Browse Articles

SILVER (supplementing tebentafusp with subcutaneous IL-2 to verifiably eradicate radiological progression): A phase 1/2 trial of IL-2 with tebentafusp upon first radiological progression on first-line tebentafusp alone.

TPS9606 Background: Metastatic uveal melanoma (mUM) remains a disease with a profound unmet clinical need. Tebentafusp, a bispecific T-cell receptor–anti-CD3 ImmTAC targeting gp100 is the first systemic therapy to demonstrate a reproducible overall survival benefit and is now the standard of care in eligible patients. Despite this advance, most patients ultimately develop radiological progression on tebentafusp, highlighting the need for rational combination strategies that can augment or restore antitumour immune activity. Interleukin-2 (IL-2) has long been recognised as a potent T-cell growth and activation factor. Pre-clinical data demonstrate that IL-2 enhances tebentafusp-mediated tumour cell killing by expanding and priming effector T-cell populations. These effects are mechanistically linked to increased cytotoxic function and improved immune synapse formation (Guc et al., 2025). Importantly, low-dose IL-2 administered subcutaneously has been shown in prior clinical studies to achieve biologically relevant serum concentrations with a substantially improved safety profile compared with historical high-dose intravenous regimens. Collectively, these data provide a strong biological and clinical rationale for combining tebentafusp with low-dose subcutaneous IL-2 in patients with mUM progressing on tebentafusp monotherapy. Methods: SILVER is an investigator-initiated, single-arm phase Ib study evaluating the safety, tolerability and preliminary efficacy of tebentafusp in combination with low-dose subcutaneous IL-2 in HLA-A*02:01–positive patients with metastatic or unresectable uveal melanoma who have RECIST-defined progression on tebentafusp alone. Patients receive IL-2 at 125,000 IU/kg subcutaneously, administered for three consecutive days prior to the initial tebentafusp dose, and then weekly 24 hours before each subsequent tebentafusp infusion. Tebentafusp is administered intravenously with step-up dosing in cycle 1, followed by standard weekly dosing thereafter. The primary endpoint is best overall response by iRECIST. Secondary endpoints include RECIST 1.1 response rate, clinical benefit rate, progression-free survival, overall survival, safety and tolerability (CTCAE v5.0), and quality of life. Extensive translational endpoints include serial diffusion-weighted MRI, ctDNA kinetics, and deep immune profiling from blood and tumour biopsies. Early treatment cycles incorporate inpatient monitoring to manage cytokine-mediated toxicities. Conclusion: By integrating robust pre-clinical rationale, an established and pragmatic IL-2 dosing strategy, and comprehensive translational analyses, this study aims to enhance tebentafusp activity and improving outcomes for patients with progressive mUM. Clinical trial information: NCT07063875 .

A US-based, retrospective, observational study of biomarker testing patterns across lines of therapy in patients with metastatic colorectal cancer.

e15526 Background: As the third most prevalent and third leading cause of cancer-related deaths in the US, colorectal cancer (CRC) represents a significant healthcare challenge. Approximately 20% of patients with CRC are diagnosed with metastatic CRC (mCRC), and outcomes for these patients are often poor. While guidelines recommend comprehensive biomarker testing for all patients with mCRC, evidence on adoption of biomarker testing, especially across lines of therapy (LoT), remain limited. This analysis describes biomarker testing and rebiopsy patterns across LoT using large, national, electronic medical records data from US-based patients with mCRC. Methods: This was a retrospective analysis of patient data using the ConcertAI Patient360 database to assess biomarker testing patterns. For inclusion, patients had to be adults with unresectable mCRC diagnosed between the years 2013–2024, who also had evaluable longitudinal data captured in the first-line (1L)+ treatment setting; patients were excluded if they had multiple concurrent primary cancers and if their date of metastasis was within 30 days of data end. Outcomes included biomarker testing and biopsy rates by LoT and year of testing. Results: Of 1817 patients included in these analyses, 1817, 916, and 495 had data available at 1L, second-line (2L), and third-line (3L), respectively. Patient characteristics were consistent across LoT; patients had a median age of 61–62 years and were mostly White, male, and treated in community settings. Testing for any biomarker occurred in 1391 (77%) patients at 1L; testing rates dropped sharply in later LoT, with 428 (47%) patients tested at 2L, and 149 (30%) patients tested at 3L. Within each LoT, testing rates increased in more recent years; testing rates in 2013−2016 vs 2023−2025 were 62% vs 91% at 1L, 30% vs 57% at 2L, and 21% vs 40% at 3L. At 1L, tissue was most frequently used for testing (n=1350; 74%), this trend continued in 2L and 3L settings; however, the proportion of patients receiving any biopsy for biomarker testing drops to 25% (n=233) and 16% (n=79) at 2L and 3L, respectively (Table). Conclusions: In this real-world analysis of patients with mCRC, while biomarker testing rates at 1L increased in more recent years, rates overall are still relatively low at 2L and 3L. Additionally, while tissue was commonly used for testing at 1L, use of tissue dropped in later LoT. These data suggest that standardization of biomarker testing planning is needed to ensure optimal patient access to biomarker-driven therapies in 1L and later LoT for all patients with mCRC. Biomarker testing and biopsy rates across LoT. 1L(N=1817) 2L(n=916) 3L(n=495) Tested for LoT 1391 (76.6) 428 (46.7) 149 (30.1) Biopsy (any type) 1413 (77.8) 233 (25.4) 79 (16.0) Blood 244 (13.4) 82 (9.0) 37 (7.5) Cytology 3 (0.2) 0 3 (0.6) Tissue 1350 (74.3) 170 (18.6) 40 (8.1) Data are n (%).

Patient-reported outcomes from IMvigor011: A phase 3 study of circulating tumor (ct)DNA–guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer (MIBC).

4627 Background: IMvigor011 (NCT04660344) showed that serial ctDNA-based molecular residual disease (MRD) monitoring can identify patients (pts) with MIBC at very high risk of recurrence who benefit from adjuvant atezolizumab (atezo), demonstrating statistically significant and clinically meaningful improvements in DFS and OS vs placebo (pbo) in pts who tested ctDNA+. Pts who persistently tested ctDNA− had low risk of recurrence or death without adjuvant treatment (tx; Powles NEJM 2025). Here we report pt-reported outcomes (PROs). Methods: Pts with MIBC and no radiographic disease were enrolled and underwent serial ctDNA monitoring for up to 1 year after cystectomy; pts who tested ctDNA+ and remained disease-free were randomized to atezo or pbo every 4 weeks (wk) for 12 cycles or up to 1 year. PROs were assessed on Day (D)1 of Cycle (C)1, C3, C5, C7, C9, and C11, and at tx discontinuation. Time to confirmed deterioration (TTCD) analysis of physical functioning (PF), role functioning (RF), and global health status/quality of life (GHS/QoL) were secondary endpoints. Symptoms, functioning, and GHS/QoL per EORTC QLQ-C30, and tx side-effect burden per EORTC IL46, were exploratory endpoints. Relevant adverse events (AEs) were graded per NCI CTCAE v5. Results: Eligible pts who tested ctDNA+ (n=250) were randomized to atezo (n=167) or pbo (n=83). QLQ-C30 completion was >94% at C1D1 and >87% during tx, and >72% and >90%, respectively, for IL46. C1D1 completion rates were similar between arms. TTCD in PF, RF, and GHS/QoL showed no evidence of a difference between arms (Table). There was no clinically meaningful difference in mean change from C1D1 in symptoms, functioning, and GHS/QoL over time through C11D1 and between arms. From C1D1 to C11D1, >90% of pts reported little or no tx side-effect burden in both arms. Relevant safety data showed consistency between AEs and PROs. Conclusions: ctDNA-guided adjuvant atezo provided clinically meaningful DFS and OS benefit without negatively impacting pt-reported QoL. Clinical trial information: NCT04660344 . Atezo(n=167) Pbo(n=83) Stratified HR a (95% CI) QLQ-C30, median TTCD b (95% CI), mo PF 25.1 (18.5, NE) NE (19.4, NE) 1.25 (0.76, 2.07) RF 18.5 (12.2, NE) NE (19.4, NE) 1.45 (0.88, 2.40) GHS/QoL 35.4 (19.3, NE) 16.5 (10.9, NE) 0.71 (0.45, 1.12) IL46 tx side-effect burden, % of pts Atezo C1D1 (n=131) Atezo C11D1 (n=60) Pbo C1D1 (n=60) Pbo C11D1 (n=22) Not at all/a little 93.9 98.3 98.3 95.5 Quite a bit 6.1 1.7 1.7 4.5 Very much 0 0 0 0 a Stratification factors: Nodal status (+ vs –); tumor stage (≤pT2 vs pT3/4); programmed death ligand-1 status (<5% vs ≥5% of immune cells); time from cystectomy to first ctDNA+ sample (≤20 vs >20 wk). b Time from randomization to first clinically meaningful deterioration (≥10-point decrease) at either: ≥2 consecutive visits; or at 1 visit followed by death due to cancer progression ≤8 wk from last deteriorated PRO visit. NE, not evaluable.

From Bayesian dose-finding to AI-enabled decision support in oncology clinical trials.

e15145 Background: Bayesian methods are increasingly used in oncology clinical development to support dose finding, adaptive trial designs, and decision-making under uncertainty. Recent FDA draft guidance on Bayesian methodology clarifies regulatory expectations and supports broader use of Bayesian approaches across development phases. However, utilization remains limited in small and mid-sized biotechnology and pharmaceutical organizations, due to limited specialized expertise and operational complexity. Advances in automation and clinical trial data integration create opportunities to extend Bayesian frameworks toward AI-enabled decision support. Methods: We review Bayesian and model-informed methods used across Phase I-III oncology trials, focusing on trial design, interim monitoring, and development decision-making. Approaches include model-assisted and model-based dose-escalation designs, Bayesian predictive probability methods, and adaptive designs such as response-adaptive randomization and platform trials conducted under master protocols. Methods are evaluated based on modeling assumptions, simulation-based operating characteristics, regulatory considerations, and feasibility for integration into automated, AI-enabled decision support workflows using standard clinical trial data. Results: Examples demonstrate the application of Bayesian methods across clinical development phases. In Phase I oncology studies, the Bayesian Optimal Interval design supports efficient dose identification while controlling toxicity risk through prespecified decision rules. In Phase II dose-expansion, Bayesian continuous monitoring supports early assessment of futility or efficacy and informs development decisions. In later phase development, Bayesian adaptive designs, including response-adaptive randomization and platform trials implemented under master protocols, support efficient evaluation of multiple treatments and adaptive trial modification. These designs have been implemented in oncology programs (NCT06726161, NCT06590857, NCT05595460, NCT07165132). For illustrative purposes, simulation results are presented to characterize operating characteristics under clinically relevant scenarios rather than actual trial parameters. Conclusions: Bayesian and predictive modeling approaches provide a consistent foundation for model-informed decision-making in oncology clinical trials and a pathway toward AI-enabled decision support. The presentation will highlight key opportunities for AI to enhance Bayesian decision frameworks, including automation and integration of real-time trial data. By standardizing and automating established Bayesian analyses, future AI-driven systems may support broader and more efficient application while maintaining statistical rigor and regulatory acceptability, consistent with recent FDA guidance.

Urinary RNA as response predictor for patients with metastatic urothelial carcinoma treated with pembrolizumab.

e16591 Background: Limited biomarkers are available to predict response and outcome in metastatic urothelial carcinoma (mUC) patients treated with pembrolizumab. The Belgian multicenter CORPORA study evaluates the use of tissue, plasma and urine RNA as companion diagnostic in this setting. Results for plasma and urine will be presented. Methods: Baseline plasma (n = 41) and urine (n = 27) were prospectively collected in mUC patients receiving pembrolizumab (200 mg Q3W). Cell-free RNA (cfRNA) isolation and library prep, using Illumina RNA prep with enrichment, was followed by short read RNA sequencing (15M reads/sample). Data analysis included principal component analysis (PCA), differential gene expression (DGE), and gene set enrichment analysis (GSEA). Association to response (RECIST 1.1), survival, and occurrence of immune-related adverse events (irAEs) was determined. Results: PCA of plasma and urine did not reveal any sample clustering. Further downstream DGE indicated no significant difference in plasma cfRNA single gene abundance for response, outcome, or irAEs. In contrast, DGE in urine identified four significantly downregulated genes ( C12orf75 , RPS28P7 , ENSG00000267469 , RPL36AP37 ) and one significantly upregulated gene ( CIDEC ) that differentiate responders from non-responders. Regarding outcome, 5 genes ( ALKBH8 , FSIP1 , GDE1 , HMGB3 , and RHOU ) were identified as candidates for progression-free survival (PFS) and overall survival (OS, Table). A total of 271 genes, including the five genes identified for outcome, were significantly differentially abundant between patients who developed grade 3+ irAEs compared to those with milder grade 1-2 toxicity. GSEA indicated responders to exhibit cellular reprogramming toward enhanced metabolic fitness and tissue remodeling, whereas non-responders show a more stress-associated transcriptional state with altered immune, cell death, and mitochondrial respiration programs. Development of irAEs on the other hand was associated with broad immune hyperactivation and tissue remodeling programs, accompanied by suppression of mitochondrial oxidative metabolism. Conclusions: Urinary cfRNA contains candidate biomarkers for pembrolizumab response prediction, prolonged survival, and the occurrence of more severe irAEs. Further research is ongoing, including comparison to tissue RNA, and study of circular RNA, fusion genes, and immune cell enumeration via deconvolution. Cox regression univariate analysis for urine mRNA and survival. PFS OS Gene HR (95% CI)* P HR (95% CI)* P ALKBH8 0.46 (0.27-0.78) 0.004 0.58 (0.35-0.95) 0.030 FSIP1 0.55 (0.31-0.96) 0.036 0.37 (0.19-0.71) 0.003 GDE1 0.49 (0.25-0.94) 0.032 0.53 (0.29-0.96) 0.037 HMGB3 0.51 (0.31-0.84) 0.009 0.36 (0.17-0.73) 0.005 RHOU 0.57 (0.34-0.94) 0.028 0.38 (0.19-0.79) 0.009 *HRs representing change in risk per one standard deviation increase in gene expression.

Impact of academic center–based care on clinical outcomes in light chain amyloidosis.

e13798 Background: Light chain (AL) amyloidosis requires coordinated hematologic and organ-specific care, often delivered through multidisciplinary teams. However, real-world data comparing outcomes between academic and non-academic centers are limited. We compared outcomes in patients with AL amyloidosis managed at academic versus non-academic centers using a global real-world database. Methods: We performed a retrospective cohort study using the TriNetX Network. Adult patients with AL amyloidosis without history of neoplasms were identified and categorized by care at academic or non-academic centers with index as the diagnosis of AL amyloidosis, and outcomes assessed one day after the index. Propensity score matching was performed using demographic and clinical characteristics, including conditions associated with congestive heart failure (CHF) and requiring steroid therapy independent of amyloidosis. Outcomes included hospitalization, steroid use, chronic kidney disease (CKD), dialysis, CHF, CHF exacerbation, and death. Patients with outcomes prior to the time window were excluded. Results: After propensity score matching, 391 patients were included in each cohort, which were balanced for age, race and comorbidities. Median follow-up was 414 and 360 days, respectively, for the academic cohort and non-academic cohort. Hospitalization occurred in 10.4% of Academic vs 23.4% of Non-academic patients (risk difference -0.130; 95% CI -0.198 to -0.061, OR 0.38, 0.229-0.629), dialysis in 3.7% vs 8.7% (risk difference -0.050; 95% CI -0.085 to -0.015, OR 0.405, 0.212-0.772) and CHF exacerbation in 5.2% vs 9.4% (risk difference -0.043; 95% CI -0.084 to -0.001, OR 0.523, 0.279-0.98). No significant differences were observed for steroid use, CKD, or chronic CHF (Risk difference, p 0.6, 0.66 and 0.9 respectively). There was no significant difference in mortality between the two groups, HR 0.825 (0.587-1.159). 153 vs 23 patients received daratumumab in the academic vs non-academic groups. Conclusions: In this large real-world analysis, care at academic centers was associated with lower rates of hospitalization, dialysis, and CHF exacerbations, despite similar baseline prevalence of CKD and CHF. These findings suggest acute decompensation and progression markers may be more sensitive to care-related differences rather than baseline comorbidity burden. Further studies are needed to identify drivers of these differences and inform strategies to optimize care. Baseline characteristics after matching. Characteristic Academic centers Non-academic centers Age at Index 64.2 +/- 13.0 64.5 +/- 12.7 Female 153 (39.1%) 161 (41.2%) Male 238 (60.9%) 230 (58.8%) Black or African American 99 (25.3%) 88 (22.5%) White 229 (58.6%) 229 (58.6%) Hispanic or Latino 26 (6.6%) 35 (9.0%) Asian 33 (8.4%) 30 (7.7%) Atherosclerotic heart disease 72 (18.4%) 69 (17.6%) Chronic obstructive pulmonary disease 38 (9.7%) 29 (7.4%)

Longitudinal overview of mortality for malignant neoplasm of the brain and cerebrovascular diseases in the U.S. from 1999 to 2023 using CDC WONDER.

e14024 Background: Malignant brain tumors and cerebrovascular diseases are major contributors to mortality in the United States. Brain tumors are associated with poor survival, while cerebrovascular disease, including stroke, remains a leading cause of death. Characterizing long-term mortality trends for these conditions may inform prevention strategies, clinical care, and public health planning. Methods: We conducted a retrospective population-based study using CDC WONDER multiple-cause-of-death data from 1999–2023. Deaths with malignant neoplasm of the brain (ICD-10 C71) and cerebrovascular disease (ICD-10 I60–I69) listed as underlying or contributing causes were identified among individuals aged 25–85+ years. Analyses followed STROBE guidelines. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Trends were stratified by age, sex, race/ethnicity, census region, and urbanization. Joinpoint regression (version 5.4.0) was used to estimate annual percent change (APC) with 95% confidence intervals. Results: From 1999 to 2023, 16,062 deaths were identified (9,062 males [56.41%], 7,000 females [43.58%]). Overall AAMR increased from 0.27 to 0.38, with higher rates in males (0.33→0.48) than females (0.24→0.29). By race/ethnicity, Whites had the highest AAMRs (0.28→0.44), while Black/African American individuals had the lowest (0.17→0.26). The largest number of deaths occurred in the South (5,877), followed by the West (3,988), Midwest (3,722), and Northeast (2,475). Mortality declined from 1999–2007 (APC −2.55%, 95% CI −4.44 to −0.63; p=0.012) and subsequently increased from 2007–2023 (APC 2.68%, 95% CI 2.06–3.31; p<0.000001). Conclusions: Mortality associated with malignant brain neoplasms and cerebrovascular disease shifted from early decline to sustained increases after 2007, with higher burden among males, older adults, and residents of the South and Midwest. These findings underscore the importance of integrated neuro-oncology and cerebrovascular risk management strategies and targeted public health interventions to address emerging disparities.

Paclitaxel plus bevacizumab with or without atezolizumab for hormone receptor-positive/HER2-negative advanced breast cancer: JCOG1919E (AMBITION) phase III trial.

1019 Background: Hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (aBC) is immunologically “cold,” with limited clinical benefit from immune checkpoint inhibitors. Since VEGF-mediated angiogenesis promotes an immunosuppressive tumor microenvironment, we hypothesize that inhibiting VEGF could reverse immunosuppressive state thereby augmenting response to immunotherapy. The JCOG1919E (AMBITION) phase III trial evaluates whether adding the anti-PD-L1 antibody: atezolizumab (ATZ) to paclitaxel (PTX) plus anti-VEGF antibody: bevacizumab (BEV) improves outcomes in patients (pts) with HR+/HER2- aBC. Methods: This multicenter, open-label, randomized phase III trial enrolled pts with HR+/HER2-aBC who had no prior chemotherapy for aBC and were endocrine-resistant or visceral crisis. Pts were randomized in a 1:1 ratio to PTX plus BEV (Arm A) or PTX plus BEV with ATZ (Arm B). Randomization was stratified by disease status (de novo stage IV vs. recurrent), liver metastasis (presence vs. absence), and PD-L1 expression (SP142 assay; negative [<1% on immune cells (ICs)] vs. positive [>=1%]). PTX was administered on days 1, 8, and 15 of a 28-day cycle, BEV on days 1 and 15, and ATZ on days 1 and 15 in Arm B. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS by blinded independent central review, and safety. Clinical trial information: NCT04732598. Results: From Sep 2021 to Sep 2023, 281 pts were randomized. At baseline, 33.1% were de novo stage IV, 68.0% had liver metastases, and 16.0% were PD-L1 positive. At a median follow-up of 30 months, median investigator-assessed PFS was 11.2 months in Arm A and 12.4 months in Arm B (hazard ratio [HR] 0.88; 95% CI, 0.67–1.15; p=0.17). Median OS was immature, but numerically longer in Arm B than in Arm A (39.1 vs. 31.2 months; HR 0.80, 95% CI, 0.58–1.11). The ORR was high and comparable between arms (71.9% vs. 73.0%). Grade ≥3 adverse events (AEs) were similar between arms. The most common immune related AEs (any grade) with ATZ were rash (17.3%), adrenal insufficiency (11.5%) and hypothyroidism (10.8%). No treatment-related deaths were observed, and no new safety signals emerged. Conclusions: PTX plus BEV with ATZ did not demonstrate a statistically significant improvement in PFS compared to PTX plus BEV as a frontline treatment for HR+/HER2- aBC, although a numerical extension in OS was observed. The safety profile of PTX plus BEV with ATZ was consistent with the known profiles. Clinical trial information: NCT04732598 . ARM A PTX+BEV (n=140) ARM B PTX+BEV+ATZ (n=141) PFS events, n 117 109 Median PFS (95% CI), months 11.2 (9.6-13.5) 12.4 (10.3-15.2) HR (95% CI) 0.876 (0.670-1.145) P-value 0.168 OS events, n 81 71 Median OS (95% CI), months 31.2 (23.9-34.7) 39.1 (30.0-47.8) HR (95% CI) 0.804 (0.584-1.108) ORR, % 71.9% 73.0%

Neoadjuvant combination versus single-agent immune checkpoint inhibition in locally advanced MSI-H/dMMR colorectal cancer: A systematic review and meta-analysis.

e15595 Background: Immune checkpoint inhibitors (ICIs) have transformed treatment for MSI-H/dMMR colorectal cancer (CRC). Neoadjuvant studies, including NICHE and NICHE-2, demonstrated high pathologic response rates with single-agent or combination ICI therapy. However, it is unknown whether combination ICI regimens improve pathologic complete response (pCR) rates compared to single-agent regimens or whether toxicity differs between combination and single-agent regimens. Methods: We systematically searched PubMed and the Cochrane Library for studies comparing neoadjuvant ICI combination therapy with single-agent therapy in MSI-H/dMMR locally advanced CRC. Pooled effect estimates were calculated using a random-effects model in R and reported as risk ratios (RR) with 95% confidence intervals (CI). Outcomes analyzed included pCR and treatment-related adverse events. Results: Three studies with 147 patients were included. Combination therapy significantly increased pCR compared with single-agent therapy (RR = 1.80; 95% CI, 1.32–3.46; p = 0.0002). Grade 3–4 immune-related adverse events were similar between groups (RR = 0.95; 95% CI, 0.17–5.33; p = 1.00); however, any-grade adverse events were higher with combination therapy (RR = 1.42; 95% CI, 1.05–1.93; p = 0.02). Conversely, bowel obstruction of any grade (RR = 1.54), bowel obstruction of grade 3 (RR = 1.52), enterocolitis (RR = 1.40), death (RR = 2.83), thyroid dysfunction of any grade (RR = 1.34), thyroid dysfunction of grade 3 (RR = 0.31), toxiderma/rash of any grade (RR = 1.46) and toxiderma/rash of grade 3 (RR = 0.31) did not differ significantly. Conclusions: In MSI-H/dMMR locally advanced CRC, neoadjuvant ICI combination therapy improves pCR with similar grade 3-4 adverse events but increased all grade toxicity. While combination therapy may offer incremental efficacy, single-agent ICIs remain highly effective with a slightly more favorable safety profile. Larger prospective studies with long-term survival endpoints are needed to define the optimal neoadjuvant strategy. Details of the therapies. Study Intervention Comparator Dosage details (intervention) Dosage details (comparator) Deng et al, 2024 Nivolumab + Ipilimumab Pembrolizumab (n= 2) orTislelizumab (n= 3) Nivolumab 3 mg/kg for 2 cycles + Ipilimumab 1 mg/kg for 1 cycle 200 mg IV infusion every 3 weeks Lemaire et al, 2025 Nivolumab + Ipilimumab Pembrolizumab Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg for 1 cycle, followed by 1 cycle of Nivolumab 3 mg/kg monotherapy 2 weeks later 400 mg every 6 weeks (n= 12) and 200 mg every 3 weeks (n= 9)The last patient received 3 cycles at 200 mg every 3 weeks, followed by 3 cycles at 400 mg every 6 weeks Wang et al, 2025 IBI310 + Sintilimab Sintilimab IBI310 1 mg/kg + Sintilimab 200 mg during the first cycle and Sintilimab 200 mg during the second cycle Sintilimab 200mg every 3 weeks (Q3W) for 2 cycles

Accelerate tobacco treatment in cancer care with evidence-based implementation strategies: How to get from here to there?

e13548 Background: Tobacco use is associated with 40% of all cancer diagnoses in the United States. Individuals with cancer who continue to smoke are at increased cancer-specific and all-cause mortality, treatment complications, and higher health care costs. As such, the American Society of Clinical Oncology emphasizes that the benefits of stopping cigarette use after a cancer diagnosis include longer and better quality of life, faster and more successful recovery, and lower risk of secondary cancers and infections. Different care models for tobacco cessation treatment programs exist. Here, we present a qualitative analysis from interviews from representatives of the Cancer Center Cessation Initiative (C3I) centers describing these care models. Methods: This analysis follows up on a cross-sectional study in 2023 that evaluated reach and effectiveness of tobacco treatments from 28 C3I centers. The centers were divided into four groups based on reach and effectiveness: Group A) High Reach/High Effectiveness, Group B) High Reach/Low Effectiveness, Group C) Low Reach/High Effectiveness, Group D) Low Reach/Low Effectiveness. Qualitative interviews were conducted with representatives from 16 of the 28 C3I centers to understand which tobacco cessation models were used and their associated outcomes. Interviews were recorded, transcribed, and deidentified. Strategies were organized into four Expert Recommendations for Implementing Change evidence-based implementation (ERIC) strategy categories: support clinicians, change infrastructure, engage consumers, and train stakeholders. Each transcript was coded by two unique coders. Inconsistencies among coders were calibrated. Strategies of Group A were further analyzed. Results: Tobacco care model strategies varied across the 4 groups. First, greater utilization of electronic health record (EHR) functions was associated with centers that had greater reach and effectiveness. Second, there was a tradeoff between reach and effectiveness, as related to engaging consumers through either automatic or tobacco treatment specialist (TTS) outreach. Automatic outreach had a greater reach and lower effectiveness, whereas TTS outreach had the opposite. Third, training stakeholders, including providers, and allowing data feedback was associated with centers that had increased reach. Conclusions: Results suggest that there is more than one path to success. High-performing programs may combine strategies from different ERIC categories, seeking synergy and ways to maximize impact for a population through broad reach and high effectiveness. EMR seems critical to achieving this. With the aim to increase smoking cessation treatments for cancer patients, these results can help guide cancer centers in their implementation of tobacco treatment programs in a strategy-supported, detailed manner while adapting to unique center needs.

Investigating the antimicrobial & antioxidant potential of copper oxide nanoparticles derived from Azolla pinnata

Theory Guided Fine‐Tune of Strain Effects in Pt Ternary Alloy via Rare Earth Templating: Achieving High Performance PEMFCs Catalysts

ABSTRACT The sluggish kinetics and insufficient durability of platinum‐based catalysts remain crucial barriers limiting proton‐exchange‐membrane fuel cells (PEMFCs) deployment. Here, we report a theory‐guided synthesis combined with rare‐earth templating to realize a previously inaccessible Pt 5 Co‐like phase with tailored atomic‐scale strain. Guided by density functional theory (DFT) calculations, we identified that a Pt 5 Co‐like sublayer can induce a unique mild compressive strain (−1.24%) to the Pt(111) shell and an optimal *OH binding energy shift (Δ E ≈ 0.11  eV ). This shift positions the alloy catalyst near the apex of the oxygen reduction reaction activity volcano. This prediction guided the synthesis of ternary alloy Pt 5 (Ce)Co@Pt multilayer nanoparticles, featuring a Ce‐stabilized core, a Pt 5 Co‐like sublayer, and a Pt‐rich shell. This catalyst demonstrates both exceptionally high activity and durability, achieving a mass activity of 2.6 A∙mg Pt −1 in rotating disk electrode testing. In fuel cell membrane electrode assembly tests, Pt 5 (Ce)Co@Pt achieves a current density of 1.9 A∙cm −2 at 0.7 V under heavy‐duty vehicle conditions. Remarkably, it maintains 1.2 A∙cm −2 after 1 80 000 AST cycles, doubling the U.S. DOE 2025 target. This work demonstrates a rational design strategy that DFT‐guided strain engineering integrates with rare‐earth templating to advance Pt‐based catalysts for fuel cell applications.

Metastatic Trajectories in Non–Small Cell Lung Cancer Guide Local and Systemic Therapies

Advances in systemic therapy have improved outcomes for metastatic non–small cell lung cancer (NSCLC), yet resistance and progression remain nearly universal. Local therapies such as radiotherapy, surgery, and image-guided ablation can extend disease control in selected patients, but existing classifications—including dynamic models of oligometastatic disease—assign a single state per patient and do not capture lesion-level heterogeneity. We introduce the concept of metastatic trajectories —the spatiotemporal dynamics of response and progression across lesions, organs, and patients—as a framework to characterize intrapatient heterogeneity and inform adaptive treatment strategies. Dimensions of metastatic trajectories include the magnitude and homogeneity of response, mechanisms of resistance, organotropism, and the pattern, site, extent, and pace of progression. This framework shifts the focus from overall disease states to individual lesion behavior over time, enabling reactive strategies based on observed trajectories and anticipatory strategies based on predicted ones. We review the biological foundations of intrapatient heterogeneity—including genomic diversification, nongenetic plasticity, and tumor-microenvironmental adaptation—that drive divergent lesion evolution and treatment response. Emerging biomarkers such as circulating tumor DNA and radiomic signatures, together with integrative genomic and functional imaging approaches, may allow tracking and prediction of trajectory evolution. Standardized reporting parameters are proposed to ensure consistent documentation and facilitate validation across studies. Integrating trajectory-based assessment into clinical practice could refine patient selection for local and systemic therapy, enable biology-informed adaptation of treatment timing and intensity, and provide a foundation for next-generation clinical trials aimed at precision management of metastatic NSCLC.

Pan-cancer landscape of oncogenic POLE and POLD1 alterations.

2650 Background: POLE and POLD1 encode key enzymes for DNA proofreading. Oncogenic alterations in POLE and POLD1 associated with defective proofreading can lead to tumor hypermutation and increased sensitivity to immune checkpoint inhibition. Prior studies have identified enrichment of POLE and POLD1 alterations in colorectal and endometrial cancers. However, characterization of POLE and POLD1 alterations in the pan-cancer setting has been limited. Utilizing the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) v19.0, we performed a comprehensive analysis of oncogenic POLE and POLD1 alterations across tumor types. Methods: The AACR GENIE v19.0 database was used to select tumor samples that were profiled for molecular alterations (somatic mutations, structural variants, copy number alterations) in POLE or POLD1. POLE and POLD1 alterations were annotated by OncoKB to determine if they were oncogenic. Tumor samples were analyzed for co-occurring molecular alterations. Categorical variables were compared using chi-square or Fisher exact tests, as appropriate. P-values were adjusted with Benjamini-Hochberg correction to control false discovery rate (significance for q<0.05). Results: Across 188,863 tumor samples that were profiled for POLE or POLD1, there were known oncogenic alterations in 786 samples (0.4%). Of note, there were 18,170 molecular alterations in POLE and POLD1 that were classified as variants of unknown significance at time of analysis. The most common tumor types with oncogenic alterations were endometrial (n=374 of 7573 samples profiled; 4.9%), colorectal (143/17821; 0.8%), glioma (49/12795; 0.4%), NSCLC (35/30542; 0.1%), ovarian (26/7728; 0.3%), breast (25/16813; 0.2%), bladder (25/6433; 0.4%), cancer of unknown primary (19/6544; 0.3%), melanoma (13/7965; 0.2%), and pancreatic (10/10369; 0.1%), and esophagogastric (9/6503, 0.1%). The most common mutations in POLE were V411L, E18K, P286R, S297F, and A456P. The most common mutations in POLD1 were R1016H, R1016C, R689W, L606M, and D402N. Oncogenic alterations in POLE and POLD1 were enriched in endometrial cancer (OR 22.8; q<0.001) and colorectal cancer (OR 2.14; q<0.001), with no other tumor types showing enrichment. Within the oncogenic POLE/POLD1 cohort, the most common co-occurring molecular alterations were in PIK3CA (n=561, 71.4% in altered vs 12.9% in unaltered, q<0.001), APC (n=526, 68.7% vs 11.8%, q<0.001), ATM (n=523, 67.8% vs 7.3%, q<0.001), and PTEN (n=523, 66.5% vs 8.7%, q<0.001). Conclusions: To our knowledge, this study represents the largest molecular analysis of oncogenic POLE and POLD1 alterations in a pan-cancer setting. These findings suggest that oncogenic POLE and POLD1 alterations may be rarely identified in a broad range of tumor types. Further studies are needed to classify the functional implication of many variants of unknown significance in POLE and POLD1.

Patient-reported digital symptom monitoring and actionable triage in oncology: A scoping systematic review.

e23274 Background: Treatment-related symptoms substantially impair quality of life (QoL) and drive unplanned acute care use in oncology. Although patient-reported digital symptom monitoring is widely studied, outcomes remain inconsistent. We examined how intervention design influences clinical impact. Methods: We conducted a scoping systematic review of prospective randomized trials and pragmatic real-world studies evaluating patient-reported digital symptom monitoring or management interventions in adult oncology populations. Eligible studies reported symptom burden, QoL and/or acute care utilization. Data were abstracted on cancer type, digital modality, triage approach, and direction of outcomes. Protocols and qualitative studies were reviewed for context but excluded from outcome synthesis. Results: Across studies involving solid tumors and hematologic malignancies, interventions used web-based portals, mobile applications or interactive voice response systems. A consistent pattern emerged across the evidence base: interventions that paired real-time symptom reporting with structured, rule-based triage and proactive clinician response demonstrated improvements in symptom burden and QoL across multiple settings. In contrast, passive monitoring or self-management alone showed limited or no benefit despite similar reporting intensity. Effects on acute care utilization were heterogeneous, with reductions most often seen in pragmatic, workflow-integrated implementations. Conclusions: The clinical value of patient-reported digital symptom monitoring lies not in symptom collection itself, but in how reported data are reviewed and acted upon by clinicians. Monitoring alone is insufficient. Implementation-ready models that embed actionable triage and clinician response workflows are essential to improve patient outcomes and reduce avoidable utilization. Intervention approaches and clinical outcomes of digital symptom monitoring in oncology. Intervention Approach Digital Modality Actionable Triage / Clinician Response Symptom Burden Quality of Life Acute Care Use Monitoring with proactive clinician response Portal / App / IVR Yes (rule-based, clinician-reviewed) Improved Improved Reduced / Mixed Monitoring with automated alerts only Portal / App Partial Mixed Mixed NR Passive monitoring or self-management App / Portal No No benefit No benefit NR Pragmatic, workflow-integrated models Mixed Yes + staffing workflows Improved Improved Reduced Heterogeneous or non-integrated implementations Mixed Variable Mixed Mixed Mixed Abbreviations: IVR = Interactive Voice Response; QoL = Quality of Life; NR = Not Reported.

A randomized trial of sentinel node biopsy omission after neoadjuvant systemic therapy in clinically node-negative or selected node-positive breast cancer.

TPS651 Background: Omission of axillary surgery has been established as a safe option in selected patients with early-stage breast cancer undergoing upfront surgery. In the neoadjuvant systemic therapy (NST) setting, however, axillary surgery remains standard practice. Ongoing trials, including EUBREAST-01, ASICS, and ASLAN, are evaluating the safety of omitting sentinel lymph node biopsy (SLNB) after NST, but these studies have largely been limited to single-arm designs and to patients with confirmed breast pathologic complete response (pCR). Retrospective studies suggest that axillary nodal clearance after NST may be predicted using tumor subtype, treatment response, and post-NST imaging, independent of breast pCR. The NeoNAUTILUS trial was designed to prospectively evaluate the safety of omitting SLNB after NST in patients predicted to have no residual axillary disease, using axillary response–based selection rather than breast pCR. Methods: NeoNAUTILUS is a prospective, multicenter, randomized, controlled, non-inferiority trial being conducted at 23 centers in Korea. Eligible participants are women aged ≥20 years with clinical T1–T3 invasive breast cancer who have completed NST and are candidates for breast-conserving surgery (BCS). Patients with clinical N0 disease of any subtype are eligible. Selected patients with clinical N1 disease are eligible if they have HER2-positive, triple-negative, or estrogen receptor–low-positive tumors and demonstrate a >30% reduction in primary tumor size on post-NST magnetic resonance imaging. All participants must have no suspicious lymph nodes on post-NST axillary ultrasound. Participants are randomized 1:1 to BCS with SLNB or BCS without axillary surgery, stratified by clinical nodal status (cN0 vs cN1) and tumor subtype. Patients remain blinded to treatment allocation until surgery. Whole-breast irradiation is planned for all patients, with protocol-defined axillary radiation fields in the no-SLNB group according to initial nodal status. The primary endpoint is 5-year invasive disease-free survival. Secondary endpoints include overall survival, distant metastasis-free survival, ipsilateral axillary recurrence, locoregional recurrence, and patient-reported quality of life. A total of 464 patients are planned for enrollment over 3 years with a minimum follow-up of 5 years. Enrollment began in May 2025 and is ongoing. Clinical trial registration: NCT06704945; KCT0010174. Clinical trial information: NCT06704945 .

Does PSA at diagnosis correlate with Decipher Score?

e17139 Background: The Decipher genomic classifier is a validated molecular biomarker that examines the activity of 22 genes and provides independent prognostic information for men with prostate cancer, supplementing standard clinicopathologic risk factors such as Gleason score, stage, and serum prostate-specific antigen (PSA). Multiple retrospective and prospective studies have demonstrated that Decipher improves risk stratification for adverse pathology, biochemical recurrence, metastasis, and cancer-specific survival, particularly in intermediate-risk and postprostatectomy settings. Methods: Analysis was conducted on data obtained from 422 males over the age of 18, in a community hospital in the last 5 years. We analyzed the PSA level closest to when the Decipher score was obtained to determine if there is any correlation between PSA level and Decipher score. Exclusion criteria: patients that had previous diagnosis of prostate cancer, Decipher or PSA result dates not available; a total of 72 patients were excluded. Pearson and Spearman rank correlation between PSA and Decipher was conducted on 350 patients. Results: After exclusion criteria, a total of 350 patients were included in the analysis. The Pearson correlation between PSA and Decipher was r = 0.13 with a p = 0.013, suggesting a statistically significant but weak linear association. In fact, after removing values above the 99th percentile, Pearson drops to r = 0.052, p = 0.33 illustrating that the signal is driven largely by outliers. Once ranks are considered, the spearman rank correlation was p≈0.07 with p≈0.17, indicating no significant monotonic relationship. Conclusions: In this community-based cohort of patients with prostate cancer, PSA level and Decipher score, had no monotonic relationship. In addition, despite reaching a statistically significant Pearson correlation, it remains very weak and largely influenced by extreme PSA outliers making it unlikely to be clinically significant. These findings support the established role of Decipher as an independent prognostic tool.

Cardiovascular toxicity of second-generation TKIs versus imatinib in first-line chronic myeloid leukemia: An updated systematic review and meta-analysis.

e18604 Background: BCR–ABL1 tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for chronic myeloid leukemia (CML). Second-generation TKIs (nilotinib, dasatinib, bosutinib) achieve deeper and more rapid molecular responses than imatinib. However, cardiovascular adverse events have emerged as a key safety concern as patients experience long-term survival and remain on therapy for years. Given the high prevalence of baseline cardiovascular risk factors in CML patients, updated quantitative estimates of cardiovascular toxicity are needed to inform individualized first-line TKI selection. While prior analyses were largely based on 5-year follow-up from pivotal trials, this updated meta-analysis incorporates new available 10-year follow-up data to better characterize long-term cardiovascular risk. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, Cochrane Central Register, and Scopus were searched through December 2025. After removing 110 duplicates from 808 identified records, 698 records were screened. Four randomized controlled trials comparing second-generation TKIs [nilotinib (300–400 mg twice daily), dasatinib (100 mg once daily), or bosutinib (400–500 mg once daily)] versus imatinib (400 mg once daily) met eligibility criteria and reported cardiovascular toxicity outcomes. Primary outcomes included composite cardiovascular events, cardiovascular death, and all-cause mortality. Pooled analyses used random-effects models, with effect estimates expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Results: Four randomized controlled trials comprising 1,944 patients were included. In pooled analyses, imatinib was associated with significantly lower risk of composite cardiovascular events—myocardial infarction and peripheral arterial disease (other cardiovascular outcomes were inconsistently defined across trials)—compared with second-generation TKIs (RR 0.28; 95% CI, 0.09–0.82; p=0.02; I²=70%). Imatinib was also associated with lower cardiovascular death (RR 0.17; 95% CI, 0.09–0.30; p<0.00001; I²=0%). All-cause mortality did not differ between groups (RR 1.28; 95% CI, 0.85–1.92; p=0.24; I²=0%). Conclusions: Among patients with chronic-phase CML receiving first-line therapy, second-generation TKIs are associated with increased cardiovascular toxicity compared with imatinib, including higher risks of composite cardiovascular events and cardiovascular death. These updated pooled estimates incorporating 10-year follow-up data support integrating baseline cardiovascular risk stratification into first-line TKI selection to balance efficacy advantages against cardiovascular toxicity. Prospective studies with standardized cardiovascular endpoints and extended follow-up are warranted.

Financial toxicity, self-efficacy, self-care, and health-related quality of life in gastrointestinal cancer survivors in Taiwan.

e23273 Background: Gastrointestinal cancer survivors frequently experience symptom burden, psychological adjustment demands, and financial strain that may compromise self-care behaviors and health-related quality of life (HRQoL). Although self-efficacy supports health-promoting behaviors and financial toxicity may impede effective self-care, integrated evidence linking these factors within Taiwan’s healthcare context remains limited. This study examined the associations among financial toxicity, cancer-related self-efficacy, self-care behaviors, and HRQoL in gastrointestinal cancer survivors in Taiwan. Methods: A cross-sectional, multicenter study was conducted between July 2025 and January 2026, enrolling 169 adult survivors with esophageal, gastric, hepatic, pancreatic, or colorectal cancer receiving treatment or routine follow-up. Structured questionnaires assessed demographic and socioeconomic characteristics, disease- and treatment-related factors, symptom severity, physical functioning, lifestyle factors, financial toxicity, cancer-related self-efficacy, and self-care ability. Multivariable linear regression analyses were performed with HRQoL as the outcome, adjusting for demographic, socioeconomic, and clinical covariates. Results: The regression model showed strong explanatory power (adjusted R ² = 0.795). Greater symptom severity was associated with poorer HRQoL ( β = −0.630, p = .001), whereas better physical functioning was positively associated with HRQoL ( β = 0.485, p = .002). Financial toxicity remained an independent negative predictor of HRQoL ( β = −0.716, p < .001). Self-care ability was the strongest positive predictor ( β = 0.907, p < .001), and cancer-related self-efficacy was also positively associated with HRQoL ( β = 0.340, p = .006). Conclusions: Among gastrointestinal cancer survivors in Taiwan, financial toxicity and self-care ability are key modifiable determinants of HRQoL, underscoring the importance of routine financial assessment and self-care–focused interventions in survivorship care.

National trends and inpatient outcomes of invasive aspergillosis in hospitalizations with hematologic malignancies: A 2020-2022 National Inpatient Sample analysis.

e18519 Background: Invasive aspergillosis is a severe opportunistic fungal infection affecting immunocompromised patients, particularly those with hematologic malignancies. We examined the inpatient burden and outcomes of invasive aspergillosis among U.S. hospitalizations involving hematologic malignancies. Methods: We performed a retrospective analysis of the 2020–2022 National Inpatient Sample, identifying hospitalizations with hematologic malignancies using ICD-10-CM codes C81–C96. Invasive aspergillosis was defined using ICD-10-CM codes B44.0, B44.1, B44.7, and B44.89; non-invasive forms were excluded. Survey-weighted analyses accounted for the complex sampling design. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay (LOS), total hospital charges, ICU-level care (mechanical ventilation and vasopressor use as proxies), and neutropenia. Multivariate regression adjusted for demographic, socioeconomic, comorbidity, and hospital-level factors. Results: Among approximately 1,789,899 U.S. adult hospitalizations with hematologic malignancies, an estimated 6,170 were complicated by aspergillosis (weighted prevalence 0.34%). Within the aspergillosis group, males predominated (63.5%), and patients younger than 65 years were more common (55.8%). White patients constituted the largest racial group (65.2%), followed by Hispanic (15.3%), Black (8.3%), and Asian patients (7.4%). Medicare was the most common primary payer (45.1%), most hospitalizations had a high comorbidity burden (Charlson score ≥3 in 68.2%), and higher ZIP-code income quartiles were more frequently represented. After multivariate adjustment, aspergillosis was independently associated with higher in-hospital mortality (OR 4.02, 95% CI 3.41–4.75), longer LOS (adjusted increase 12.4 days, 95% CI 10.94–13.78), and higher total hospital charges (adjusted increase $305,750, 95% CI $249,237–$362,264; all p < 0.05). Aspergillosis was also associated with increased illness severity, including higher odds of mechanical ventilation (OR 3.96), vasopressor use (OR 3.08), overall ICU-level care (OR 3.73), and neutropenia (OR 2.59; all p < 0.05). Conclusions: Invasive aspergillosis was an infrequent complication among hospitalizations with hematologic malignancies but was associated with severe inpatient illness and substantial healthcare utilization, highlighting the need for early prognostic awareness and individualized care planning.