliminary antitumor activity of nesuparib combined with standard first-line chemotherapy in patients with locally advanced or metastatic PDAC. Methods: This multicenter, open-label, Phase Ib dose-finding study evaluated oral nesuparib plus GemAbraxane or mFOLFIRINOX in advanced PDAC. Nesuparib was administered orally using a 3+3 dose-escalation design with intermittent schedules, including DL1 (25 mg, 5 days on/2 days off), DL-1 (12.5 mg, 5 days on/2 days off), and DL-2 (12.5 mg, 3 days on/4 days off). Primary objectives were to assess safety and determine the maximum tolerated dose and recommended Phase II dose. Secondary objectives included preliminary efficacy. Results: As of December 31, 2025, 27 patients were enrolled and treated (GemAbraxane, n = 14; mFOLFIRINOX, n = 13). Most patients had metastatic disease. In the GemAbraxane arm, acceptable tolerability was confirmed at DL-1 and DL-2, whereas tolerability was not established in the mFOLFIRINOX arm. Across both treatment arms, grade 3/4 AEs were mainly hematologic toxicities. Rates of anemia, thrombocytopenia, and neutropenia were 57.1%, 64.3%, and 92.9% in the GemAbraxane arm, compared with 84.6%, 92.3%, and 84.6% in the mFOLFIRINOX arm, respectively. No treatment-related deaths occurred, and most AEs were manageable with standard supportive measures. Non-hematologic AEs were mostly low-grade and manageable. In the GemAbraxane arm, the objective response rate (ORR) and disease control rate (DCR) were 53.8% and 92.3%, respectively, including one patient with a complete response (CR) of the target lesion and overall survival exceeding 3 years. Median progression-free survival (mPFS) was not reached, and median overall survival (mOS) was 14.2 months (data immature and follow-up is ongoing). In the mFOLFIRINOX arm, the ORR was 38.5% with a DCR of 92.3%, while mPFS and mOS were 7.33 and 18.5 months, respectively. Conclusions: Nesuparib combined with GemAbraxane demonstrated acceptable tolerability and encouraging antitumor activity in advanced PDAC. These findings support further evaluation of nesuparib using a 12.5 mg intermittent dosing schedule in the first-line treatment setting; a Phase II trial is currently ongoing. Clinical trial information: NCT05257993 . Outcome Nesuparib + GemAbraxane (n=13) Nesuparib + FOLFIRINOX(n=13) PR 7 (53.8%) 5 (38.5%) SD 5 (38.5%) 7 (53.8%) PD 1 (7.7%) 1 (7.7%) ORR 53.8% 38.5% DCR 92.3% 92.3% mOS 14.20 mo (data immature) 18.50 mo mPFS Not reached 7.33 mo

Clinical outcomes of heart failure in breast cancer patients receiving HER2-directed therapy: A retrospective analysis (2016–2020).

e13003 Background: HER2-directed therapies are a used in the treatment for HER2-positive breast cancer but are associated with cardiotoxicity, including heart failure. Symptomatic heart failure has been reported in a minority of patients receiving HER2-directed regimens. We evaluated inpatient clinical outcomes and healthcare utilization among breast cancer hospitalizations with documented exposure to HER2-directed therapy complicated by heart failure. Methods: We analyzed the National Inpatient Sample (NIS) database (2016–2020). Adult hospitalizations with a primary diagnosis of breast cancer and documented exposure to HER2-directed therapy were identified using ICD-10 codes. Admissions with versus without heart failure (HF) were compared. Categorical and continuous variables were assessed using the chi-square test and Student’s t-test, respectively. Multivariable regression was used to adjust for demographic and clinical confounders and to estimate adjusted odds ratios (aOR). Statistical significance was defined as p &lt; 0.05. Results: A total of 193,684 breast cancer hospitalizations with exposure to HER2-directed therapy were identified; 17,431 had a comorbid diagnosis of HF. Patients with HF were older (mean age 70 years, p &lt; 0.001). Overall, 98% were female and 2% were male (p &lt; 0.001). The cohort was predominantly White (66%), followed by Black (25%) and Hispanic (5%) patients (p = 0.007). HF-associated admissions had a longer mean length of stay (6.5 vs 4.2 days) and higher mean total hospital charges ($65,380 vs $65,278) compared with admissions without HF. In multivariable analyses adjusting for demographics and comorbidities, HF was associated with significantly higher odds of cardiogenic shock (1.3% vs 0.06%; aOR 36; p &lt; 0.001), sepsis (7.4% vs 5.0%; aOR 1.3; p = 0.001), ventricular arrhythmias (3.8% vs 0.7%; aOR 4.5; p &lt; 0.001), and acute hypoxic respiratory failure (29% vs 7.6%; aOR 3.3; p &lt; 0.001). Cardiac arrest was not significantly different after adjustment (0.5% vs 0.3%; aOR 1.1; p = 0.7). Conclusions: Among breast cancer hospitalizations with exposure to HER2-directed therapy, comorbid heart failure was associated with higher inpatient morbidity and healthcare utilization. These findings underscore the importance of risk stratification and proactive cardio-oncology–informed management to potentially reduce complications in this population. In-hospital outcomes and resource utilization among patients with and without heart failure. Outcomes Heart Failure Without Heart failure Adjusted OR P value Length of Stay 6.5 days 4.2 days – – Total Charges 65380 65278 – – Cardiogenic Shock 234/17815 106/175869 36 &lt;0.001 Sepsis 1329/17815 8809/175869 1.3 0.001 Cardiac Arrest 015/17815 560/175869 1.1 0.7 AHRF 5265/17815 13399/175869 3.3 &lt;0.001 Ventricular Arrhythmias 684/17815 1350/175869 4.5 &lt;0.001

Evaluation of survival after induction immunochemotherapy followed by concurrent chemoradiotherapy in unresectable esophageal cancer: A systematic review, meta-analysis, and network meta-analysis.

e16137 Background: Concurrent chemoradiotherapy (CCRT) remains the standard treatment for nonsurgical esophageal cancer (EC); however, the prognosis remains poor. The clinical benefits of the combination of immunotherapy with CCRT for unresectable EC remain controversial. Therefore, we performed a systematic review and meta-analysis of published studies to evaluate the potential benefits of different combined immunotherapeutic strategies based on CCRT for patients with unresectable EC. Methods: We employed single-arm, pairwise and network meta-analysis methods to analyze the overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and safety of several combined treatment strategies based on CCRT. Results: 28 single-arm trials and 34 controlled trials involving a total of 8104 participants were included. Single-arm meta-analysis have demonstrated that CCRT plus consolidation immunotherapy (CCRT-IO) has the highest 1-year OS rate of 85.7% (95%CI 73.6-97.8, I² = 86.4%) and 2-year OS rate of 67.3% (95%CI 58.8-75.9, I² = 35.2%). However, due to the limited number of available studies, pairwise and network meta-analyses could not be performed. The pairwise meta-analysis showed that, compared with CCRT alone, induction immunochemotherapy plus CCRT (ICT-CCRT) had significantly improved OS (0.49, 95%CI 0.32-0.74, I² = 0.0%) and PFS (HR 0.54, 95%CI 0.37-0.79, I² = 0.0%). The network meta-analysis showed that ICT-CCRT yielded the best OS and PFS results, with substantial benefits over CCRT alone (HR 0.73, 95% CI 0.58-0.92; HR 0.77, 95% CI 0.60-0.98). Conclusions: The study revealed that ICT-CCRT significantly improves patient survival compared to CCRT. CCRT-IO has also been associated with a survival benefit, achieving the highest 1- and 2-year OS rates in single-arm studies. Due to the limited number of available studies, a statistical comparison of survival benefits between CCRT-IO and ICT-CCRT was not feasible.