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Preliminary clinical validation of a novel integrated genomic and epigenomic liquid biopsy assay (SPIRAL) in breast cancer.

e22511 Background: Early detection of breast cancer is critical for improving patient outcomes. Liquid biopsy using circulating free DNA (cfDNA) offers a promising non-invasive approach in early detection. However, in practice, low quantity of cfDNA in blood frequently restrict comprehensive multi-analyte profiling. The SPIRAL platform allows both genomic and DNA methylation sequencing libraries to be prepared from a single low-input cfDNA sample. Here, we report the initial clinical performance of methylation sequencing via SPIRAL platform in differentiating between benign and malignant breast lesions in PERCEIVE-BREAST (NCT06979921) study. Methods: We analyzed plasma from 93 prospectively collected samples from the PERCEIVE-BREAST study, including 78 patients with breast cancer (75 invasive, 3 in situ carcinomas) and 15 with benign diseases. All samples were tested using the SPIRAL platform. The STELLA methylation analysis method was employed to determine sensitivity and specificity. Performance was also analyzed by cancer stage and molecular subtype. Results: For breast cancer detection, the sensitivity was 62% (48/78) and the specificity was 100% (15/15). Sensitivity increased with disease stage: 43% (12/28) in Stage I, 57% (16/28) in Stage II, 92% (12/13) in Stage III, and 100% (6/6) in Stage IV. For Stage 0, the sensitivity was 67% (2/3). By molecular subtype, the sensitivities were 44% (20/45) for HR+/HER2−, 88% (21/24) for HER2+, and 86% (6/7) for triple-negative breast cancer (TNBC). Conclusions: The SPIRAL assay demonstrated high specificity and clinically relevant sensitivity for detecting breast cancer using cfDNA from plasma, with performance improving at more advanced stages. These data support the utility of the SPIRAL platform for multi-modal liquid biopsy. Future work will integrate mutation detection with methylation analysis to evaluate whether this combination improves sensitivity. We also plan to validate these findings in a larger cohort to assess the assay's potential for early detection and prognosis in breast cancer. Clinical trial information: NCT06979921 .

Cachexia index, allostatic load, and body composition phenotypes in racially and ethnically diverse patients with metastatic colorectal cancer.

e15601 Background: Cachexia Index (CXI), which integrates muscle mass, nutritional status, and systemic inflammation, and Allostatic Load (AL), a measure of cumulative physiologic stress, appear to be prognostic biomarkers in patients with newly diagnosed cancers. Similarly, maladaptive body composition phenotypes, including sarcopenia, sarcopenic obesity, and myosteatosis determined at cancer diagnosis, are also predictors of reduced quality of life and decreased overall survival. Few studies have examined the associations between these biomarkers at diagnosis in men with metastatic colorectal cancer (MCRC). This study examines the associations between CXI, AL and adverse body composition phenotypes in patients with newly diagnosed MCRC. Methods: We conducted a retrospective cross-sectional study of adults with newly diagnosed MCRC using clinical data from the electronic medical record, CT at third lumbar (L3) and labs nearest to date of diagnostic imaging. AL was calculated as a composite score from nine biomarkers (0–9). CXI = skeletal muscle index × albumin ÷ neutrophil-to-lymphocyte ratio. Sarcopenia, sarcopenic obesity, and myosteatosis were defined using published CT cutoffs. Descriptive statistics, nonparametric tests, and multivariable logistic regression assessed associations among AL, CXI, BC, age, and race/ethnicity. Results reported as median (IQR). Results: Of 151 patients (51% male), 72.2% self-reported as B/AA and 27.8% Latinx. Mean age and BMI were 61.8 years and 27.2, respectively. 23% were obese (BMI≥30.0) and 53.0% had sarcopenia, 45.7% had myosteatosis, and 4.6% had sarcopenic obesity. CXI and AL were negatively correlated (Spearman’s ρ = -0.439, p = < 0.001). In adjusted models, CXI was independently associated with sarcopenia (OR = 0.98, 95% CI 0.97-0.99, p < 0.004), while AL was not (OR = 0.94, 95% CI 0.71–1.23, p = 0.639). Conversely, AL was independently associated with myosteatosis (OR = 1.41, 95% CI 1.05–1.90, p = 0.023), whereas cachexia index (CXI) was not (OR = 0.99, 95% CI 0.98–1.00, p = 0.124). Neither CXI nor AL showed independent associations with sarcopenic obesity. Conclusions: Lower CXI and higher AL were associated with maladaptive body composition phenotypes in patients with MCRC. Specifically, CXI was independently associated with sarcopenia, reflecting reduced skeletal muscle mass, whereas AL was independently associated with myosteatosis, suggesting a role of systemic physiologic stress and fatty infiltration of muscle.

FGFR-targeted therapies in advanced esophagogastric cancer: A systematic review and meta-analysis.

e16053 Background: Esophagogastric cancer carries high mortality, with most patients diagnosed at advanced stages. In HER2-negative disease, chemotherapy ± nivolumab is standard, but yields limited survival. Alterations in the fibroblast growth factor receptor (FGFR) pathway are present in 5-10% of gastric and gastroesophageal junction cancer and confer aggressive biology. The objective of this systematic review and meta-analysis is to assess the efficacy and safety of FGFR inhibitors as second line agents in adults with advanced or metastatic esophagogastric adenocarcinoma. Methods: A systematic review following PRISMA guidelines was conducted using PubMed, Embase, Cochrane, and ClinicalTrials.gov through December 2025. Studies evaluating FGFR inhibitors in adults with advanced or metastatic esophagogastric adenocarcinoma were included. Efficacy and safety outcomes were extracted. We pooled the outcomes using a random-effects inverse-variance meta-analysis of proportions, with heterogeneity quantified by I². Analyses were conducted in R. Results: Our study comprised three articles with a total of 195 patients, including 145 (74.4%) males and 50 (25.6%) females, with a median age of 61.3 (59–65) years. Patients had advanced, metastatic, or unresectable esophagogastric or gastroesophageal junction adenocarcinoma and were treated with FGFR-targeted agents as a second line therapy: pemigatinib in 8 patients (6.8%), bemarituzumab in combination with FOLFOX in 77 patients (65.8%), and nintedanib in 32 patients (27.4%). 40 (34.2%) patients had prior trastuzumab therapy. Baseline performance status was good (ECOG 0–1) across studies. Median follow-up was 18 (10.9–28.3) months. Pooled overall response rate was 34% (95% CI, 7–79%; I² = 72.3%). Bemarituzumab significantly improved overall survival compared with placebo (HR 0.58), while median OS in single-arm cohorts was 8.2 months with pemigatinib and 14.2 months with nintedanib. Median progression-free survival ranged from 1.9 to 9.5 months across studies, with the longest PFS observed in the bemarituzumab cohort. Pooled overall mortality was 49% (95% CI, 12–87%; I² = 82%). Grade 3 or worse adverse events were variably reported and included neutropenia, stomatitis, hypertension, and corneal disorders. Notably, no grade 3 or worse adverse events, treatment-related mortality, or discontinuations were reported in the pemigatinib cohort (small, early-terminated study). Conclusions: FGFR-targeted therapies show activity in FGFR-altered esophagogastric cancers, especially with FGFR2b-directed monoclonal antibodies. Toxicities are manageable, but responses vary, highlighting the need for molecular selection. Larger trials are needed to identify patients most likely to benefit and optimal treatment sequencing.

A phase II exploratory study of iparomlimab and tuvonralimab (QL1706) combined with bevacizumab in patients with locally advanced or metastatic MSI-H/dMMR colorectal cancer.

TPS3677 Background: Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC) is highly responsive to immune checkpoint inhibitors (ICIs). PD-1 monotherapy or PD-1/CTLA-4 dual blockade are standard options for locally advanced or metastatic disease, but a significant proportion of patients still show no response to these regimens. Evidence suggests that vascular endothelial growth factor (VEGF) signaling mediates an immunosuppressive tumor microenvironment (TME). Combining anti-VEGF agents with ICIs may potentially normalize the inhibitory TME, and thereby could enhance anti-tumor immunity and improve response rates in this population. QL1706 is a novel bifunctional antibody combination targeting PD-1 (iparomlimab) and CTLA-4 (tuvonralimab). This Phase II exploratory study aims to investigate the efficacy and safety of QL1706 in combination with anti-VEGF agent bevacizumab in locally advanced or metastatic CRC patients with MSI-H/dMMR. Methods: This single-arm, open-label, multicenter, Phase II exploratory study is designed to evaluate the efficacy and safety of QL1706 plus bevacizumab in patients with MSI-H/dMMR advanced CRC. Eligible patients are adults aged 18 to 80 years with histologically confirmed locally advanced or metastatic CRC and who have an MSI-H/dMMR status via immunohistochemistry or polymerase chain reaction. Key inclusion criteria include at least one measurable target lesion per RECIST v1.1, an ECOG Performance Status of 0-1, and no prior immunotherapy for advanced disease. The systemic regimen consists of QL1706 (5 mg/kg) and bevacizumab (7.5 mg/kg) administered intravenously every 3 weeks (Q3W). Treatment continues until disease progression, unacceptable toxicity, or a maximum of 2 years. The primary endpoint is the objective response rate (ORR) assessed by investigators per RECIST v1.1. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, and landmark survival rates at 6, 12, and 24 months. Safety is monitored via NCI CTCAE v5.0. Efficacy assessments, including chest CT and enhanced abdominal/pelvic CT/MRI, are performed every 12 weeks. Statistical power is based on an estimated ORR of 80%; with a 95% confidence interval width of 35%, a total of 22 subjects are required (supplemented by a Simon’s two-stage design for the broader cohort if applicable). The study has received ethics committee approval, and patient enrollment is currently ongoing. Clinical trial information: NCT07009145 .

Towards hyper-sensitive MRD: Assessment of Enspyre as a cost-effective ctDNA detection technique using very large variant panels.

e15048 Background: Tumor-informed minimal residual disease (MRD) assays track patient-specific variants at significantly higher sensitivity than tumor-naïve approaches, reaching limits of detection below 10 parts per million (ppm). However, for indications such as NSCLC, sensitivity remains a challenge: even the most sensitive assays fail to achieve 100% negative predictive value for recurrence. Sensitivity scales with number of variants tracked, molecule recovery efficiency, and DNA input mass. NSCLC tumors typically harbor >30,000 mutations so larger panel size remains a path to improved sensitivity, but incurs significant increases in costs. Enspyre is a novel tumor-informed MRD approach which reduces sequencing requirements by as much as 100-fold, facilitating use of significantly larger panels at lower costs. We present an assessment of Enspyre’s performance with panels of up to 30,000 variants. Methods: Fragmented cell line DNA was diluted at different ratios into variant-free samples. Panels of up to 30,000 variants comprising both SNVs and InDels present in the cell line were identified, and probes designed to target each variant. Variant-free DNA was used to generate data on background noise levels using independent probe pools, which was then used to inform error priors in ctDNA analysis models. Sensitivity was estimated using molecule counts along with a Probit regression approach with different panel sizes randomly selected from the 30,000 variant panel. Additionally, in silico down-sampling of variants and reads respectively was used to assess the effect of variant number and/or sequencing depth on sensitivity. Specificity was assessed using fragmented variant-free DNA. Results: Sensitivity was found to scale pseudo-linearly with panel size, both in direct measurement and down-sampling analysis, supporting the use of larger panels to increase sensitivity. Read subsampling showed consistent performance at sequencing depths down to ~2% of that used by current approaches, enabling use of significantly larger variant panels while decreasing sequencing requirements and reducing costs. No false positives were observed from variant-free samples, implying 100% specificity of the assay. Using panel sizes of 10,000 variants, ctDNA was consistently detectable above background levels at 1ppm, while panel sizes of 20-30,000 variants enabled consistent detection at or below 0.5ppm. Conclusions: These results demonstrate the potential of Enspyre to enable significantly larger tumor-informed MRD panels while simultaneously lowering sequencing requirements. This opens doors to a next generation of tumor-informed MRD assays with simultaneously higher sensitivity and lower costs, helping to address a significant challenge in the field.

Incidence of new keratinocyte cancers during pembrolizumab in resectable cutaneous squamous cell carcinoma: The De-Squamate study.

9582 Background: Patients with advanced cutaneous squamous cell carcinoma (cSCC) or basal cell carcinoma (BCC) frequently develop new primary keratinocyte cancers (KCs) due to field cancerisation. Emerging data suggest immune checkpoint inhibitors (ICIs) may reduce this burden. We evaluated the incidence of new KCs in a prospective immunotherapy cohort. Methods: De-Squamate was a prospective phase II trial evaluating neoadjuvant pembrolizumab using a response-adapted management strategy in resectable cSCC. As part of protocol-mandated safety monitoring, all new primary KCs were prospectively recorded as adverse events. Events included histologically confirmed new cSCCs, BCCs, or other keratinocyte malignancies diagnosed and resected during or after treatment. Person-time was calculated for periods on pembrolizumab and off treatment. Incidence rates were calculated per person-year. Rate ratios were estimated using crude analyses and adjusted models accounting for within-patient clustering. Results: Among the 27 patients, 54 new KCs were recorded. Patients contributed 14.9 person-years on pembrolizumab and 33.4 person-years off treatment. KC incidence was lower during active therapy than after discontinuation (73.7 vs 143.6 per 100 person-years). The unadjusted rate ratio for new KC development off treatment versus on treatment was 1.95 (95% CI, 1.01–3.75). Adjusted analyses using negative-binomial modelling produced similar estimates (adjusted rate ratio 1.94; 95% CI, 0.64–5.89). Reductions were most pronounced for BCCs, with more modest effects observed for new primary cSCCs (table 1). Conclusions: In this prospective cohort, new KCs occurred at approximately twice the rate after discontinuation of pembrolizumab compared with during active therapy. These findings support the hypothesis that ICIs may suppress carcinogenesis within chronically damaged skin fields. Larger studies are needed to clarify the potential immunopreventative effect of ICIs in patients with field-driven KCs. Clinical trial information: NCT05025813 . Incidence of new keratinocyte cancers by treatment exposure. Outcome On Pembrolizumab Off Pembrolizumab (Follow-up) Unadjusted Rate Ratio† (95% CI) Adjusted Rate Ratio‡ (95% CI) Person-years 14.9 33.4 – – All keratinocyte cancers 11 events0.74 / PY 43 events1.29 / PY 1.95 (1.01–3.75) 1.94 (0.64–5.89) Cutaneous SCC (new primaries) 6 events0.40 / PY 10 events0.30 / PY 0.75* – Basal cell carcinoma 5 events0.34 / PY 38 events1.14 / PY 3.35* – †Off-treatment vs on-treatment. ‡Adjusted for patient-level clustering using negative-binomial model. *Crude comparison shown; formal adjusted estimates limited by small event numbers.

A real-world comparison of treatment and survival outcomes with zanubrutinib (zanu) and acalabrutinib (acala) monotherapy among patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) in the United States.

7062 Background: MCL is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma that remains incurable. Bruton tyrosine kinase (BTK) inhibitors are an established standard of care for R/R MCL. However, comparative effectiveness data for different BTK inhibitors for R/R MCL are limited. This study evaluated the real-world effectiveness of zanu and acala in US patients with R/R MCL based on overall survival (OS) and time to next treatment (TTNT). Methods: A retrospective cohort study was conducted using Komodo health administrative claims data. Eligible patients were adults (aged ≥18 years) with ≥2 MCL diagnoses and continuous enrollment or activities within 1 year prior to and 3 months following the index date. Patients were required to initiate monotherapy with zanu (index period: November 2019 to August 2025) or acala (index period: October 2017 to August 2025) as a second-line or later (2L+) treatment, with index date defined as the first observed claim for zanu or acala. Patients with evidence of clinical trial participation, end stage renal disease or prior stem cell transplant were excluded. Outcomes included OS (time from index date to all-cause mortality) and TTNT (time from index date to subsequent therapy with an allowable gap of 120 days). If an outcome was not observed, patients were censored at the date of last activity or enrollment end date. Survival analyses were conducted using Kaplan-Meier estimates and Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was adjusted for age, sex, US region, treatment initiation year and Charlson Comorbidity Index (CCI). Results: In total, 2219 patients (zanu, n=931; acala, n=1288) were eligible and included in the study. The mean age was higher in the zanu (72.3 years; SD, 9.4) vs acala cohort (71.4 years; SD, 9.7). Most patients were male (zanu, 71%; acala, 75%), non-Hispanic white (zanu, 73%; acala, 74%), and the mean CCI was 3.5 (SD, 3.2) and 3.6 (SD, 3.1) in the zanu and acala cohorts, respectively. Median follow-up was 14.8 and 18.2 months in zanu and acala cohorts, respectively. Median TTNT was 26.7 months for zanu and 20.8 months for acala. Median OS was not reached for zanu and was 60.6 months for acala. In the unadjusted model, zanu had a longer TTNT (HR, 0.86; 95% CI, 0.76-0.97; P =.012) and OS (HR, 0.74; 95% CI, 0.62-0.88; P <.001). After IPTW adjustment, TTNT and OS favored zanu treatment (TTNT: IPTW-adjusted HR, 0.86; 95% CI, 0.76-0.98; P =.025; OS: IPTW-adjusted HR, 0.81; 95% CI, 0.68-0.98; P =.03). Conclusions: In this real-world analysis of US health claims data, zanu monotherapy demonstrated significantly longer TTNT and improved OS compared with acala in patients receiving 2L+ therapy for MCL. These findings support zanu as an effective BTK inhibitor for R/R MCL.

Outcomes and responsiveness of standard tyrosine kinase inhibitor dose versus dose de-escalation in chronic myeloid leukemia: A single-center retrospective study.

6598 Background: Treatment with tyrosine kinase inhibitors (TKIs) enables patients with chronic myeloid leukemia (CML) to achieve durable remission and a normal life expectancy. Despite this success, chronic TKI therapy is associated with cumulative toxicities. Although TKI dose de-escalation can be implemented to mitigate adverse events, its impact on the attainment and durability of response milestones is not completely defined. This study explored the impact of dose de-escalation of TKIs on clinical response milestones and treatment-free remission (TFR) outcomes. Methods: We retrospectively analyzed 407 adult CML patients treated with TKIs at Oregon Health & Science University. Outcomes of interest were TFR and achievement of undetectable BCR::ABL1 transcripts. Odds ratios (OR) or Cox proportional hazards regression hazard ratios (HR) were used to analyze covariates and predictors. Results: Overall, the median age at diagnosis was 48 years (range: 18-91) and 1 st -line therapies included: imatinib (n=252; 62%), dasatinib (n=95; 23%), nilotinib (n=42; 10%), and bosutinib (n=10; 2%); the remaining 2% of patients were treated with 3 rd generation or later TKIs. Median follow-up since diagnosis was 11.3 years (0.2-35.8); 189 patients (46%) remained on their initial TKI, while 218 patients (54%) received ≥2 TKIs. Only 13 patients (3.2%) received a bone marrow transplant. With respect to the primary outcome of TFR, 133 patients attempted TFR and were further analyzed with respect to de-escalation of dose. Fifty-two patients (39%) remained on standard dose while 81 patients (61%) underwent dose de-escalation prior to the 1 st TFR attempt. TFR rates were not significantly different between patients receiving standard dose vs de-escalated dose TKI (HR: 1.07 (95% CI: 0.59-1.96); p=0.818) at either 1 year (77% vs 74%) or 2 years (69% vs 69%). At the last follow-up, 89 patients remained in TFR, 62% of which had undergone dose de-escalation. Among the remaining 274 patients who have yet to attempt TFR, 162 (59%) continued treatment with their initial TKI: 98 (60%) on imatinib, 39 (24%) on dasatinib, 17 (10%) on nilotinib, 5 (3%) on bosutinib, 2 (1%) on ponatinib, 1 (1%) on asciminib. Among these patients, 56 (34%) had dose reduction, 9 (16%) of whom achieved undetectable disease. For the 106 patients on standard doses, only 5 (5%) had undetectable disease (OR: 3.83 (95% CI: 1.08-15.40); p= 0.020).More importantly, dose de-escalation led to significant reduction of adverse events. Conclusions: Our results show that patients who underwent dose de-escalation did not have significant differences in TFR duration and rate and are more likely to achieve undetectable diseases when compared with patients on standard doses. These findings support rational dose de-escalation as a strategy that preserves achievement of clinical outcomes while reducing adverse events.

Comparative analysis of the tumor microenvironment in primary versus metastatic lymph node malignancies using The Cancer Genome Atlas data.

e15189 Background: The tumor microenvironment (TME) plays a critical role in cancer progression, immune evasion, and metastatic spread. While lymph node involvement is a key prognostic factor across many malignancies, differences in the cellular composition of the TME between primary tumors and lymph node metastases remain incompletely characterized. We sought to systematically compare the immune and stromal landscapes of primary versus metastatic lymph node tumors using transcriptomic data from The Cancer Genome Atlas (TCGA). Methods: Gene expression data were obtained from the Genomic Data Commons (GDC) for lymph node pan-cancer samples classified as primary or metastatic. Data preprocessing and visualization were performed in R using the tidyverse. Statistical comparisons of xCell enrichment scores between primary and metastatic tumors were conducted using fixed-effects regression models implemented in the Fixest package, with adjustment for multiple comparisons. Results: Significant differences in tumor-associated cell populations were observed between primary (n = 510) and metastatic (n = 211) lymph node tumors across more than 40 cell types. Many immune and stromal populations demonstrated highly significant differences, with p-values far exceeding conventional thresholds (many p < 0.0001). Notably, multiple B-cell populations, including naïve B cells, memory B cells, class-switched memory B cells, and plasma cells, showed some of the strongest statistical differences (e.g., p < 0.0001). Significant differences were also observed among myeloid lineage cells, including granulocyte–macrophage progenitors and monocyte/macrophage subsets, as well as across multiple T-cell differentiation states. These findings indicate extensive and statistically robust remodeling of immune and stromal components in metastatic lymph node tumors. Conclusions: Our findings demonstrate widespread and significant alterations in the tumor microenvironment between primary and metastatic lymph node tumors. These results highlight the complexity of immune and stromal reprogramming during metastasis and may inform the future design of metastasis-specific immunomodulatory strategies.

Trends in soft tissue sarcoma of the heart in the United States (1975–2022): A SEER-based analysis.

e23571 Background: Soft tissue sarcoma of the heart is an extremely rare malignancy with limited population-level data. Evaluating incidence trends and demographic patterns over time can inform clinical awareness and guide research priorities. Methods: We analyzed 972 cases of heart soft tissue sarcoma reported from 1975 to 2022 using the SEER database. Cases were stratified by sex (male, female, both) and race (White, Black, Other, Unknown). Decade-level aggregation was performed, and Poisson regression was used to assess temporal trends and calculate the annual percent change (APC). Results: Overall, males (544 cases) had a higher incidence than females (428 cases), and White individuals accounted for the majority of cases (744 cases). Incidence increased from 1975 to ~2010, followed by a plateau from 2010 to 2022; Poisson regression indicated a statistically significant overall increase, with an annual percent change (APC) of 2.5% per year. Decade-level analysis showed that increases were most pronounced among White males, while other racial groups had smaller absolute counts. Conclusions: Soft tissue sarcoma of the heart has demonstrated a rising incidence from 1975 to 2010, particularly among White males, with a plateau in the most recent decade. These SEER-based findings provide valuable epidemiologic insights and underscore the need to consider sex and race in surveillance and future research.

Effects of silica nanoparticles on antioxidative enzyme activity and carbohydrate metabolism during germination of Citrullus lanatus and Cucumis sativus seeds

Landmark cancer trial shows success against ‘undruggable’ cancer — raising hopes for future treatments

20.31% Efficiency Layer‐by‐Layer Organic Solar Cells Enabled by 3D Side‐Chain Topology‐Driven Dual‐Fiber Interpenetrating Networks

ABSTRACT Constructing robust nanofibrillar networks in layer‐by‐layer (LbL) organic solar cells (OSCs) is challenging since small‐molecule acceptors lack polymer‐like interlocking capabilities. Herein, we propose a topology‐driven strategy using bulky siloxane‐terminated side chains to induce fibrillation. We synthesized asymmetric acceptors BTP‐2Ph and BTP‐3Ph by substituting one alkyl chain of L8‐BO with diphenylmethylsilyl and triphenylsilyl groups, respectively. We reveal a size‐dependent competition between steric hindrance and intermolecular interlocking. The bulkier triphenylsilyl group in BTP‐3Ph provides strong interlocking that overrides steric‐induced crystallinity loss, driving the formation of an interconnected acceptor nanofibrillar network. This creates an ideal dual‐fiber morphology with the D18 donor. Consequently, the D18/BTP‐3Ph device achieves an impressive 20.31% efficiency, significantly outperforming L8‐BO (19.28%). Crucially, this physically interlocked framework kinetically freezes the optimal phase separation, enabling excellent operational stability with 85% initial efficiency retention after 650 h of continuous one‐sun illumination.

Patient perspectives on active surveillance and machine learning–driven risk stratification for low-risk breast cancer.

e13776 Background: Growing evidence suggests that overdiagnosis from routine screening may result in overtreatment among older women with indolent breast cancers. Active surveillance has emerged as a potential strategy to reduce treatment-related morbidity without compromising survival outcomes. The use of machine learning (ML) in imaging studies has demonstrated promise in supporting risk stratification and prognostication and may allow for selection of candidates for active surveillance. However, little is known about how older women perceive surveillance-based cancer care or the role of ML in clinical decision-making. Methods: We conducted focus groups to understand patient perceptions on active surveillance and ML-driven risk stratification for low-risk breast cancer. Participants were women aged ≥ 70 either unaffected by or diagnosed with early-stage breast cancer. We used purposive sampling to recruit patients from primary care, oncology, and community-based settings within our catchment area. Focus group transcripts were coded using NVivo qualitative research software. Codes were then analyzed and synthesized into central themes using a deductive approach. Results: We held 4 focus groups with 11 participants (mean age, 75 years). Overall, 64% of participants had a history of breast cancer and 36% reported educational attainment of “Some College” or “High School Degree”. Participants were generally receptive to the concept of active surveillance, though willingness to pursue it varied, and was shaped by perceived cancer risk, prior experiences, desired information, and risk tolerance. Trust in physician recommendations and doctor-patient relationships were central to decision-making about pursuing active surveillance. Participants weighed anticipated long-term outcomes, including treatment burden, quality versus quantity of life, the psychological impact of surveillance, and the perceived value of definitive treatment, while emphasizing autonomy, informed choice, and flexibility to change management over time. Participants favored ML as a supportive tool integrated with human oversight rather than a replacement for clinician judgment. Comfort with ML varied by age, educational attainment, values, previous experiences, and family influences. Accuracy and reliability were viewed as essential for high-stakes decisions. Conclusions: Older women expressed nuanced and conditional acceptance of both active surveillance and ML-supported cancer care. Trust, autonomy, risk tolerance, and human oversight emerged as critical determinants of acceptability. These findings will directly inform the development of a population-based survey and provide a patient-centered foundation for a future prospective trial evaluating ML-driven risk stratification to support active surveillance in older women with indolent breast cancers.

Survival outcomes of upfront surgery versus systemic therapy followed by surgery in patients with synchronous pancreatic ductal adenocarcinoma and liver metastases: A multicenter retrospective cohort study.

e16370 Background: The optimal treatment strategy for patients with synchronous pancreatic ductal adenocarcinoma with liver metastases (sPDACLM) remains uncertain, and the role of surgery in selected patients is controversial. Comparative evidence regarding survival outcomes between upfront surgery (US) and surgery following systemic therapy (SS) in this population is limited. This study aimed to compare overall survival (OS) among patients with sPDACLM treated with different therapeutic strategies and identify prognostic factors associated with survival. Methods: This multicenter retrospective cohort study included patients with sPDACLM treated at seven tertiary medical centers in China between 2017 and 2025. Patients were categorized into three groups: upfront surgery group (US), effective systemic therapy followed by surgery (E-SS), defined as achievement of partial response [PR] per RECIST 1.1 with a > 85% reduction or normalization of serum CA19-9 after systemic therapy; and ineffective systemic therapy followed by surgery (I-SS), defined as fails to achieve PR or < 85% reduction in CA19-9 after systemic therapy. The primary endpoint was OS. Results: A total of 72 patients were included, comprising 21 in the US group, 24 in the E-SS group, and 27 in the I-SS group. Baseline characteristics differed substantially among groups, with 21 of 24 covariates demonstrating a standardized mean difference (SMD) > 0.1. Kaplan–Meier analysis showed significantly improved survival in the E-SS group compared with the US group (median OS: 31.9 vs. 8.0 months; 1-year OS: 90.47% vs. 33.33%; 3-year OS: 40.50% vs. 15.23%) and the I-SS group (median OS: 17.0 months; 1-year OS: 66.62%; 3-year OS: 0%) (P < 0.0001). Univariate Cox regression identified effective systemic therapy as a favorable prognostic factor for OS (hazard ratio [HR], 0.265; 95% CI, 0.123–0.571; P < 0.001). After adjustment for clinically relevant covariates, multivariable Cox analysis confirmed that effective systemic therapy (adjusted HR [aHR] = 0.225, 95% CI: 0.099–0.512; P < 0.001) and tumors located in the pancreatic body–tail region (aHR = 0.443, 95% CI: 0.222–0.882; P = 0.03) were independently associated with prolonged OS. Sensitivity analyses yielded consistent results, supporting the robustness of the findings. Conclusions: Among patients with sPDACLM, treatment strategies incorporating systemic therapy are associated with improved survival compared with upfront surgery. Moreover, tumors arising in the pancreatic body–tail region represent an independent favorable prognostic factor. These findings support prioritizing systemic therapy in the management of sPDACLM, with subsequent surgical resection following systemic therapy offering a clinically meaningful survival benefit.

Utilization patterns of venetoclax-based regimens for AML in a community-based setting and representative populational analyses.

e18621 Background: Azacitidine with Venetoclax was approved in 2020 for older patients ineligible for intensive chemotherapy (DiNardo C, et al. NEJM 2020). Ony 3% of this trial population were of racial minority. Since then, a few studies have assessed disparate AML outcomes among racial minorities in modern era of therapeutics; outcomes have largely involved social determinants of health (SDOH) (Bouligny, I, et al Blood 2022). The ease of administration and efficacy of this regimen allow for its use in the community setting. We aim to analyze Venetoclax utilization patterns based on age, race, and outcomes in our patient population in Memphis, TN. Methods: A retrospective cohort study involving three cancer centers in Memphis, TN from January 2017 to March 2023 was conducted. Inclusion criteria were patients ages 18-85 diagnosed with Acute myeloid leukemia (AML) and in receipt of Venetoclax-based therapies. Number of lines of therapy, demographics, adverse events, and other outcomes were annotated per case. Of 558 patients reviewed,101 patients met inclusion criteria. For simple comparative analysis, Fischer Exact test was performed. Cox proportional hazard and log-rank test were utilized to assess survival outcomes. Results: Median age at diagnosis was 68 years, and 45.5% of patients were female gender. 24.8% of patients were non-Hispanic Black (NHB), 74.3% non-Hispanic White (NHW) and 1% Hispanic patients. Mean number of medical co-morbidities per case was 1.82. 9.2% of patients were good risk per ELN criteria, 32.6% intermediate, and 58.9% were poor risk. Azacitidine was used in the first line setting with Venetoclax in 74% of patients and in 31% in the second line. Between NHB and NHW cohorts, the median age at diagnosis of AML was 63 vs. 70.5 years, p=.0026 respectively. NHW patients had higher ELN intermediate risk disease; 38.4% versus 14.3%, p= .0235. There was no difference between cohorts regarding complete response rates (p= .4858). Survival data was available for 76 patients; log-rank test stratified by cytogenetic risk and age showed no statistically significant difference observed (p = 0.60). Median OS for NHB was 16.2 months (95% CI 8.4- N/A) and NHW was 19.53 months (95% CI 12.93- 31.56). After adjustment for cytogenetic risk and age in a Cox proportional hazards model, AML outcomes did not differ significantly between NHW and NHB patients (HR = 0.95, 95% CI 0.45–2.02; p = 0.88). Regarding adverse events, 22.7% of NHB developed acute renal failure compared to 1.4% of NHW, p= .0035. Conclusions: This retrospective cohort study highlights the utilization patterns of Venetoclax and race-based differences in Memphis, TN. The median age of diagnosis of AML in NHB patients was lower at diagnosis; further germline predisposition data needs to be evaluated. NHB patients had a higher percentage of development of renal failure, which needs to be validated with a larger cohort.

From concept to clinic: Implementation and early outcomes of MCED screening at RUSH Health System.

e13591 Background: Approximately one-third of Americans will develop cancer, yet guideline-recommended screening exists for only five cancer types, leaving many, including aggressive malignancies, without early detection options. Multi-cancer early detection (MCED) blood tests based on cell-free DNA methylation patterns offer a novel strategy to detect a shared cancer signal across multiple tumor types, including those without standard screening, with high specificity and a low false-positive rate. Here, we describe the implementation of an MCED test (Galleri) into routine care within the RUSH Health System. Methods: Over a 14-month period (May 2024–July 2025), RUSH Health System (Chicago, IL), encompassing three hospitals and over 2300 providers, developed an implementation model for MCED screening. Results: RUSH leveraged a centralized model for MCED implementation within the existing germline genetic high-risk screening program. In the months preceding and post-implementation, eight medical education sessions were delivered to 176 individuals in primary care, OB/GYN, and the laboratory. Three additional sessions post-implementation, educated 92 providers and stakeholders. In the model, patient activation could occur through (1) patient self-referral by completing an online intake form or (2) provider-driven for interested patients by a direct ordering pathway built into the electronic medical record (EMR). For negative MCED results ordered through the high-risk team, a phone call is made to all patients within 24 hours followed by written communication. For positive MCED tests within RUSH, providers can refer to the high-risk team to coordinate all diagnostic follow-up or order sets were built into the EMR for each cancer signal origin to guide providers in the diagnostic workup. Between July 2025 and January 2026, over 500 individuals were counseled on MCED screening, 422 orders were placed, and 303 screens were completed. Of the completed screens, the median age was 61 years and 58.5% were female. Most screens (n = 284, 92%) were ordered through the high-risk screening program: 84% patient self-referrals and 16% provider-driven referrals. The remaining 25 orders were placed directly by 11 providers outside of the high-risk screening program. Among those screened at RUSH to date, two received a positive MCED result, one of whom has been confirmed to have anal cancer and one whose workup is ongoing. Conclusions: This implementation and early data illustrate one approach by which a health system integrated MCED screening and is scaling adoption of a novel technology into clinical practice. The model facilitates access for interested patients while providing structured support for providers.

Phase 1 basket study of telisotuzumab adizutecan (Temab-A, ABBV-400), a c-Met protein–targeting antibody-drug conjugate: Results from patients with platinum-resistant ovarian/primary peritoneal/fallopian tube cancer (PROC).

5514 Background: c-Met protein is expressed in several tumor types, including PROC, and is linked with poor clinical outcomes. Temab-A comprises a c-Met protein-targeting antibody conjugated to a topoisomerase 1 inhibitor. Phase 1 studies evaluating Temab-A monotherapy in solid tumors showed antitumor activity and a manageable safety profile (NCT05029882, NCT06084481). Here, we report on the efficacy and safety of Temab-A in PROC. Methods: This phase 1, open-label basket study (NCT06084481) enrolled patients (pts) ≥18 years with histologically/cytologically confirmed recurrent PROC, with Eastern Cooperative Oncology Group performance score ≤1. Pts must have had measurable disease per investigator-assessed RECIST v1.1 criteria, have had platinum-resistant disease, and have received ≥1 but ≤5 prior lines of systemic therapy, with ≤2 prior therapies since the development of platinum resistance. Pts received Temab-A at 2.4 mg/kg every 3 weeks. Primary endpoints were safety and efficacy. Results: As of Sept. 11, 2025, 41 pts with PROC received Temab-A. Tumor histology included serous carcinoma (n=26), clear cell carcinoma (n=7), and other rare histologies (n=8). The median age was 64 years (range 43–89), and the median number of prior lines of systemic therapy was 3 (range 1–6). Median follow-up was 5.1 months. Objective response rate (ORR) was 37%. Duration of response, progression-free survival, and overall survival were immature at data cutoff. Efficacy data are shown in the Table. The most common treatment-related adverse events (TRAEs) of any Grade (G) included anemia (59%), nausea (59%), and fatigue (39%); G ≥3 TRAEs occurring in ≥10% of pts were anemia (34%), neutrophil count decreased (17%), and white blood cell count decreased (15%). The adjudicated interstitial lung disease/pneumonitis rate was 5% (G1, n=2). TRAEs led to treatment discontinuation in 5%, dose interruption in 39%, and dose reduction in 37% of pts. There were no TRAEs that led to death. Temab-A pharmacokinetics in pts with PROC were consistent with those in other tumor types. Exploratory biomarker analyses are ongoing. Conclusions: Temab-A had a manageable safety profile and showed antitumor activity in pts with PROC. Clinical trial information: NCT06084481 . Efficacy of Temab-A. a . Outcome Pts with PROC (N=41) Best overall response, n (%)Complete responsePartial responseStable diseaseProgressive diseaseNot assessed b 019 (46)16 (39)5 (12)1 (2) Objective response rate c , n (%)95% CI 15 (37)22, 53 Clinical benefit rate c , n (%)95% CI 35 (85)71, 94 a Responses were assessed by investigators per RECIST v 1.1 criteria. b Pts without postbaseline scan. c Confirmed. CI, confidence interval.

Immunotherapy use without approval: Patterns, biases, and biomarkers in patients with ovarian cancer.

e17588 Background: Immunotherapy use has attracted increasing attention in ovarian cancer but currently has no disease specific FDA indications. We determined the factors and tumor biomarkers associated with immunotherapy use in ovarian cancer over the last 17 years. Methods: This was a retrospective analysis of the 2022 submission of the National Cancer Database (NCDB) epithelial ovarian cancer cohort. This cohort included women aged 18 and older diagnosed with ovarian cancer from 2004-2021 with information on immunotherapy use. Patient factors included age at diagnosis, race/ethnicity, insurance status, and comorbidities. Cancer factors included disease stage, histology, and tumor size. Patients with epithelial ovarian cancer who underwent testing at a commercial laboratory (2010-2025) were identified from the Myriad Collaborative Research Registry V2. Myriad Precise tumor testing results were used to identify incidence of immunotherapy related tumor biomarkers such as mismatch repair instability (MSI), tumor mutational burden (TMB) and PD-L1 positivity. P-values <0.05 were considered statistically significant. Results: From 2004-2021, 196,087 patients were identified in the NCDB database. In total, 7,767 (4.0%) of patients were treated with immunotherapy. Patients who received immunotherapy were more likely to be older (18-39 years: 2.0% vs 65+: 4.7%, p<0.001), be of Asian race (White: 3.8% vs Asian 4.7%, p<0.001), have more medical comorbidities (Charlson-Deyo Comorbidity Score 0: 3.9% vs 2+: 4.7%, p<0.001), and have higher stage disease (Stage 1: 0.4% vs Stage IV: 8.4%, p<0.001) compared to those who did not receive immunotherapy. After adjusting for confounders, patients with stage IV had an adjusted odds ratio (aOR) of 16.12 [95% CI: 13.99-18.57, p<0.001] of receiving immunotherapy. Clear cell histology was associated with increased use of immunotherapy (aOR: 1.18 [1.05-1.32], p<0.001. Patients who were treated with surgery for their cancer were less likely to get immunotherapy (3.8 vs 5.6%, p<0.001). Patients who did not get treated with chemotherapy were unlikely to get immunotherapy alone (0.1% vs 5.1%, p<0.001). Use of immunotherapy has increased over the last 17 years. From 2008-2021, immunotherapy use in ovarian cancer increased 50.6% per year [42.2-64.2, p<0.001]. In 2021, 16.0% of patients were treated with immunotherapy, compared to 0.5% in 2004. In the Myriad data, 3,095 patients received Precise tumor testing. The rate of MSI positivity was 1.13% (N=35), the rate of PD-L1 positivity was 15.61% (N=483), and the rate of TMB high was 7.08% (N=219). Conclusions: Immunotherapy use in ovarian cancer has increased substantially over 17 years in the absence of an FDA-specific indication, with evidence of PD-L1 enrichment in studied populations.

Challenges and strategies for multidisciplinary care of ocular adverse events: Real-world perspectives from oncologists and eye specialists.

e23436 Background: Advances in antibody-drug conjugates (ADCs) offer potential for enhanced efficacy with reduced systemic toxicity. However, ADCs are associated with ocular adverse events (OAEs), spurring a need for multidisciplinary collaboration between oncology teams and eye specialists (ES). To inform strategies that may strengthen collaboration, this study aimed to evaluate practices and challenges in the management of OAEs across oncology and eye care settings. Methods: A nationwide survey was disseminated electronically in September 2025 to 29,000 oncologists and 26,000 ES. The survey was closed after 100 responses were received from each group. Results: A total of 100 medical oncologists, 89 ophthalmologists, and 11 optometrists completed the survey. The majority (83% and 79%) of oncologists and ES, respectively, practiced in community settings. Most oncologists (70%) reported managing OAEs weekly or daily. Most oncologists (74%) reported they refer most/all patients with OAEs to ES; however, only 38% of ES reported they receive most/all referrals for OAEs from oncologists and 38% reported patients frequently initiate appointments for OAEs themselves. Oncologists primarily refer to ophthalmologists (81%) versus optometrists (13%). Most oncologists (80%) said they refer patients immediately upon symptom recognition and 67% are seen within 1-2 days; conversely, only 47% of ES reported patients receive immediate referral and 48% are seen in 1-2 days. The top barriers to OAE management reported by oncologists were lack of effective prophylactic strategies (50%), insufficient training (45%), difficulty in early identification (37%), and unfamiliarity with eye care products (36%). Barriers cited by ES were lack of standardized protocols (44%), insufficient training (39%), limited access to patient information (30%), and suboptimal communication with oncologists (20%). When asked about strategies to improve OAE management, both groups prioritized standardized protocols and improved communication between oncologists and ES (Table). Conclusions: Oncologists and ES report differing views of referral patterns for OAEs, with oncologists perceiving higher rates of initiating referrals than ES. Increasing awareness to include optometrists in referral patterns may facilitate faster care coordination. Both groups identified needs for training, improved communication, and standardized protocols. These findings can inform education and implementation strategies to improve multidisciplinary management of OAEs. Providers’ perceptions of strategies to improve the management of OAEs. Oncologists Eye Specialists Standardized management protocols 66% 42% Better communication between specialists 43% 38% Provider training 25% 44% Faster referral to eye specialists 32% 17% Patient education 33% 20% More consistent monitoring 22% 14%