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Multicentre trial of telemonitored circadian rhythms and electronic patient-reported outcomes (ePROs) for improving tolerability of initial mFOLFIRINOX cycles in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC): MultiDom (NCT04263948).

4204 Background: Severe Adverse Events (SAEs) requiring emergency admissions (EAs) alter quality of life and treatment efficacy, and increase health costs. Toxicities, EAs, and reduced survival have been linked to the disruption of circadian rhythms, whose relevance is tested here in a multicentre, prospective, longitudinal, single-arm interventional trial. Methods: Continuous telemonitoring and automatic analyses of circadian rhythms and daily body weight and ePROs over 50 days (d) aim to reduce EAs in PDAC pts receiving the first 3 cycles of mFOLFIRINOX. The hypothesis (H 0 ) is that EAs involve <15% of the pts, rather than a historical rate of 15-30%. Pts data were collected through telecommunicating chest sensor, balance and tablet connected to a multidimensional digital platform. The main circadian parameter was (I<O), the % of accelerations per min In-Bed that are below the median accelerations per min Out-of-Bed. Control(I<O) is 97-100%. An (I<O) ≤96% defined circadian disruption. Electronic alerts were sent out if (I<O) ≤96%, body weight loss ≥5%, or self-rated symptoms ≥7 using the MD Anderson Symptoms Inventory (MDASI). Results: 28 males and 24 females had a median age of 65 years (33-82), and WHO performance status of 0-1 in 92% of them. PDAC was metastatic in 69% of cases, including liver in 50%. An EA occurred in 2 pts (3.8% [95% CL, 1.1-13%]), thus validating H 0 . SAEs in both EA pts were grade (Gr) 3 febrile neutropenia and diarrhea; and Gr 3 leuco-neutropenia and hypokaliemia respectively. Symptom-free circadian disruption preceded EA by 8 d in both pts. Circadian disruption occurred at least once in 65-75% of the pts on treatment, and lasted > 20 d in 27 pts (52%). Severe fatigue and anorexia were self-reported by 62% and 58% of the treated pts respectively. Main Grade 3-4 toxicity was neutropenia in 17% of the pts [95% CL, 9-30]. Disease control rate at 2 months was 75% [53-100]. Multidom revealed (i) a high level of pt engagement supported both by data compliance rates of 84-92% for circadian rhythms, 93-100% for body weight, and 86-100% for ePROs; and by median duration of platform use of 46 d (IQR, 38-50]; (ii) 1881 medical type e-alerts for circadian disruption (43%), MDASI symptoms (25%), and body weight loss (12%); (iii) 883 categorized responses to medical e-alerts, and (iv) highest global score of self-rated pt experience of participation (median, 5/5 (4 to 5). Conclusions: Combining telemonitoring of circadian rhythms, body weight and symptoms in remote PDAC pts on mFOLFIRINOX revealed potential benefit on pts real life through informed proactive telecare, and likely improved treatment safety. Actual benefits from such telemonitoring-telecare platform with circadian metrics need further confirmation in trials involving pts at risk of SAEs. Clinical trial information: NCT04263948 .

Immunologic and clinical outcomes of perfluoroalkyl substances (PFAS) exposure in solid tumors treated with pembrolizumab.

2539 Background: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two major PFAS with persistent and widespread human exposure. Epidemiologic studies in non-cancer individuals suggest PFAS-associated immune dysregulation and anti-inflammatory effects. We assessed immunologic and clinical effects of PFAS on patients (pts) with advanced solid tumors treated with pembrolizumab. Methods: In the investigator-initiated INSPIRE study (NCT02644369) (n = 106) of advanced solid cancer pts treated with pembrolizumab (head and neck squamous cell cancer, triple-negative breast cancer, high-grade serous carcinoma, melanoma and other mixed solid tumors), we quantified baseline PFOS and PFOA via HPLC-tandem mass spectrometry. PFAS were evaluated as continuous variables and dichotomized at the median ( < median vs > median; PFOS 3.6 ng/ml; PFOA 1.0 ng/ml). Associations with clinical and demographic factors were assessed using correlation/regression analyses. Association with toxicity and objective response (ORR) used Wilcoxon rank-sum tests; progression-free survival (PFS) and overall survival (OS) used Cox proportional hazards models. Immune correlates (immune infiltration measured by multiplex IHC, bulk-RNA sequencing of tumor tissue and plasma cytokine levels measured by Luminex multiplex cytokine assay) were evaluated using median-split Wilcoxon comparisons with Benjamini-Hochberg false discovery rate (FDR) control (q < 0.2). Results: Baseline PFOS and PFOA levels were moderately correlated (Pearson r = 0.49, p < 0.001). PFOS levels were significantly higher with increasing age (median age 59.4 years; range 21.1-81.8; p = 0.016). PFOA levels were significantly higher with increasing age (p = 0.001), in males (p = 0.042), and in the melanoma cohort (p = 0.015), and significantly lower in pts with prior systemic therapy (p = 0.001). For immune parameters, higher PFOA exposure was associated with reduced CD4 T-cell infiltration in tumor and stromal areas (q = 0.07). RNA sequencing of genes and immune signatures showed no associations reaching FDR significance. 10 cytokines were significantly lower in pts with high PFOA levels: IL-16, IL-2R, IL-3, HGF, IFN-γ, MCP-2/CCL8, MDC/CCL22, TNF-RII, TSLP, and BLC/CXCL13 (all q = 0.15) in ovarian cancer and melanoma pts. Neither PFOS nor PFOA levels showed significant associations with ORR, toxicity, PFS or OS. Conclusions: PFOS and PFOA levels vary by demographic and clinical factors but show no direct association with toxicity and treatment outcomes in pts treated with pembrolizumab. Elevated PFOA exposure correlates with reduced T-cell infiltration and cytokine suppression, potentially inducing systemic and local immune dysregulation. These findings highlight immunologic effects of PFAS and warrant mechanistic and longitudinal studies.

Circulating cadherin-17 (CA17) in blood as a diagnostic biomarker for gastric cancer.

10569 Background: The asymptomatic onset of gastric cancer (GC) frequently leads to delayed diagnosis resulting in poor survival. Conventional biomarkers (CA72-4, CEA) lack sensitivity, while emerging cfDNA methods remain costly and complex for routine screening. Our proprietary antigen, Cadherin-17 (CDH17), is selectively overexpressed in gastrointestinal (GI) malignancies. We developed a fully automated, high-throughput Chemiluminescence Immunoassay (CLIA) using proprietary antibodies to monitor the blood circulating levels of CA17 – the soluble form of Cadherin-17 protein in liquid biopsies. CA17 screening offers a complementary minimal invasive diagnostic method that identifies high-risk GC individuals for follow up endoscopy evaluations. Methods: A CLIA assay was designed to quantify circulating CA17 protein levels in human serum. The assay was established on the iShine i1910 automated platform, which integrates magnetic microparticle and acridinium ester labelling to generate luminescent signals. Four proprietary monoclonal anti-CA17 antibody clones were evaluated in various capture and detection pair combinations to identify the optimal antibody pairing for assay performance. Serum samples from 114 non-cancer individuals and 113 patients with histologically confirmed gastric cancer were analysed. Assay and biomarker performance was assessed by receiver operating characteristic (ROC) curve analysis to determine assay sensitivity and specificity. Results: Four capture/detection antibody pairings were evaluated. The clone 1–clone 2 combination demonstrated superior detection accuracy, yielding an AUC of 0.959 (90.3% sensitivity, 91.4% specificity). This optimal pairing revealed a highly significant difference in CA17 levels between the non-cancer and GC groups (Mann-Whitney test, ), confirming its ability to reliably distinguish high-risk individuals. In contrast, the clone 1–clone 3, clone 5–clone 1, and clone 1–clone 4 combinations exhibited inferior performance, with AUCs of 0.784, 0.705, and 0.680, respectively. Conclusions: The CA17 CLIA assay demonstrates high sensitivity and specificity for GC detection. As a minimally invasive blood-based test, it enables early identification of high-risk individuals for subsequent confirmatory endoscopy. This cost-effective blood test has the potential to allow screening of GC at the early stages and will significantly impact on patient survival.

Lucicebtide (ST101) plus chemoradiation in newly diagnosed GBM patients: Efficacy, pharmacodynamics, and safety from phase 2 window-of-opportunity study.

2079 Background: Glioblastoma (GBM) is a lethal brain malignancy with no cure. Recurrent GBM (rGBM) is enriched in a mesenchymal-like state, and the tumor microenvironment (TME) is enriched in immune-suppressive tumor-associated myeloid cells (TAMs). C/EBPß is a master regulator of the mesenchymal GBM state and in sustaining immunosuppressive TAMs. Lucicebtide (ST101) is a first-in-class peptide antagonist of C/EBPß with demonstrated anti-tumor activity and TAM reprogramming in preclinical models. Methods: The WoO study enrolled 2 cohorts; 9 pts with rGBM that received 2-4 doses of lucicebtide 500mg QW prior to surgery and resumed lucicebtide after surgery to progression and 9 ndGBM pts that received 2-3 doses of lucicebtide 500mg QW prior to surgery and resumed lucicebtide + chemoradiation after surgery until progression. Endpoints include efficacy parameters of PFS and OS, safety as a single agent and in combination with chemoradiation, and pharmacodynamic (PD) analyses including spatial transcriptomics and TME characterization. Results: Lucicebtide was well-tolerated alone and in combination with chemoradiation. Tissue analysis indicates BBB penetration, tumor uptake, and C/EBPß target engagement. Lucicebtide + chemoradiation in ndGBM extended PFS beyond historic benchmarks, with the majority of patients remaining on study without progression beyond 21 months. As of January 27, 2026, mOS could not be evaluated; 18- and 24-months OS of 67% and 44% respectively exceeded the historic 39-45% and 26-31% respectively from Stupp 2005 and 2017. In rGBM, lucicebtide improved mPFS of 4.0 months and mOS to 12.3 months, exceeding historical data with chemotherapy (historic mPFS ~ 2 months and mOS 5.6-9.8 months). Spatial transcriptomics revealed significant reductions in C/EBPß regulon activity in tumor cells and macrophages, resulting in a dramatic reduction in the mesenchymal signature in tumor cells. Importantly, lucicebtide altered the infiltration patterns and phenotypes of the TME, including increased effector CD8⁺ infiltration and an increase in the M1/M2 ratio that were associated with disease control. Conclusions: Lucicebtide is well-tolerated as monotherapy and in combination with SoC. Improvements in PFS and OS have been seen in GBM patients following lucicebtide exposure. Analysis of tumor resections demonstrate penetration across the BBB and target engagement, and on-target pharmacodynamic activity, including a dramatic reduction in mesenchymal gene signature in tumor cells and a remodeling towards a more permissive immune TME. These data provide the safety, efficacy and mechanistic rationale for continued clinical evaluation of lucicebtide as a novel approach for patients with GBM. Clinical trial information: NCT04478279 .

Safety and efficacy of BAT8006 in combination with BAT1308 in patients with advanced endometrial cancer.

5512 Background: BAT8006 is a folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), while BAT1308 is a recombinant humanized anti-PD-1 monoclonal antibody. Both agents have individually demonstrated acceptable tolerability and promising antitumor activity in solid tumors. Herein, we report a phase Ib/II trial designed to evaluate the safety and efficacy of BAT8006 in combination with BAT1308 for patients with advanced endometrial cancer. Methods: Eligible patients included those with pathologically confirmed endometrial cancer who had experienced disease recurrence or progression following at least 1 line of platinum-based chemotherapy or immunotherapy-based regimen, with no more than 3 prior lines of systemic therapy. Enrolled patients received BAT8006 (76 mg/m² or 84 mg/m²) in combination with BAT1308 (fixed dose of 300 mg) every 3 weeks until disease progression, intolerable toxicity, or other protocol-specified reasons. The primary endpoints were safety and ORR as assessed by investigators per RECIST v1.1. Results: As of December 25, 2025, a total of 45 patients with advanced endometrial cancer were enrolled in this study. The median age of the cohort was 62 years (range, 27–75 years). Among these patients, 80.0% had ECOG PS of 0, and 80.0% presented with metastatic disease at baseline. All patients had received prior platinum-based chemotherapy; additionally, 48.9% had undergone prior immunotherapy, and 15.6% had received two or more prior lines of systemic therapy. The proportion of patients with FRα positivity (defined as FRα expression ≥1%) was 62.2%. TRAEs were reported in 41 patients (91.1%). Grade ≥3 (G3) TRAEs occurred in 24 patients (53.3%), and SAEs were observed in 17 patients (37.8%). The most common TRAEs (incidence ≥20%) included leukopenia (77.8%), anemia (77.8%), neutropenia (62.2%), nausea (55.6%), thrombocytopenia (53.3%), vomiting (48.9%), lymphopenia (35.6%), pyrexia (26.7%), decreased appetite (26.7%), increased alanine aminotransferase (22.2%), and asthenia (22.2%). No cases of interstitial lung disease were reported. IrAEs occurred in 3 patients (6.7%). TRAEs resulted in dose reduction in 10 patients (22.2%) and treatment discontinuation in 2 patients (4.4%). No treatment-related deaths were recorded. Efficacy was evaluable in 34 patients. The overall ORR was 38.2% (95% CI: 22.2–56.4), and DCR was 70.6% (95% CI: 52.5–84.9). In the BAT8006 (76 mg/m²) + BAT1308 cohort, ORR was 44.4% (95% CI: 21.5–69.2) and DCR was 72.2% (95% CI: 46.5–90.3). In the BAT8006 (84 mg/m²) + BAT1308 cohort, ORR was 31.3% (95% CI: 11.0–58.7) and DCR was 68.8% (95% CI: 41.3–89.0). Conclusions: These findings suggest that BAT8006 in combination with BAT1308 may represent an effective therapeutic strategy for advanced endometrial cancer, with a manageable safety profile. Further prospective studies are warranted to validate the efficacy and safety of this combination regimen. Clinical trial information: CTR20242449.

Early versus delayed inpatient radiotherapy in head and neck cancer and associated in-hospital outcomes.

e18088 Background: Early initiation of radiotherapy (RT) in head and neck cancer (HNC) may improve outcomes by enhancing tumor control and reducing in-hospital complications. However, the patterns, predictors, and short-term outcomes associated with early inpatient RT remain poorly characterized. Methods: Using the Nationwide Inpatient Sample (NIS), we identified adult HNC admissions receiving inpatient RT between 2016–2020. Patients were stratified by RT timing: ≤48 hours (“early RT”) versus >48 hours (“delayed RT”). Weighted chi-square and independent-samples t-tests were used for unadjusted comparisons, and multivariable logistic regression determined predictors of early RT. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. Results: Among approximately 454,000 weighted hospitalizations, 1.2% received RT within 48 hours. Early RT patients were younger (60.5 ± 14.3 vs 63.4 ± 14.7 years; p <0.001), had similar length of stay (6.6 vs 6.7 days; p =0.52), slightly lower total charges ($78,291 vs $85,013; p <0.001), and a higher Charlson Comorbidity Index (7.47 vs 7.34; p =0.007). Early RT occurred more often at large (72.0%), urban teaching hospitals (69.6%), and in the Mid-Atlantic region (44.4%) ( all p <0.001). Early RT was also more common among patients with private insurance (39.1% vs 26.0%), higher-income ZIPs (23.4% vs 20.1%), and Black race (17.5% vs 12.3%), p <0.001 for all. Unadjusted analyses showed significantly lower rates of in-hospital death (1.6% vs 4.8%), myocardial infarction (6.1% vs 7.6%), congestive heart failure (6.4% vs 9.9%), cerebrovascular accidents (3.4% vs 5.4%), sepsis (5.0% vs 11.9%), hemorrhage (6.3% vs 13.4%), organ failure (29.4% vs 36.9%), and major adverse cardiac events (MACE) (0.9% vs 4.5%) among early RT patients ( all p <0.001). In adjusted models, early RT was independently associated with frailty (aOR 1.81; 95% CI 1.70–1.92). Early RT was inversely associated with in-hospital death (aOR 0.71; 95% CI 0.56–0.90), sepsis (aOR 0.56; 95% CI 0.49–0.64), MACE (aOR 0.37; 95% CI 0.27–0.49), hemorrhage (aOR 0.60; 95% CI 0.53–0.67), and DNR status (aOR 0.82; 95% CI 0.73–0.93). Conclusions: Early initiation of inpatient RT (≤48 hours) confers a clear survival advantage and fewer in-hospital complications, reflecting the power of coordinated, time sensitive cancer care. Establishing early RT as a standard of practice could redefine inpatient oncology quality metrics and elevate institutional performance nationwide.

Patterns, resource impact, and disparities in low value care during terminal hospitalizations for lung cancer: A national analysis (2016-2019).

e23228 Background: High-intensity interventions near the end of life, including invasive mechanical ventilation (IMV) and inpatient antitumor therapy, may offer limited benefit for patients with advanced lung cancer while contributing substantially to resource use. National patterns of these practices during terminal hospitalization and their associated disparities remain poorly characterized. Methods: We conducted a retrospective cohort study using the 2016-2019 Nationwide Inpatient Sample. Adults (≥18 years) who died during a hospitalization with a lung cancer diagnosis were included. Exposures were the receipt of IMV and/or inpatient antitumor therapy (chemotherapy, immunotherapy, or radiation), categorized into four mutually exclusive patterns: Neither, IMV only, Antitumor only, Both. Survey-weighted linear and logistic regression models were used, adjusting for age, sex, race, insurance, income quartile, hospital region, hospital location and teaching status (urban or rural, teaching or not), and year. Missing data were limited and analyses were conducted using complete cases. Sensitivity analyses added a proxy for clinical complexity (number of diagnosis codes). A study protocol was developed before implementation and reviewed by the Duke Health Institutional Review Board with a waiver of consent. Results: Among 28,127 lung cancer patients who had terminal hospitalization, 31.4% of patients received IMV only, 2.1% received inpatient antitumor therapy only, and 1.2% received both interventions. Compared with patients who received neither intervention, receiving inpatient antitumor therapy was associated with a longer adjusted length of stay, with an increase of 9.14 days for antitumor therapy alone (95% CI, 8.13-10.15; P < 0.001) and 11.40 days for combined IMV and antitumor therapy (95% CI, 9.63-13.17; P < 0.001). Adjusted hospital charges were 3.41 times higher among patients receiving antitumor therapy alone and 5.42 times higher among those receiving both interventions (P < 0.001). Disparities were observed by race and insurance status, with Medicaid patients experiencing the longest adjusted stays and Medicare patients incurring the highest charges. Findings were robust in sensitivity analyses accounting for clinical complexity. Conclusions: Invasive mechanical ventilation and inpatient antitumor therapy are commonly used during terminal hospitalization for lung cancer and are associated with substantially prolonged hospitalization and higher costs. Significant disparities in these low-value care procedures were associated with race and insurance status. Our findings highlight the need for value-based strategies to promote more appropriate use of end-of-life care.

PONV risk score and gender as predictors of delayed ambulation in outpatient thyroid and parathyroid surgery.

e18087 Background: Enhanced Recovery After Surgery (ERAS) protocols aim to improve perioperative outcomes by promoting early ambulation, which is linked to fewer complications and shorter length of stay. However, in outpatient head and neck surgery, achieving early ambulation is challenging due to airway concerns, discomfort, and postoperative nausea and vomiting (PONV). While inpatient studies have linked delayed ambulation to higher complication rates, longer hospitalizations, and increased opioid use, few studies have examined factors affecting ambulation in the outpatient setting. This is a key gap as ERAS protocols expand to same-day discharge. Identifying predictors of delayed ambulation may help tailor ERAS protocols and allow targeted interventions to improve recovery. Methods: We retrospectively reviewed 1,788 patients undergoing thyroidectomy or parathyroidectomy at the Josie Robertson Surgery Center between January 2016 and December 2022. After exclusion, 1,331 patients were left for analysis. Ambulation was objectively measured using a real-time locating system (RTLS). Delayed ambulation was defined as occurring on the first postoperative day. Multivariable regression adjusted for surgery end time was used to evaluate predictors of delayed ambulation, including age, gender, American Society of Anesthesiologists (ASA) score, operative time, intravenous fluids, estimated blood loss, opioid use, PONV risk score (Apfel score), and perioperative antiemetic use. Results: Median time from recovery room arrival to first ambulation was 5.3 hours (IQR 4.0-7.6), with 19% of patients experiencing delayed ambulation. Delayed ambulation was associated with longer operative time (median 118 minutes vs. 110 minutes; p=0.002), higher intravenous fluids (median 1,250 mL vs. 1,100 mL; p<0.001), and female sex (OR 2.42; 95% CI 1.67, 3.60; p<0.001). Compared to Apfel 1-2 scores, patients with Apfel 3 score had the highest odds of delayed ambulation (OR 2.41; 95% CI 1.67, 3.55). After adjusting for surgery end time and antiemetic use, female sex and Apfel 3 score remained strong predictors of delayed ambulation among patients not receiving preoperative aprepitant (p<0.001). Among those receiving aprepitant, a history of motion sickness or PONV was associated with a reduced risk of delayed ambulation (OR 0.54; p=0.041). Conclusions: Apfel score and female sex were independent predictors of delayed ambulation. High-risk patients may benefit from preoperative aprepitant. Those with a history of motion sickness and PONV have a reduced risk of delayed ambulation. Early risk identification and targeted antiemetic strategies may improve ambulation and recovery in outpatient head and neck surgery.

A multicenter phase 1/1b study of AMG 436 as monotherapy and combination therapy in patients with advanced MSI-H/dMMR solid tumors.

TPS3173 Background: Microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) tumors are characterized by high mutational burden and replication stress. These tumors rely on Werner syndrome protein (WRN), a DNA helicase required for DNA replication and repair, to sustain tumor cell survival. As a result, this reliance on WRN creates a synthetic lethal vulnerability, making WRN inhibition a promising therapeutic strategy. AMG 436 is a selective, covalent WRN inhibitor that is designed to exploit this dependency in MSI-H/dMMR tumors. AMG 436 represents a tumor-intrinsic approach that is mechanistically distinct from immune checkpoint inhibitors (ICIs), the current standard of care. This first-in-human Phase 1/1b trial evaluates AMG 436 as monotherapy and in combination with immune checkpoint inhibitors and/or chemotherapy in adults with MSI-H/dMMR solid tumors, including ICI-naïve and post-ICI populations. Methods: This study is a Phase 1/1b, open-label, multicenter trial enrolling approximately 464 adult participants with metastatic or locally advanced MSI-H/dMMR solid tumors. The study consists of 4 parts: Part 1 involves monotherapy dose exploration; Part 2 explores combination doses with chemotherapy or an immune checkpoint inhibitor; Part 3 focuses on monotherapy dose expansion and randomized dose optimization; and Part 4 involves combination dose expansion with chemotherapy and/or ICIs. The primary objectives are to assess safety and determine the maximum tolerated dose or recommended dose for expansion, with primary endpoints being the incidence of dose-limiting toxicities (DLTs) during the DLT evaluation period and the incidence of treatment-emergent adverse events and serious adverse events. Secondary objectives include pharmacokinetics and preliminary antitumor activity per RECIST v1.1. Descriptive statistics will be used to summarize safety, pharmacokinetic, and efficacy data. Key eligibility criteria are adults with MSI-H/dMMR status, ECOG 0–1, and adequate organ function. Enrollment is ongoing globally across North America, South America, Europe, and Asia-Pacific. Participants may remain on treatment for up to 2 years, with total trial duration including follow-up extending up to 5 years. Clinical trial information: 177459.

Chiral Self‐Sorting Assembly of Au ₁₆ Rings for Cancer Therapy via Enantioselectivity‐Induced Ferroptosis and Apoptosis

ABSTRACT Chirality‐induced biochemical response has emerged as a prominent research focus. This research demonstrates the chiral self‐sorting assembly of atomically precise Au 16 supramolecular rings via aurophilic interactions. Enantiomers ( M R,R M’ R,R )‐Au 16 Cl 8 and ( P S,S P’ S,S )‐Au 16 Cl 8 are fabricated through homochiral self‐sorting assembly and are unaffected by anion types. But the chiral self‐sorting assembly of ( M R,R M’ A,A )‐Au 16 (PF 6 ) 8 and ( P S,S P’ A,A )‐Au 16 (PF 6 ) 8 in a heterochiral system is influenced by anion types. Crucially, ( M R,R M’ R,R )‐Au 16 Cl 8 displayed superior in vitro antitumor efficacy with IC 50 = 0.812 ± 0.002 µM against 4T1 cells compared to ( P S,S P’ S,S )‐Au 16 Cl 8  enantiomer. This enantioselectivity stems from asymmetric glutathione (GSH)‐catalyzed decomposition of chiral supramolecular Au 16 rings in the tumor microenvironment (apparent kinetic constants:  k M = 14.97 × 10 −5 min −1 × M −1  vs.  k P = 8.56 × 10 −5  min −1 × M −1 at 8 mM GSH), releasing the thioredoxin reductase (TrxR) inhibitor dppm 2 Au 2 Cl 2 . The chiral Au 16 rings induce dual cell death via TrxR‐inhibition‐mediated apoptosis and GPX4‐suppression‐driven ferroptosis, validated by ROS (reactive oxygen species) accumulation, lipid peroxidation and caspase‐3 activation. ( M R,R M’ R,R )‐Au 16 Cl 8 (20 mg/kg) achieved 55.4% tumor growth inhibition in 4T1‐bearing mice with no detectable organ toxicity, outperforming auranofin in biosafety. This work establishes chiral self‐sorting Au 16 assemblies as promising platforms for enantioselective cancer therapy with high efficacy and low toxicity.

An overview of structural, optical, and magnetic properties of Mn-doped, Cu-doped, and (Mn, Cu)-codoped ZnS nanoparticles and its applications

AhR inhibition promotes axon regeneration

Attention-enhanced GNN model for fungal disease classification in spinach leaves using monospectral imaging

PRSS23 promotes ovarian cancer peritoneal dissemination independent of protease activity

Audiometric outcomes for intravenous sodium thiosulfate for cisplatin-induced ototoxicity prevention in adults with head and neck cancer.

e18110 Background: Cisplatin-induced ototoxicity (CIO) is a well-known complication of platinum-based chemotherapy that can cause hearing loss, substantially impairing quality of life, communication, and long-term survivorship. While sodium thiosulfate (STS; Pedmark) has demonstrated reduced rates of CIO in the pediatric population, there remains a critical evidence gap regarding its efficacy in adult pts with head and neck cancer (HNC). This study evaluates the effect of intravenous (IV) STS on audiometric outcomes in adult pts with HNC treated with cisplatin. Methods: A retrospective review of 7 adults (n=13 ears) with HNC treated for cure, planned cumulative cisplatin dose ≥150 mg/m², and treated between 11/2024-9/2025. 4/7 pts received chemoradiotherapy (CRT) with weekly cisplatin. 1 pt received cisplatin as part of induction therapy (IC) in addition to CRT and 3/7 received IC alone. According to FDA guidelines, IV STS was administered ≥6 hours after cisplatin completion, with a planned 1:1 cisplatin:STS dosing strategy. Conventional pure-tone audiometry was performed, including extended high-frequency testing and distortion product otoacoustic emissions (DPOAE). Primary endpoints included change in four-tone pure-tone averages (PTA; 500Hz, 1000Hz, 2000Hz, and 4000Hz) following initiation of treatment. Secondary outcomes included changes in extended high frequency PTA (ehfPTA; 9000Hz-20,000Hz) and DPOAE. Clinically significant hearing deterioration from baseline was defined as ≥10dB change in fPTA from baseline. Results: Of the 7 included patients (n=13 ears, 1 pt with prior unilateral sensorineural hearing loss), 57.1% were male (4/7), mean age of 51.1 years, and average cumulative cisplatin dose of 217.1mg/m 2 . The average time of last audiogram from initial cisplatin treatment was 73.4 days. There was no significant change in four-tone PTA from baseline to last audiogram (0.0dB) and there were no pts with clinically significant decline from baseline (0%, 0/7). 3 pts (n=6 ears) received comprehensive ehfPTA and DPOAE testing before and after treatment, with 1 ear (16.7%, 1/6) and 3 ears (50%, 3/6) experiencing a loss of response at highest baseline pure-tone threshold and DPOAE, respectively. Conclusions: Delayed IV STS was associated with preservation of clinically significant hearing in adults with HNC receiving curative-intent cisplatin, despite measurable changes on extended high-frequency audiometry and DPOAE testing. These findings support the use of comprehensive audiometric monitoring, including extended ehfPTA and DPOAE, to detect subclinical ototoxicity. The results extend the otoprotective paradigm established in pediatric oncology to the adult setting and suggest that STS is a feasible otoprotective strategy during platinum-based therapy. Prospective randomized studies with longer audiometric follow-up are warranted.

StrateGIST 3: A randomized, phase 3 study of velzatinib (IDRX-42) versus sunitinib in patients with advanced gastrointestinal stromal tumors after imatinib therapy.

TPS11588 Background: Most gastrointestinal stromal tumors (GISTs) are driven by mutations in KIT . Tyrosine kinase inhibitors (TKIs) such as imatinib and sunitinib (first- and second-line therapies for GIST, respectively) are available, but resistance can develop and is primarily mediated by additional KIT mutations in the ATP binding pocket (exon [ex] 13/14) and activation loop (ex 17/18). While sunitinib targets mutations in exon 13/14 in the second-line setting, it has low response rates and short progression-free survival (PFS). Therefore, there is a need for novel therapies with broad mutation coverage, and for patients (pts) with disease progression on, or intolerance to, approved therapies. Velzatinib (subject to USAN approval) is a novel, highly selective, oral KIT TKI that potently and selectively inhibits primary and secondary resistance KIT mutations. In StrateGIST 1, an ongoing, phase 1/1b study in adult pts with advanced GIST, velzatinib exhibited promising clinical activity and favorable safety in 2 nd - and later-line pts at the recommended phase 3 dose of 300-mg QD tablet (or exposure-equivalent 400-mg QD capsule). As of December 15, 2025, median PFS (95% CI) was 13.7 (7.4–18.4) months and confirmed ORR (95% CI) was 33% (19.5–48.0) in 2 nd -line pts (N=46) at the recommended phase 3 dose, supporting the further evaluation of velzatinib in pts with advanced GIST after progression on, or intolerance to, imatinib. Methods: StrateGIST 3 is a phase 3, randomized, multicenter, open-label study (NCT07218926) to evaluate velzatinib vs sunitinib in adult pts with advanced GIST after progression on or intolerance to imatinib. Recruitment for this study opened on December 3, 2025, and the total duration of the study is estimated to be approximately 5 years. Pts must have documented mutation status of KIT and/or PDGFRA , and will be excluded if they have GIST that is wild type for both KIT and PDGFRA or if they have an activating PDGFRA exon 18 mutation. Approximately 450 pts will be randomized (1:1) to receive either velzatinib (300-mg QD tablet, continuous dosing) or sunitinib (50 mg QD, 4 weeks on/2 weeks off). The randomization will be stratified by activating mutation (ex 11 vs ex 9 vs other) and intolerance to first-line imatinib (yes vs no). The primary endpoint is PFS according to modified RECIST for GIST (mRECIST-GIST), by blinded independent central review (BICR). The key secondary endpoint is overall survival, and additional secondary endpoints include PFS per investigator assessment, PFS-2, confirmed objective response rate per BICR and per investigator, time to response per BICR and per investigator, health-related quality of life and functioning, plasma drug concentrations, and safety and tolerability. This trial is now recruiting. This study (NCT07218926) is funded by GSK. Clinical trial information: NCT07218926 .

Pilot RCT of a patient-centered communication intervention to promote values-based treatment decision-making in older adults with AML.

12092 Background: Older adults with acute myeloid leukemia (AML) often have limited involvement in high-stakes treatment decisions that involve tradeoffs between survival and quality of life. We developed a patient-centered communication intervention (UR-GOAL) to support values-based decision-making. We assessed how patients and oncologists discuss values during treatment decision-making and explored whether UR-GOAL improves these discussions. Methods: This pilot RCT randomized patients ≥60 years old with newly diagnosed AML to UR-GOAL vs. usual care. UR-GOAL uses best-worst scaling to help patients prior to deciding on treatment to prioritize their values, which are shared with the oncologist. Two team members blinded to arm independently coded transcribed treatment conversations for values talk, defined as discussion of what matters to patients in treatment decisions. Values included patient, disease/treatment, and sociocultural priorities; examples include quality of life, treatment effectiveness, and physician recommendation, respectively. Coders assessed the depth of values discussion (the extent to which the oncologist explored patient values beyond acknowledgment), patient engagement (e.g. patient elaborating on values and asking questions), and values alignment (whether the oncologist incorporated patients’ most important values into the treatment plan). Differences in coding were resolved by consensus. Continuous outcomes were compared using t-tests or ANOVA and categorical outcomes using chi-square or Fisher’s exact tests. Results: We included 92 patients (mean age 74 and SD 7; 63% male; 93% white). A mean of 6.0 values was discussed per encounter (SD 3.0), with fewer explored in depth (mean 1.5; SD 1.5). The number of values discussed in total and in depth did not differ between arms (total values: UR-GOAL 6.4 vs. usual care 5.7, p = 0.28; and in depth: UR-GOAL 1.4 vs. usual care 1.6, p = 0.14). However, patients showed a trend toward greater engagement in values discussions in the UR-GOAL arm compared with usual care (78% vs. 59%, p = 0.07). The values most commonly expressed by patients as most important in driving treatment decisions were treatment effectiveness (44%) and care logistics (e.g. treatment in hospital vs. clinic, 19%), followed by physician recommendation (7%), treatment toxicity (4%), and quality of life (3%). Values aligned with the treatment plan in 70% of cases (UR-GOAL 76% vs. usual care 63%, p = 0.26). Patients whose values aligned discussed more values compared with those whose values were not aligned, not discussed, or indeterminate (6.9 vs. 4.0, p < 0.01). Conclusions: Older adults with AML discuss several values with their oncologists during treatment decision-making, though fewer in depth. The UR-GOAL communication intervention may promote patient engagement in shared decision-making and value alignment. Clinical trial information: NCT05335369 .

Prediction of postoperative recurrence in non–small cell lung cancer using machine learning approaches.

e20020 Background: Early-stage NSCLC can have favorable survival outcomes; however, postoperative recurrence remains common and clinically challenging. This study aimed to develop machine learning (ML) models to predict recurrence after curative resection using routinely available clinicopathologic variables, to test the stability of model performance across different feature-selection strategies, and to interpret ML findings alongside conventional Cox regression results. Methods: We retrospectively analyzed 265 patients who underwent curative-intent surgical resection at Ankara Bilkent City Hospital (January 2020–June 2025). The primary endpoint was recurrence (yes/no). Seventeen clinical, pathological, and treatment-related variables were evaluated. Multiple supervised ML classifiers were trained using (i) the full feature set and (ii) reduced feature subsets generated by ANOVA, chi-square, and Kruskal–Wallis–based selection. Performance was assessed using accuracy, AUC, F1 score, and confusion matrices. Prognostic associations were examined using univariate and multivariate Cox regression, and model interpretability was explored using feature importance and SHAP analyses. Results: Recurrence occurred in 82/265 (30.9%) patients. Using all variables, AdaBoost achieved the highest accuracy (≈0.79), with SVC-RBF and several neural network/Naïve Bayes models showing comparable accuracy (≈0.77). Across ANOVA-, chi-square–, and Kruskal–Wallis–selected feature sets, overall performance remained largely consistent, and no single selection method was uniformly superior. Discriminative performance was highest for SVC-RBF (AUC ≈0.81), whereas AdaBoost yielded the best balance between precision and recall (F1 ≈0.87). Across models, key predictors repeatedly included histologic subtype, tumor size, tumor grade, and ECOG performance status. SHAP analysis identified ECOG performance status and tumor size as the dominant contributors to individual recurrence predictions. Several of these factors were also supported as prognostic variables in Cox regression analyses. Conclusions: In conclusion, ML models can reliably predict postoperative recurrence in resected NSCLC using standard clinicopathologic data. Ensemble (AdaBoost) and kernel-based (SVC-RBF) approaches showed the most favorable and stable performance, offering complementary strengths that may support individualized postoperative risk assessment.

Phase 1, multicenter, open-label study of HSK46575 in patients with metastatic castration-resistant prostate cancer progressing after next-generation hormonal agents and chemotherapy.

5047 Background: The development and progression of prostate cancer are regulated by steroid hormones. HSK46575 Tablet is a novel oral small-molecule inhibitor of cytochrome P450 11A1 (CYP11A1), which can block the production of all downstream steroid hormones and their precursors, thereby reducing the activation of the androgen receptor (AR) signaling pathway and inhibiting tumor progression. Herein, we report the safety and efficacy of HSK46575 in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This multicenter, open - label Phase I clinical trial had two parts: Phase Ia (dose escalation and expansion) and Phase Ib (dose optimization). Eligible patients were mCRPC patients who failed at least one NHA treatment and either failed, were intolerant to, or refused at least one line of chemotherapy. Phase Ia's dose escalation used a "3 + 3" design to explore four doses (3 mg, 10 mg, 30 mg, 60 mg), and dose expansion was done at 30 mg due to good safety and preliminary efficacy.The primary endpoints were safety and the recommended Phase II dose (RP2D). Results: As of November 4, 2025, 27 subjects were enrolled, with a median follow-up of 3.7 months and a median age of 68 years (range: 51-82 years). Among them, 15 (55.6%) had AR ligand -binding domain (AR-LBD) mutations, and 12 (44.4%) had received taxane-based chemotherapy before. No dose-limiting toxicities were observed in any dose group. Treatment-related adverse events (TRAEs) occurred in 18 subjects (66.7%), most of which were Grade 1-2. The most common TRAEs were alanine aminotransferase elevation (18.5%), sinus bradycardia (11.1%), and nausea (11.1%).No adverse events leading to permanent treatment discontinuation or death were observed. Prostate-specific antigen (PSA) assessment was available for 26 subjects, with PSA response rates confirmed after at least 3 weeks. The PSA 30 and PSA 50 response rates were 42.3% and 34.6% in the total population, 71.4% and 57.1% in AR-LBD mutant subjects (n = 14), and 75% and 58.3% in the 30 mg dose group with AR-LBD mutations (n = 12). The PSA 50 response rate was 12.5% (1/8) in the 30 mg dose group with AR-LBD wild-type. Fourteen subjects were eligible for soft tissue assessment, 8 of whom had AR-LBD mutations. One partial response (PR) was seen during treatment in an AR-LBD mutant patient in the 30 mg dose group, leading to an objective response rate (ORR) of 14.3% in this population. . The radiographic progression-free survival (rPFS) has not been reached. The 6-month rPFS rates were 67.5% in the total population and 76.2% in the AR - LBD mutation population. Conclusions: HSK46575 shows a manageable safety profile and preliminary antitumor activity, especially in the population with AR - LBD mutations. These findings support further exploration in the mCRPC population. Clinical trial information: NCT07007910 .

Diagnostic accuracy of Color Doppler ultrasound for detecting portal venous thrombosis in hepatocellular carcinoma patients: A meta-analysis.

e16158 Background: Portal venous thrombosis (PVT) is a frequent and clinically significant complication in patients with hepatocellular carcinoma (HCC), influencing prognosis and therapeutic planning. Color Doppler ultrasound is widely available and often used as an imaging tool. However, its diagnostic performance relative to contrast-enhanced computed tomography (CT) remains uncertain. This meta-analysis aimed to synthesize available evidence on the diagnostic accuracy of Color Doppler in detecting PVT in HCC patients, using CT as the reference. Methods: A systematic literature search of PubMed, Embase, Web of Science, Scopus, Cochrane Library and grey literature from inception to December 2025 was conducted. True-positive, false-positive, false-negative, and true-negative data were extracted to construct 2×2 contingency tables for each study. Analyses were performed using Stata version 17 and R version 4.5.1. Results: Six eligible studies were included (N = 694, mean ages 43.19 ± 7.49 to 58.6 ± 10.2 years). Most patients were male (57.5%). The pooled sensitivity was 0.86 (95% CI 0.80 to 0.91) and specificity was 0.93 (95% CI 0.91 to 0.95). The DOR was 91.2, with LR+ = 13.2 and LR- = 0.14. Conclusions: Color Doppler ultrasound shows high diagnostic accuracy for detecting portal venous thrombosis in hepatocellular carcinoma, with high specificity and sensitivity. These findings indicate towards its utility as a possible first-line, non-invasive screening tool, particularly in resource-limited settings. However, further multicenter studies are needed to confirm generalizability across diverse clinical contexts.