Browse Articles

B-cell Enrollment Efficiency Program (BEEP): Streamlining accrual to early-phase lymphoma trials at a single center.

e19084 Background: Enrolling patients with lymphoma into clinical trials is challenging due to stringent organ function eligibility criteria (Khurana A, 2021). This challenge is exacerbated by therapy-related CD20 antigen loss in heavily treated relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) patients. To streamline accrual to phase 1 and 1b trials we developed BEEP, an inaugural system tailored to optimize enrollment of extensively treated R/R B-NHL patients. Our initial experience is reported here. Methods: Eligible R/R B-NHL adult patients were nominated into BEEP by their primary oncologist for trial screening. Individual patients were pre-screened for each of the 10 active first-in-human studies in BEEP, and real-time feedback was provided to the primary oncologist. Patient status was updated regularly until a patient was enrolled in a trial, initiated another line of therapy, or died. Results: A total of 47 patients with R/R B-NHL were enrolled into BEEP between 05/01/2025 and 12/31/2025. Cohort median age was 63 years (range 27-84), with an 85% male predominance, 74% white racial composition, and a median of 5 prior lines (range 3-12) of systemic therapy. Histologic diagnoses were notable for 27 large B-cell lymphoma patients (13 DLBCL, 11 transformed indolent NHL, 3 Richter’s transformation), 19 low-grade lymphoma patients (9 low-grade follicular, 4 CLL, 3 mantle cell, 2 marginal zone, 1 Waldenström macroglobulinemia) and 1 accelerated CLL patient. Therapy-related antigen loss was observed in 17 patients (14 CD20-negative only, and 3 CD20/CD19 dual-negative). Of the 47 BEEP patients, 10 enrolled in clinical trials (8 in BEEP, 1 internal non-BEEP trial, and 1 external trial), 25 urgently initiated another line of therapy, and 12 remained on their pre-BEEP treatment waiting for a trial. A total of 6 patients died before trial enrollment (3 while waiting for a trial and 3 after starting another line of therapy). Universal exclusion from BEEP trials was observed in 8 patients (4 with active CNS involvement, 2 with renal insufficiency, 1 with CD20 loss/hepatic dysfunction, and 1 with CD20 loss/GVHD). A lack of available slots was the main reason screen-eligible patients were awaiting enrollment. Conclusions: Enrolling R/R B-NHL patients into phase I clinical trials remains an ongoing challenge. Our BEEP experience confirmed the unmet need in trials for patients with secondary CNS involvement, CD20 antigen loss, and limited organ function. Dynamic slot availability remains the biggest impediment to enrolling screen-eligible patients. Future phase 1 trials will need to adopt designs enabling continuous accrual without complete dose-limiting toxicity data, explore CD20/CD19-independent targeted agents, and reassess restrictive organ function eligibility criteria.

Neoadjuvant sacituzumab govitecan in patients with muscle-invasive bladder cancer: Final results and biomarker analyses of the SURE-01 trial.

4619 Background: To evaluate neoadjuvant sacituzumab govitecan (SG), followed by radical cystectomy (RC), in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for/refuse neoadjuvant chemotherapy (NAC). We report the results of the primary analysis and final biomarker analyses of the open-label, phase 2 SURE-01 trial (NCT05226117). Methods: Patients aged ≥18 years, ECOG PS 0-1, with histologically confirmed cT2-T4aN0M0 MIBC, ineligible/refusing NAC, and scheduled for RC received 4 cycles of SG 10 mg/Kg on D1 and D8, every three weeks (Q3W), followed by RC. The primary outcome measure was the pathological complete response (pCR) rate. Transcriptome-wide analyses and comprehensive genomic profiling assays were performed on baseline tumor samples. Results: From 03/22 to 07/25, 44 patients were treated and efficacy evaluable. After the initial 8 patients enrolled, the protocol was amended with a SG dose of 7.5 mg/Kg, with primary prophylaxis for neutropenia, due to the occurrence of two deaths (one treatment-related). Subsequent Grade 3-4 treatment-related adverse-events (TRAE) occurred in 5 pts (13.9%). Twenty-six patients (59.1%) had a cT3-4 stage, 20 (45.5%) had a variant histology. Fourteen patients (31.8%) refused to undergo RC and underwent a repeated transurethral resection of the bladder tumor. The median follow-up was 22 months (interquartile range: 15-26). In the intention-to-treat population: the ypT0N0-x rate was 29.5% (95% confidence interval [CI]: 16.7-45.2). We observed an enrichment of ypT0 responses in non-Luminal subtypes (46% vs 14% of Luminal), with the Infiltrated Luminal subtype having the highest proportion of ypT0 (62%). Variance by subtype revealed that TOP1 had the lowest scores in the Infiltrated Luminal subtype. A few signatures involving metabolism and tumor microenvironment were statistically significantly associated with a lower odds ratio of ypT0, whereas TROP2 expression (p=0.72) was not. The 24-month event-free survival (EFS) rate was 71.4% (95%CI: 58-87.8) and the 24-month overall survival (OS) rate was 80.2% (95%CI: 67.7-95). Longer EFS was observed for participants with lower TOP1-expressing tumors (p=0.04). Conclusions: To our knowledge, SURE-01 is the first to report results of an antibody-drug conjugate monotherapy targeting TROP2 in the neoadjuvant setting for patients with MIBC. Neoadjuvant SG at the reduced dose of 7.5mg/kg demonstrated compelling activity and survival estimates, with a manageable safety profile, corroborating TROP2 as a suitable target for MIBC. Molecular biomarkers pointing to the payload were associated with neoadjuvant SG activity. Clinical trial information: NCT05226117 .

Thromboelastography-guided platelet transfusion and associations with utilization and outcomes in patients with hematologic malignancies.

6590 Background: Thromboelastography (TEG) is a viscoelastic assay assessing clot formation and global hemostasis. In patients with hematologic malignancies, transfusion support is essential, yet evidence guiding optimal transfusion strategies is limited. This study evaluated transfusion utilization and outcomes associated with TEG use in hematologic oncology patients. Methods: We conducted a retrospective cohort study at a tertiary care hospital (October 2022–2025) including hospitalized patients with acute and chronic leukemias or multiple myeloma who received blood product transfusions. Primary outcomes were platelet transfusion utilization (standardized units) and platelet response. Secondary outcomes included hospital length of stay (LOS) and in-hospital mortality. Welch’s t-test and chi-square testing were used, with multivariable regression adjusting for demographic and clinical covariates. Results: Among 975 platelet transfusion episodes, 68 (5.3%) were TEG-guided. Unadjusted analyses showed slightly lower platelet utilization with TEG-guided transfusions compared with standard care (1.03 vs 1.06 units, p<0.001). Platelet count increments did not differ significantly (Δ 17.9 vs 16.3, p=0.57). TEG-guided patients had longer LOS (39.8 vs 31.9 days, p<0.001) and higher in-hospital mortality (p<0.001), reflecting greater illness severity. After adjustment, differences in utilization, platelet response, and LOS were no longer significant. TEG use remained strongly associated with in-hospital mortality (adjusted OR 29.8, 95% CI 8.83–100.77, p<0.001). Conclusions: TEG use in hospitalized patients with hematologic malignancies receiving platelet transfusions was uncommon and not associated with improved transfusion efficiency or platelet response. TEG-guided transfusions occurred primarily in high-acuity settings with prolonged hospitalization and increased mortality, suggesting TEG functions more as a marker of illness severity than a routine tool for optimizing platelet transfusion. Further studies are needed to clarify its role in malignant hematology care. Platelet transfusion outcomes by TEG use in hematological malignancy encounters. Outcome TEG guided (n=68) Non-TEG guided (n=1214) P Value (unadjusted) P value (adjusted) Number of encounters 68 1214 --- --- Standardized platelet units, mean 1.03 1.06 0.14 0.34 Platelet count response (DELTA), mean 17.9 16.3 0.57 0.93 Length of stay, mean days 39.8 31.9 <0.001 0.51 In-hospital mortality, % 94.1 44.7 <0.001 0.0008 Adjusted p values from multivariable regression models including demographics, malignancy subtype, baseline platelet count, transfusion dose, care location, transfusion priority, and timing variables. DELTA = post-pre platelet count.

Refining breast cancer risk stratification for selection of women at intermediate to high risk for supplemental MRI screening using artificial intelligence.

10564 Background: Supplemental MRI screening for women at increased breast cancer risk can detect additional cancers that are occult on mammography. However, its adoption is limited by restricted availability and high false-positive rates. Improved risk stratification is therefore needed to optimize the use of supplemental MRI screening. This study aimed to evaluate the feasibility of a mammography-based artificial intelligence (AI) system for stratifying women at intermediate to high risk for supplemental MRI screening. Methods: This retrospective study included consecutive women who underwent abbreviated breast MRI following negative mammography between January 2020 and December 2024. The study cohort comprised women at intermediate to high breast cancer risk, including those with known genetic predisposition, personal history of breast cancer, prior benign or high-risk breast biopsy, or family history of breast cancer. A commercially available AI system was applied to all mammograms, generating both exam-level and breast-level scores representing the likelihood of a malignancy on a scale of 0 to 100. MRI outcomes, false-positive examinations, cancer detection, and positive predictive value (PPV) were evaluated. Univariate analyses were performed to explore associations between breast density and AI-based selection results. Results: In 1,588 women (median age, 51 years; range, 24-87), 1,804 screening mammograms and MRI examinations were performed. Of these examinations, 220 resulted in recall, yielding 24 mammographically occult breast cancers (12 ductal carcinoma in situ and 12 invasive cancers) diagnosed within one year and 166 false-positive examinations. The AI system achieved an area under the curve (AUC) of 0.694 (95% CI, 0.499-0.888) in women without a personal history of breast cancer and 0.611 (95% CI, 0.430-0.792) in women with a personal history of breast cancer. Using AI-based selection, 239 of 1,588 women (14.9%) were selected for supplemental MRI, resulting in an 81% reduction in false-positive examinations (31 vs 166) and an improvement in PPV to 20.5% (8 of 39). 6 of 8 detected cancers (75%) were invasive. Breast density was not associated with the AI-based selection strategy. Conclusions: Mammography-based AI substantially reduced false-positive supplemental MRI examinations while preferentially selecting women at higher risk for invasive breast cancers, without compromising cancer detection. These findings suggest that AI can refine risk stratification and optimize selection of women to improve the efficiency of supplemental MRI screening.

Efficacy and safety of combined transarterial embolization/chemoembolization and hepatic arterial infusion chemotherapy versus transarterial embolization/chemoembolization alone in unresectable neuroendocrine tumor liver metastases.

e16309 Background: Neuroendocrine Tumor Liver Metastases (NETLM) represent the most critical prognostic factor in patients with disseminated neuroendocrine tumors, frequently leading to significant morbidity and mortality. For patients with unresectable NETLM, locoregional therapies targeting the liver are essential for disease management and symptom palliation. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are established locoregional therapies for unresectable neuroendocrine tumor liver metastases (NETLM). The potential survival benefit of adding hepatic arterial infusion chemotherapy (HAIC) to these therapies remains unclear. This study aimed to compare the efficacy and safety of TAE/TACE alone versus TAE/TACE combined with HAIC (TAE/TACE+HAIC) in patients with unresectable NETLM. Methods: A retrospective analysis was conducted on 101 patients with unresectable NETLM treated at Peking University Cancer Hospital between February 2012 and November 2024. Of these, 67 patients received TAE/TACE alone and 34 patients received TAE/TACE+HAIC. Propensity score matching (PSM) was employed to minimize selection bias. The primary endpoint was progression-free survival (PFS) and secondary endpoints included hepatic progression-free survival (hPFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: PSM resulted in 21 patient pairs with comparable baseline characteristics between TAE/TACE and TAE/TACE+HAIC cohorts. Among these patients, 5 were classified as G1, 33 as G2, and 4 as G3. TAE/TACE matched cohort exhibited a higher median OS compared with the TAE/TACE+HAIC cohort(71.3 months vs. 34.2 months; P = 0.01), while hPFS (15.8 months vs. 14.9 months; P = 0.7) and PFS (11.7 months vs. 11.2 months; P = 0.9) were similar. ORR and DCR did not differ significantly (ORR: 42.9% vs. 57.1%, P = 0.54; DCR: 100% vs. 95.2%, P = 1.0). The patients underwent a total of 233 treatments. No treatment-related deaths occurred and serious adverse events were comparable, except for higher rates of elevated transaminases (14.5% vs. 4.5%; P = 0.02) and hyperbilirubinemia (5.3% vs. 0%; P = 0.01) in the combined group. Conclusions: TAE/TACE alone was associated with superior survival outcomes and a more favorable safety profile in patients with unresectable NETLM. These findings suggest that TAE/TACE alone may be a more effective and safer treatment approach for this patient population. The combination therapy should be approached with caution due to unimproved survival outcomes and increased liver-related toxicities.

Survival outcomes of stage IIB/IIC cutaneous melanoma treated with wide local excision and adjuvant immunotherapy without sentinel lymph node biopsy.

9563 Background: The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) reported no significant difference in 10-year overall survival (OS) in patients with thick melanomas who had only wide local excision (WLE) versus WLE and sentinel lymph node biopsy (SLNB). With expanded immunotherapy eligibility for stage IIB/C melanoma per KEYNOTE-716, does omission of sentinel node negatively impact nodal basin disease control? Thus, we studied patients with stage IIB/C cutaneous melanoma treated with WLE and adjuvant pembrolizumab. Methods: We performed a single-institution retrospective review and included patients with stage IIB/C cutaneous melanoma treated with only WLE and adjuvant pembrolizumab with at least 6 months of follow-up. The primary endpoints were OS and cumulative incidence of nodal metastasis (CINM). Secondary endpoints were recurrence-free survival (RFS) and nodal metastasis-free survival (NMFS). Survival was estimated via Kaplan-Meier survival analysis and compared to the thick melanoma observation arm of MSLT-1. Results: Thirty-three patients met inclusion criteria between 2021-2025. Our sample was 58% male, 100% White, non-Hispanic, and median age at surgery was 59 ± 13 years. Twenty-sex (79%) patients were clinical group stage IIB. Tumor subtypes included acral lentiginous (3%), desmoplastic (3%), nodular (45%), spindle cell (3%), and superficial spreading (24%). Median follow-up was 24.3 ± 12.3 months. Four deaths occurred at 11, 17, 32, and 42 months, and OS probability was 96.2% at 12 months and 84.0% at 36 months. We observed 11 recurrences (33.3%). Six occurred in regional lymph nodes at 3, 3, 7, 7, 20, and 34 months, and 5 were distant metastases at 6, 11, 19, 20, and 25 months. At 12 months, RFS probability was 80.4%, 65.9% at 24 months, and 47.9% at 36 months. The probability of NMFS was 87.5% at 12 months, 82.8% at 24 months, and 69.0% at 36 months. Our CINM, over a median follow-up duration of 24.3 ± 12.3 months, was 18.2%, of which 3 began nivolumab/relatlimab and had complete radiological response and no subsequent recurrence. Of the 5 distant metastases, 3 underwent radiation or surgery for brain lesions and 1 began nivolumab/relatlimab for a chest wall nodule, both groups had complete radiologic response with no recurrence. Per MSLT-1, melanoma-specific survival of thick melanomas was between 76.1 ± 5.2% and 53.8 ± 7.6% at 60 months, and CINM was 33.2 ± 4.5% at 36 months. Conclusions: In our cohort, OS and CINM were comparable or better to the thick melanoma observation arm of MSLT-1. Our data suggests that omission of SLNB is highly likely to not negatively impact outcomes and may be offered to patients with significant operative risk. A larger sample with longer follow-up is needed to substantiate this conclusion.

TIDAL: A phase II study of the DLL3-directed T-cell engager tarlatamab in DLL3-positive metastatic prostate cancer.

TPS5142 Background: T-cell engagers directed at canonical prostate adenocarcinoma surface antigens (e.g., STEAP1, KLK2) have demonstrated substantial activity in prostate adenocarcinoma; however, alternative tumor-directed targets are needed for pts whose tumors have undergone lineage plasticity. Delta-like ligand 3 (DLL3) is a surface target variably expressed across the spectrum of neuroendocrine/small cell malignancies. Tarlatamab (Imdelltra, Amgen, Thousand Oaks, CA) is a bispecific T-cell engager targeting DLL3 and CD3, with regulatory approval for small cell lung cancer, and emerging evidence of activity in DLL3-positive prostate cancer. TIDAL is a multi-center, prospective, single arm phase II trial (NCT07111507) evaluating the safety and efficacy of tarlatamab in DLL3-positive advanced prostate cancer. Methods: Key eligibility criteria include metastatic prostate cancer with progression on ≥1 prior systemic therapy in the metastatic setting and DLL3-positive disease (IHC ≥50%), irrespective of histologic subtype. Pts without measurable disease by RECIST 1.1 criteria can be enrolled; however, at least 50% of pts enrolled must have measurable disease. Pts will receive tarlatamab in 28-day cycles with a 1 mg priming dose on cycle 1 day 1 (C1D1), followed by a target dose of 10 mg on C1D8, C1D15, and days 1 and 15 of subsequent cycles. All pts are hospitalized for ≥24 hours of monitoring following C1D1 and C1D8 infusions. Mandatory tumor biopsy and circulating tumor DNA (ctDNA) collection are performed at screening and cycle 2, with required ctDNA and optional biopsy at end of treatment (EOT). CT and bone scan are performed every 8 weeks for the first 24 weeks, then every 12 weeks. The primary endpoint is radiographic progression-free survival at 24-weeks. Secondary endpoints include overall response rate (ORR), median duration of response, median rPFS, median composite PFS, median overall survival, and safety. Correlative studies will evaluate associations between tumor DLL3 expression, circulating immune profiles, and clinical outcomes. A subset of pts will be co-enrolled in an imaging biomarker study (NCT04199741) utilizing a novel DLL3 PET tracer ( 89 Zr-DFO-SC16.56). As of January 14, 2026, 4 of the planned 32 pts have been enrolled. Clinical trial information: NCT07111507 .

Triglyceride-glucose-based indices in relation to vitamin D concentrations among adults with metabolic syndrome

Background The concurrent global epidemics of 25-hydroxyvitamin D (25[OH]D) deficiency and metabolic syndrome (MetS) pose substantial public health challenges. This study investigated the association of the triglyceride-glucose (TyG) related indices with serum 25(OH)D concentration in MetS patients. Methods In this study, we have recruited 1,297 participants (869 men, 428 women) with MetS who underwent regular health checkups between 2021 and 2023. Participants’ demographic, laboratory, and clinical parameters were retrieved, and data were divided into three groups based on the TyG index. Parameters were compared across the TyG index tertiles. Correlation analysis was used to find the association of the TyG index and related indices with 25(OH)D. Results The TyG-body mass index (TyG-BMI) demonstrated a statistically significant but weak negative correlation with serum 25(OH)D levels (r = −0.09, P < 0.001), whereas no significant association was observed between the standard TyG index and 25(OH)D (r = 0.007; P = 0.81). Comparative analysis among tertiles revealed significant differences in lipid profiles and glucose parameters (P < 0.001). Males demonstrated significantly higher TyG index values (P < 0.001), while females showed significantly elevated TyG-BMI (P < 0.001). Serum 25(OH)D concentrations were significantly higher in males compared to females (19.2[8.87] vs 16.6[9.50] ng/mL, P < 0.001). Only 92 (7%) of our study population had a normal level of 25(OH)D (≥30 ng/mL). Conclusion The association between TyG-BMI and vitamin D is weak and of limited clinical relevance. Further prospective studies should be conducted to evaluate the association of these indices with 25(OH)D.

Enhanced superconducting nanowire single-photon detector performances using silicon capping

Niobium titanium nitride-based superconducting nanowire single photon detectors (SNSPDs) are known for their high performance across a wide spectral range, from the x-ray to the mid-infrared. Nonetheless, fabrication challenges and performance degradation attributable to surface oxidation and lack of uniformity in films thinner than 5 nm remain a significant barrier for achieving high-quality detectors. In this work, we study the influence of a silicon capping layer on film properties and on the performance of SNSPDs. A silicon capping layer effectively suppresses oxidation and increases the superconducting transition temperature. This enables superconductivity in films as thin as 3 nm at 3 K, increases critical current in patterned nanowires, and significantly extends the saturation plateau from the visible to the near infrared (up to 2050 nm): These detectors maintain sub-50 ps timing jitter, even for nanowires as wide as 250 nm and with detection areas of 20 × 20μm2. Our results establish that thinner films protected by a capping layer allow for the fabrication of wider wires, decreasing nanofabrication challenges and extending the operating temperature range for efficient single photon detection.

High-capacity nanocrystalline Ni-rich LCNO cathode (c/a=4.982): Enhanced Li⁺ kinetics via combustion synthesis

Revised Solvent Rule Unlocks Non‐Conventional Solvents for Na ⁺ ‐Solvent Co‐Intercalation in Graphite

ABSTRACT Solvent selection for electrochemical Na + ‐solvent co‐intercalation in graphite has been constrained by an empirical rule requiring both high reductive stability and strong solvating power, thereby historically confining viable solvent candidates primarily to glyme‐based ethers. Here, we re‐examine this solvent selection rule and reveal that the cyclic consumption of Na + ‐solvent complexes at the graphite electrode and their regeneration at the counter electrode leads to a net cancellation of solvation energy in coupled electrode systems, thereby decoupling solvation power from co‐intercalation feasibility. To validate this decoupling, we designed a fluorinated ether with deliberately attenuated solvating power but high reductive stability, as a proof‐of‐concept solvent. Successful co‐intercalation was observed with this weakly solvating fluorinated ether, whereas typical carbonate solvents with superior solvation capability failed due to reductive decomposition above the intercalation threshold, confirming that solvation strength is not the determining factor. Leveraging this insight, we further designed and identified aminated ethers as a previously unexplored subclass of ethers capable of co‐intercalation. This work revises the empirical dual‐factor rule and eliminates solvation capability as a constraint, which broadens the range of viable solvents for graphite‐based sodium‐ion batteries.

Retraction Note: Spin polarized first principles study of electro-magnetic and optical properties of K2NaXI6 (X :Cr Fe) double halide perovskites

Transport mechanism of the SLC4 proteins—Lessons from recent structural and computational studies

Zelenectide pevedotin (BT8009) plus pembrolizumab in 1L cisplatin-ineligible locally advanced/metastatic urothelial carcinoma: Update on Duravelo-1 B7.

4564 Background: Zelenectide pevedotin (zele, formerly BT8009) is a highly selective Bicycle Drug Conjugate (BDC) targeting Nectin-4 and conjugated to MMAE. Zele has a lower molecular weight (4.2 kDa) and a shorter plasma half-life (< 1 hour) than antibody drug conjugates (ADCs), with potential to rapidly penetrate solid tumors and minimize healthy tissue exposure. Preliminary results of zele + pembrolizumab (pembro) in previously untreated, cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (la/mUC) patients (pts) (expansion cohort B7, NCT04561362; Duravelo-1), showed promising antitumor activity and a generally tolerable safety profile (Giannatempo et al., 2025). Here, we present updated results with extended follow-up and further efficacy data. Methods: Cisplatin-ineligible pts by Galsky criteria who had received no prior systemic anticancer treatment for la/mUC were eligible. Pts received IV zele 5 mg/m 2 on Days (D)1/8/15 + pembro 200 mg on D1 of a 21-D cycle. The primary endpoint was confirmed objective response rate (cORR) per Investigator using RECIST v1.1. Secondary endpoints included safety and additional efficacy endpoints. Treatment-related adverse events (TRAEs) were determined for all pts who received at least one dose of study drugs. Results: As of July 1, 2025, 22 pts were treated: median age 77 years, 45% had ECOG performance status (PS) of 2, and 45% had creatinine clearance < 60 mL/min. Median duration of treatment for zele and pembro was 23.4 weeks (range 1.0–84.1) and 26.9 weeks (range 3.0–85.9), respectively. Median follow-up was 11.8 months (range 1.0–19.4); 14 pts remained on study at the time of data analysis. Median progression-free survival (mPFS) was 13.0 months (95% CI 3.8–NE). cORR was 50% (n = 11/22), and disease control rate was 82% (n = 18/22), including 5 complete responses and 6 partial responses (PR); 2 additional pts had unconfirmed PRs. Median duration of response (mDOR) was not mature. The most common Gr ≥3 TRAEs included ALT increase (18%) and neutropenia and asthenia (14% each). Of AEs of clinical interest (AECIs), treatment-related Gr 3 events included peripheral neuropathy (14%; leading to drug withdrawal in 2 pts) and skin reactions (9%; these events were not serious and did not lead to withdrawal); no Gr 4 or 5 treatment-related AECIs occurred. Conclusions: Treatment with zele + pembro has promising clinical benefits in pts with la/mUC and a historically poor prognosis with first-line therapies (~50% ECOG PS of 2), including: mPFS of 13.0 months, 50% cORR, and mDOR not reached. Additionally, zele + pembro demonstrates a safety profile with the potential to differentiate from ADC combinations, including no skin-related serious AEs. These data support the Phase 2/3 study of zele as monotherapy and in combination with pembro versus chemotherapy in pts with la/mUC (NCT06225596; Duravelo-2). Clinical trial information: NCT04561362 .

Experience of Spanish centers with echoendoscopically implanted ³² P microparticles associated with chemotherapy in locally advanced pancreatic adenocarcinoma.

4232 Background: Phosphorous 32 microparticle ( 32 P) brachytherapy delivered by echoendoscopy (EUS) represents an innovative therapy in pancreatic cancer (PC). The device to implant it is approved in unresectable locally advanced PC in combination with gemcitabine-based chemotherapy. Our aim is to present the preliminary efficacy and safety results of a series that brings together the experience of thirteen centres in Spain. Methods: After being assessed by a multidisciplinary committee, patients signed consent to receive intratumoural 32 P by EUS. Complications associated with intratumoural 32P injection via EUS, associated adverse events (AEs) and preliminary efficacy results (progression-free survival [PFS], distant and locoregional, and overall survival [OS]) were analysed. Results: Fifty one patients (32 females and 19 males; age 65.5 years [range 48, 84]; 36 ECOG 1 and 14 ECOG 0) with unresectable locally advanced PC (30 in head, 5 in uncinate, 5 in neck and 11 in body; tumour size 30.8 mm [range 12, 60]) were included. The median time from tumour diagnosis to procedure was 5.9 months [0, 28.9]. Twenty-four patients (47 %) had received at least one previous line of treatment; four had received two prior lines. Fifty patients (98%) received gemcitabine-based chemotherapy concomitant with intratumoural 32P (42 gemcitabine plus nabpaclitaxel; 8 gemcitabine monotherapy. There were two AEs related to 32P injection by EUS: G1 epigastric pain (1 patient) and G2 asthenia (1 patient). A total of 30 patients (58.8%) had chemotherapy-related AEs, with 8 cases of G3 neutropenia (1 febrile neutropenia) and/or G3 thrombopenia; 22 had G1-2 toxicities: neurotoxicity (5), asthenia (4), neutropenia (3), thrombopenia (2), anaemia (4), nausea (2), diarrhoea (2), anorexia (1), onycholysis (1), mucositis (1), and constipation (1). Seven patients (13,7%) underwent surgery after intratumoural treatment (5 R0 and 2 R1). With a median follow-up of 8.7 months after injection (range: 1.02 months to 40.77 months), 25 patients (49.2 %) have progressed, 19 of them distantly, and nine also locoregionally. The median PFS since 32P injection is 8.5 months (95% CI 5.3, 17). 33 patients are alive at the end of follow-up (64.7%) with a median OS since 32P injection of 15.6 months 95% CI [10.2, 26.9]. Conclusions: Our experience suggests that intratumoural 32P associated with gemcitabine-based chemotherapy is safe. Patients after 32P injection achieve long overall survival. Surgical rescue was achieved in a high percentages of initially unresectable cases.

Outcomes of first-line immune checkpoint inhibitor combinations versus tyrosine kinase inhibitors in advanced hepatocellular carcinoma: A meta-analysis.

e16243 Background: This meta-analysis compares survival and safety outcomes of FDA-approved first-line ICI combinations versus TKI monotherapy and ICI monotherapy in advanced HCC. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and Google Scholar for randomized controlled trials (2018–2025) evaluating first-line systemic therapies in unresectable/metastatic HCC. Primary endpoint: progression-free survival (PFS) and overall survival (OS) . Secondary: grade 3/4 adverse events (AEs) per CTCAE. Kaplan-Meier curves were digitized, and individual patient data (IPD) reconstructed for pooled estimates using random-effects models to derive hazard ratios (HRs), median survivals (with 95% CIs), and heterogeneity (I²). Results: A total of 4,429 patients were included across key trials. Pooled median PFS (95% CI) and OS (95% CI) were: dual ICI (nivolumab/ipilimumab, tremelimumab/durvalumab) 5.51 months (4.75-5.76) and 19.58 months (17.56-23.32); ICI + bevacizumab (atezolizumab/bevacizumab) 5.75 months (5.55-6.74) and 19.09 months (17.10-21.27); ICI + TKI 6.17 months (5.58-7.07) and 19.23 months (16.82-21.88); TKI monotherapy 5.42 months (4.76-5.51) and 15.30 months (13.96-16.27); ICI monotherapy 3.73 months (3.34-3.89) and 16.84 months (13.85-not estimable). All ICI combinations significantly improved OS versus TKI monotherapy (p < 0.001); PFS benefits were variable but generally favored combinations. Among dual ICIs, nivolumab/ipilimumab showed the highest median PFS (9.33 months) and OS (24 months) compared with tremelimumab/durvalumab (PFS 3.84 months, OS 16.7 months) and atezolizumab/bevacizumab (PFS 6.86 months, OS 19.09 months). Versus tremelimumab/durvalumab, atezolizumab/bevacizumab and nivolumab/ipilimumab had favorable PFS (HR 0.76, 95% CI 0.64-0.89, p < 0.05; HR 0.60, 95% CI 0.51-0.72, p < 0.05) and OS (HR 0.93, 95% CI 0.76-1.13, p = 0.4; HR 0.79, 95% CI 0.65-0.95, p < 0.05). Grade 3/4 AEs were highest with ICI + TKI (72.4%), followed by TKI monotherapy (42.7%), ICI + bevacizumab (38.7%), and lowest with dual ICI (32.7%). Notable toxicities included hypertension/platelet abnormalities (ICI + TKI), diarrhea (TKI monotherapy/dual ICI), bilirubin elevation/fatigue (dual ICI), and anemia (ICI + bevacizumab). Conclusions: First-line ICI-based combinations significantly improve survival over TKI monotherapy in advanced HCC, with dual ICI and ICI + bevacizumab regimens showing comparable OS benefits and more favorable toxicity profiles than ICI + TKI approaches. Dual ICI offers an optimal efficacy-toxicity balance in this pooled analysis. These findings support personalized first-line selection based on patient-specific efficacy expectations and tolerability risks, warranting further head-to-head and biomarker-driven studies.

Impact of the COVID-19 pandemic on outcomes in malignant bowel obstruction: A National Inpatient analysis using explainable machine learning (2020–2023).

e13572 Background: Malignant bowel obstruction (MBO) is a high-mortality complication of advanced abdominal and pelvic malignancies, most commonly ovarian, colorectal, pancreatic, and gastric cancers. Obstruction typically arises from peritoneal carcinomatosis, direct tumor invasion, or extrinsic compression, and frequently reflects advanced-stage disease. The COVID-19 pandemic disrupted oncology screening and care delivery. We utilized explainable artificial intelligence (XAI) to develop a mortality prediction model and to characterize temporal changes in mortality risk factors from the peak-pandemic period (2020–2021) to the post-pandemic recovery period (2022–2023). Methods: We performed a retrospective analysis of the National Inpatient Sample (NIS) from 2020 to 2023. MBO was defined by ICD-10-CM intestinal obstruction codes in hospitalizations with gastrointestinal, genitourinary, or pelvic malignancies, including colorectal, pancreatic, gastric, ovarian, uterine, and cervical cancers. An XGBoost model was trained (70:30 split) to predict in-hospital mortality using 45 clinical, demographic, hospital, and socioeconomic features. Model interpretability was assessed using SHapley Additive exPlanations (SHAP) to rank feature importance. Temporal comparisons were performed between 2020–2021 and 2022–2023. Results: Among 84,472 MBO hospitalizations, the XGBoost model achieved an AUC of 0.85 (95% CI, 0.83–0.87), outperforming the Charlson Comorbidity Index (AUC 0.68). In 2020–2021, active COVID-19 infection was a leading contributor to mortality risk. In 2022–2023, the relative contribution of COVID-19 decreased, while features consistent with advanced disease and physiologic compromise (e.g., peritoneal carcinomatosis, cachexia, sepsis) increased in importance, suggesting a shift toward higher acuity at presentation. Socioeconomic disparities persisted; the lowest household income quartile remained a top-10 predictor of mortality across all years (p < 0.05). Conclusions: This XAI framework provides a robust tool for mortality risk stratification in MBO across diverse abdominal and pelvic tumor types. Shifts in feature importance from 2020–2021 to 2022–2023 suggest evolving drivers of mortality in emergency oncology admissions following pandemic-related disruptions in care.

A phase I window-of-opportunity trial of intraperitoneal, intratumoral lipopolysaccharide in peritoneal metastases: Safety and immune remodeling from the RIOT-1 study.

2603 Background: Peritoneal metastases (PM) from gastrointestinal malignancies exhibit immune exclusion and limited responsiveness to systemic immunotherapy. Regional intratumoral immune activation may reprogram the tumor microenvironment (TME). RIOT-1 evaluated the safety, feasibility, and biological effects of intraperitoneal intratumoral lipopolysaccharide (LPS), a Toll-Like Receptor-4 (TLR4) agonist, administered during diagnostic laparoscopy. Methods: RIOT-1 (NCT05751837) was a single-center, open-label Phase I window-of-opportunity trial. Twelve patients with appendiceal or colorectal PM received paired intratumoral injections of 1 µg E. coli O113-derived LPS and normal saline into spatially distinct tumor deposits at laparoscopy, followed by planned cytoreductive surgery 14 days later. The primary endpoint was safety. Secondary endpoints included immune and molecular remodeling assessed by immunohistochemistry (IHC), PhenoCycler multiplex immunofluorescence, spatial neighborhood analysis (CytoMAP), and high-resolution mass-spectrometry proteomics. Key proteomic findings were validated by targeted IHC staining. Results: Intratumoral LPS administration was feasible and well tolerated, with no grade ≥3 adverse events and no interference with subsequent cytoreductive surgery. IHC demonstrated significant post-LPS increases in M1-like macrophages (CD68⁺CD86⁺), M2-like macrophages (CD68⁺CD206⁺), and CD1a⁺ antigen-presenting cells (all p<0.05). PhenoCycler and CytoMAP analyses revealed LPS-specific reorganization of the immune microenvironment, characterized by enrichment of myeloid- and APC-dominant neighborhoods and altered tumor–immune spatial relationships compared with saline-injected controls. Proteomic profiling quantified 5,178 proteins and revealed LPS-specific enrichment of neutrophil degranulation, cytokine-mediated signaling, RNA translation, and autophagy–lysosomal pathways, distinct from biopsy/carrier-associated structural remodeling observed with saline. Upregulated proteins including LYZ, FCER1G, NAIP, and CD68 were confirmed by IHC, supporting localized innate immune activation and metabolic reprogramming. Conclusions: Intraperitoneal intratumoral LPS delivery in PM is safe and biologically active, inducing reproducible innate-dominant immune and metabolic remodeling validated across spatial, proteomic, and histologic platforms. These data establish clinical proof-of-mechanism for regional TLR4 agonism and support further dose-optimization and rational combination strategies in peritoneal malignancies. Clinical trial information: NCT05751837 .

Baseline brain metastases as a prognostic factor in extensive-stage small cell lung cancer treated with first-line chemo-immunotherapy: A systematic review and meta-analysis.

e20139 Background: Extensive-stage small cell lung cancer (ES-SCLC) frequently presents with brain metastases, affecting approximately 20% of the patients at diagnosis. The prognostic impact of baseline brain metastases on survival outcomes in patients treated with contemporary chemo-immunotherapy remains unclear, creating uncertainty in first-line treatment selection for this high-risk population. We conducted a systematic review and meta-analysis to evaluate the impact of baseline brain metastases on treatment outcomes in ES-SCLC. Methods: This PRISMA-compliant systematic review and meta-analysis was prospectively registered in PROSPERO. PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched from database inception through January 2026 to identify randomized controlled trials evaluating PD-1/PD-L1-based chemo-immunotherapy versus platinum-etoposide chemotherapy in adults with ES-SCLC. Two reviewers independently screened studies and extracted data, with discrepancies resolved by consensus. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled separately for patients with baseline brain metastases (BM+) and without brain metastases (BM−) using random-effects models with Hartung–Knapp adjustment. Analyses were performed using R. Prespecified subgroup analyses were conducted based on follow-up duration and immunotherapy regimen. Results: Twelve randomized controlled trials were included. Among patients with baseline brain metastases (BM+), pooled OS from seven studies did not show a significant survival benefit (HR 0.84, 95% CI 0.66–1.08, I² = 0.0%, P = 0.145), nor did pooled PFS from five studies (HR 1.03, 95% CI 0.60–1.79, I² = 0.0%). Subgroup analyses revealed no significant heterogeneity. In contrast, among patients without baseline brain metastases (BM−), pooled OS from nine studies demonstrated a significant survival benefit (HR 0.72, 95% CI 0.69–0.76, I² = 0.0%, P < 0.001), with corresponding improvement in PFS (HR 0.70, 95% CI 0.60–0.82, I² = 0.0%). These findings indicate a differential treatment effect according to baseline brain metastasis status. Conclusions: First-line chemo-immunotherapy does not apprear to confer a significant survival benefit in ES-SCLC patients with baseline brain metastases, reflecting a differential treatment effect by brain metastasis status. These findings suggest that baseline brain metastases should be considered in treatment selection and future clinical trial design and highlight the need for optimized systemic strategies for this high-risk population.

Durvalumab (D) in combination with BCG induction and maintenance (I + M) therapy for BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): 5-year overall survival (OS) analysis and patient-reported outcomes (PROs) from POTOMAC.

4624 Background: In the Phase 3 POTOMAC study (NCT03528694), 1 year of D in combination with BCG (I + M) resulted in a statistically significant and clinically meaningful improvement in disease-free survival vs BCG (I + M) alone, with a manageable safety profile, in patients (pts) with BCG-naive, high-risk NMIBC. We report a planned updated 5-year OS analysis and PROs. Methods: Eligible pts were randomized 1:1:1 to D + BCG (I + M), D + BCG (I only), or BCG (I + M). Secondary endpoints included 5-year OS and PROs, evaluated every 8 weeks by EORTC QLQ-C30 and every 4 weeks by EORTC QLQ-NMIBC24 and PRO-CTCAE. Prespecified priority subscales were global health status/quality of life (GHS/QoL), physical functioning, and fatigue for QLQ-C30; and urinary symptoms, intravesical treatment (tx) issues, future perspective/worries, and sexual functioning for QLQ-NMIBC24. Change from baseline (CFB; mixed model for repeated measures) was assessed; a ±10-point score was considered clinically meaningful. Results: At data cutoff Oct 3, 2025 (median follow-up 72 months), the OS HR was 0.81 (95% CI, 0.54–1.19) with a 5-year OS rate of 87.6% (95% CI, 83.5%–90.8%) for D + BCG (I + M) vs 86.3% (95% CI, 82.1%–89.6%) for BCG (I + M). Median OS was not reached in either arm. For PRO analyses (data cutoff Apr 3, 2025), QLQ-C30 and QLQ-NMIBC24 baseline compliance rates were ≥74% and ≥79%, respectively, with similar baseline scores between arms. Overall, both arms showed deterioration in QLQ-C30 adjusted mean CFB scores, with suggested clinically meaningful deterioration for fatigue with D + BCG (I + M); however, the difference between arms was small (Table). Overall QLQ-NMIBC24 adjusted mean CFB scores were numerically small and similar between arms (Table). PRO-CTCAE measures were similar between arms. Conclusions: Addition of 1 year of D to BCG (I + M) continued to show no detriment to OS at >5.5 years of follow-up and had no major impact on PROs for pts with BCG-naive high-risk NMIBC. Clinical trial information: NCT03528694 . Subscales D + BCG (I + M)Adjusted mean CFB (95% CI) a BCG (I + M)Adjusted mean CFB (95% CI) a Estimated difference of means (95% CI) QLQ-C30 GHS/QoL b −7.6 (–9.19, −6.07) −4.9 (–6.46, −3.41) −2.7 (–4.85, −0.54) Physical functioning b −5.5 (–6.76, −4.15) −2.8 (–4.11, −1.56) –2.6 (–4.43, –0.81) Fatigue c 10.1 (8.32, 11.90) 6.1 (4.37, 7.88) 4.0 (1.50, 6.46) QLQ-NMIBC24 Urinary symptoms c 1.7 (−0.06, 3.41) 0.4 (−1.27, 2.15) 1.2 (–1.19, 3.65) Intravesical tx issues c 1.5 (−0.38, 3.28) 2.7 (0.89, 4.50) −1.2 (−3.79, 1.29) Future perspective/worries c −5.5 (−7.54, −3.39) −3.2 (−5.29, −1.19) −2.2 (−5.11, 0.66) Sexual functioning b 2.2 (0.47, 3.91) 1.1 (–0.60, 2.80) 1.1 (−1.30, 3.48) a Higher scores indicate better health (GHS/functioning) or greater burden (symptoms). b Positive difference favors D + BCG (I + M). c Negative difference favors D + BCG (I + M).