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Early treatment failure despite first-line immunotherapy in real-world MSI-H/dMMR gastroesophageal cancer.

4029 Background: Clinical trials of first-line (1L) immunotherapy (IO) in gastroesophageal cancer (GEC) demonstrate greater benefit in patients with microsatellite instability–high or mismatch repair–deficient (MSI-H/dMMR) tumors compared with the overall trial population. However, the benefit is not universal, and outcomes remain suboptimal for a subset of patients. Real-world (RW) evidence describing outcomes with 1L IO in MSI-H/dMMR GEC is limited. This study characterized treatment patterns and outcomes among RW MSI-H/dMMR GEC patients treated with 1L IO to better define residual unmet need. Methods: Using the Flatiron Health electronic health record-derived deidentified database, adults (≥18 years) diagnosed with locally advanced unresectable, metastatic, or recurrent gastric (GC), gastroesophageal junction (GEJ), or esophageal cancer (EC) between 17 Apr 2021 and 31 Dec 2024 were identified. Patients were required to have documented MSI-H or dMMR status and no trastuzumab exposure. Data were available through 08 Sep 2025. Time to next treatment or death served as a RW proxy for progression. Results: Among 3,047 eligible patients, MSI-H/dMMR prevalence varied by disease site and stage, ranging from 5.8% in metastatic GC to 17.6% in locally advanced GC; from 2.4% to 10.4% in GEJ disease; and from 3.4% to 4.4% in EC. A total of 199 MSI-H/dMMR GEC patients were identified (median age 75 years [IQR 66–82]; 36% female; 37% metastatic at diagnosis; 95% adenocarcinoma). Of the 155 MSI-H/dMMR patients who received 1L therapy, 32% received IO alone, 31% IO plus chemotherapy, and 37% chemotherapy alone. Among patients treated with 1L IO ± chemotherapy, 37% initiated 2L therapy or died within 6 months, increasing to 47% and 54% by 9 and 12 months, respectively. Baseline characteristics were largely similar between patients with and without progression within the first 12 months (Table). Conclusions: In this real-world cohort of MSI-H/dMMR GEC patients, a substantial proportion experienced early treatment failure despite 1L IO. More than one-third initiated second line therapy or died within 6 months, and over half progressed or died within 1 year. These findings underscore heterogeneity in benefit from 1L IO and highlight an ongoing need for improved risk stratification and alternative precision-based treatment approaches. Characteristics of MSI-H/dMMR GEC patients by progression status at 12 months post start of 1L IO therapy. ProgressorsN=35 Non-progressors**N=30 Age, Median [IQR] 72 [66, 83] 73 [64, 80] Female, % 34.3 40.0 Location, % GC 62.9 63.3 GEJ 8.6 13.3 EC 28.6 23.3 Status*, % Metastatic 48.6 46.7 Non-metastatic 45.8 50.0 ECOG at 1L*, % 0/1 25.7 26.7 2+ 57.1 50.0 *Some patients are missing disease status and/or ECOG. **Patients included in non-progressors were required to have activity in the data at least 12 months after 1L IO initiation.

Trastuzumab deruxtecan in patients with HER2-low recurrent/metastatic salivary gland carcinoma: Results from the phase II MYTHOS trial.

6011 Background: Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody–drug conjugate with established efficacy across multiple HER2-expressing malignancies. Salivary gland carcinoma (SGC) is a rare disease with limited treatment options, particularly for tumors with HER2-low expression. The MYTHOS trial is a multicenter, investigator-initiated phase II study evaluating T-DXd efficacy in recurrent or metastatic (RM) SGC patients with HER2 overexpression or HER2-low expression. Here, we report the efficacy and safety results of the HER2-low cohort (Cohort 2). Methods: Eligible patients had histologically confirmed RM SGC with HER2-low expression (IHC 1+ or IHC 2+/ISH−), as determined by central assessment according to the ASCO/CAP 2018 breast cancer guidelines, and no indication for curative treatment. Patients received T-DXd at 5.4 mg/kg intravenously every 3 weeks. The primary endpoint was confirmed objective response rate (ORR) assessed by independent central review (ICR) according to RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The required sample size for Cohort 2 was 33 patients, based on a threshold ORR of 25%, an expected ORR of 50%, 83% power, and a two-sided alpha of 0.05 using an exact binomial test. The primary efficacy decision was based on the prespecified Simon’s two-stage minimax design in the first 33 patients; efficacy in the full analysis set (FAS) was summarized descriptively. Results: A total of 36 patients were included in the FAS, including 30 with salivary duct carcinoma (SDC). HER2-low status comprised IHC 2+/ISH− in 14 and IHC 1+ in 22; 25 had received prior systemic therapy for RM disease. Median follow-up was 25.1 months. The ORR by ICR was 38.9% (14/36; 95% CI, 23.1–56.5%), and the DCR was 94.4% (95% CI, 81.3–99.3%). Median PFS was 8.7 months (95% CI, 6.5–13.3), and median OS was 24.8 months (95% CI, 18.7–NE). In a prespecified subgroup analysis by histology, the ORR by ICR was 46.7% (14/30; 95% CI, 28.3–65.7%) in SDC and 0% (0/6; 95% CI, 0–45.9%) in other SGC subtypes. Common grade ≥3 adverse events (>10%) were neutrophil count decreased (36.1%), lymphocyte count decreased (19.4%), white blood cell count decreased (11.1%), and decreased appetite (11.1%). Drug-related interstitial lung disease (ILD)/pneumonitis occurred in 9 (25.0%; grade 1/2 in 7, grade 3 in 1, and grade 5 in 1). There was one drug-related death due to ILD/pneumonitis. Conclusions: Although the prespecified primary efficacy endpoint was not met, T-DXd demonstrated clinically meaningful antitumor activity in patients with HER2-low RM SGC, particularly in those with SDC. The safety profile was generally consistent with the known profile of T-DXd in the Japanese population, with ILD/pneumonitis remaining an important identified risk requiring careful monitoring. Clinical trial information: jRCT2011210017.

Risk factors and long-term prognostic impact of trastuzumab deruxtecan-related interstitial lung disease in metastatic breast cancer.

1043 Background: Trastuzumab deruxtecan (T-DXd) has demonstrated substantial efficacy in HER2-positive and HER2-low metastatic breast cancer (MBC). Interstitial lung disease (ILD), however, remains a clinically significant safety concern. While ILD incidence has been reported, its long-term prognostic impact and associated risk factors are not well established. Methods: This retrospective, single-center study evaluated patients with MBC treated with T-DXd. ILD was defined as clinically and radiologically confirmed ILD, which led to T-DXd discontinuation per institutional protocol. Time to treatment failure (TTF) and overall survival (OS) were analyzed according to ILD occurrence. Potential clinical and treatment-related risk factors for ILD were assessed using univariable and penalized multivariable Cox regression models. Results: At a median follow-up of 12.7 months, 15 of 132 patients (11.4%) developed ILD leading to treatment discontinuation. Among these 15 patients, 9 (60%) had grade 1 disease, 3 (20%) had grade 2, and 3 (20%) had grade 3 disease; no grade 4 or fatal events were observed. There were no significant differences in TTF (P = 0.59) or OS (P = 0.21) between patients with and without ILD. Among patients who developed ILD, onset occurred significantly earlier in those with HER2-low disease compared with HER2-positive disease (median 6.0 vs. 14.6 months, P = 0.029). In univariable analyses, age ≥65 years (HR 3.39, 95% CI 1.18-9.68; P = 0.023), prior immune checkpoint inhibitor (ICI) therapy (HR 4.74, 95% CI 1.01-22.34; P = 0.049), and prior abemaciclib exposure (HR 4.11, 95% CI 1.19-14.14; P = 0.025) were significantly associated with ILD. In the penalized multivariable model, prior abemaciclib exposure remained the only independent risk factor (HR 10.38, 95% CI 1.07-NA; P = 0.042). Conclusions: Although ILD onset tended to occur earlier in HER2-low MBC, its development did not significantly affect long-term TTF or OS. Prior exposure to abemaciclib is a significant independent risk factor for T-DXd-related ILD, warranting careful monitoring in this population.

Trends and disparities in cancer mortality among adults with psychoactive drug use disorders in United States, 1999–2023.

e15132 Background: Psychoactive drug use is a growing public health concern and is linked to increased cancer risk through biological effects and associated high-risk behaviors. However, population-level data on cancer mortality among psychoactive drug users remain limited, highlighting the need to examine trends and disparities to inform prevention and public health strategies. Methods: We analyzed CDC WONDER data to estimate age-adjusted mortality rates (AAMRs) for cancer (ICD-10 C00–C48) among adults aged ≥25 years with psychoactive drug use disorders (ICD-10 F10–F19). Temporal trends and average annual percent changes (AAPCs) were assessed using Joinpoint regression, stratified by sex, race, and geographic factors, including urbanization and census region. Results: From 1999 to 2023, cancer among psychoactive drug users accounted for 1,899,390 deaths (744,099 females and 1,273,561 males), with most deaths occurring at the decedent’s home (43.4%) and predominantly among older adults. The AAMR increased from 4.85 in 1999 to 34.33 in 2023 (AAPC: 9.50%; p < 0.001), with significant rises during 1999–2005 (APC: 41.65; 95% CI: 31.90–52.12) and 2005–2012 (APC: 4.70; 95% CI: 1.03–8.51), followed by a significant decline through 2023 (APC: −2.09; 95% CI: −3.37 to −0.79). Men consistently exhibited higher AAMRs than women from 1999 (7.03 vs. 3.22) to 2023 (45.38 vs. 25.26). Non-Hispanic(NH) Whites had the highest AAMR, followed by NH American Indian or Alaska Native,NH Blacks and Hispanic or Latino populations, while Asians or Pacific Islanders had the lowest rates. Regionally, the Midwest showed the highest AAMR, whereas the West had the lowest. Non- metropolitan populations had higher average AAMRs than metropolitan populations (55.36 vs. 32.29). From 1999 to 2020, Vermont ranked highest in the top 90th percentile, while from 2020 to 2023, Kentucky held the highest rank. Conclusions: Cancer mortality among psychoactive drug users remains a major public health concern, with higher rates observed among older adults, males, Black populations, and rural residents, underscoring the need for targeted prevention, early detection, and equitable, integrated care. Deaths and Age-adjusted Mortality Rates (AAMRs) per 100,000 for trends related to Cancer among psychoactive drug users from 1999 to 2023. Variable Deaths AAMR (95%CI) 1999 AAMR (95% CI)2023 Overall 1,899,390 4.79(4.69 to 4.89) 43.29(43.02 to 43.56) Male 1,273,561 6.29(6.12 to 6.46) 53.43 (53.01 to 53.87) Female 744,099 3.42(3.3 to 3.53) 33.63 (33.30 to 33.97) NH Whites 1,634,542 5.35 (5.22 to 5.47) 57.97(57.58 to 58.37) NH Blacks 177,341 5.22 (4.9 to 5.54) 33.52(32.84 to 34.19) Midwest 569,261 4.45 (4.24 to 4.65) 64.63 (63.90 to 65.36) West 273,007 5.82 (5.58 to 6.06) 25.83 (25.40 to 26.27) Metro 1,225,615 (2020) 4.36 (4.26 to 4.47) (2020) 40.13 (39.85 to 40.41) Non- metro 375,699 7.02 (6.72 to 7.33) 79.96 (78.98 to 80.94)

Trends in early-onset colorectal cancer: A 20-year epidemiological study at a referral center in northeastern Mexico.

e15695 Background: Colorectal cancer (CRC) ranks as the third most common malignancy and the second leading cause of cancer-related deaths globally. Early-onset CRC (yCRC), diagnosed in individuals under 50 years, represents an emerging concern, with projections estimating that by 2030, 10% of colon and 25% of rectal cancers will occur in this demographic. In Latin America, there is a significant evidence gap regarding the epidemiological and clinicopathological characteristics of yCRC. This study aims to characterize the disease behavior in the Mexican population to inform early detection strategies and guide future research. Methods: We conducted an observational, retrospective, descriptive study. Data from 2,426 patients with late-onset CRC (LOCRC) and 355 patients with yCRC, diagnosed between January 1999 and January 2023, were extracted from the Electronic File System of the University Cancer Center at José Eleuterio González University Hospital. Epidemiological, clinicopathological, and molecular variables were analyzed using descriptive statistics in SPSS (version 23.0). Results: The analysis reveals a concerning upward trend in yCRC incidence, with a 107% increase in cases during the 2014-2018 period, nearly double the 60% growth observed for LOCRC in the same interval. The age group 45-49 years had the highest absolute number of yCRC cases. The yCRC cohort was predominantly male (56%), and a striking 37.6% presented with stage IV disease at diagnosis. Notably, only 1% of yCRC cases were detected through screening. While 94% lacked traditional comorbidities like hypertension or diabetes, modifiable risk factors were prevalent: 31% were smokers, 44% were overweight or obese, and 96% reported a characteristic Northern Mexican diet style. Hereditary cancer syndromes were identified in only 1.6% of yCRC cases. Conclusions: In conclusion, this study confirms a sharp rise in yCRC incidence in Mexico, highlighting it as a critical public health issue. The high proportion of advanced-stage disease and minimal screening detection underscore severe gaps in early diagnosis for young adults. The distinct profile—predominance of modifiable lifestyle factors over hereditary syndromes or traditional comorbidities—suggests a significant role for environmental and behavioral etiologies specific to this population. These findings advocate for urgent policy revisions, including updated screening guidelines for high-risk individuals under 50, targeted public health campaigns addressing lifestyle risks, and the initiation of prospective studies to elucidate causative mechanisms. This work provides the first comprehensive characterization of yCRC in a Mexican cohort, forming a foundational basis for strategies to curb this emerging epidemic.

Histopathological patterns of breast cancer at diagnosis among patients in the Federal Capital Territory, Abuja: Findings from the Network for Oncology Research in Sub-Saharan Africa (NORA) study.

e24095 Background: Breast cancer is the most diagnosed malignancy among women in Nigeria. Histopathological characteristics at diagnosis-such as tumor size, stage, grade, and histological subtype-are critical for guiding treatment decisions and prognostication. However, data describing these features remain limited in many low- and middle-income settings, including Nigeria. Methods: We conducted a cross-sectional study among 94 consenting women aged ≥18 years with histologically confirmed breast cancer, recruited between 2023 and 2024 from two tertiary hospitals in the Federal Capital Territory, Abuja. The hospitals were purposively selected based on the availability of oncology and pathology services, and eligible patients receiving care during the study period were consecutively enrolled. Sociodemographic and clinical information was collected using a semi-structured questionnaire, while histopathological characteristics were abstracted from medical records. Data were managed using REDCap and analyzed descriptively. Results: The mean age at diagnosis was 48.3 ± 11.4 years. Invasive ductal carcinoma was the predominant histological subtype, accounting for 91.0% of cases. Tumors were frequently large at presentation, with 60.6% classified as T3 ( > 5 cm) and 5.3% as T4, while only 2.1% were T1 ( < 2 cm). Stage at diagnosis was documented for 90 patients, among whom 63.3% were classified as Stage I–II and 36.7% as Stage III–IV. Histological grade was reported in fewer than half of cases: 4.5% were well differentiated, 20.2% moderately differentiated, and 20.2% poorly differentiated; 55.1% had no recorded tumor grade. Conclusions: Among breast cancer patients receiving care in Abuja, invasive ductal carcinoma and large tumor sizes at diagnosis were common. The high proportion of missing histological grade information highlights gaps in pathology documentation. Strengthening the completeness and standardization of histopathological reporting may improve clinical decision-making and support cancer research in this setting.

Explainable AI to predict molecular classes of renal cell carcinoma from digital pathology images.

4556 Background: There is an unmet need to develop rapidly deployable and reliable biomarkers to guide treatment decisions in clear cell renal cell carcinoma (ccRCC). Transcriptome-based molecular classification is promising in predicting differential clinical outcomes to angiogenesis blockade alone or with an immune checkpoint inhibitor (ICI), but these approaches require molecular profiling that is costly and time-consuming. This study evaluates whether explainable artificial intelligence (AI) can accurately predict molecular classes of ccRCC from diagnostic H&E slides. This approach enables scalable, pathology-based assessment of treatment response–related biology without the need for additional tissue or sequencing. Methods: We acquired digital whole slide images of H&E stained primary ccRCC tumors from TCGA, OSU Total Cancer Care Alliance, and an in-house built set of selected biopsies. RNA-Seq cluster assignments from IMmotion151 study were reconstructed from published gene log-fold-change cluster enrichment scores and non-negative least squares regression on matching RNA-Seq of our samples. After assigning samples to their highest scoring group, we trained a multi-group attention-based multiple-instance learning (ABMIL) classifier to predict RNA-Seq groups from digital whole slide images broken into 112um patches and encoded using UNI foundation model embeddings. Results: A total of 555 cases with both H&E and RNA-seq data were included. Class prediction from RNA-Seq were 40% Angio-Stromal, 30% Complement-Ox, 16% Angio, 8% Teff-Prolif, 4% Prolif, 2% Stromal-Prolif and 0% snoRNA. Predicting these classes from H&E-stained images, showed AUROC values of 0.76 (Angio-Stromal), 0.78 (Complement-Ox), 0.83 (Angio), 0.85 (Teff-Prolif), 1.00 (Prolif) and 0.91 (Stromal-Prolif) respectively. Similar AUROC values with more modest curves were seen on a hold-out set (10%) where Angio-Stromal/Complement-Ox (0.61/0.61) and Teff-Prolif (0.59) were the lowest AUROC values and Prolif (0.99) was the highest. Importantly, incorrect predictions most often yielded a group prediction where the predicted group shared some biological identity with the ground truth group label (eg. Angio-Stromal and Angio). We also utilized the attention values from ABMIL to evaluate spatial prediction saliency, which showed the model focused primarily on tumor regions, even for predictions of primarily stromal defined classes. Conclusions: Our results demonstrate that diagnostic H&E slides contain histologic features that can predict ccRCC molecular subsets using explainable AI. Supporting scalable pathology-based inference of tumor biology linked to treatment response.

Precisely Controlled Electrochemical Phosphonylation: Tailoring π‐Conjugated Polymer Properties for High‐Performance Organic Electrochemical Transistors

ABSTRACT To achieve high performance, organic electrochemical transistor (OECT) channels must support efficient transport of electronic charges and ions. When designing polymeric mixed conductors, maintaining an appropriate balance between hydrophilic and hydrophobic characteristics plays a crucial role. Conventional hydrophilic side‐chain modification involves costly synthesis and limits molecular design flexibility. Here, we demonstrate a degree of functionalization (DOF)‐tunable electrochemical C–H phosphonylation strategy that enables precise post‐functionalization of semicrystalline, high‐mobility conjugated polymers, thereby providing a versatile route to optimize the hydrophilic–hydrophobic balance without monomer redesign. We applied this approach to semicrystalline polymers, for example, poly[2,5‐bis(3‐tetradecylthiophen‐2‐yl)thieno[3,2‐b]thiophene] (PBTTT) and diketopyrrolo‐pyrrole‐dithienylthieno[3,2‐b]thiophene (DPP‐DTT), which exhibit excellent charge mobilities. The functionalization was successfully carried out in Nafion‐composite films, yielding samples with DOF values up to 0.91. Systematic investigation revealed that the moderate functionalization (DOF = 0.06–0.16) enhanced the µC * values in OECTs by nearly two‐fold compared to pristine polymers. In addition, the phosphonylated materials exhibited improved switching characteristics. These results quantitatively reveal a trade‐off between enhanced ionic accessibility and retention of efficient charge‐transport pathways in the polymers with increased DOF. This precisely tunable functionalization of the hydrophobic conjugated polymers represents a practical strategy for designing mixed ionic and electronic carrier conductors, further facilitating the development of high‐performance OECT materials.

Interface-engineered novel PPy-TiO₂-SnO₂ ternary nanocomposite for high-sensitivity low-concentration CO₂ gas sensing

Interlocked Interface Enhances Mechanical Integrity for Thermal‐Cycling‐Stable Perovskite Solar Cells With 26.82% Certified Efficiency

ABSTRACT Perovskite solar cells (PSCs) experience mechanical damage and failure (i.e. degradation and fracture) induced by temperature changes under thermal cycling. However, few studies have been able to simultaneously suppress interface delamination and delay chemical degradation to ensure the mechanical integrity of perovskite film under thermal shock, making it challenging to improve the thermal cycling stability of PSCs. We report a universal interlocking strategy via the modification of polymethyl(hydro)/polymethylvinylsilazane (PHVS), which achieves interfacial interlocking through the condensation reactions with substrates, hydrogen bonding with the perovskite film, and a self‐crosslinking reaction. The interlocked interface significantly enhances the interfacial adhesion toughness and releases the residual stress of the perovskite film, thereby suppressing the interface delamination and delaying the chemical degradation under thermal cycling. The PHVS‐modified PSCs exhibit a certified efficiency of 26.82%. The encapsulated PSCs retain 96% of their original efficiency after 200 cycles of thermal cycling testing, and the perovskite modules maintain 95% of their original efficiency after 1000 h, day and night, outdoor testing. This work highlights the significance of enhancing the mechanical integrity of perovskite films under thermal cycling and provides a promising approach for achieving thermal cycling‐stable PSCs with high efficiency.

Covalent Adaptable Ionic Networks for Robust, On‐Demand Dismantlable and Fully Recyclable Adhesives

ABSTRACT On‐demand debonding is a critical yet challenging requirement for advanced adhesives. Herein, we report a rational design strategy for robust, on‐demand debondable, and fully recyclable adhesives via constructing covalent adaptable ionic networks (CAINs). Integrating the advantages of poly(ionic liquid)s (PILs) and covalent adaptable networks (CANs), the CAINs exhibit exceptional adhesion strength (>15 MPa on stainless steel), significantly outperforming most reported adhesives based solely on PILs or CANs. The material also maintains a shear strength of 11.0 MPa after immersion in liquid nitrogen, demonstrating excellent low‑temperature tolerance. Bis(trifluoromethanesulfonyl)imide anions endow the adhesives with remarkable hydrophobicity and excellent waterproof performance. Importantly, facile on‐demand debonding is achieved via ethanol treatment under mild conditions, enabling complete substrate separation and efficient material recovery with minimal performance degradation over multiple cycles. Mechanistic studies indicate that the covalent crosslinked network is the primary contributor to high adhesion, while hydrogen bonding plays a secondary supportive role. This work establishes a versatile platform for designing high‐performance dismantlable adhesives with superior recyclability, advancing sustainable adhesive technologies in advanced manufacturing and materials engineering.

A Design Strategy for Durable Anionic Redox via Fluorine‐Induced Electronic Structure Modulation in In Situ Formed Disordered Phases

ABSTRACT Disordered cathode materials are attractive candidates for next‐generation lithium‐ion batteries (LIBs), but the intrinsic instability of anionic redox hinders their commercialization. Unlike conventional Li‐excess disordered systems limited by compositional constraints of Li 1+x M 1‐x O 2 , Immm ‐Li 2 NiO 2 offers a platform to access highly lithiated chemistries that enable in situ disorder formation during electrochemical cycling. This allows lattice O to contribute to charge compensation; however, O 2 release at high voltages compromises reversibility and cycling stability. To address this, fluorination generates a quadrupolar Li‐O‐M‐F configuration that lowers the Li─O─Li band energy level and delays the onset of anionic redox. This electronic structure modification suppresses O 2 evolution, enhances structural stability, and improves cycling performance. By coupling electrochemically induced disorder with stabilization through Li‐O‐M‐F units, this work establishes a new framework for engineering durable, high‐capacity cathodes, offering a blueprint for material design strategies that transcend stoichiometric restrictions and unlock stable anion redox functionality.

Changes in peripheral blood T lymphocyte subsets before and after systemic therapy in patients with HER2-positive advanced breast cancer

Flexible Multiband Photonic Synapses for Nociceptive Perception and Neuromorphic Computation via Fluorinated InP Quantum Dots

ABSTRACT Organic photonic synaptic transistors (OPSTs), emulating biological synaptic behaviors under optical stimulation, serve as essential hardware components for neuromorphic visual systems. To satisfy various demands, state‐of‐the‐art OPSTs typically require multispectral responsiveness that is often pursued by leveraging the excellent optoelectronic properties and solution‐processability of quantum dots (QDs). However, this strategy suffers from complex fabrication procedures, limited mechanical flexibility and toxic cadmium/lead compositions in QDs, which raise serious environmental and biosafety concerns. In this work, we demonstrate a fully solution‐processed and self‐supporting flexible OPST based on environmentally benign indium phosphide (InP) QDs. Through ligand exchange with fluorinated thiols, the QDs demonstrate improved photostability and enhanced energy level alignment with organic semiconductors. Furthermore, the interfacial dipole induced by fluorinated ligands enables long‐term charge retention. The resulting QD‐OPST devices exhibit broadband excitatory postsynaptic current (EPSC) responses, tunable synaptic plasticity, remarkable mechanical durability and ultralow energy consumption of 0.016 fJ, effectively mimicking cornea‐like nociceptor behaviors. In addition, the QD‐OPSTs display pronounced color selectivity, enabling blue‐feature recognition while suppressing red‐green background noise. This study provides a feasible strategy for developing high‐performance, eco‐friendly, and flexible photonic synapse devices, highlighting great potential for applications in visual perception and brain‐inspired computing.

Clinical outcomes with 14- vs 28-day monitoring after CAR-T therapy.

e13590 Background: The US Food and Drug Administration recently eliminated the Risk Evaluation and Mitigation Strategies (REMS), which increased monitoring for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor T-cell (CAR-T) therapy. As a result, the time a patient must remain near the authorized treatment center (ATC) post infusion was reduced from four weeks to two weeks. Our hypothesis was there will be no difference between CRS/ICANS, mortality, readmission rates, and infection rates between the 28 day vs 14 day monitoring period cohorts. Methods: We performed a retrospective review of 42 adult patients who underwent CAR-T therapy at the University of Kansas Medical Center. Endpoints of CRS/ICANS prevalence, ICU admission, 30 day readmission, and 30 day infection were compared between 14 day and 28 day discharge cohorts using Fisher’s exact test for categorical variables and Wilcoxon rank-sum tests for continuous variables. Overall survival was estimated by Kaplan–Meier methods and compared using the log-rank test. Multivariable logistic regression adjusting for age and care setting was performed for selected outcomes. Results: 42 patients underwent CAR-T therapy, 22 of which discharged at 14 days and 20 at 28 days. Median follow-up was 3.3 months (14-day) and 8.4 months (28-day). Baseline characteristics and CAR-T products were comparable between groups. There were no statistically significant differences in rates of any CRS (81.8% vs 75.0%, p = 0.714), CRS grade ≥2 (16.7% vs 0%, p = 0.233), any ICANS (36.4% vs 55.0%, p = 0.352), ICU admission (13.6% vs 31.6%, p = 0.260), 30 day readmission (54.5% vs 30.0%, p = 0.131), or 30 day infection (13.6% vs 10.5%, p = 1.000) for 14 day vs 28 day discharge, respectively. Overall response rates and complete response rates at day 30, day 90, and best overall response were similar between cohorts. There were no deaths within 30 days in either group, and 31–90 day mortality did not differ significantly. Multivariable analyses adjusting for age and care setting showed no significant association between discharge timing and readmission, ICU admission, CRS, or ICANS. Conclusions: Our results suggest the elimination of REMS did not adversely impact patient safety: there was no significant increase in rates of CRS, ICANs, ICU admission, 30 day readmission, and 30 day infection between the 14 day and 28 day monitoring cohorts. Limitations of this study include small sample size and a short median follow-up, due to the small cohort of patients who have received CAR-T since the REMS elimination in June 2025. Although the median follow-up is limited, based on the literature we would expect the main safety signals for this change to manifest by day 90, which was reached in both groups. Future research should probe if similar findings occur in larger cohorts or for longer monitoring periods, especially as more time passes since the updated guidance.

Assessing the long-term impact of a public cancer screening program in Brazil: Ten years of experience.

e22505 Background: Cancer represents a major global health burden, with profound impacts on public health, society, and healthcare systems, and remains one of the leading causes of mortality worldwide. Given its high morbidity and mortality, strategies focused on cancer prevention and early diagnosis are critical for improving patient prognosis and reducing disease burden. However, social and economic inequalities substantially affect access to healthcare services, including cancer screening, thereby limiting the effectiveness of early detection efforts. In this context, the implementation of public, free-of-charge, effective, and accessible cancer screening programs is essential to promote equitable early diagnosis at the population level. The aim of this study is to evaluate the effectiveness and outcomes of a public cancer screening program implemented over a ten-year period (2014–2025) in a large municipality in Brazil. Methods: The cancer screening program, entitled Mutirão do Câncer, has been conducted annually in a central public square in the municipality of Montes Claros, Minas Gerais, Brazil. The program is held on a single day each year and operates continuously for approximately 12 hours. During this period, individuals seeking healthcare services undergo cancer screening evaluations across multiple specialties, including mastology, gynecology, urology, dermatology, dentistry, and nutrition. Accordingly, a multidisciplinary team—comprising physicians, dentists, researchers, the nursing team, nutritionists, physiotherapists, and students—provides cancer prevention education, clinical assessments, and laboratory testing for individuals identified as being at risk for or suspected of having cancer. Results: From 2014 to 2025, a total of 27,219 individuals were evaluated through the program for cancer screening and prevention strategies. Among them, 2,882 individuals were screened for cervical cancer, 6,425 for breast cancer, 3,351 for oral cancer, 4,865 for prostate cancer, and 3,951 for skin cancer. Moreover, 3,348 received nutritional interventions and guidance related to cancer prevention. Throughout the years, the program diagnosed 321 patients with cancer, with prostate (49%) and skin (43%) cancers being the most common diagnoses. Between 2014 and 2025, over 5,500 patients underwent clinical/laboratory evaluation for breast, prostate, and cervical cancer upon presenting with risk factors or findings suggestive of malignancy. All patients diagnosed in the last two editions are still undergoing cancer treatment. Conclusions: This initiative constitutes a robust and free public cancer screening strategy with demonstrated effectiveness and strong potential to be replicated and adapted in other settings, thereby amplifying its public health impact.

Utidelone in heavily pretreated metastatic castration-resistant prostate cancer progressing after docetaxel and novel hormonal agents: Results of a completed phase II trial.

5059 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after both docetaxel and novel hormonal agents (including abiraterone and/or androgen receptor pathway inhibitors [ARPIs]) have a poor prognosis with limited treatment options. This study aimed to evaluate the efficacy and safety of utidelone, a genetically engineered epothilone analogue with antitumor activity in taxane-resistant cancers, in these patients. Methods: In this prospective, single-arm, phase II clinical trial, eligible male patients were aged 18 to 75 years with mCRPC who had progressed on docetaxel and at least one prior ARPI or abiraterone. Patients received utidelone monotherapy (30 mg/m²/day intravenously for 5 days, every 3 weeks) until progression, intolerable toxicity, or death. Recruitment has been completed with 43 patients enrolled at Sun Yat-sen University Cancer Center from March 23, 2022, to December 10, 2025. The primary endpoint was prostate specific antigen (PSA) response rate, defined as a 50% or greater reduction in serum PSA. Secondary endpoints included radiographic progression-free survival (rPFS) according to PCWG3 criteria, OS, and safety. Results: Analysis was performed on the full cohort. The median age was 66 years, and patients had received a median of 4.0 (range, 2-8) prior lines of treatment. All patients were pre-treated with docetaxel and 97.7% with abiraterone; 90.7% patients had progressed after ARPI, and 14.0% after radionuclide therapy. Visceral metastases were present in 32.6% patients, and 67.4% had de novo metastatic disease. Among 28 patients with available genetic data, BRCA1/2 mutations were identified in 3 (10.7%). By the data cut-off (January 4, 2026), the PSA50 response rate (≥50% decline) was 23.3%, and 32.6% of patients achieved a PSA30 response (≥30% decline). The median rPFS was 6.7 months, and median OS was 11.4 months. Most of the treatment-related adverse events (TRAEs) were grade 1 or 2 and were considered manageable. Grade 3/4 TRAEs consisted of anemia (14.0%), peripheral sensory neuropathy (2.3%), vomiting (2.3%), and diarrhea (2.3%). No treatment-related deaths occurred. Conclusions: Utidelone monotherapy exhibits promising antitumor activity and manageable safety profile in heavily pretreated mCRPC patients, including those who have progressed on ARPIs, abiraterone, and docetaxel. The study results support further investigation of this regimen. Clinical trial information: ChiCTR2200061635.

Safety and efficacy of intratumoral (IT) ruxotemitide (LTX 315) in combination with pembrolizumab in patients with unresectable advanced melanoma or triple-negative breast cancer (TNBC).

2602 Background: Advanced unresectable cutaneous melanoma or TNBC are associated with poor prognosis and limited treatment options. Ruxotemitide is an oncolytic peptide that induces immunogenic cell death and reshapes the tumor microenvironment to boost antitumor immune responses. We report aggregate safety and efficacy from two trials that assessed intratumoral ruxotemitide combined with pembrolizumab in patients with advanced or metastatic melanoma or TNBC. Methods: Two studies enrolled respectively patients with melanoma stage IIIB–IV (M1b) or unresectable TNBC and at least one injectable lesion (as cutaneous, subcutaneous or lymph node). Patients with melanoma were required to have failed prior PD-1\PD-L1 blockers treatment while TNBC patients were naïve of immunotherapy. Patients were required to have adequate organ function. Patients received IT ruxotemitide (up to seven injections during the first 29 days) in combination with pembrolizumab 200 mg IV every 3 weeks until disease progression or for up to 24 months. Safety and efficacy were analyzed across both studies. Tumor assessments were based on RECIST v1.1. Results: 41 patients were enrolled, with a median age of 61 years. 26 of pts (63.4%) had received three or more prior lines of therapy, and 22 pts (53.7%) had previous checkpoint blockade treatment. 22 patients (53.7%) had melanoma, 18 patients TNBC (43.9%) and 1 patient (2.4%) a carcinoid tumor. 4 patients had a partial response (2 with melanoma and 2 with TNBC). All responses in melanoma patients were durable, lasting more than 24 months. 1 patient with TNBC achieved a PR for one year. The safety profile was consistent with known effects of IT immunotherapy and pembrolizumab. The most common treatment emergent adverse events (TEAEs) related to ruxotemitide were injection-site reactions (78%), injection site erythema (26.8%), fatigue (22%), hypotension, injection site swelling or pruritus (14.6% each). Grade 3 TEAEs related to ruxotemitide included injection site pain (19.5%) and hypertension (4.9%). There were no related grade 4 TEAEs or deaths. Conclusions: IT ruxotemitide plus pembrolizumab demonstrated durable antitumor activity and manageable safety in heavily pretreated patients with advanced or metastatic melanoma or TNBC with injectable disease. These findings support further clinical evaluation of this combination in melanoma and TNBC. Clinical trial information: NCT01986426 and NCT04796194 .

Worst-case scenarios, triggers, and coping strategies among head and neck cancer caregivers.

e18097 Background: Head and neck cancers (HNCs) place a heavy burden on patients and informal caregivers (e.g., family, friends) involved in cancer care and recovery. As patients live longer with treatment advances, both patients and caregivers face uncertainty about the future, including fears of cancer progression and recurrence. These fears can lead to anxiety and depression, which can negatively affect their lives and patient care. Among patients, research has begun studying the role of worst-case scenarios (WCS) to inform intervention development; however, WCS have not been examined among cancer caregivers. This study presents data on cancer caregivers’ self-reported WCS, including their triggers, coping strategies, disclosure to others, perceived control, and time spent thinking of WCS. Methods: HNC caregivers provided written, open-ended responses on their WCS regarding their patient, WCS triggers, and coping strategies for managing WCS. Responses were coded into major, non-exclusive themes. Sharing of WCS, controllability, and time spent on their WCS were also quantified. Results: HNC caregivers (N=21) were 86% female, and the majority were spouses (mean age 57 ±16 years). The WCS themes most endorsed were cancer progression/future uncertainty (n=11 instances, 36%), death (n=6, 19%), suffering/deterioration (n=4, 13%), and well-being/mental health (n=4, 13%). Triggers of WCS were primarily patient illness and cancer side effects/symptoms (e.g., altered speech); some participants (29%) had no triggers. The most common coping strategies used to manage WCS were prayer and spirituality, staying positive, and avoidance. Most caregivers (81%) did not share their WCS with anyone, but of those who did (19%), most reported sharing with their patient. Most (76%) found their fears to be either completely or mostly controllable, whereas others (24%) found them to be moderately or somewhat controllable. Time spent thinking about WCS ranged from not thinking about it daily (n=12, 60%) to <5 min (n=3, 15%), 5-10 min (n=3, 15%), 10-30 min (n=1, 5%), and 1-2 hours (n=1, 5%). Conclusions: Overall, caregivers reported managing WCS with various coping strategies, and most reported that WCS were controllable, with little time spent thinking about them. Nonetheless, a small subset had greater difficulty managing WCS. Findings may guide the development of targeted support for those experiencing high distress due to WCS (e.g., exposure-based interventions).

Real-world data on CLDN18.2 expression in gastric and gastroesophageal cancer patients.

e16038 Background: Gastric cancer (GC) and gastroesophageal junction cancer (GEJC) are highly lethal malignancies that are frequently diagnosed at advanced stages, where treatment is more challenging and prognosis remains poor. CLDN18.2 has emerged as a therapeutic target in GC and GEJC, with the FDA approval of an antibody combined with fluoropyrimidine–platinum chemotherapy for first-line treatment of locally advanced or metastatic HER2-negative, CLDN18.2-positive G/GEJ tumors. The aim of this study is to report the proportion of CLDN18.2-IHC positive samples in patients with GC and GEJC. Methods: A retrospective analysis was conducted in data from a cohort of 152 patients with GC/GEJC and other types pf carcinomas who were assessed for CLDN18.2 positivity by IHC with the VENTANA CLDN18(43-14A) RxDx Assay. CLDN18.2 positivity was defined as ≥ 75% of viable tumor cells demonstrating moderate to strong (2+/3+) membranous CLDN18 staining. Results: CLDN18.2 positivity was identified in 38 of 120 (31.6%) patients with gastric adenocarcinoma and in 7 of 26 (26.9%) patients with GEJ adenocarcinoma, while no positivity was observed among patients with other types of carcinomas (0/6). Conclusions: The findings of this study indicate that a substantial proportion of patients with GC or GEJC are CLDN18.2-positive and may be eligible for targeted therapy in combination with chemotherapy. This therapeutic approach has been shown, in clinical trials, to improve progression-free and overall survival compared with standard chemotherapy.