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Differential detection of BRCA-associated cancer risk and Lynch syndrome in genomic screening.

e13537 Background: Hereditary cancer syndromes such as BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) account for many preventable cancers. Identification of carriers often relies on family history, guideline-based testing, or cancer diagnosis, leading to missed prevention opportunities. Voluntary population genomic screening allows assessment of how participation patterns influence detection of hereditary cancer risk. The Healthy Nevada Project (HNP), a voluntary genomic screening program in Northern Nevada, enables real-world assessment of hereditary cancer risk in a community cohort. With approximately 10% participation of the region’s adult population, HNP allows population-level comparison of observed prevalence with national benchmarks and condition-specific enrichment. Methods: We analyzed 48,143 Healthy Nevada Project participants with demographic and exome-derived variant data. Pathogenic or likely pathogenic variants in BRCA1/2 and Lynch syndrome mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM) were identified. Crude prevalence estimates were calculated and compared with widely cited national benchmarks. BRCA1/2 prevalence was examined by sex to assess patterns relevant to genetic testing. Results: HBOC prevalence was 0.733% (1 in 136), exceeding national expectations of approximately 0.20–0.33% (1 in 300–500) reported by the CDC. In contrast, LS prevalence was 0.332% (1 in 301), closely matching the widely cited national rate of approximately 0.36% (1 in 279) referenced in CDC Lynch syndrome materials. The overall cohort was predominantly female (67.8% female, 32.2% male). Despite this imbalance, BRCA1/2 pathogenic variant prevalence was comparable between men and women, consistent with autosomal inheritance. Conclusions: In this voluntary genomic screening cohort, BRCA-associated cancer risk appeared enriched relative to national estimates, whereas LS prevalence aligned with population expectations. These findings should be interpreted in the context of substantial self-selection, including greater participation by women, older adults, and those with family history. Notably, comparable BRCA1/2 prevalence across sexes despite lower male participation highlights persistent gaps in awareness and testing of male carriers, despite their elevated risks for prostate and gastrointestinal malignancies. The contrasting prevalence patterns suggest that condition-specific awareness and perceived cancer risk preferentially enrich BRCA-associated findings while leaving LS under-recognized. Reliance on voluntary pathways may therefore contribute to missed opportunities for early surveillance and cascade testing, underscoring the value of upstream genomic risk identification to support more equitable detection of hereditary cancer syndromes in oncology care.

Characterization of germline pathogenic variants in melanoma patients.

9590 Background: Approximately 10% of melanomas arise from hereditary predisposition. NCCN guidelines recommend genetic counseling for patients with ≥3 invasive melanomas, or a mix of invasive melanoma, pancreatic cancer, and/or astrocytoma in an individual or family. However, predictors of germline pathogenic/likely pathogenic variants (P/LPV) in patients undergoing germline testing remain poorly characterized. Methods: A retrospective study of all melanoma patients referred for any indication to the University of Michigan Cancer Genetics Clinic from 2015-2024 was performed. Patients who declined testing or had known hereditary cancer syndromes (personal or familial) were excluded. Baseline demographics, referral reasons, melanoma characteristics, and genetic testing results were collected. Chi-square and Fisher’s exact tests were used to evaluate associations with P/LPV (p<0.05). Results: Among 624 patients, median age at melanoma diagnosis was 52 (IQR 38-63); 60.1% were female. The most common referral reasons were new melanoma diagnosis (64.4%), family history of non-melanoma cancers (57.1%), or family history of melanoma (39.4%). Overall, 88 (14.1%) harbored P/LPV (92 variants across 26 genes). P/LPV in established melanoma-risk genes were identified in 42 patients (6.7%): CDKN2A (n=16), MITF (n=8), POT1 (n=5), BRCA1/2 (n=6), BAP1 (n=3), TP53 (n=3), and PTEN (n=1). The strongest associations with any P/LPV were personal history of ≥2 additional non-skin primary cancers (OR 2.35; p=0.014) and ≥2 primary melanomas (OR 1.80; p=0.017). Diagnostic category (in situ, invasive, metastatic) and subtype (cutaneous, uveal, mucosal, acral, unknown primary) showed statistical significance with P/LPV (p<0.001), though effect sizes were modest. Age at diagnosis (<45, <55, <65), sex, and family history of melanoma or pancreatic cancer in 1˚ or 2˚ relatives were not associated with P/LPV. In a secondary analysis restricted to established melanoma-risk genes (n=42), ≥2 primary melanomas remained strongly predictive (OR 4.11; p<0.001) and 1˚ family history of melanoma became significant (OR 2.01; p=0.03), while ≥2 additional non-skin primary cancers was not associated (p=0.40). Conclusions: In this melanoma cohort excluding patients with known hereditary syndromes, 14.1% had a P/LPV. Personal tumor burden, not family history, was the strongest predictor of a positive test, suggesting current NCCN criteria may miss high-risk individuals by emphasizing family history. For established melanoma-risk genes specifically, both personal history of multiple melanomas and 1˚ family history of melanoma were predictive, supporting a gene-specific approach to risk assessment. These findings support expanding referral criteria to include patients with ≥2 primary melanomas or ≥2 additional non-skin primary cancers, agnostic of family history, to better identify individuals most likely to benefit from germline testing.

Nivolumab plus temozolomide (Nivo/Tem) vs. temozolomide monotherapy in refractory melanoma.

e21507 Background: While immunotherapy (IT) is first-line therapy for advanced melanoma, many patients are refractory, necessitating alternative treatments. Patients with refractory melanoma have limited treatment options, particularly when they have poor performance status. This study evaluated the clinical outcomes and safety of combining Nivo/Tem compared to Tem monotherapy in refractory melanoma. Methods: We conducted a single-center retrospective cohort study of 44 patients with metastatic melanoma. Eligible patients had documented disease progression on prior anti-PD-1+/- ipilimumab or relatlimab and other available systemic treatments. Patients with prior chemotherapy or uveal melanoma were excluded. Patients treated with Nivo/Tem (n=25) were compared to a control group receiving Tem alone (n=19). Endpoints included objective response rate (ORR), Clinical Benefit Rate (CBR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using the Kaplan-Meier method. Cox proportional hazards models estimated hazard ratios (HR) and 95% CI, including exploratory interaction testing by baseline LDH. Results: Baseline characteristics were comparable, (p>0.05), including median lines of therapy (2 vs. 2), M1c/d stage (84% vs. 79%), and elevated LDH (75% vs. 74%). ORR (32% vs 10.5%; p=0.108) and CBR (48% vs 31.6%; p=0.421) were numerically higher in the combination arm but did not reach statistical significance. Median OS was 359 days for Nivo/Tem vs. 167 days for Tem (HR 0.44; 95% CI:0.20-0.93; p=0.032). Median PFS was 111 days for Nivo/Tem vs. 59 days for Tem (HR 0.53; 95% CI: 0.28-1.01; p=0.055), which approached but did not reach statistical significance. Multivariate analysis identified a significant treatment-LDH interaction for both OS (p=0.024) and PFS (p=0.018). Outcomes were similar in the normal LDH group, whereas the higher risk of death and progression was significantly attenuated in the combination group; the HR for combination therapy was 0.34 (p=0.01) for OS and 0.45 (p=0.02) for PFS. Conclusions: Nivo/Tem improved OS compared to Tem alone in immunotherapy-refractory melanoma, with both OS and PFS benefits particularly pronounced in patients with elevated LDH. Improvement in ORR did not reach statistical significance but appeared to have clinical significance. These findings suggest that chemo-immunotherapy may be a viable salvage strategy for patients with aggressive, refractory disease, particularly when other options are not viable.

Bone marrow immune cell state analysis and selective APC alterations in prolonged cytopenia following CAR T-cell therapy.

e19018 Background: Prolonged cytopenia (PSC) following chimeric antigen receptor (CAR) T-cell therapy is common and associated with infectious morbidity. Early post–CAR T infections are predominantly bacterial, with later viral complications and less frequent invasive fungal infections. We evaluated whether PSC is associated with transcriptional impairment of innate antimicrobial programs or with selective differences in immune cell states within the bone marrow. Methods: We analyzed publicly available bone marrow scRNA-seq data from 22 CAR T recipients (Strati et al., GSE216005), sampled beyond day 30 post-infusion and classified as PSC or non-PSC per original clinical annotation. Antigen-presenting cells (APCs; monocytes and dendritic cells) and myeloid populations were evaluated using predefined transcriptional modules capturing HLA class II antigen presentation, interferon-associated HSPC injury, innate bacterial and antifungal sensing, neutrophil antimicrobial effector function, and neutrophil immaturity. To avoid cell-count–driven inference, primary analyses were performed at the patient level using median module scores and per-patient fractions of transcriptionally defined cell states, with Wilcoxon rank-sum testing. Results: Patient-level median immune signatures showed substantial overlap between PSC and non-PSC patients across interferon-associated HSPC injury programs, APC interferon signaling, neutrophil antimicrobial effectors, innate bacterial sensing, antifungal pathways, and neutrophil immaturity states. In contrast, cell-state–aware analyses revealed a significant difference in APC composition: non-PSC patients exhibited a higher fraction of APCs in an HLA class II–low transcriptional state, whereas PSC patients demonstrated relative depletion of this state (Wilcoxon p = 0.007). Neutrophil antimicrobial, bacterial, and antifungal transcriptional programs were preserved across groups. Conclusions: In this CAR T bone marrow scRNA-seq cohort, PSC was not associated with global transcriptional impairment of innate antimicrobial programs but was associated with a selective shift in APC state composition. These findings suggest that PSC-associated infection risk may be driven more by the severity and duration of cytopenia and altered immune regulation than by intrinsic dysfunction of remaining innate immune cells. Despite clear mechanistic immune differences at the cell-state level, patient-level comparisons of several immune programs were underpowered, underscoring the need for larger, multicenter immune-phenotyping cohorts to inform infection-risk stratification and supportive care strategies following CAR T therapy.

Using large language models to extract diagnosis, recurrence, and death dates from breast cancer electronic medical records.

e13005 Background: Breast cancer research needs accurate extraction of clinical event dates (e.g., recurrence dates) from the electronic medical record (EMR). Manual chart review is time-consuming and error-prone. We evaluated whether unadapted, HIPAA-compliant, commercially available large language models (LLMs) could extract event dates with accuracy comparable to research coordinators, benchmarked against medical oncologists, in patients with complex breast cancer histories. Methods: We randomly selected 99 patients from an institutional cohort. Ground truth was established by oncologist review of all EMR data, except CareEverywhere. Abstracted events included: original diagnosis date; first locoregional recurrence (LRR); first distant metastatic date; vital status; and an exact or estimated date of death. In parallel, research coordinators abstracted original diagnosis and metastatic dates. For the LLMs, a patient’s full chart was ingested into a patient-specific vector database. Relevant evidence chunks were retrieved using hybrid lexical + semantic retrieval. Chunks were sent to the LLMs with structured, sequential prompts that enforced definitions and prioritized pathology provenance. Estimation was used only if no explicit date was found. Identical evidence and prompts were used with Gemini 2.5, GPT-4, and GPT-5. We report only the best-performing model for each event due to space constraints. Results: All 99 patients had a documented year of original diagnosis. Thirty-one had LRR, 78 developed distant disease, and 13 presented with de novo metastatic disease. As of the censor date (01/10/2026), 83 patients died, with 49 having an exact date of death. Agreement for vital status for the best performing model (GPT-5) was 99%. Time to first recurrence for stage 1-3 patients was 29 [17–49] months (median [IQR]); the best LLM estimate (GPT-5) of recurrence differed by 3.8 ± 12.7 months (mean ± SD) with 87% of events ≤ 90 days. Cohort overall survival was 67 [43–99] months. The best LLM (GPT-5) estimate of survival differed by 2.1 ± 3.5 months, with 71% ≤ 90 days. When the EMR had the exact date of death, concordance was high (98% ≤ 90 days); when estimation was used, concordance was low (28% ≤ 90 days). Original diagnosis date within ± 90 days was 98% for research coordinators and GPT-5. For LRR, the best LLM (Gemini) had an F1 score of 0.80; among correctly identified events, 91% were ≤ 90 days. For 91 metastatic events, the best LLM (GPT-4) had an F1 of 0.96, with 72% ≤ 90 days. Research coordinators had an F1 of 0.96 with 76% ≤ 90 days. Conclusions: Commercial LLMs, when provided the full chart and a provenance-aware prompting framework, can reliably extract explicit dates and clinical details, and are similar to trained research coordinators. However, for complex details in patients with recurrent breast cancer histories spanning years and often institutions, agreement with clinicians remains below thresholds needed for fully automated extraction.

Guideline adherence in action: Baseline neuroimaging rates for NSCLC—A Northern Ireland North West Cancer Centre single-institution experience.

e20653 Background: Brain metastases are common in patients with Non-Small Cell Cancer (NSCLC) and significantly impact treatment selection and outcomes. Clinical guidelines recommend baseline neuroimaging; however real-world adherence has historically been inconsistent. We evaluated changes in neuroimaging utilization among patients with NSCLC to assess improvement in staging practices. Methods: A retrospective review of patients with newly diagnosed NSCLC evaluated at North West Cancer Centre in 2020 and 2023. Baseline neuroimaging utilization was assessed, including computed tomography (CT) brain, magnetic resonance imaging (MRI) brain, or no brain imaging prior to treatment initiation. Imaging patterns were compared descriptively between cohorts. Results: A total of 60 and 50 patients were evaluated in 2020 and 2023 respectively. In 2020, 60% of patients (36 out of 60) had CT brain imaging. By 2023, this number rose to 41 out of 50 patients (82%). MRI utilisation increased slightly, from 3 patients (5%) in 2020 to 4 patients (8%) in 2023. The proportion of patients who did not receive any baseline brain imaging dropped from 21 out of 60 (35%) in 2020 to just 5 out of 50 (10%) in 2023. Baseline neuroimaging adherence improved from 65.0% in 2020 to 90.0% in 2023. The difference in proportions was 25.0% (95% CI: 39.7% to 10.3%). A two-proportion z-test demonstrated that this increase was statistically significant (z = -3.07, p = 0.0021), indicating a robust improvement in guideline adherence over time. The increased imaging rates led to earlier and more accurate detection of brain metastases, enabling timely multidisciplinary decision-making and optimised treatment planning. Conclusions: Over the three-year study period, a substantial improvement in the utilisation of baseline brain imaging for patients newly diagnosed NSCLC has been witnessed. Adherence to guideline-recommended neuroimaging increased markedly from 65% to 90%. This upward trend was accompanied by a significant reduction in the proportion of patients who remained un-staged at diagnosis, underscoring the effectiveness of targeted institutional efforts. Notably, the enhanced imaging rates translated into earlier and more accurate detection of brain metastases, facilitating timely multidisciplinary decision-making and optimised treatment planning. These results reflect a successful alignment of clinical practice with national guidelines and demonstrate the tangible impact of focused quality improvement initiatives within a single regional cancer centre.

Verification of clinical benefit following FDA accelerated approval in oncology: A time-to-event analysis.

e23041 Background: The FDA Accelerated Approval (AA) program enables earlier access to therapies for patients with serious and life-threatening conditions based on a surrogate or intermediate endpoint likely to predict clinical benefit. Sponsors are required to conduct post-approval confirmatory trials to verify clinical benefit in a timely manner. This analysis evaluated the time to verify clinical benefit among oncology indications approved under the AA pathway. Methods: This retrospective observational analysis utilized publicly available data from the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) AA report. Data were extracted from the source report and converted to a structured dataset. Indications were classified as oncology or non-oncology and were further categorized as hematologic or solid tumors. Analyses were restricted to oncology indications granted AA before January 31, 2025. Descriptive statistics were used to summarize cohort characteristics. Time to conversion to traditional approval was evaluated using the Kaplan-Meier method, with landmark conversion estimates reported. Differences in time to conversion between hematologic and solid tumor indications were assessed using the log-rank test. Analyses were conducted using R. Results: Among 333 AA records, 227 oncology indications met inclusion criteria. Of the AA indications, 146 (64.3%) were solid tumors and 81 (35.7%) were hematologic malignancies. At the time of the analysis, 132 (58.1%) indications had converted to traditional approval, 60 (26.4%) had not yet converted, and 35 (15.5%) were withdrawn. Median time to conversion was 54.1 months (95% CI: 46.3-63.0). The cumulative probability of conversion was 33.2% (95% CI: 26.3-39.5) at 36 months and 71.4% (95% CI: 62.4-78.2) at 84 months. Among converted indications, time to conversion ranged from 5.5 to 210.6 months. Time to conversion differed significantly between hematologic and solid tumor indications (Χ 2 = 14.9, p = 0.0001). Conclusions: The AA pathway facilitates earlier patient access to oncology therapies; however, time to conversion from accelerated to traditional approval varies widely. The median time to conversion was approximately 4.5 years, with hematologic malignancies converting significantly earlier than solid tumors.

Efficacy of YES, an mHealth intervention for adolescent and young adults (AYA) with breast cancer (BC), to address AYA survivorship concerns.

12009 Background: AYA BC survivors often have unmet concerns that are understudied and sub-optimally addressed. Primary results from the YES trial (NCT04906200) demonstrated that YES, an AYA-focused mHealth intervention, improved quality of life and reduced specific symptoms in AYA BC survivors at 6 months (mo) post-enrollment. Here we report a pre-specified secondary analysis of YES on reducing AYA survivorship concerns. Methods: We conducted a multicenter (Dana-Farber Cancer Institute, The Ohio State University, Columbia University Medical Center) RCT of YES, an mHealth intervention which provides tailored information, resources and support in response to monthly electronic patient-reported outcome monitoring, a journal platform, and a chat room. Participants age ≤39 at diagnosis (dx) of stage 0-3 BC, < 3 years post-dx were randomized 1:1 to YES or Usual Care (UC). Survivorship concerns were measured at baseline, 3, and 6 mo with AYA HOPE survey items; participants rated their level of concern across a range of domains. Generalized linear mixed effects models analyzed the binary endpoint of somewhat/very vs no/low concern for each issue. Odds of being somewhat/very concerned about a domain at 6 mo were compared between arms, adjusting for baseline concern. Results: From 6/2021-12/2024, 360 participants were randomized (YES:179; UC: 181) following baseline survey completion. Participant characteristics were balanced between arms. Median time from dx was 19 (IQR: 12-27) mo. Median age at dx was 34 (IQR: 31-37) yrs; 61% had stage 2 or 3 BC. Overall, a majority of participants endorsed high levels of concern at baseline related to: long-term side effects of treatment (67%), long-term health effects of cancer (70%), recurrence (79%), checking for signs of recurrence (57%), possibility of a new cancer (67%), exercise (60%), nutrition (58%), familial cancer risk (51%), and body image (56%). Other endorsed concerns included: fertility (43%), financial support for medical care (37%), financial concerns (38%), talking about cancer experience with family/friends (27%), having enough information about treatment (25%), meeting other AYAs (22%), alcohol and cancer (15%), and smoking cessation (3%). At 6 mo, adjusting for baseline concern, the YES group (vs UC) had lower odds of being somewhat/very concerned about finances (OR: 0.36, 95% CI: 0.13 – 0.98, p = 0.05), financial support for medical care (OR 0.35, 95% CI 0.13-0.96, p = 0.04), family cancer risk (OR 0.36, 95% CI 0.17-0.77, p = 0.009), and alcohol and cancer (OR 0.15, 95% CI 0.03-0.75, p = 0.02). Conclusions: Concerns across a range of survivorship domains are prevalent in AYA BC survivors. The YES mHealth intervention reduced concerns about several survivorship issues, supporting the potential for this highly scalable intervention to help manage these concerns as an adjunct to routine clinical care for AYA BC survivors. Clinical trial information: NCT04906200 .

Prognostic factors in malignant thymic neoplasms: A comprehensive real-world analysis from a Brazilian tertiary center.

e20174 Background: Malignant thymic neoplasms are rare and biologically heterogeneous tumors, with limited prospective data to guide prognostic stratification. Real-world cohorts incorporating clinical, radiological, pathological, and laboratory variables may help clarify which factors truly drive outcomes. Methods: We conducted a retrospective single-center study including patients with malignant thymic neoplasms treated at a Brazilian tertiary cancer center. Variables collected included demographic and clinical characteristics, comorbidities (Charlson Comorbidity Index, CCI), autoimmune disease, radiological features, tumor stage, histological subtype, surgical treatment, and laboratory parameters (BMI, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, and platelet count). Associations with surgery, recurrence, and death were assessed using chi-square or Fisher’s exact tests and non-parametric tests as appropriate. Overall survival (OS) was estimated using Kaplan–Meier and compared with the log-rank test. Results: Forty-eight patients were included, with balanced sex distribution and a high prevalence of autoimmune disease, particularly myasthenia gravis. Approximately 60% underwent surgical resection, most with complete (R0) margins. Surgery was significantly associated with myasthenia gravis, earlier stage, absence of nodal involvement, less aggressive histology, and smaller tumor size. Recurrence was infrequent and showed no consistent associations. Death was associated with higher CCI (≥2), symptomatic presentation, lower BMI, and aggressive histology. Median OS was 139 months. Patients with B3 thymoma or thymic carcinoma had significantly worse OS compared with other histological subtypes (log-rank p = 0.006), while cancer-specific death was rare among non-B3/C tumors. Conclusions: Histological subtype—particularly B3 thymoma and thymic carcinoma—emerged as the dominant prognostic determinant in malignant thymic neoplasms. Higher CCI, symptomatic presentation, and lower BMI were also associated with mortality. Cancer-specific death was uncommon outside aggressive subtypes, reinforcing the central role of histology and stage in risk stratification and clinical decision-making.

Introducing the Dutch Quality Registry for Acute Internal Medicine (DRAIM): Method of development and opportunities of use from a single-centre pilot study

Background The Dutch Quality Registry for Acute Internal Medicine (DRAIM) aims to evaluate and improve the quality of care for internal medicine patients presenting in the Dutch acute care chain. Using an online dashboard, comprising organizational, process, and patient characteristics, DRAIM provides insight into local institutional characteristics and enables comparisons with a benchmark. The aim is to identify potential bottlenecks, develop of interventions to optimize acute care and to create a learning environment. Methods DRAIM is a multicenter quality registry. However, this study reports findings from a single-centre pilot conducted in one teaching hospital. Data for this cohort was collected from November 2019 to June 2023, including patients presenting in the Emergency Department (ED) for internal medicine. Data was extracted from the Electronic Health Record, including patient and organizational characteristics, such as presenting complaint, and process- and outcome measures, such as length of stay in the ED (LOS-ED). Results A total of 6,071 patients aged ≥65 years were included. Older adults were more likely to experience adverse outcomes, including longer LOS-ED, increased hospital admissions, extended hospital stays, and higher in-hospital mortality rates. Additionally, 2.366 patients (46.6%) presented with general malaise. Compared to patients with other presenting complaints, those with general malaise had longer LOS-ED and higher hospital admission rates. These findings prompted the development and implementation of a standardized care-pathway for patients with non-specific complaints in the ED. Conclusion This single-centre pilot demonstrates the potential of DRAIM to provide valuable insights into acute-care processes and identify bottlenecks in patient flow. While findings cannot yet be generalised nationally, they highlight important trends, such as the vulnerability of older patients and those presenting with non-specific complaints. Future use of DRAIM for multicentre studies will validate these observations and facilitate the evaluation and improvement of the Dutch acute-care network.

Extraction of essential oil from Lavandula angustifolia flowers for the green synthesis of AgNPs and evaluation of their antifungal activity

A Design Strategy for Durable Anionic Redox via Fluorine‐Induced Electronic Structure Modulation in In Situ Formed Disordered Phases (Adv. Mater. 35/2026)

High‐Performance Hydrogen‐Aided Sn‐Air Battery

ABSTRACT The growing demand for energy storage has driven the need for secure, cost‐effective batteries. Although aqueous tin‐air batteries (SnABs) offer high theoretical energy density and intrinsic safety, their commercialization faces significant challenges due to high charging overpotential and limited cycle life, primarily caused by sluggish oxygen evolution reaction (OER) kinetics. Here, a hydrogen‐aided Sn‐air battery (Sn‐HAB) is reported, which replaces the sluggish OER with an efficient hydrogen oxidation reaction (HOR) at the cathode during charging, substantially reducing the overpotential. Moreover, a tinophilic brass mesh (BM) substrate is introduced to regulate Sn deposition, enabling a dense and dendrite‐free morphology at 100 mA cm −2 . As a result, the Sn‐HAB operates from 0 to 1000 mA cm − 2 , achieving a charging voltage of 1.0 V (versus 2.5 V for SnABs at 100 mA cm − 2 ) and a cycle life exceeding 900 cycles—nearly 20 times longer than conventional SnABs. An anode‐free (without bulk Sn) configuration maintains stable operation for over 800 cycles, and ampere‐hour‐level cells demonstrate scalability. This work overcomes the rate and efficiency limitations of SnABs, establishing a pathway toward safe, low‐cost aqueous energy storage systems.

Multi-Strategy optimisation algorithm for multi-UAV path planning in complex mountainous environments

A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis

Updated efficacy of dalpiciclib and nonsteroidal aromatase inhibitors (NSAIs) in estrogen receptor–positive (ER+) recurrent/metastatic (R/M) ovarian cancer and uterine neoplasms.

5559 Background: Initial results from our trial showed the anti-tumor activity and good tolerance of CDK4/6 inhibitor dalpiciclib combined with NSAIs in patients (pts) with ER+ R/M ovarian cancer and uterine neoplasms (SGO, 2024, #S283; IGCS, 2025, #397). Here, we report updated results. Methods: This single-center, single-arm, open label, phase 2 trial enrolled pts with ER+, R/M ovarian cancer and uterine neoplasms which met the following criteria: pretreated low-grade serous ovarian carcinoma (LGSOC), pretreated uterine endometrioid carcinoma (EC), uterine leiomyosarcoma (LMS), or untreated low-grade endometrial stromal sarcoma (LGESS). Pts received dalpiciclib (150mg po d1-21 q28d) and NSAIs (mainly letrozole 2.5mg po qd) until disease progression, unacceptable toxicity or consent withdrawn. The primary endpoint was 12-week progression-free survival (12wPFS) rate. A Simon’s two-stage design was used (one-sided α=0.05, power=80%), and the null hypothesis (P0=0.2) would be rejected if totally >10 of 33 pts achieved primary endpoints. Results: As the data cutoff (Jan 5, 2026), 35 pts with a median of one prior therapy for R/M disease were enrolled, including 11 with LGSOC, 15 with EC, 8 with LGESS and 1 with LMS. With a median follow-up of 11.4 months (range, 0.1-52.2), 22 of 29 efficacy-evaluable pts had reached the primary endpoint, with a 12wPFS rate of 75.9% (95% CI 56.5-89.7), suggesting the value of further investigation. Detailed efficacy results are shown in Table 1. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 82.9% (29/35) of pts, mostly neutrophil count decreased (71.4%), white blood cell count decreased (45.7%) and platelet count decreased (14.3%). Sixteen pts had dose reduction of dalpiciclib, mostly due to hematologic toxicities. No serious adverse events or treatment-related deaths occurred. Twelve pts were still on-treatment, with 3 pts treated for >4 years. Conclusions: The trial achieved its positive primary endpoint, showing meaningful efficacy of dalpiciclib + NSAIs in ER+ R/M ovarian cancer and uterine neoplasms. No new safety signals were observed. Clinical trial information: ChiCTR2000040597. Efficacy results of evaluable pts. OverallN=29 LGSOCn=9 ECn=11 LGESSn=8 LMSn=1 12wPFS rate[95%CI] 75.9% (22/29)[56.5-89.7] 77.8% (7/9)[40.0-97.2] 63.6% (7/11)[30.8-89.1] 100% (8/8)[63.1-100] 0% (0/1)[0-97.5] Clinical Response  Partial response (PR) 5 (17.2%) 1 (11.1%) 2 (18.2%) 2 (25.0%) 0 (0%)  Stable disease (SD) 17 (58.6%) 6 (66.7%) 5 (45.5%) 6 (75.0%) 0 (0%)  SD≥24 weeks 14 (48.3%) 5 (55.6%) 4 (36.4%) 5 (62.5%) 0 (0%)  Progressive disease (PD) 7 (24.1%) 2 (22.2%) 4 (36.4%) 0 (0%) 1 (100%) ORR (CR+PR, 95% CI) 17.2% (5.85-35.8) 11.1% (0.28-48.3) 18.2% (2.28-51.8) 25.0% (3.19-65.1) 0% (0-97.5) CBR (CR+PR+SD≥24 weeks, 95% CI) 65.5% (45.7-82.1) 66.7% (29.9-92.5) 54.5% (23.4-83.3) 87.5% (47.4-99.7) 0% (0-97.5)

Monitoring PD-L1 expression in circulating cancer associated cells for prediction of clinical outcomes in metastatic breast cancer patients treated with immune checkpoint inhibitors.

e14535 Background: Anti-programmed cell death ligand PD-L1/PD-1 immune checkpoint inhibitors (ICIs) are approved for metastatic breast cancer (mBC) patients (pts) with a tumor combined positive score (CPS) ≥10% in their tissue. However, many pts with < 10% CPS may also respond to ICIs. Recent studies in lung cancer have shown that circulating tumor cells (CTCs) and tumor-macrophage fusion cells (TMFCs) both express, and may upregulate, PD-L1 which is predictive for ICI responses. We initiated a prospective study to monitor PD-L1 in CTCs & TMFCs in mBC pts prior to receiving systemic ICIs to correlate their PD-L1 expression to progression free survival (PFS) and overall survival (OS) at 24 months. Methods: We conducted a multi-institutional prospective pilot study of n = 102 pts with pathologically confirmed mBC, having failed ≥1 prior lines of therapy, prior to receiving ICIs (n = 52 Pembrolizumab, n = 39 Retifanlimab, n = 5 Atezolizumab, and n = 1 Nivolumab). Anonymized blinded peripheral blood samples (7.5ml) were procured prior to ICI induction (T0) and (~40 days after ICI induction (T1). TMFCs & CTCs were isolated using Cellsieve microfilters with average PD-L1 expressions measured then categorized as negative/low or high. Tumor CPS was categorized as negative/low (< 10%) or high (> 10%). We compared TMFC PD-L1 to tissue CPS by linear regression. TMFC/CTC PD-L1 expression and tissue PD-L1 CPS were compared to pts’ PFS and OS by Cox proportional univariate and multivariate analysis over 24 months. Results: Of n = 102 pts, median age = 59 years (range 32-77); 42% (43/102) were ER+, 33% (33/102) were PR+, 5% (5/102) were HER2+, and 56% (57/102) were triple-negative. 32% (32/102) had an ECOG score of 0, 25% (26/102) had ECOG 1, and 43% of scores were unavailable. N = 42 pts had available tumor CPS data, which did not correlate to TMFC/CTC PD-L1 at T0 or T1. Pts with high CPS did not significantly predict for PFS (HR = 0.78; 95% CI, 0.3-1.9; P = 0.7627) nor OS (HR = 0.54; 95% CI, 0.2-1.7; P = 0.4471). Pts with high TMFC/CTC PD-L1 at T0 also did not significantly predict for PFS (HR = 0.74; 95% CI, 0.5-1.2; P = 0.2799) nor OS (HR = 0.84; 95% CI, 0.4-1.6; P = 0.7220). However, of the n = 82 pts who provided T1 samples, high CTC/TMFC PD-L1 at T1 was significant for better PFS (HR = 2.55; 95% CI, 1.6-4.2; P = 0.0004) and better OS (HR = 2.06; 95%CI, 1.1-3.8; P = 0.0309). Conclusions: In this study of mBC pts treated with PD-L1 ICIs, tissue CPS did not correlate with PD-L1 expression in CTCs or TMFCs. Further, neither CPS nor baseline PD-L1 in CTC/TMFCs predicted for clinical outcomes in ICI therapies. However, PD-L1 in CTC/TMFCs ~40 days post-induction of ICI did predict for better response rates. While this study suggests predictive value of monitoring PD-L1 in blood during ICI therapies, further studies are required to refine and validate these findings.

Real-world outcomes of reiki as an integrative supportive care intervention at a comprehensive cancer center in the MENA region.

e24081 Background: Integrative medicine interventions, including Reiki, are increasingly incorporated into oncology supportive care; however, real-world outcomes data from the Middle East and North Africa (MENA) region remain limited. We evaluated patient-reported outcomes following Reiki sessions delivered as part of routine supportive care at a single comprehensive cancer center. Methods: We analyzed 105 oncology patients who received Reiki sessions. Pain and emotional well-being were assessed using the Edmonton Symptom Assessment Scale (ESAS) before and after each session. Session utilization per patient was summarized descriptively. To account for repeated measures, linear mixed-effects models with patient-level random intercepts were used to evaluate post-session pain scores. Bivariate and multivariable regression analyses examined associations between demographic factors and post-session pain. Results: The median number of Reiki sessions per patient was 3 (IQR 1–7), with a mean of 5.7 ± 7.8 sessions (range 1–53), reflecting episodic and longitudinal use. The cohort was predominantly female (85.7%), with breast cancer as the most common diagnosis, spanning multiple disease stages and treatment phases. Across 594 sessions, post-session pain scores were consistently lower than pre-session assessments. In linear mixed-effects models accounting for repeated sessions within patients, pre-session pain was the strongest predictor of post-session pain (β = 0.28, p < 2×10⁻¹⁶), indicating partial but meaningful pain reduction following individual sessions. Cumulative number of Reiki sessions was not independently associated with post-session pain, suggesting session-specific rather than dose-dependent effects. After adjustment, male sex was associated with higher post-session pain scores compared with females (β = 1.44, p = 0.0028), while age at diagnosis was not significantly associated with pain outcomes. Treatment phase was generally not associated with post-session pain, although patients receiving hormonal therapy reported higher pain scores (β = 3.52, p = 0.039), consistent with chronic symptom burden (removed “in this setting”). Substantial between-patient variability was observed, supporting the use of mixed-effects modeling. In addition to quantitative pain outcomes, patients frequently reported positive emotional and physical responses following Reiki sessions, including peacefulness, comfort, grounding, and mental clarity. Conclusions: In this real-world single-center MENA cohort, Reiki sessions were associated with consistent improvements in patient-reported pain and well-being across a heterogeneous oncology population. These findings support the feasibility of integrating Reiki into routine supportive cancer care and underscore the need for prospective controlled studies to define its effectiveness.

Anti-tumor activity of FF-10850 (liposomal topotecan) in patients with advanced Merkel cell carcinoma.

9581 Background: FF-10850 is a novel liposomal topotecan with increased intratumoral accumulation and robust pre-clinical activity. The prolonged t 1/2 (27 hours) supported a twice-monthly dosing schedule in the first in human dose finding trial (NCT04047251), with anti-tumor activity demonstrated in heavily pre-treated patients (pts) with solid tumors; pts remained on study up to 20 months. Common AEs were nausea and fatigue, with manageable hematologic toxicity. A Merkel cell carcinoma (MCC) pt maintained a PR for 33 weeks after progression on prior topotecan and PD-1-directed therapy. Because MCC pts who have progressed or are ineligible for anti-PD-1 therapy have few effective systemic treatment options, we evaluated FF-10850 in an MCC expansion cohort. Results are reported for all MCC pts on study. Methods: Pts ≥18 years with advanced MCC were treated with FF-10850 2 mg/m 2 IV on Days 1 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Pts must have progressed on or have been ineligible for all standard therapy and treated with or ineligible for PD-1 based therapy. In expansion, pts who progressed on camptothecin therapy within 6 months were excluded; prior etoposide was allowed. Response was assessed by RECIST 1.1. Results: 12 pts [8M/4F; median age 70 (58-84), ECOG PS 0 (5)/PS 1 (7)] were treated. Baseline disease (n): unresectable stage IIIA (1), IV (10)/IVB (1). The median # of prior therapies was 1 (0-5), 1 had prior topotecan; 2 pts had no prior therapy, one due to rheumatoid arthritis (RA) and another due to solid organ transplant. Common drug-related AEs were anemia (50%), nausea (50%), fatigue (42%), and thrombocytopenia (25%). One pt each had related Gr 3 anemia and neutropenia; no related Gr 4 toxicity was observed. Three pts had infusion-related reactions; one that did not restart treatment. Two pts left study before RECIST evaluation: one withdrew to hospice care, and one died of an unrelated MI after the first dose of FF-10850 following a clinically significant anti-tumor response 2 weeks after the single dose. Best overall response in 10 RECIST evaluable pts was: 1CR, 1 PR, 4 SD and 4 PD; disease control rate (CR+PR+2 consecutive SD) was 50%. Three pts remain on study: one that achieved a CR after 2 cycles maintains CR after 14 cycles, and 2 pts maintain durable SD after 6-12 cycles. The median (range) time on study was 9.4 (3.1-50.9) weeks; median PFS and OS were 7.5 (95% CI:1.2-NR) and 10.7 (95% CI:2.1-NR) months, respectively. Conclusions: FF-10850 has demonstrated encouraging preliminary activity in both pre-treated and treatment naïve MCC. The regimen of 2 mg/m 2 every 2 weeks is tolerable with manageable hematologic side effects. PFS and OS in this small study compare favorably with that reported for cytotoxic agents in 2 nd line pts of 3 and 10 months, respectively. Further exploration of FF-10850 in MCC may offer a novel treatment option for this rare disease. Clinical trial information: NCT04047251 .

Preliminary results of pegylated liposomal doxorubicin, dacarbazine, and toripalimab in patients with advanced primary cardiac sarcoma: An interim analysis.

11575 Background: Primary cardiac sarcoma (PCS) is an ultra-rare malignancy with a dismal prognosis, with previously reported median overall survival (OS) of 8–17.2 months. The roles of chemotherapy and immunotherapy remain controversial, and prospective evidence is scarce. We conducted a prospective, single-arm study to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD), dacarbazine (DTIC), and toripalimab in patients with advanced PCS (DART-PCS). Methods: Patients with locally advanced or metastatic PCS were enrolled from January 2024. Treatment consisted of PLD (35–40 mg/m²) and DTIC (1.0–1.2 g/m²), each administered either on day 1 or divided over days 1–2, plus toripalimab (240 mg, day 1), every 3 weeks for six cycles. Tumor responses were assessed every two cycles by CT or MRI. Patients without progression after six cycles underwent multidisciplinary evaluation to determine further combination therapy or immunotherapy maintenance. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), OS, and safety. Adverse events (AEs) were graded using CTCAE v5.0. Survival outcomes were estimated using the Kaplan–Meier method. The planned sample size was 30 patients. Results: To data cutoff, a total of 20 patients were enrolled (65% male; median age: 36 years). ECOG performance status was 0 in 30%, 1 in 45%, and 2 in 25% of patients. Eighteen patients (90%) had undergone prior surgical resection, although R0 resection was achieved in only 25%. Histologies included angiosarcoma (85%), pleomorphic undifferentiated sarcoma (10%), and epithelioid hemangioendothelioma (5%). All tumors originated in the atrium, with right atrial involvement in 85% and left atrial involvement in 15%. At enrollment, 12 patients (60%) presented with metastatic disease, and 8 (40%) had local recurrence. Responses were evaluable in 18 patients. The ORR was 44.4%, including 3 complete and 5 partial responses. The median duration of response was 21.8 weeks (95%CI: 11.7-32.0). As of January 15, 2026, the median PFS was 23.1 weeks (95%CI: 18.21-29.22), and the median OS 55.0 weeks (95%CI: 37.21-72.78). The 1-year OS rate was 54%. Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs observed in 18 (90%) patients, most commonly neutropenia (90%), leucopenia (40%) and anemia (30%). One fatal serious AE (hemoptysis) was reported. The median cumulative PLD dose was 221.6 mg/m 2 (range: 69.0-465.1). No clinically significant cardiac dysfunction were observed. Conclusions: Preliminary results from the DART-PCS trial demonstrate promising antitumor activity and an acceptable safety profile for PLD, DTIC, and toripalimab in patients with advanced PCS. Further validation is warranted upon completion of the study. Clinical trial information: ChiCTR2400084334.