Browse Articles

The value of tumor deposits in prognosis evaluation and clinical stage optimization of colorectal cancer: A real-world population-based retrospective cohort study.

3642 Background: The location and weight of tumor deposit (TD) in the TNM staging system may be seriously underestimated, which affects the accuracy of TNM staging in predicting prognosis. We conducted a study to further clarify the role of TD in predicting the prognosis, the weighting of TD, and the possible value of optimizing the TNM staging system of CRC. Methods: The subject was CRC patients diagnosed by postoperative pathology in our hospital from January 2013 to December 2021, including 2642 TD (+) and 1162 TD (-) patients. TD (-) patients were regarded as the control group according to category matching principle of the diagnosis, treatment and the period as TD (+) patients. Cox univariate and multivariate were analyzed. K-M curve was applied to analyze survival. Results: (1) The clinical and pathological characteristics are as follows: The TD positive rate was 25.3%. In stage I-III, more advanced tumor T and N-stage, primary sites in the left-sided colon or rectum, poorer histologic grade, and more nerve invasion and vascular infiltration (all p<0.05) were observed in TD (+) patients. In stage IV patients, TD (+) patients were more likely to have multiple metastases ( p <0.05). (2) Patients with TD (+) had worse prognosis than patients with TD (-), with shorter DFS and OS in stage I-III (3-y DFS and OS rate, all p <0.05), with shorter PFS in stage IV (3-y PFS rate, p<0.05). The univariate and multivariate analysis showed that TD (+) was one of independent prognosis factors in CRC patients. And the prognosis shows a trend of getting worse as the number of TD increases. (3) The relationship between TD and N staging: Patients with TD (+), LN (-) had similar OS as patients with TD (-), LN (+) (3-y OS rate, p=0.418). Patients with TD (+), LN (-) had similar OS as patients with TD (-), N2 (3-y OS rate, p=0.695). Patients with TD (+), LN (-) had shorter OS than patients with N2a, TD (-) (3-y OS rate, p=0.029) and longer OS than patients with N2b, TD (-) (3-y OS rate, p=0.034). When TD and LN were counted together for N-staging, the OS between patients with new N2 and primary N2 was similar (3-y OS rate, p=0.382). (4) The relationship between TD and M staging: The survival of patients with TD more than 4 was similar to stage IV patients (2-y OS rate , p=0.061); when the number of LN more than 6 and TD (+) coexisted, OS was similar with stage IV patients (2-y OS rate, p=0.554). When TD and M were counted together for M-staging, the OS between patients with new M1 and primary M1 was similar (3-y OS rate: p=0.149). Conclusions: TD (+) patients are related with unfavorable prognostic clinical and pathological factors. TD was one independent prognosis factor in CRC patients. The location and weight of TD in the TNM staging system may be seriously underestimated. The prognostic accuracy of TNM staging may be improved when the weight of the presence and quantity of TD is increased. Clinical trial information: 2023-ks-143.

Rosmarinic acid-loaded folic acid-chitosan nanoparticles: Synthesis, characterization, and anticancer effects on liver cancer cell line HepG2

Quasi‐Solid Iodine Electrode for High‐Areal‐Capacity Aqueous Iodine Batteries

ABSTRACT Zinc–iodine batteries (ZIBs), operating via either the two‐electron I − /I 0 (2eZIB) or four‐electron I − /I 0 /I + (4eZIB) redox couples, offer high theoretical energy density and sustainability. However, achieving practical high energy density requires high iodine content and mass loading, which slow iodine redox kinetics and exacerbate I + hydrolysis and shuttling. Here, we present a robust quasi‐solid electrode (QE) architecture in which molecularly dispersed iodine that spatially confined within a polyacrylonitrile (PAN)–N‐methyl‐2‐pyrrolidone (NMP) gel network—otherwise volatile—enabling high iodine retention during electrode processing. Iodine not only acts as the active material but also drives gel‐phase formation and stabilization via NMP·I 2 charge‐transfer complexation and strong polyiodides–PAN interactions, integrating a robust, elastic structure further reinforced by the kosmotropic effect in ZnSO 4 electrolyte. This architecture accelerates both I − /I 0 and I 0 /I + redox kinetics, achieves high‐loading (up to 100 mg cm −2 ), high iodine fraction in the electrode (∼53 wt.%), and record areal capacities (17.5 mAh cm −2 in 2eZIBs and 23.44 mAh cm −2 in 4eZIBs), along with suppressed self‐discharge and scalable ampere‐hour pouch‐cell stability. This shuttle‐free design combines efficient mass transfer with mechanical robustness, providing a promising solution for energy‐dense iodine batteries.

All‐Dry and Scalable Direct Recycling of Spent Ternary Black Mass Toward Long‐Life Ah‑Level Pouch Cell

ABSTRACT The direct recycling of spent cathode materials is a promising strategy for a sustainable supply chain but remains challenging for industrial‐sourced cathode black mass due to its complex morphology and heterogeneous impurities. Here, we report an all‑dry and scalable process that directly regenerates spent LiNi 0.5 Co 0.2 Mn 0.3 O 2 (NCM523) black mass into high‑performance cathode materials. By integrating plasma‐assisted mechanochemistry with thermal annealing, the process simultaneously refines particle morphology, enhances the relithiation kinetics, and converts trace impurities (Al, Na) into beneficial dopants through plasma‐enabled defluorination and homogeneous incorporation. This enables complete recovery of the layered structure with controlled single‐crystal morphology and preferential (003) facet exposure. The regenerated NCM523 delivers a high specific capacity and long‐term cycling stability, retaining 82.6% of its initial capacity after 300 cycles at a high cut‐off voltage of 4.5 V. Practical scalability of this approach is demonstrated through the batch processing of kilogram‐level black mass, and a 2 Ah pouch cell maintains 97.1% capacity retention over 1000 cycles. This work provides a practical solution for transforming battery black mass into high‑value cathode materials.

Efficacy and safety of non-covalent BTK inhibitors: A systematic review focused on indolent lymphomas.

e19081 Background: Covalent Bruton’s tyrosine kinase inhibitors (cBTKi) have transformed the treatment of B-cell malignancies; however, long-term efficacy is limited by intolerance, off-target toxicities, and acquired resistance, most commonly due to mutations at the BTK C481 binding site. Non-covalent (reversible) BTK inhibitors, including pirtobrutinib (LOXO-305), nemtabrutinib (ARQ-531) which bind BTK independently of C481. Although early-phase trials have shown activity across several B-cell malignancies, their role in indolent B-cell lymphomas remains unclear. We therefore conducted a systematic review to evaluate the efficacy and safety of non-covalent BTK inhibitors across B-cell malignancies, with a focus on indolent lymphoma subtypes. To our knowledge, this is the first systematic review evaluating efficacy and safety of non-covalent BTK inhibitors in indolent B-cell lymphomas. Methods: A systematic review was performed according to PRISMA 2020 guidelines. PubMed, Embase, and ClinicalTrials.gov were searched in November 2025 for clinical trials and observational studies evaluating non-covalent BTK inhibitors in relapsed or refractory indolent B-cell lymphomas, including follicular lymphoma (FL), marginal zone lymphoma (MZL), and Waldenström’s macroglobulinemia (WM). Studies reporting efficacy and/or safety outcomes were included. Extracted data included overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), follow-up duration, and treatment-related adverse events. Risk of bias was assessed using the ROBINS-I tool. Results: Five studies involving 215 patients met inclusion criteria: FL (n=89), MZL (n=48), and WM (n=78). Median age ranged from 59–68 years. Patients were heavily pretreated (median 3–4 prior lines), including anti-CD20 antibodies, chemotherapy, and cBTKi; most cBTKi discontinuations were due to progression or intolerance. ORR ranged from 39–50% in FL (weighted mean 46%), 50–64% in MZL (weighted mean 56%), and 68% in WM. Responses were observed in patients previously exposed to cBTKi, including those with documented resistance, supporting activity independent of C481 binding. Median DoR was 5.5–5.8 months in FL and 8.5 months to not reached in MZL. In WM, the estimated 6-month DoR was 86%. Median follow-up ranged from 7–16 months. Treatment was generally well tolerated. Common adverse events included fatigue, diarrhea, contusions, and cytopenias. Grade ≥3 toxicities were mainly hematologic (neutropenia, anemia, thrombocytopenia). Treatment discontinuation due to adverse events was infrequent (2–17%). Conclusions: Non-covalent BTK inhibitors are effective, well tolerated, and capable of overcoming cBTKi resistance in relapsed or refractory indolent B-cell lymphomas (excluding CLL/SLL), supporting further prospective studies and real-world use.

Interim analysis results from Duravelo-2: Zelenectide pevedotin (zele; BT8009) + pembrolizumab in patients (pts) with previously untreated locally advanced/metastatic urothelial carcinoma (la/mUC).

4516 Background: Zele is a highly selective Bicycle Drug Conjugate (BDC) targeting Nectin-4, a protein overexpressed in la/mUC. There remains an unmet need in la/mUC for safer and more tolerable treatments. Here, we report an interim analysis (IA) for zele + pembrolizumab (pembro) dosage selection from the Phase 2/3 Duravelo-2 study (NCT06225596/BT8009-230) in previously untreated (untx) pts with la/mUC. Methods: Adults with la/mUC were enrolled into 2 cohorts: previously untx pts eligible for platinum-based chemotherapy (Cohort [Co]1) or pts with ≥1 prior systemic therapy (Co2). IA was conducted to determine the optimized dosage of zele + pembro (Co1) or zele monotherapy (Co2). Herein, we report IA results from Co1. Pts in Co1 were randomized 1:1:1 to: zele 5 mg/m 2 on Days [D]1/8/15 + pembro 200 mg on D1; or zele 6 mg/m 2 on D1/8 + pembro 200 mg on D1; or gemcitabine + cisplatin/carboplatin ± avelumab on a 21-D cycle. Dosage optimization included safety, efficacy, and pharmacokinetic data in pharmacometric and utility score analyses to quantify benefit-risk. Results: IA was performed at 27 weeks of follow-up (N=30 each zele dose group). Median zele treatment (tx) duration was 6.21 months. Confirmed ORRs by BICR among randomized, dosed pts with measurable disease at baseline were 55% (16/29; 7 complete responses [CR], 9 partial responses [PR]; 95% CI 35.7–73.6) and 58% (15/26; 8 CR, 7 PR; 95% CI 36.9–76.6) with zele 5 mg/m 2 and 6 mg/m 2 , respectively. Zele-related adverse events (AEs) were reported in 97% (47% Gr ≥3) of pts at 5 mg/m 2 and 90% (40% Gr ≥3) at 6 mg/m 2 . Gr ≥3 zele-related AEs for 6 mg/m 2 (≥5% pts) included neutropenia (10%), neutrophil count decreased (7%), and anemia (7%). AEs related to pembro were reported in 80% (37% Gr ≥3) and 53% (13% Gr ≥3), respectively. Zele-related AEs of clinical interest (AECIs) for 6 mg/m 2 are summarized in the Table. Notably, no zele-related severe skin reactions of any Gr were reported at the 6 mg/m 2 dosage. Zele dose reductions and discontinuations due to zele-related AEs occurred in 20% and 3%, respectively, for 6 mg/m 2 . At Week 27, >50% of pts remained on tx. Conclusions: Zele at 5 mg/m 2 on D1/8/15 + pembro and 6 mg/m 2 on D1/8 + pembro on a 21-D cycle demonstrate encouraging response rates and safety profiles with the potential to differentiate from ADCs in previously untx pts. The 6 mg/m 2 D1/8 regimen demonstrated a more favorable benefit-risk profile to meet the need for safer and more tolerable treatments, with substantially reduced toxicity, better tolerability, improved potential for combinability, and enhanced convenience, leading to fewer discontinuations. Clinical trial information: NCT06225596 . Zele-related AECIs in pts with previously untx la/mUC treated with zele 6 mg/m 2 on D1/8 + pembro (N=30). AECI, n (%) Any Grade Grade ≥3 Peripheral neuropathy 11 (37) 1 (3) Skin reactions 5 (17) 0 Eye disorders 3 (10) 0 Hyperglycemia 0 0

Updated results from the phase 2 IZALCO study: Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in relapsed/refractory multiple myeloma.

7564 Background: In combination with conventional doublet and triplet therapy, isatuximab (Isa) provides significant benefit to patients (pts) across the multiple myeloma (MM) spectrum. Subcutaneous (SC) administration of Isa could be a more convenient option for pts and caregivers. The Phase (Ph)3 IRAKLIA trial in relapsed/refractory MM (RRMM) pts demonstrated non-inferiority in efficacy and pharmacokinetics of Isa SC delivered via a wearable on-body injector (OBI) in combination with pomalidomide and dexamethasone (Pd) vs Isa IV Pd. The Ph2 IZALCO study (NCT05704049) also showed efficacy and safety of Isa SC plus carfilzomib and dexamethasone (Kd), either by manual or OBI injections, in RRMM pts. Following exposure to both methods, pts showed higher preference for OBI vs manual SC injection. Here we present updated efficacy and safety results from IZALCO. Methods: Isa SC 1400 mg was given weekly in Cycle (C)1 then biweekly. In Part 1, pts received Isa injected SC manually. In Part 2, pts were randomized to Isa administered SC via OBI (Isa SC OBI; C1-C3) followed by manual SC injection (C4-C6), or to manual SC injection (C1-C3) followed by Isa SC OBI (C4-C6). Starting at C7, pts could choose either treatment method. All pts were treated with carfilzomib (20 mg/m 2 on Day [D]1-2 then 56 mg/m 2 on D8-9, 15-16 at C1, then D1-2, 8-9, and 15-16) and dexamethasone (20 mg on D1-2, 8-9, 15-16, and 22-23). Results: A total of 74 RRMM pts were enrolled (8 in Part 1; 66 in the randomized cohort, Part 2). At the data cut-off of November 10, 2025, 59 pts remained on study. At study entry, pts had median age of 65 (44-85) years, median weight of 75.9 (40.0-129.0) kg, and median of 1 prior line of therapy (1-5), and 56.8% had ISS stage I. The median duration of Isa SC OBI administration was 12 mins and manual SC injection was 6 mins. None of the Isa SC injections, manual or OBI, were interrupted. Median time to best response was 5.3 months (mos) (95% CI: 3.25-6.24). At median follow-up of 21.9 mos, median PFS was not reached (NR) (95% CI: 16.23-NR). PFS at 18 mos was 61.5% (95% CI: 48.7–72.0). OS at 18 mos was 80.8% (95% CI: 69.8-88.2); median OS was not reached (95% CI: NR-NR). Overall, grade (G) ≥3 TEAEs occurred in 66.2%, and serious TEAEs in 51.4% pts. Infusion reaction (IR) on C1D1 occurred in 2 pts (2.7%) with manual SC injections; no IRs occurred with OBI. Six (8.1%) pts had 13 injection-site reactions (ISR), all G1, in 2425 (0.54%) manual or OBI injections. Only 1 ISR was deemed related to OBI. Pt satisfaction with injection method remained consistently high with Isa SC OBI up to C25D15. Conclusions: Updated results of the IZALCO study continue to show the efficacy and safety of Isa SC plus Kd delivered either by manual injection or Isa SC OBI, while demonstrating high pt satisfaction and preference for Isa SC OBI. These findings are consistent with those reported in the Ph3 IKEMA study (Isa IV plus Kd). Clinical trial information: NCT05704049 .

Beyond <i>ESR1</i> : Multi-pathway genomic drivers of endocrine resistance in HR⁺/HER2⁻ breast cancer.

1071 Background: Endocrine resistance in HR⁺/HER2⁻ breast cancer is often associated with acquisition of ESR1 point mutations, but many patients at progression remain ESR1 wild type. Identifying ESR1 -independent, multi-pathway acquired resistance mechanisms is critical for guiding subsequent therapy. Methods: We analyzed 1,429 HR⁺/HER2⁻ breast cancer samples (468 tissue, 1,171 cfDNA), including 210 paired cases, from patients with metastatic breast cancer undergoing molecular testing for treatment guidance or disease monitoring. Next-generation sequencing performed at Datar Cancer Genetics assessed SNVs, CNAs, and gene fusions. Alterations implicated in endocrine resistance were analysed for incidence, specimen type, and co-alteration patterns. Results: ESR1 -wild-type tumors frequently harbored clinically relevant endocrine resistance mechanisms, most commonly involving the PI3K/AKT, FGFR, ERBB2, MAPK , and cell-cycle pathways. At least one resistance-associated alteration was identified in 40.4% (473/1172) of evaluable ESR1 -wild-type cases, while 14.8% (173/1172) harbored alterations across multiple resistance pathways, highlighting substantial ESR1 -independent resistance biology. Among ESR1 -driven mechanisms, ESR1 SNVs were detected slightly more frequently in cfDNA than tissue (13.7% vs 12.8%), despite inclusion of cfDNA samples obtained during clinical surveillance, supporting the sensitivity of liquid biopsy for detecting emergent resistance. ESR1 fusions represented a distinct, non-overlapping resistance mechanism, identified in 7.4% (28/379) of tissue samples, most commonly ESR1–CCDC170 (71%) and ESR1–AKAP12 (14%); 21 fusion-positive cases lacked ESR1 SNVs, underscoring the need for fusion assessment to fully capture ESR1 -driven resistance. Dynamic pathway activation was further supported by acquired PI3K pathway mutations, detected in cfDNA in 3.3% (4/122) of cases initially PIK3CA -wild-type in paired tissue samples. Conclusions: Endocrine resistance in HR⁺/HER2⁻ breast cancer is mediated by multiple actionable genomic pathways beyond ESR1 , including PI3K/AKT, FGFR, ERBB2, MAPK , and cell-cycle alterations. These findings expand opportunities to personalize therapy and guide clinical trial selection by targeting non- ESR1 resistance mechanisms. Incidence of endocrine resistance-associated genomic alterations beyond ESR1 point mutations in tissue and liquid biopsy for HR⁺/HER2⁻ breast cancer. Endocrine Resistance Biomarker ESR1 -Mutant Cases (%) ESR1 Wild-Type Cases (%) ESR1 fusions 11.1 6.7 FGFR1 alterations 13.2 7.0 CCND1 amplification 15.2 7.0 FGFR2/3 alterations 3.7 2.0 HER2 -mutant, non-amplified 2.5 2.6 PIK3CA mutation 43.7 25.1 PTEN mutation 2.0 1.6 AKT1 mutation 5.6 3.6 MAPK Pathway( RAS/RAF/MEK ) 4.6 4.0

Phase I light-dose escalation study in locally advanced pancreatic ductal adenocarcinoma: Intra-arterial (IA) padeliporfin vascular-targeted photodynamic therapy (VTP).

TPS4267 Background: Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) with &gt; 180° vascular encasement of major abdominal arteries is considered unresectable and is associated with poor prognosis. Standard-of-care options, including chemotherapy and chemoradiation, achieve limited conversion to resectability with high recurrence rates. Thus, a therapeutic approach that can effectively downstage LA-PDAC to resection is clinically needed. Activation of vascular-targeted photodynamic therapy (VTP) by Padeliporfin illumination at 753nm results in photochemical generation of oxygen and nitric oxide radicals that cause rapid occlusion followed by break down of the tumor vasculature, tumor necrosis and break-down of the extracellular matrix. Photosensitivity at &gt; 6 hours is avoided due to 1.19 hours Padeliporfin half-life without accumulation in epithelial tissue. Padeliporfin-VTP activation by intra-arterial (IA) illumination has the potential to selectively ablate tumor tissue encasing the artery, reducing vascular encasement and enabling subsequent surgical resection. Robust feasibility and safety preclinical studies in normal swine and efficacy in mouse tumor models have demonstrated feasibility of light transmission through the arterial wall at a dose sufficient to induce tumor ablation at the artery interface and acceptable safety profile, supporting clinical translation. Methods: NCT05919238 is an ongoing multi-center Phase I light dose-escalation study. Key inclusion criteria are stage III LA-PADC with solid tumor contact &gt; 180° in head/uncinate process of the pancreas for the total encasement length up to 3cm and with target artery internal diameter 5-10 mm. VTP is applied via IA placement of an optical fiber, inside a standard angioplasty balloon, in the target artery adjacent to the tumor. Ten minutes intravenous administration of Padeliporfin at a fixed dose of 4 mg/kg immediately followed by 753nm laser illumination through the inflated balloon, for two 5-minute cycles with 1-minute break. The study is designed to evaluate three light power densities: 200, 400 and 600mW/cm. The primary objectives include determination of Maximum Tolerated light Dose (MTD) and/or recommended phase 2 dose (RP2D) and evaluation of safety. Secondary objectives are to determine rate of surgical downstaging and resectability as well as the pattern of disease progression following VTP treatment, based on pre- and post-VTP contrast computed tomography (CT) scans and tissue specimens, in case surgery is performed. The study comprises two parts: part A with 3+3 light dose escalation schema; part B (expansion cohort) with the RP2D/MTD, derived in Part A. As of 28 October 2025, Cohort 1 of Part A with an LPD of 200mW/cm have been completed without DLTs. Enrolment to cohort 2, with LPD 400mW/cm, began in November 2025. Clinical trial information: NCT05919238 .

Real-world efficacy of nirogacestat compared to prior standard-of-care (SOC) systemic agents in desmoid tumors.

e23542 Background: Desmoid tumors are rare, locally aggressive fibroblastic neoplasms for which systemic therapy has historically included tyrosine kinase inhibitors (e.g., sorafenib, pazopanib) and hormonal/anti-inflammatory approaches. Nirogacestat, a gamma-secretase inhibitor, was recently proven effective versus placebo in a phase III trial and approved for desmoid tumors. We performed a real-world comparison of nirogacestat versus other systemic therapies. Methods: We retrospectively analyzed 31 UCI Health patients treated from 2019–2025 (nirogacestat n=18; other SOC: sorafenib/pazopanib/tamoxifen+sulindac n=13). Response was assessed by RECIST v1.1. ORR (CR+PR) was compared with Fisher’s exact test. PFS was estimated by Kaplan–Meier and compared by log-rank; HRs were calculated with Cox regression. Results: Median follow-up was 8.3 months (range, 1.57–22.87) with nirogacestat and 41.6 months (2.8–207.2) with other SOC. ORR was 44.4% with nirogacestat versus 23.1% with other therapies, a difference not statistically significant (p=0.45). Among responders with available dates, median time to response was 6.4 months (3.7–10.0; n=6) vs 6.7 months (3.4–22.1; n=3). Median PFS was not reached with nirogacestat and was 58.0 months with other SOC (95% CI, 11.5–104.5); log-rank p=0.685. Univariable Cox regression showed no significant PFS difference (HR 0.73, 95% CI 0.16–3.41; p=0.686). No deaths were observed during follow-up; OS was not estimable. Conclusions: Nirogacestat showed a higher tumor response rate than other systemic therapies(sorafenib, pazopanib, or tamoxifen/sulindac) in this real-world analysis. However, no significant PFS improvement was observed, likely due to the small sample size and shorter follow-up for the nirogacestat group. These findings support the activity of nirogacestat in desmoid tumors and warrant validation in larger, long-term studies. Best overall response and time to response with nirogacestat versus other standard systemic therapies in desmoid tumors (real-world, retrospective cohort). Outcome Nirogacestat (n=18) Other SOC* (n=13) CR, n (%) 1 (5.6) 1 (7.7) PR, n (%) 7 (38.9) 2 (15.4) SD, n (%) 7 (38.9) 8 (61.5) PD, n (%) 3 (16.7) 2 (15.4) ORR (CR+PR), n (%) 8 (44.4) 3 (23.1) Median time to response among responders, months (range)† 6.4 (3.7–10.0) 6.7 (3.4–22.1) *Other SOC includes sorafenib, pazopanib, or tamoxifen+sulindac. †Time to response calculated among responders with available response dates. Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; SOC, standard of care.

Phase 1a/1b study of the safety, pharmacokinetics, and antitumor activity of ziftomenib in combination with imatinib in patients with advanced gastrointestinal stromal tumors (GIST) after imatinib failure.

TPS11589 Background: GIST is the most common mesenchymal neoplasm of the digestive tract and is mainly driven by gain-of-function oncogenic mutations in the receptor tyrosine kinase KIT. Patients with GIST are typically treated with anti-KIT tyrosine kinase inhibitors (TKIs) such as imatinib. However, few patients achieve a complete response, and most eventually progress due to secondary KIT alterations that cause resistance to therapy. Other TKIs are approved in later lines but have shown only moderate clinical outcomes, highlighting the need for additional therapeutic approaches. Preclinical studies have shown that the menin-KMT2A complex epigenetically upregulates KIT expression in GIST cells. Ziftomenib is a potent and highly selective menin inhibitor that disrupts formation of the menin-KMT2A complex. Ziftomenib plus imatinib has demonstrated synergistic antitumor activity in imatinib-sensitive and -resistant GIST models, with reduced KIT protein levels and downstream oncogenic signaling observed in imatinib-resistant GIST patient-derived xenografts treated with the combination. Together, ziftomenib plus imatinib may enhance KIT recycling while reducing KIT transcription. This combination is currently being investigated clinically in patients with imatinib-sensitive and -resistant advanced GIST. Methods: KOMET-015 (NCT06655246) is an ongoing phase 1a/1b, open-label study to determine the safety, tolerability, recommended phase 2 dose (RP2D), and preliminary antitumor activity of ziftomenib plus imatinib (400 mg or &lt;400 mg if previously reduced due to intolerance) for advanced/metastatic GIST. KOMET-015 includes dose-escalation, RP2D determination, and dose-expansion parts. Eligible patients (≥18 yrs) must have a biopsy-proven diagnosis of advanced/metastatic KIT -mutant GIST (T670X excluded) that progressed on imatinib (for dose-escalation and RP2D determination parts), with an ECOG PS of ≤2 and measurable disease per RECIST v1.1 modified for GIST (mRECIST). Dose escalation will be based on an i3+3 design to evaluate the safety and tolerability of up to 4 dose levels (with potential for additional doses) of ziftomenib combined with imatinib. Based on escalation, up to 2 dose levels will be selected for comparison to determine the RP2D. The dose-expansion part will examine the preliminary clinical activity of the RP2D in patients assigned to 1 of 3 cohorts: Cohort A: patients who progressed on imatinib as immediate prior therapy, Cohort B: patients who failed imatinib and had received ≥2 lines of therapy, and Cohort C: imatinib-naive patients. Tumor response will be assessed per mRECIST. All adverse events will be recorded, monitored, and graded based on CTCAE v5.0. The trial is open and actively recruiting in the United States. Clinical trial information: NCT06655246 .

Baseline dyslipidemia in treatment-naïve breast cancer: Molecular subtype–specific patterns in a large cohort.

e12692 Background: Cardiovascular disease has emerged as a major cause of long-term morbidity and mortality among breast cancer survivors. However, cardiometabolic risk profiles present at the time of breast cancer diagnosis—prior to any anticancer therapy—remain incompletely characterized, particularly across molecular subtypes. Evidence from large, real-world cohorts evaluating baseline dyslipidemia in treatment-naïve patients is limited. We aimed to characterize the prevalence and subtype-specific patterns of dyslipidemia at diagnosis in women with newly diagnosed breast cancer. Methods: We conducted a retrospective cohort study of 5,246 women with pathologically confirmed, treatment-naïve breast cancer diagnosed between 2014 and 2024. All clinical characteristics, laboratory measurements, and electrocardiographic data were collected at diagnosis before surgery or systemic therapy. Molecular subtypes were classified as Luminal A, Luminal B (HER2−), Luminal B (HER2+), HER2-enriched, and triple-negative breast cancer (TNBC) according to ASCO/CAP guidelines based on immunohistochemistry and in situ hybridization results. Dyslipidemia was defined as abnormal levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, or triglycerides using guideline-based lipid thresholds. Subtype-specific comparisons were performed, and multivariable logistic regression analyses were used to identify factors associated with dyslipidemia. Results: Overall, 54.1% of patients exhibited dyslipidemia at diagnosis, with significant heterogeneity across molecular subtypes (P &lt; 0.001). The prevalence was highest in Luminal A tumors (59.2%) and lowest in Luminal B (HER2−) tumors (43.9%). Elevated total cholesterol (29.5%) and triglycerides (25.7%) were the most common lipid abnormalities, while abnormalities in LDL-C and HDL-C demonstrated marked subtype-specific variation. Notably, patients with advanced-stage TNBC showed a particularly high prevalence of elevated LDL-C. In multivariable analyses, intravascular tumor thrombus was independently and consistently associated with dyslipidemia across all molecular subtypes (P &lt; 0.001). Age and lymph node metastasis demonstrated subtype-dependent associations with dyslipidemia. Conclusions: More than half of women with newly diagnosed, treatment-naïve breast cancer present with dyslipidemia at diagnosis, with distinct patterns across molecular subtypes. These findings highlight the presence of clinically relevant cardiometabolic risk before initiation of anticancer therapy and support early lipid assessment as part of baseline cardio-oncology risk stratification. Incorporating lipid profiling at diagnosis may inform personalized survivorship planning, particularly for high-risk subtypes such as TNBC.

Comparative real-world safety outcomes of Pola-R-CHP versus R-CHOP in high-grade diffuse large B-cell lymphoma (DLBCL): A TriNetX study.

e19000 Background: The POLARIX trial established polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) as a potential new standard of care for previously untreated intermediate- and high-risk DLBCL, demonstrating a significant 5-year progression-free survival benefit over rituximab, cyclophosphamide, doxorubicin, oncovorin, and prednisone (R-CHOP), with similar overall survival and safety profiles. However, the generalizability of these trial findings to diverse patient populations and routine clinical practice remains to be fully elucidated. Methods: We conducted a retrospective propensity score-matched (PSM) study using the TriNetX Global Collaborative Network database. We identified adults (≥18 years) with DLBCL/high-grade lymphoma (ICD-10: C83.3) who received either Pola-R-CHP (n=1,045) or R-CHOP (n=18,382). We applied 1:1 PSM for age, sex, race, comorbidities, and transplantation status. The primary outcome was all-cause mortality. Secondary outcomes included hematologic toxicities, infections, cardiomyopathy, and healthcare utilization. Hazard ratios (HR) were calculated with 95% confidence intervals (95% CI), and Kaplan–Meier survival curves were generated. Results: Median follow-up was 347 days for Pola-R-CHP and 365 days for R-CHOP after PSM for demographics, comorbidities, and baseline disease characteristics. After matching, 1,045 patients were included in each cohort. At the 1-year median follow-up, the Pola-R-CHP cohort had a lower all-cause mortality than the R-CHOP cohort (7.0% vs. 13.3%; HR 0.595, 95% CI 0.445–0.794, P&lt;0.001). Kaplan-Meier analysis also showed the survival benefits of Pola-R-CHP. Neutropenia was lower with Pola-R-CHP than with R-CHOP (31.1% vs. 37.5%; P = 0.05), as was the rate of thrombocytopenia (13.2% vs. 16.3%; P = 0.068), but neither reached statistical significance. Peripheral neuropathy was higher with Pola-R-CHP than with R-CHOP (22.2% vs. 19.1%; HR 1.28, 95% CI: 1.049 –1.571, p=0.015). No statistically significant between-groups differences were observed in cardiomyopathy, hospitalization rates, emergency room visits, disease progression, anemia, sepsis, or pneumonia. Conclusions: This real-world PSM study demonstrated significantly reduced all-cause mortality in Pola-R-CHP vs. R-CHOP. While many toxicities were similar, Pola-R-CHP showed a higher rate of peripheral neuropathy. These findings suggest that Pola-R-CHP is a better upfront option with improved survival benefits and no new safety concerns in patients with DLBCL.

Clinical associations of cannabis use among patients receiving immune checkpoint inhibitors: A real-world analysis.

11143 Background: Cannabis use is common in patients with cancer, yet its clinical associations during immune checkpoint inhibitor (ICI) therapy is poorly defined. We evaluated the association between documented cannabis use and clinical outcomes among patients receiving ICIs. Methods: We conducted a retrospective cohort study of adults ≥18 years in the TriNetX US Collaborative Network with advanced or metastatic solid tumors treated with ICIs since January 1, 2019. Cannabis exposure was defined by diagnostic codes for cannabis-related disorders or prescriptions for cannabis-derived products documented 3 months prior to 2 years after ICI start. Patients who died in 60 days were excluded. Primary outcome was 3-year overall survival (OS); secondary outcomes included 2-year inpatient and emergency department (ED) visit, with joint sprain as a negative control outcome. Propensity matching adjusted for demographics, comorbidities, cancer type and stage, and tobacco and alcohol use. Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) and Kaplan–Meier analyses were calculated. Results: After matching, 3,634 patients were included in the OS cohort. Patients with no documented cannabis use had significantly higher 3-year OS and median survival versus cannabis users (HR 0.67; 95% CI 0.63-0.72; median OS 34.8 vs 18.7 months). This association was observed across all tumor subgroups except head and neck squamous cell carcinoma (HNSCC) (Table 1). Among 2,855 matched patients in the healthcare utilization cohort, patients without cannabis use had lower healthcare utilization within 2 years, including fewer ED visits (RR 0.83; 95% CI 0.79-0.87) and inpatient admissions (RR=0.82; 95% CI 0.79-0.84). These findings were consistent across subgroups except for ED visits in HNSCC (Table 1). Joint sprain showed no association with cannabis exposure (RR 0.93, 95% CI 0.64-1.35). Conclusions: Cannabis use during ICI therapy was associated with lower survival and higher healthcare utilization in multiple solid tumors. This may reflect unmeasured symptom burden or clinical vulnerability but also raises the hypothesis of a potential interaction between cannabis exposure and ICI therapy. Prospective studies incorporating symptom severity, dose, timing, and route of exposure are needed to clarify these relationships. Clinical outcomes by cannabis exposure. Group Overall survival HR (95% CI) OSp-value ED Visit RR (95% CI) EDp-value Inpatient visit RR (95% CI) Inpatient visitp-value Overall 0.67 (0.63–0.72) &lt;0.01* 0.83 (0.79–0.87) &lt;0.01* 0.82 (0.79–0.84) &lt;0.01* NSCLC 0.73 (0.68–0.79) &lt;0.01* 0.85 (0.81–0.90) &lt;0.01* 0.85 (0.82–0.89) &lt;0.01* RCC 0.60 (0.50–0.73) &lt;0.01* 0.81 (0.73–0.91) &lt;0.01* 0.78 (0.72–0.85) &lt;0.01* Melanoma 0.52 (0.40–0.69) &lt;0.01* 0.70 (0.59–0.83) &lt;0.01* 0.73 (0.65–0.82) &lt;0.01* HNSCC 0.93 (0.74–1.16) 0.52 1.05 (0.89–1.25) 0.56 0.87 (0.77–0.98) 0.02* *Statistically significant (p &lt; 0.05).

Evaluation of long-term follow-up non-respondence in a prospective study of financial toxicity of patients after radiation therapy.

e23266 Background: Barriers to enrollment and retention of socioeconomically vulnerable patients limit the diversity and generalizability of longitudinal oncology studies. Financial toxicity (FT) may be underestimated if patients who are at highest risk are less likely to complete long-term follow-up (FU). We evaluated socioeconomic and clinical factors associated with non-respondence at 1-year follow-up in a prospective FT survey study of patients undergoing radiation therapy (RT). Methods: All patients ≥18 years that were undergoing RT for any malignancy were eligible. Surveys were completed at baseline (pre-RT), 1-month, and 1-year post-RT, which included the Comprehensive Score for Financial Toxicity (COST) tool and questions regarding demographics and social determinants of health (SDOH). Lower COST scores indicate higher FT. Respondents to the 1-year FU were classified as those who completed the survey between 6-18 months post-RT. Non-respondents were those who did not respond or passed away within the response window. Patients who passed prior to the 1-year FU survey window were ineligible. Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests were used to compare factors associated with respondents and non-respondents. Results: Of 305 patients completing survey, 241 were eligible for analysis: 36% completed the 1-year FU survey, while 64% did not. Non-respondents were more likely to report lower COST scores (higher FT), have a non-English primary language, not be married/partnered, have an educational level of high school or less, hold either private insurance or MassHealth, and have an annual income of &lt; $40,000 (all P&lt; 0.05). Non-respondents also received a greater number of fractions of RT (P&lt; 0.05). When excluding patients who passed during the response window, all variables remained statistically significant except for partnership status. Cancer and treatment characteristics, other than the number of fractions of RT, were not significantly different between the groups. Conclusions: Long-term FU nonresponse was associated with specific SDOH and number of RT fractions. This suggests multiple socioeconomic factors and certain treatment aspects could potentially impact long-term study FU data. As randomized controlled trials follow patients across a longitudinal period, these challenges may similarly affect long-term outcome assessment. These findings can inform strategies to reduce attrition, which will ultimately improve diversity and representativeness in clinical trials.

Phase I/II study of liposomal curcumin in combination with standard radiation and temozolomide in patients with newly diagnosed high-grade gliomas.

2069 Background: Liposomal curcumin (LC) is an intravenous formulation designed to enhance curcumin delivery and modulate inflammatory, oxidative, and oncogenic pathways relevant to high-grade glioma (HGG), including dysregulated kynurenine metabolism. Preclinical studies demonstrate synergy between LC and chemoradiation. This Phase I/II study was designed to determine the recommended Phase II dose (RP2D) of weekly IV LC with radiotherapy and temozolomide (RT/TMZ) in newly diagnosed HGG (primary objective), assess safety and feasibility (secondary objective), and preliminary efficacy (exploratory objective). Methods: This open-label, sequential dose-escalation study used the TITE-BOIN Bayesian design to evaluate LC at 300, 350, and 400 mg/m². Patients received standard chemoradiation (2 Gy × 5 days/week × 6 weeks with concomitant TMZ 75 mg/m²/day), followed by standard adjuvant TMZ and weekly LC infusions over 3 hours for a target of 34 doses, with optional continuation. Eligible patients had newly diagnosed HGG (WHO grade 3 or 4) and KPS ≥70%. Patients were evaluable if they received ≥80% of planned LC infusions and ≥60% of planned TMZ dosing during the 10-week toxicity evaluation period. Radiographic response was assessed per RANO 2.0. Results: Twenty-five patients were treated: 300 mg/m² (n=6), 350 mg/m² (n=12), and 400 mg/m² (n=7); all patients assigned to 400 mg/m² were treated at 350 mg/m² per Safety Review Committee recommendation. All patients had glioblastoma or molecular glioblastoma, IDH-wildtype, WHO grade 4 per 2021 WHO classification (MGMT promoter methylation status: 7 methylated, 1 indeterminate, 17 unmethylated). Median age was 56 years (range, 43–75); median KPS was 90 (range, 70–100). Two protocol-defined dose-limiting toxicities occurred at 400 mg/m²: grade 4 pancytopenia and grade 1 hemolysis. LC-related grade ≥3 toxicities occurred in 4 patients (16%) and included confusion, seizure, thromboembolic event, cerebral edema, lymphopenia, thrombocytopenia, fatigue (all grade 3), and pancytopenia (grade 4). There were no LC-related deaths. Based on the TITE-BOIN design and cumulative safety data, 350 mg/m² was identified as the RP2D. With a median follow-up of 12.9 months (range, 2.4-27.3 months) as of 1/23/2026, median progression-free and overall survival have not been reached. At 6 and 12 months from first LC infusion, 95% and 87% of uncensored patients (n=18, n=13), respectively, remained alive. Conclusions: LC combined with standard chemoradiation was safe and well tolerated, with encouraging exploratory signals of disease control in newly diagnosed glioblastoma. Further evaluation in an expanded Phase II/III study is planned. Clinical trial information: NCT05768919 .

Predictors of mechanical ventilation in metastatic cancer hospitalizations: A National Inpatient Sample study.

11044 Background: Invasive mechanical ventilation (MV) represents a major escalation of supportive care in metastatic cancer and is consistently associated with high short-term mortality in prior observational cohorts. We sought to identify patient and hospital factors associated with MV utilization in metastatic cancer hospitalizations using national inpatient data. Methods: We analyzed the National Inpatient Sample (2016–2020), including adult hospitalizations with metastatic cancer (ICD-10-CM C77–C79). MV was identified using ICD procedure codes. Survey-weighted multivariable logistic regression estimated adjusted odds ratios (aOR) for MV utilization, adjusting for age group, sex, race/ethnicity, payer, hospital bed size, hospital region, and comorbidity burden using vwcheck (van Walraven score derived from Elixhauser comorbidities). Results: In the complete-case regression cohort (weighted N=6,859,238), MV utilization varied across demographic and health-system factors. MV was less likely with older age (≥65 vs 18–44: aOR 0.80, 95% CI 0.75–0.87) and in females (aOR 0.96, 95% CI 0.93–0.99). Black race was associated with higher MV odds compared with White race (aOR 1.18, 95% CI 1.13–1.23). Compared with Medicare, Medicaid (aOR 1.08, 95% CI 1.01–1.14) and self-pay (aOR 1.17, 95% CI 1.05–1.30) had higher MV odds. MV was more likely in medium vs small hospitals (aOR 1.08, 95% CI 1.03–1.14) and large vs small hospitals (aOR 1.08, 95% CI 1.03–1.13). Regional variation persisted (South vs Northeast: aOR 1.11, 95% CI 1.06–1.17; West vs Northeast: aOR 1.07, 95% CI 1.01–1.13). Higher vwcheck was strongly associated with MV (aOR 1.07 per unit). Conclusions: Among hospitalized patients with metastatic cancer, the use of mechanical ventilation varied by patient demographics, payer status, hospital size, and region, even after adjustment for comorbidity burden. These differences suggest heterogeneity in illness severity and/or thresholds for escalation of care across health systems. Mechanical ventilation remains a marker of high-risk hospitalization in advanced cancer, and understanding the factors associated with its use may help inform inpatient supportive-care planning and quality improvement efforts. Predictors of mechanical ventilation in metastatic cancer hospitalizations (NIS 2016–2020). Predictor Adjusted OR (95% CI) p-value Age ≥65 vs 18–44 0.80 (0.75–0.87) &lt;0.001 Female vs male 0.96 (0.93–0.99) 0.01 Black vs White 1.18 (1.13–1.23) &lt;0.001 Medicaid vs Medicare 1.08 (1.01–1.14) 0.02 Self-pay vs Medicare 1.17 (1.05–1.30) 0.004 Medium vs small hospital 1.08 (1.03–1.14) 0.002 Large vs small hospital 1.08 (1.03–1.13) 0.001 South vs Northeast 1.11 (1.06–1.17) &lt;0.001 West vs Northeast 1.07 (1.01–1.13) 0.01 van Walraven score (per unit) 1.07 (1.06–1.08) &lt;0.001

The impact of ketogenic diet and psychological factors on tumor shrinkage in breast cancer patients receiving neoadjuvant chemotherapy: A prospective clinical trial.

e23287 Background: The response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is influenced by metabolic and psychosocial factors. Although ketogenic diets (KD) are thought to increase chemotherapy sensitivity, the predictive value of quality of life (QoL) on pathological response remains unclear. This study investigated the impact of KD intervention and QOL (particularly anxiety and emotional functioning) on tumor shrinkage in patients with BC receiving NAC. Methods: The study included overweight and obese women (aged 19–64 years) diagnosed with BC who were scheduled to receive NAC. All patients received NAC containing anthracycline and taxane as a standard procedure. After anthracycline treatment, patients (n:38) were randomly divided into two group (1:1): the first group (n:19) received KD, and the second group (n:19) received healthy diet. Patients were evaluated before treatment (T0), after anthracycline treatment (T1), and after taxane treatment (T2). Waist to hip ratio and body fat percent were measured. Serum biomarkers, including glucose, insulin, HOMA-IR, and oxidative stress indices (TAC/TOS), were analysis. The QOL was assessed using EORTC QLQ-C30 and EORTC QLQ-BR23. The data were evaluated using the SPSS 22 statistical package program. Predictors of tumor response were identified using univariate regression, followed by two multivariate models: Model 1 (baseline factors only) and Model 2 (baseline and dynamic change factors). Results: Ketogenic diet use did not significantly predict tumor shrinkage (β = -0.06, t = -0.38, p = 0.704). In a multivariate regression model focusing on baseline factors, future anxiety was the only independent predictor of the of tumor shrinkage (β = -0.32, t = -2.05, p = 0.048), where higher anxiety was associated with reduced treatment benefit. When baseline (T0) and dynamic factors (change between T0 and T2) were analyzed together, the only independently significant predictor of tumor shrinkage was the change in emotional functioning (β = 0.39, t = 2.51, p = 0.017). Improvements in emotional functioning over time were positively correlated with greater tumor regression. Other factors, including waist to hip ratio, body fat percents, serum biomarkers, showed no significant association with response in multivariate models. Conclusions: While KD did not directly influence the magnitude of tumor shrinkage in this study, psychological and emotional factors emerged as significant independent predictors of treatment response. The negative impact of future anxiety and the benefit of improved emotional functioning suggest that providing support to improve QOL during treatment may be beneficial in terms of treatment response for BC patients receiving NAC. Clinical trial information: NCT05234502 .

A phase 1/2 study of the next-generation nectin-4–targeting antibody-drug conjugate CRB-701 (SYS6002) in patients with recurrent or metastatic head and neck squamous cell carcinoma.

6062 Background: CRB-701 is a next-generation Nectin-4–targeted monomethyl auristatin E (MMAE)-based antibody–drug conjugate with differentiated safety, efficacy and pharmacokinetics compared with other agents in the same class. As previously reported, CRB-701 demonstrated antitumor responses independent of Nectin-4 expression levels in solid tumors, notably in patients with heavily pretreated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, as well as urothelial carcinoma. Here, we provide data from this phase 1/2 trial in patients with recurrent or metastatic (R/M) HNSCC enrolled in dose escalation (part A) and dose optimization (part B) (NCT06265727). Methods: Patients with R/M HNSCC who had received ≥ 1 line of therapy were enrolled. Part A employed a Bayesian Optimal Interval design with four doses (1.8, 2.7, 3.6 and 4.5 mg/kg; each every 3 weeks [Q3W]) to determine the maximum tolerated dose. In part B, the pharmacologically active dose range identified in part A was evaluated using a time-to-event Bayesian optimal phase 2 design. Patients were randomized 1:1 to receive CRB-701 at 2.7 or 3.6 mg/kg Q3W. The primary endpoints for parts A and B were dose-limiting toxicities and objective response rate (ORR), respectively. A scan ≥ 4 weeks after the initial response was required to confirm partial and complete responses. Safety, tolerability and pharmacokinetics were also assessed. Nectin-4 expression and human papilloma virus (HPV)/p16 status were evaluated retrospectively. Results: As of September 2025, 60 patients with HNSCC were enrolled across parts A and B. The median (range) number of previous therapies was 3.0 (1–9) in the 2.7 mg/kg group and 3.0 (1–8) in the 3.6 mg/kg group; 85% of patients were refractory to immunotherapy and platinum-based regimens. The confirmed ORR was 33.3% (4/12 patients; unconfirmed ORR also 33.3%) at the 2.7 mg/kg dose, and 33.3% (7/21 patients; unconfirmed ORR, 47.6% [10/21 patients]) at the 3.6 mg/kg dose. Responses were observed regardless of HPV/p16 status. The safety profile of CRB-701 was broadly consistent with earlier findings: keratitis, fatigue, alopecia, dysgeusia and anemia were the most frequently reported treatment-emergent adverse events (≥ 15% of overall solid tumor population [N = 167]). An expanded efficacy analysis reporting an additional 6 months of follow-up, including ORR, duration of response and progression-free survival will be presented at the congress. Subgroup analyses by HPV status, treatment history and disease extent will also be presented. Conclusions: CRB-701 has shown promising efficacy in patients with heavily pretreated R/M HNSCC, along with a favorable safety profile compared with other MMAE-based therapies. Further investigation of CRB-701 is warranted in this difficult-to-treat patient population. Clinical trial information: NCT06265727 .

Impact of chronic atrial fibrillation on outcomes of acute pulmonary embolism in pancreatic cancer patients.

e16368 Background: Chronic atrial fibrillation increases thromboembolic risk and may worsen outcomes in acute pulmonary embolism. Pancreatic cancer patients face elevated thrombotic risk, yet the impact of chronic atrial fibrillation in this population remains poorly characterized. This retrospective study evaluated the association between chronic atrial fibrillation and clinical outcomes in pancreatic cancer patients hospitalized with acute pulmonary embolism. Methods: We evaluated adult patients with pancreatic cancer hospitalized for acute pulmonary embolism. Patients were stratified by the presence or absence of chronic atrial fibrillation. Baseline demographic and clinical characteristics were compared between groups. Multivariable logistic regression models were used to assess the independent association between chronic atrial fibrillation and clinical outcomes, adjusting for relevant confounders including age, comorbidity burden, and other baseline characteristics. Results: Among 13,095 pancreatic cancer patients hospitalized with acute pulmonary embolism, 195 (1.49%) had chronic atrial fibrillation. Patients with chronic atrial fibrillation were significantly older (74.79 vs 67.83 years, p &lt; 0.001), had higher comorbidity burden (Charlson Comorbidity Index 6.97 vs 6.20, p = 0.032), and longer hospital stays (6.79 vs 4.86 days, p = 0.013). After multivariable adjustment, chronic atrial fibrillation was independently associated with increased odds of acute kidney injury (aOR 2.775, 95% CI 1.366–5.637, p = 0.005). No significant differences were observed in in-hospital mortality (aOR 1.570, 95% CI 0.520–4.737, p = 0.423), catheter-directed thrombolysis (aOR 2.943, 95% CI 0.366–23.683, p = 0.310), blood transfusion (aOR 1.009, 95% CI 0.239–4.249, p = 0.991), vasopressor use (aOR 4.443, 95% CI 0.527–37.461, p = 0.170), mechanical ventilation (aOR 1.437, 95% CI 0.190–10.836, p = 0.725), cardiac arrest (aOR 1.614, 95% CI 0.212–12.310, p = 0.644), shock (aOR 2.790, 95% CI 0.637–12.214, p = 0.173), acute encephalopathy (aOR 1.599, 95% CI 0.365–7.010, p = 0.533), intracranial hemorrhage (aOR 7.305, 95% CI 0.868–61.445, p = 0.067), gastrointestinal bleeding (aOR 1.738, 95% CI 0.488–6.183, p = 0.393), mechanical thrombectomy (aOR 1.492, 95% CI 0.186–11.995, p = 0.707), sepsis (aOR 1.726, 95% CI 0.404–7.374, p = 0.461), major bleeding (aOR 1.522, 95% CI 0.808–2.867, p = 0.193), or intensive care unit admission (aOR 0.840, 95% CI 0.114–6.216, p = 0.864). Conclusions: In pancreatic cancer patients hospitalized with acute pulmonary embolism, chronic atrial fibrillation was independently associated with increased risk of acute kidney injury but not with other cardiovascular complications or in-hospital mortality. Further research is needed to evaluate long-term outcomes in this high-risk population.