Browse Articles

Green synthesis, characterization, and thermal stability of Albizia adianthifolia leaf–mediated CaO nanoparticles for anticorrosion applications

Flexible Multiband Photonic Synapses for Nociceptive Perception and Neuromorphic Computation via Fluorinated InP Quantum Dots (Adv. Mater. 31/2026)

Multifunctional Bio‐Based Packaging for Perishable Foods: Structural Design, Scalable Fabrication, and Versatile Applications

ABSTRACT Food loss and food safety remain pressing global challenges, with roughly one‐third of food lost or wasted annually and approximately 420 000 deaths attributed to foodborne diseases. Conventional preservation and detection methods—such as refrigeration and centralized laboratory testing—are effective but often are energy‐ and infrastructure‐intensive, and provide delayed feedback. As a systems‐level alternative, multifunctional bio‐based packaging integrates two or more functions within and/or across preservation and quality monitoring, evolving from passive barriers into structure‐informed platforms that couple material chemistry, hierarchical architecture, and transport regulation. This review summarizes advances from 2020–2025 across radiative cooling systems, modified atmosphere packaging, active platforms, intelligent sensing labels, and superhydrophobic surfaces. We synthesize design principles through a structure–transport–function lens and emphasize commodity‐specific operating windows linking physiology to permeability/selectivity, release kinetics, and sensing reliability. To enable cross‐study comparison, we define integration paradigms (superposition, coupling, and quantitatively validated synergy) and adopt standardized benchmarking based on the shelf life multiplier. Translation readiness is assessed via scalable manufacturing, migration and biosafety, ISO‐aligned LCA, TEA, and consumer acceptance. Finally, we propose a food‐matrix‐informed framework for next‐generation bio‐based packaging that unites dynamic preservation and sensing with standardized validation and scalable green manufacturing, guiding rational development toward safer, more sustainable, and waste‐minimized food systems.

ConvECA-Net: A lightweight convolutional neural network for fault diagnosis of tapered roller bearings

A tungsten-specific maturation pathway governs cofactor assembly of a CO2-reducing formate dehydrogenase in Methylorubrum extorquens

Hospitalized oncology patients with diarrhea: Clinical outcomes and prognostic factors.

11136 Background: Diarrhea is a frequent cause of hospitalization in oncology patients and may lead to substantial morbidity and mortality. However, data on short-term outcomes and prognostic factors in hospitalized cancer patients with diarrhea are limited. This study aimed to evaluate clinical outcomes and identify factors associated with poor prognosis in this population. Methods: Medical records of 6,349 oncology patients hospitalized over a 3-year period were retrospectively reviewed. A total of 163 adult patients hospitalized primarily for diarrhea were included; patients with immune checkpoint inhibitor–related diarrhea were excluded. Collected variables included demographic characteristics, disease stage, Eastern Cooperative Oncology Group (ECOG) performance status, febrile neutropenia at admission, systemic anticancer therapy, serum albumin level, and diarrhea grade. Primary outcomes were intensive care unit (ICU) admission and 30-day mortality. Logistic regression analysis was used to identify independent predictors of mortality. Results: Diarrhea accounted for 2.6% of all oncology-related hospitalizations, and 83.4% of patients had grade ≥3 diarrhea. ICU admission was more frequent in patients with ECOG ≥2 compared with those with ECOG < 2 (42.4% vs 14.4%, p < 0.001) and in patients with grade ≥3 diarrhea (27.9% vs 7.4%, p = 0.024). The overall 30-day mortality rate was 16.0% and was higher in patients with ECOG ≥2 (39.0% vs 2.9%, p < 0.001), metastatic disease (23.5% vs 7.7%, p = 0.006), and grade ≥3 diarrhea (19.1% vs 0%, p = 0.009). Febrile neutropenia was not associated with ICU admission or mortality. In multivariable analysis, ECOG ≥2 (OR: 17.1, p < 0.001) and lower serum albumin level (OR: 0.42, p = 0.049) were independent predictors of 30-day mortality. Diarrhea grade was excluded from the multivariable model due to complete separation. Conclusions: Diarrhea in hospitalized oncology patients is associated with substantial ICU utilization and short-term mortality, independent of febrile neutropenia. Poor functional status and low serum albumin are key prognostic factors, highlighting that diarrhea should be regarded as a potentially life-threatening condition requiring early risk stratification and prompt supportive care.

Vaccine-induced immune responses, HLA genotyping, and molecular profiling in patients with metastatic ovarian cancer (the PESCO trial).

5600 Background: PESCO, a phase 1/2 trial of Maveropepimut-S (MVP-S) in combination with Pembrolizumab and metronomic cyclophosphamide, showed safety and efficacy signals in metastatic ovarian cancer (OC). MVP-S uses the lipid-based DPX delivery platform to stimulate T cell immune response to survivin epitopes restricted by 5 HLA class I haplotypes (A1, A2, A3, A24, B7). Survivin is highly expressed in OC. We report exploratory correlative analysis including immune responses, HLA typing and molecular profiling. Methods: The study included a phase 1 dose escalation and expansion cohorts: A (platinum-sensitive high-grade serous [HGS]), B (platinum-resistant HGS), and C (rare OC histologies). Survivin-specific T-cell responses were assessed by flow cytometric detection of IFNγ following ex vivo PBMC re-stimulation with pooled survivin epitopes at on-treatment timepoints. A positive immune response was predefined as >0.1% IFNγ⁺ CD8⁺ T cells. HLA genotyping was mapped to MVP-S–restricted alleles. Molecular profiling was performed using next-generation sequencing (NGS) and/or whole-genome transcriptomic sequencing (WGTS). Results: Across 44 patients (pts), 37 (84%) carried ≥1 vaccine-relevant HLA allele and 23 (52%) carried ≥2. The most frequent alleles were A24 (16/44; 36%), A02 (15/44; 34%), A03 (12/44; 27%), B07 (11/44; 25%), and A01 (8/44; 18%). Survivin-specific immune responses were detected in 15/24 (62%) immune-evaluable pts and were strongly enriched among pts with clinical benefit: CR 1/1 (100%), PR 7/7 (100%), SD 6/10 (60%), versus PD 1/6 (16%); overall, 14/15 (93%) immune responders had clinical benefit. The longest survivin-specific response persisted for 195 weeks in a pt with MMR deficient tumor who had CR for 3 years. Exploratory HLA-outcome analysis suggested enrichment of A24 in pts with clinical benefit but absent in PD. NGS was performed in 44 pts and WGTS in 36. NGS identified at least one SNV/indel in 43/44 (97.7%) pts. In Phase 1 and Cohorts A/B (n=34, 68% HGS), TP53 was dominant (76.5%, 86% in HGS), followed by MYC (17.6%), NF1 (14.7%), and BRCA1/2 (each 8.8%). In Cohort C (n=10, 8 clear cell), ARID1A (70%) and PIK3CA (60%) were frequent. In platinum resistant pts (n=24), alterations included TP53 (67%), BRCA1/2 (21%), CCNE1(17%). Tumors with cell cycle/replication stress alterations were enriched among pts with PD (29% vs 8% in non-PD; P = 0.099) and immune non-responders (37.5% vs 6.7% in IFN responders; P = 0.103). Tumor mutation burden was low in all 26 pts tested. Conclusions: Survivin-specific immune responses were strongly enriched among pts with clinical benefit, supporting survivin as an active target in OC. HLA typing demonstrated broad coverage of MVP-S epitopes across pts. Molecular subtype may have influenced immune responses in this study. Our findings support biomarker-integrated studies to optimize immunotherapy combinations in OC. Clinical trial information: NCT03029403 .

Predictors of fibrotic progression in myeloproliferative neoplasms: A real-world retrospective cohort study.

e18607 Background: Progression to myelofibrosis (MF) is associated with worse survival and influences treatment decisions, yet predictors of fibrotic progression in polycythemia vera (PV) and essential thrombocythemia (ET) remain poorly characterized. Methods: Patients with pathologically confirmed PV or ET were identified from a retrospective chart review. Demographics (age, sex, race, ethnicity), clinical features (thrombosis and bleeding history, performance status, symptom burden, organomegaly), bone marrow pathology (cellularity, trilineage hematopoiesis, megakaryocyte proliferation and atypia, fibrosis grade), molecular markers ( JAK2 , CALR , MPL , ASXL1 , EZH2 , TET2 , SRSF2 , IDH1/2 , SF3B1 , TP53 ), cytogenetics, laboratory values, and treatment history (phlebotomy, hydroxyurea, interferon, ruxolitinib) at first bone marrow biopsy were recorded. MF progression was defined as hematologist-confirmed transformation to MF. Kaplan-Meier analyses estimated median MF-free survival (MFS), defined as time to MF progression or death. Univariable followed by multivariable Cox proportional regression were performed to identify candidate MFS predictors. The proportional hazards assumption was assessed using Schoenfeld residuals. Hazard ratios (HR) with 95% confidence intervals (CI) were computed, with p<0.05 indicating statistical significance. Results: A total of 505 PV and 198 ET patients were identified. The majority were White (PV: 92%; ET: 86%). PV patients were predominantly male (54%) whereas ET patients were predominantly female (66%). MF progression occurred in 160 (32%) PV and 32 (16%) ET patients. Death was observed in 139 (28%) PV and 10 (5%) ET patients. Median MFS was 158.5 months (95% CI: 143.0-183.0) for PV and 308.0 months (95% CI: 175.0-NR) for ET. In PV, older age at diagnosis (HR 1.04; 95% CI: 1.02-1.07; p<0.001) and shorter time since PV or ET diagnosis to biopsy (HR 0.995; 95% CI: 0.990-0.999; p=0.048) independently predicted worse MFS. In ET, bone marrow hypercellularity (HR 5.67, 95% CI: 1.40-23.0, p=0.015) independently predicted worse MFS. Conclusions: PV patients demonstrated shorter MFS compared to ET. Older age at diagnosis in PV, whereas bone marrow hypercellularity in ET was significantly associated with fibrotic progression or death. Active surveillance of at-risk patients may facilitate early detection and timely treatment initiation. Disease Variable HR (95%CI) P-value PV Age at diagnosis 1.04 (1.02-1.07) <0.001 Time since PV or ET diagnosis to biopsy 0.995 (0.990-0.999) 0.048 ET Bone marrow hypercellularity 5.67 (1.40-23.0) 0.015

Identifying cancer cachexia using clinical reasoning artificial intelligence (AI).

1613 Background: Cancer cachexia, a severe wasting syndrome, affects up to 87% of cancer patients 1 and contributes to ≥20% of cancer deaths 2 . Despite this burden, ~85% of healthcare providers are unfamiliar with diagnostic criteria 3 , leaving patients often undiagnosed. This study evaluated whether a Clinical Reasoning AI model configured on four cachexia guidelines (Fearon 4 , Evans 5 , GLIM 6 and mGPS 7 criteria) and designed to emulate clinician chart review, could accurately identify cancer cachexia. Methods: Using structured (vitals, labs) and unstructured (clinical notes) electronic health record data the Clinical Reasoning AI employed retrieval-augmented generation 8 and agentic techniques with large language models (LLMs) to: (1) retrieve clinically relevant information based on the clinical guidelines via natural language processing (NLP) and embedding, and (2) apply guideline-based reasoning to classify patients into Group 1 (no cachexia features), Group 2 (meets ≥1 guideline regardless of documented diagnosis), or Group 3 (documented cancer cachexia). Accuracy was assessed against a gold standard of 50 patients classified by two independent clinicians, with conflicts resolved by a third. Performance was compared against baseline methods: ICD coding (ICD-9 799.4; ICD-10 C80.9), NLP using keywords like cancer or cachexia, and LLMs (Vanilla OpenAI GPT-o4-mini) prompted without explicit instruction to use guidelines. Results: The Clinical Reasoning AI demonstrated high precision, sensitivity, and specificity, outperforming baselines, particularly for Group 2 patients. ICD and NLP methods could not detect Group 2, due to code- and keyword-based constraints. Performance of LLMs without guidelines worsened with structured and unstructured data, indicating sensitivity to data overload and inability to prioritise clinically relevant information. Conclusions: These results show that embedding clinical guidelines within a structured retrieval-and-reasoning architecture enabled accurate identification of cancer cachexia, addressing a critical gap where standard coding and keyword methods fail. The guideline-driven approach maintained accurate clinical reasoning while processing complex EHR data. The Clinical Reasoning AI model is currently being deployed at the point of care to assess real-world implementation and impact on patient outcomes. Group 2 Group 3 AI Model Precision Sensitivity F1 Specificity Precision Sensitivity F1 Specificity ICD N/A N/A N/A N/A 0.759 0.815 0.786 0.696 Simple NLP N/A N/A N/A N/A 0.727 0.593 0.653 0.739 Vanilla OpenAI GPT-o4-mini (unstructured data only) 0.500 0.500 0.500 0.765 0.594 0.704 0.644 0.438 Vanilla OpenAI GPT-o4-mini (structured and unstructured data) 0.500 0.062 0.111 0.971 0.385 0.185 0.250 0.652 Clinical Reasoning AI with GPT-o4-mini 0.762 1.00 0.865 0.853 0.964 1.00 0.982 0.957

Multimodal immunoprofiling of peripheral blood using foundation models of the immune system for predicting immunotherapy response and toxicity in the RADIOHEAD pan-cancer cohort.

2533 Background: While immune checkpoint inhibition (ICI) is an emerging gold standard for cancer therapy, positive response is limited among treated patients and up to 70% experience toxicity. Early and accurate response prediction that accounts for immune-related adverse events (irAEs) is crucial for identifying patients who may benefit from ICI. We present AI-powered approaches for predicting ICI response by transcriptional and cellular profiling of blood immune cells from a pan-cancer cohort. Methods: Peripheral blood mononuclear cells (PBMC) were isolated at pre- (baseline) and early on-treatment for flow cytometry and RNA-seq profiling from the RADIOHEAD cohort (Quandt et al. 2025) receiving ICI (n=1,070). Patients were clustered based on variational autoencoder embeddings for real-world progression-free survival (rwPFS) and irAEs derived by a peripheral immune system encoder trained on the BostonGene patient database (n=45,000). The logrank test and Fisher’s exact test were used to analyze survival and compare irAE frequencies between clusters, respectively. RNA-seq trajectory features were identified using hierarchical clustering, along with elastic net-regularized and simple multivariate Cox regression models for feature selection. Results: Pre-trained immunotype models (Dyikanov et al. 2024) applied to baseline PBMC revealed that G2-primed (memory CD4+ T cell-enriched) and G5-suppressive (monocyte enriched) immunotype scores stratified patients into responders (R) and non-responders (NR) (p = 0.00001). T cell receptor (TCR) dynamics revealed a significantly greater decrease in TCR diversity in NR during treatment (p = 0.046). We discovered a baseline gene set containing immune checkpoint and cancer antigen genes as well as a longitudinal trajectory set of monocyte and myeloid cell activation markers that both stratified patients by rwPFS (p=0.006; 0.03). Trained immune system embeddings identified a novel severe-risk patient group with both a high irAE incidence (p = 0.025) and short rwPFS. This group displayed both active inflammatory and tolerance pathways that stratified patients with irAEs by rwPFS (p = 0.003). Conclusions: Using pre-trained multimodal immune system projections, we 1) independently confirmed the association of peripheral immunotypes with ICI response; and 2) identified a novel severe-risk signature from patients with high irAE incidence (≥Grade 3) and short rwPFS. We also found that greater TCR diversity and T cell differentiation were associated with ICI response, while innate myeloid activation and trafficking correlated with non-response. Our unique AI-driven analytical framework underscores the potential of peripheral blood immunoprofiling for ICI treatment selection and patient stratification in prospective trials.

Phase 2 trial of epcoritamab in combination with rituximab-mini CVP for older unfit/frail or anthracycline-ineligible adult patients with newly diagnosed diffuse large B-cell lymphoma: Interim futility analysis.

7002 Background: The median age at diagnosis of diffuse large B-cell lymphoma (DLBCL) is approximately 65 years, with nearly one third of patients in the US diagnosed at age >75 years. This older unfit/frail population is particularly vulnerable to treatment-related toxicity due to comorbidities and limited cardiac reserve, frequently leading to treatment discontinuation, and outcomes with standard attenuated anthracycline-based chemoimmunotherapy remain suboptimal. There is therefore a critical unmet need for effective, better-tolerated non-anthracycline treatments. We hypothesize that epcoritamab combined with non-anthracycline chemotherapy (R-miniCVP) can achieve high and durable CR rates. Methods: This is an open-label, single-arm phase 2 trial conducted at MD Anderson Cancer Center (NCT06045247). Eligible patients have histologically confirmed DLBCL and are unfit/frail per FIL simplified geriatric assessment, or not eligible for anthracycline due to reduced ejection function (<50%), or prior anthracycline exposure therapy. Patients receive one cycle of R-miniCVP for debulking, followed by epcoritamab added from cycle 2 using step-up dosing, then 48 mg on day 1 of each subsequent cycle. After 6 cycles, patients achieving CR complete treatment, while patients with PR continue epcoritamab to 12 cycles. The primary endpoint is CR rate after 6 cycles. Results: We plan to enroll 40 patients. At the data cutoff, 22 patients have completed six cycles of therapy. The median age of 22 patients was 80 years (range, 71-87); 27% had PS 2, and 86% had an IPI ≥3. All patients completed planned treatment. The CR rate after 6 cycles was 86% (95% CI, 65-97%). Two patients achieved PR and continue on epcoritamab. One patient achieved PR after cycle 3 but progressed after cycle 6 and subsequently died of progressive lymphoma following 2 additional lines of therapy. With a median follow-up of 11 months (range: 5-23 months), the 1-year progression-free survival was 94.7% (95% CI, 68-99%). Cytokine release syndrome occurred in 12 patients (55%), all grade 1 and occurred around C2D15, which fully resolved in 1-2 days in all patients. Four of them received tocilizumab. One patient developed grade 2 neurotoxicity after C2D15, which resolved within 24 hours after switching prednisone to dexamethasone. The trial protocol was amended to change prophylactic steroid from prednisone to dexamethasone, after which no further neurotoxicity was observed. Conclusions: The combination of epcoritamab with R-mini-CVP demonstrated encouraging efficacy with a favorable tolerability profile in older, unfit or frail patients who may be unable to tolerate full-dose chemotherapy. Based on these promising early-phase results, the study is planned for expansion into a multicenter trial with a larger patient cohort. Clinical trial information: NCT06045247 .

Efficacy and safety of DR4/DR5 agonist aponermin monotherapy in advanced chondrosarcoma: Preliminary report from a prospective, multicenter study.

11532 Background: Reported median progression-free survival (mPFS) of Chondrosarcoma is less than 4 months for patients receiving first-line systemic therapy. Aponermin, a recombinant circularly permuted human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), induces tumor cell apoptosis by activating the extrinsic apoptotic pathway. This study aimed to evaluate the efficacy of Aponermin in patients with advanced chondrosarcoma. Methods: This prospective, multicenter, single-arm study (Registration No: ChiCTR2500104488) was approved by an independent ethics committee. The planned enrollment was 32 patients aged 18-75 years with histologically confirmed advanced chondrosarcoma, documented evidence of disease progression within 6 months prior to enrollment, ECOG performance status ≤2, and measurable disease per RECIST 1.1. Patients received intravenous Aponermin 10 mg/kg (days 1-5, every 14 days as one cycle) until disease progression, unacceptable toxicity, or investigator's decision to discontinue. The primary endpoint was objective response rate (ORR). Secondary endpoints included 4-month PFS rate, disease control rate (DCR), overall survival (OS), and safety. Results: As of January 23, 2026, 21 patients were enrolled and treated. Median age was 51 years (range: 26-70), with a median of 2 prior surgeries (range: 1-6). Eight patients had received prior drug therapy. Histopathological subtypes included: conventional grade 1, 19% (4/21); conventional grade 2, 47.6% (10/21); conventional grade 3, 4.8% (1/21); mesenchymal, 9.5% (2/21); and one case each (4.8%) of myxoid, dedifferentiated, clear cell, and unknown subtype. Twenty patients were evaluable for efficacy. Median treatment duration was 3.6 months (range: 0.5-14.0), with 4 patients still on treatment. Although no objective responses were observed，80.0% (16/20) of DCR was achieved. Median PFS was 4.2 months (95% CI: 2.9-5.5), and the 4-month PFS rate was 57.9%. Median OS was not reached. Notably, Among patients achieving DCR, 50% maintained clinical benefit for over 4 months, including one patient with conventional grade 3 chondrosarcoma with SD lasting 7.4 months, two patients with conventional grade 2 with SD exceeding 10.0 months, and one patient with clear cell subtype with SD lasting 14 months. Aponermin demonstrated a favorable safety profile. Treatment-related adverse events occurred in approximately 9.5% (2/21) of patients, including one case (4.8%) of grade 1 allergic reaction and one case (4.8%) of hand-foot syndrome, both alleviated with symptomatic treatment. Conclusions: Aponermin monotherapy demonstrated promising disease control and a favorable safety and tolerability profile in advanced chondrosarcoma. Given the limited sample size and ongoing enrollment, final efficacy and safety assessments await study completion. Clinical trial information: ChiCTR2500104488.

Comparing becotarug plus osimertinib with a real-world osimertinib therapy cohort in platinum-refractory, advanced non–small cell lung cancer with EGFR exon 20 insertion.

8546 Background: EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is a rare subtype with limited therapeutic options and poor prognosis. Becotarug plus osimertinib showed encouraging activity and acceptable safety in a phase 1 study (NCT04448379). To assess its efficacy in EGFR 20ins-positive NSCLC, a phase 2 single-arm trial (NCT05132777) was initiated. To provide a comparator, a multicenter retrospective real-world study (NCT05513664) was served as an external control arm. Methods: Eligible patients in the phase 2 study had unresectable stage IIIB–IV NSCLC with EGFR exon 20 insertion mutations and ≥1 prior platinum-based chemotherapy; those relapsing within six months after neoadjuvant or adjuvant chemotherapy were also eligible. The external control comprised a real-world cohort treated with osimertinib, matched 1:1 on age, sex, stage, ECOG PS, brain metastases, and number of prior systemic therapies. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) in the trial arm and real-world ORR in the control arm. Secondary endpoints included disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS). Safety was evaluated by incidence and severity of adverse events. Results: Of the 126 and 96 patients enrolled in the trial and control arms, respectively, 112 and 91 patients met criteria for the pre-matching cohort. After 1:1 propensity-score matching, 158 patients (79 per arm) comprised the post-matching population. Baseline characteristics were well balanced between arms, with 62.0% and 60.8% of patients, respectively, having received ≤1 prior line of systemic therapy. The IRC-assessed ORR was 46.8% (95% CI, 36.24–57.73) in the trial arm versus 7.6% (95% CI, 3.53–15.60) in the control arm. Notably, the lower bound of the trial-arm 95% CI (36.24%) exceeded the control-arm point estimate (7.6%). The absolute ORR difference was 39.2% (95% CI, 25.96–50.87; P < 0.0001), corresponding to an odds ratio of 10.72 (95% CI, 4.18–27.51). Furthermore, in a propensity score–matched analysis restricted to patients receiving osimertinib monotherapy (64 per arm), the combination therapy produced a greater ORR (42.2% [95% CI, 27.5-54.8], P < 0.0001). Higher DCR were achieved in trial arm compared to control arm (77.2% [95% CI, 66.8-85.1] vs 64.6% [95% CI, 53.6-74.2], P = 0.080). The median PFS in trial arm was significantly longer than that in control arm (6.9 vs. 4.8 months, P = 0.007). Other efficacy endpoints showed consistent trends favoring the combination therapy. The most common adverse events were EGFR-related mucocutaneous toxicities in both arms. Conclusions: This study further supports the efficacy and tolerability of becotarug plus osimertinib in patients with platinum-refractory, EGFR 20ins-positive NSCLC. Clinical trial information: NCT05513664 ; NCT05132777 .

Clinical utility of whole transcriptome sequencing for fusion detection in advanced solid tumors: SCRUM-Japan MONSTAR-SCREEN-2.

3127 Background: Fusion variants represent established therapeutic targets in precision oncology yet are incompletely captured by conventional targeted DNA panel sequencing. Recent studies have reported that RNA sequencing enables detection of oncogenic fusions and structural variants that escape conventional DNA panel sequencing, particularly complex rearrangements occurring in intergenic regions. Herein, we evaluated the landscape of fusion variant detection by whole transcriptome sequencing (WTS) in advanced solid tumors from the SCRUM-Japan MONSTAR-SCREEN-2, a nationwide molecular profiling project. Methods: Patients with advanced solid tumors were enrolled; tumor tissues were profiled using whole exome/transcriptome sequencing (MI CancerSeek, Caris Life Sciences, Phoenix, AZ, USA). For fusion detection comparison, we performed an in silico analysis cross-referencing each fusion detected by WTS against publicly available information from conventional DNA panels including both target gene lists and breakpoint information where available, to evaluate theoretical detectability. Results: Among 2,768 patients enrolled as of March 2024, WTS data from baseline tissue samples were available in 2,253 pts across 33 cancer subtypes: the most common subtypes were colorectal adenocarcinoma (n=520), gastric adenocarcinoma (n=306), breast cancer (n = 198), prostate cancer (n=177) and pancreatic cancer (n=156). Pathogenic gene fusions and structural variants were detected by WTS in 122 of the 2,253 patients (5.4%), with a total of 126 pathogenic fusions identified. Among 126 pathogenic fusions, 75 (59.5%) represented variants that would theoretically have escaped detection by targeted panel DNA sequencing methodologies, including druggable kinase fusions (FGFR2, FGFR3, and BRAF). Among 18 patients treated with kinase fusion-targeted therapy with evaluable response data, 1 (5.6%) showed complete response, 3 (16.7%) showed partial response and 11 (61.1%) showed stable disease. WTS identified a MYO5A-BRAF fusion in a patient with melanoma that was undetectable by conventional DNA panel sequencing. Based on this finding, the patient received combination BRAF and MEK inhibitor therapy, achieving stable disease for four months, demonstrating the therapeutic relevance of WTS-guided treatment selection. Conclusions: WTS detected fusion variants at a high frequency, highlighting the importance of WTS in precision oncology. Clinical trial information: UMIN000043899.

Safety and efficacy of elranatamab as early intervention in patients with high-risk smoldering myeloma: First results from the phase 2 ERASMM (EMN34) study.

7500 Background: Early intervention with lenalidomide or daratumumab significantly delays disease progression to active disease in high-risk (HR) smoldering multiple myeloma (SMM) patients (pts). The BCMAxCD3 bispecific antibody elranatamab (Elra) demonstrated strong anti-MM activity with favorable safety profile in relapsed MM. Using T-cell engagers in the early stage of the disease, with a potentially less exhausted immune system, may lead to improved efficacy. Here we report initial efficacy and safety results of Elra monotherapy in HR SMM pts enrolled in the phase 2 ERASMM Study (EMN34; NCT06183489). Methods: ERASMM is an international open-label multicenter phase 2 study of Elra as single agent in adult pts with HR SMM, defined as the presence of ≥2 Mayo 2018 “20-2-20” criteria. Treatment consisted of a fixed duration (2 years) of single-agent SC Elra with priming doses of 12 mg (C1D1) and 32 mg (C1D4), followed by 76 mg on days 8 and 15 during cycle 1, 1 and 15 during cycles 2–3, and 1 during cycles 4–24 (28-day cycle). The primary objective was the rate of complete response (CR). Safety was a key secondary endpoint. Other secondary objectives included overall response rate (ORR), measurable residual disease (MRD), progression-free survival (PFS), PFS2, time to active MM, and overall survival (OS). Results: Fifty pts with previously untreated HR SMM were included from May 2024 to September 2025 in 17 centers collaborating with the European Myeloma Network. Median age was 65 years (range 58–71). All pts had HR SMM, including M-spike >20 g/L in 42 (84%), bone marrow plasma cells >20% in 36 (72%), or free-light chain ratio >20 in 33 (66%). As of December 4, 2025, the median follow-up was 10 months (range 2.3–18.23). Thirty-four (68%) patients experienced a cytokine release syndrome event, all grade 1–2, except for grade 3 events in 2 pts. No ICANS events were observed. Infections occurred in 25 (50%) pts, including 14% grade 3–4. Other common (≥20%) non-hematologic adverse events (AEs) were skin rash (34%), diarrhea (26%), AST/ALT increase (28%), fatigue (20%), and peripheral neuropathy (20%), mostly grade 1–2. Four patients discontinued treatment due to AEs, including AST/ALT increase (n=1), Guillain–Barré syndrome (n=1), and infections (n=2). The ORR was 92%, including a very good partial response or better (≥VGPR) in 82% of pts, and a complete response or better (≥CR) in 45%. The 9-month PFS and OS rates were 95% and 100%, respectively. Conclusions: In HR SMM pts, single-agent Elra was highly active, with a 92% ORR, 45% of pts achieving ≥CR, and a favorable safety profile. Data on safety and efficacy (response, MRD, PFS) will be updated for the meeting. These data support further investigation of Elra as a therapeutic option for HR SMM. Clinical trial information: NCT06183489 .

Does the global cancer research funding by public and philanthropic investments address important research gaps?

e23032 Background: Public and philanthropic funding are vital to all domains of cancer research, yet little is known about how the funding landscape has evolved over the years and whether the public investments in cancer research are aligned with disease burden and research priorities. Methods: We conducted a cross-sectional analysis of cancer research grants recorded in the International Cancer Research Partnership database and European Commission programs from 2007 to 2022. Awards were converted to 2022 US dollars, adjusted for inflation, and classified by cancer site and the six Common Scientific Outline (CSO) categories- biology, etiology, prevention, early detection and diagnosis, treatment, and survivorship and outcomes research. Funding trends were assessed using joinpoint and linear regression. GLOBOCAN 2022 data for incidence, mortality, and mortality-to-incidence ratio (MIR) were extracted to assess alignment of funding amount with cancer burden. Results: Combined public and philanthropic cancer research funding increased from US$7.00 billion in 2007 to US$10.90 billion in 2022 (APC 2.46%). Observed investment in 2022 exceeded the inflation-adjusted projection of 2007 funding (US$9.87 billion). In 2022, funding was highest for treatment (US$3.31 billion), followed by biology (US$2.53 billion). Funding for treatment research constituted the highest proportion and funding for early detection, diagnosis, and prognosis (US$1.85 billion) and prevention (US$0.97 billion) represented a small portion of the total portfolio. Survivorship and outcomes research accounted for US$1.15 billion in 2022 and showed sustained growth over time (APC 2.51%). All categories had significant increases in funding amount per year except for the category of etiology. In 2022, breast cancer accounted for 6.9% of total cancer deaths but received 19.5% of total research funding, whereas upper gastrointestinal cancers represented 13.4% of deaths and received only 3.0% of funding. Funding distribution showed a moderate correlation with incidence (R² 0.41; R 0.64), a weak correlation with mortality (R² 0.10; R 0.32) and no correlation with MIR (R² 0.01; r −0.11). Conclusions: Public and philanthropic investments in cancer research increased from 2007 to 2022 at an annual rate of 2.46%. However, the funding distribution showed disproportionately low funding for the categories of cancer etiology, prevention, and survivorship. Certain tumor types were also likely to be disproportionately less funded relative to their public health burden. Our study highlights the underfunded categories and tumor types to be considered for increased and perhaps, targeted funding as part of future funding decisions.

Antibody-drug conjugate plus immunotherapy versus chemotherapy-immunotherapy in PD-L1–positive metastatic triple-negative breast cancer: A trial-anchored analysis.

e13122 Background: Pembrolizumab plus chemotherapy is an established first-line for unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) with PD-L1 CPS ≥10. Antibody-drug conjugates (ADCs) have demonstrated activity in metastatic TNBC, and recent phase III data support ADC-immunotherapy in the frontline. However, comparative efficacy and tolerability versus chemotherapy-immunotherapy in PD-L1-positive disease remain undefined. We performed a trial-anchored synthesis in the PD-L1 CPS ≥10 population. Methods: We conducted a synthesis of phase II-III randomized trials in unresectable locally advanced or metastatic TNBC. The primary analysis population was PD-L1 CPS ≥10. Outcomes included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and treatment discontinuation due to adverse events (AEs). Given a single randomized head-to-head trial and heterogeneity in PD-L1 assays, a pooled meta-analysis was not performed. Results were synthesized using a trial-anchored framework, with exploratory indirect estimates generated for contextualization. Results: In ASCENT-04/KEYNOTE-D19 (N = 443; PD-L1 CPS ≥10), sacituzumab govitecan plus pembrolizumab improved PFS versus chemotherapy plus pembrolizumab (median 11.2 vs 7.8 months; HR 0.65, 95% CI 0.51 - 0.84), with higher ORR (60% vs 53%) and longer DoR (16.5 vs 9.2 months). Treatment discontinuation due to AEs was lower with ADC-immunotherapy (12% vs 31%). In KEYNOTE-355 (PD-L1 CPS ≥10), pembrolizumab plus chemotherapy improved PFS versus chemotherapy alone (HR 0.65, 95% CI 0.49 - 0.86). An exploratory indirect comparison showed a PFS HR of 0.42 (95% CI 0.29 - 0.62) for ADC + immunotherapy versus chemotherapy alone. Conclusions: In PD-L1 CPS ≥10 metastatic TNBC, an exploratory indirect comparison suggests that ADC plus immunotherapy may substantially improve progression-free survival versus chemotherapy alone, supporting ADC-immunotherapy as a first-line option. Frontline outcomes in PD-L1 CPS ≥10 metastatic TNBC (ASCENT-04/KEYNOTE-D19). Outcome SG plus Pembrolizumab Chemo plus Pembrolizumab Absolute Difference Clinical Interpretation Median PFS (months) 11.2 7.8 +3.4 Longer disease control Objective response rate (%) 60 53 +7 Higher response likelihood Median duration of response (months) 16.5 9.2 +7.3 More durable responses Discontinuation due to AEs (%) 12 31 −19 Improved tolerability Approximate NNT (discontinuation) — — ~5 One discontinuation prevented per ~5 treated Abbreviations: SG, sacituzumab govitecan; PD-L1, programmed death-ligand 1; CPS, combined positive score; PFS, progression-free survival; ORR, objective response rate; DoR, duration of response; HR, hazard ratio; AEs, adverse events; NNT, number needed to treat.

Enhancing communication about cancer management and cancer care delivery for older adults with dementia and their care partners.

TPS12166 Background: Dementia affects 7–10% of older adults with cancer and is associated with worse cancer outcomes. Many patients (pts) have reduced decisional capacity, leading care partners (CPs) to play a major role in cancer management decision-making, which can increase CP burden and negatively affect their well-being. Cancer communication in this population is complex, requiring clinicians to balance pt preferences, CP input, and dementia-related considerations. Despite this, no standard approach exists to support triadic communication in this setting. COACH-Cog is a triadic communication intervention that promotes shared decision-making by integrating CP involvement while centering pt values in cancer care. Methods: Eligibility: Pts are age ≥65 with a diagnosis of dementia and cancer (any type or stage), have an identified CP, and receive oncology care from a participating clinician. CPs are age ≥18 and identified by the pt. Oncology clinicians (physicians or advanced practice providers) must practice at the Wilmot Cancer Institute. Study Design: This is a pilot cluster-randomized trial (clinician-level randomization). The COACH-Cog intervention includes: 1) a brief clinician training video on dementia and its relevance to cancer care; 2) distribution of pt geriatric assessment results with care recommendations to clinicians, pts, and CPs; and (3) CP communication coaching to elicit dementia-related concerns and develop questions for the next oncology visit. Baseline measures include pt geriatric assessment and dementia severity, CP well-being (burden, quality of life, depression, anxiety), and pt/CP communication and decision-making preferences. Pts and CPs receive either COACH-Cog or usual care based on clinician randomization. The subsequent clinical encounter is audio-recorded. Outcome Measures: The primary outcome is CP autonomy support, which evaluates how supported CPs feel in the decision-making process. Secondary outcomes include healthcare communication and CP well-being. Tertiary outcomes assess goal-concordant care and decisional regret. Exploratory outcomes evaluate communication impact by integrating qualitative clinical encounter data with quantitative measures. Current enrollment includes 36 clinicians and 36 pt/CP dyads (target 40 clinicians, 130 dyads). Accrual initiated April 2025. Data collection will conclude May 2027 (NCT06313853; NIA R01 AG077053). Novel/Innovative aspects: (1) This is the first study to prospectively enroll patients with dementia in an oncology intervention trial; (2) We are evaluation of a novel triadic communication intervention targeting clinicians, pts, and CPs; and (3) We have incorporated standard procedures for assessing consent capacity and engaging Legally Authorized Representatives for pts lacking capacity given enrollment of pts with dementia. Clinical trial information: NCT06313853 .

The association of GLP-1 receptor agonist use with survival and immune-related adverse events in patients receiving immune checkpoint inhibitors: A multi-institutional real-world analysis.

11000 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed in patients with cancer for metabolic comorbidities and weight management. However, their impact on outcomes in patients receiving immune checkpoint inhibitors (ICIs) remains poorly characterized. We evaluated the association between concurrent GLP-1 RA use and survival and immune-related adverse events (irAEs) in a large real-world oncology population. Methods: We conducted a federated electronic health record–based cohort study using the TriNetX Research Network (113 healthcare organizations). Adult patients with solid and hematologic malignancies treated with PD-1/PD-L1 or CTLA-4 inhibitors were identified. Patients were stratified by exposure to GLP-1 RAs. Propensity score matching was performed to balance demographics, comorbidities, and baseline clinical characteristics. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare overall survival at 3 and 5 years. Incidence of irAEs, including neutropenia and pyrexia, was assessed using risk and odds ratios. Results: A total of 3,807 patients receiving ICIs with concurrent GLP-1 RAs were matched to 173,423 patients receiving ICIs without GLP-1 RAs. At 3 years, GLP-1 RA exposure was associated with improved survival (hazard ratio [HR] 0.69, 95% CI 0.64–0.75; log-rank p<0.001). This survival advantage persisted at 5 years (HR 0.71, 95% CI 0.65–0.76; log-rank p<0.001). Survival probability at the end of follow-up was higher in the GLP-1 RA cohort across both time horizons. No statistically significant survival benefit was seen at the 1-year end point, (HR 0.65, 95% CI 0.59-0.71; log-rank p=0.521). GLP-1 RA use was associated with a lower incidence of selected irAEs. At 3 years, neutropenia occurred in 5.7% of GLP-1 RA users versus 6.5% of non-users (OR 0.87, 95% CI 0.71–1.06), and pyrexia was significantly reduced (risk difference −2.5%, OR 0.73, 95% CI 0.61–0.87). Similar trends were observed at 5 years, with numerically lower neutropenia rates in the GLP-1 RA cohort (OR 0.84, 95% CI 0.68–1.02). Conclusions: In this large real-world analysis, concurrent GLP-1 RA use in patients receiving ICIs was associated with significantly improved long-term survival and a reduced burden of selected immune-related adverse events. These findings suggest a potential synergistic or protective effect of GLP-1 RAs in the immunotherapy setting and warrant prospective investigation to clarify underlying mechanisms and clinical implications. Outcome 5-Year GLP-1 n/N (%) 5-Year No GLP-1 n/N (%) Death 1091/3411 (32) 1545/3410 (45) Malaise & Fatigue 552/2190 (25) 628/2160 (29) Sepsis 444/3016 (15) 521/2964 (18) Cachexia 119/3395 (4) 179/3368 (5) Pneumonia 405/2811 (14) 494/2747 (18)

National trends in palliative care use among hospitalized cancer patients: A seven-year analysis of demographic and socioeconomic disparities.

12073 Background: The 2016 ASCO guidelines recommend that patients with advanced cancer receive dedicated palliative care (PalC) services early in the disease course, concurrent with active treatment, within 8 weeks of diagnosis. Despite these efforts, disparities persist in the use of PalC across various demographic groups. Our study evaluated the pattern and temporal trends in PalC use among adult cancer patients to identify inequities across various clinical factors. Methods: We analyzed adult cancer hospitalizations from the 2016-2022 National Inpatient Sample. PalC was identified using ICD-10 code Z51.5. Utilization trends were examined by hospital type, demographics (age, sex, race/ethnicity), income quartile, and insurance type. Trends in mean age and in-hospital mortality among PalC recipients were calculated. Survey-weighted regression models assessed temporal trends, accounting for complex sampling design (p < 0.05 significant). Results: We analyzed 18,574,934 hospitalizations from 2016 to 2022. PalC utilization increased significantly from 10.61% in 2016 to 14.01% in 2022 (p < 0.001), representing a 32% relative increase. The mean age of PalC recipients rose from 68.61 years to 69.63 years (p < 0.001), while in-hospital mortality remained stable at approximately 28-29% (p = 0.144). Utilization increased across all subgroups (all p < 0.001). By hospital type, urban teaching hospitals had the highest overall utilization (12.40%, range 10.72-14.01%), followed by urban nonteaching hospitals (12.07%, range 10.81-14.63%), and rural hospitals had the lowest (10.77%, range 8.81-12.71%). Black patients had the highest overall utilization (13.44%, range 11.75-15.20%), followed by White (12.15%, range 10.52-14.02%) and Hispanic patients (11.57%, range 10.04-12.48%). Females had higher utilization than males (12.72% vs 11.83%). By insurance, Medicaid had 12.79% utilization (range 11.18-14.60%), Medicare 12.72% (range 11.00-14.52%), and private insurance 10.13% (range 8.86-11.56%). The lowest income quartile had 12.47% utilization (range 10.73-14.31%) compared to 12.04% (range 10.45-13.50%) in the highest quartile. All demographic and socioeconomic subgroups demonstrated significant increasing trends over the study period. Conclusions: PalC utilization increased significantly across all groups, with stable mortality rates. However, disparities remain, with lower utilization in rural hospitals, among privately insured patients, and among Hispanic populations. Despite progress in overall adoption, these findings highlight ongoing inequities in PalC access that require targeted interventions to achieve equitable guideline implementation.