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Language use and its relationship to patient experience and treatment compliance in genitourinary oncology.

e23254 Background: Disparities associated to language in cancer care are well-documented however inadequately defined in genitourinary oncology. This study investigates the impact of language proficiency on patient satisfaction and treatment adherence within a heterogeneous outpatient genitourinary (GU) oncology cohort. Methods: We conducted a cross-sectional survey of 138 patients receiving care at a tertiary GU oncology clinic. Participants were categorized as primary English speakers (n=67) or non-English speakers (n=71). The survey assessed outcomes including patient satisfaction and treatment compliance, defined as consistent adherence to treatment without reported delays due to communication or understanding. Categorical variables were compared using chi-square or Fisher’s exact tests, and continuous variables using Student’s t-test or Wilcoxon rank-sum test. To identify factors independently associated with high satisfaction and treatment compliance, we performed multivariable logistic regression. Predictor variables were selected through forward stepwise modeling if they had a univariable P-value <0.25 and clinical relevance. The Akaike information criterion (AIC) and likelihood ratio tests were used to evaluate the model's performance. Results: Non-English speakers reported lower satisfaction (43.7% vs. 70.1%, P=0.003) and less clarity in treatment discussions (36.6% vs. 70.1%, P<0.001). Perceived oncologist understanding was also lower (42.3% vs. 73.1%, P<0.001). In multivariable analysis, high satisfaction was independently associated with English as a primary language (aOR 3.02, 95% CI 1.48–6.17, P=0.002) and younger age (aOR 0.97 per year, 95% CI 0.94–0.99, P=0.04). Among non-English speakers, high clarity in explanations (aOR 3.33, P=0.025) and earlier cancer stage (aOR 0.24, P=0.049) predicted greater satisfaction. Treatment compliance was reported similarly across groups (67.2% English vs. 63.4% non-English, P=0.31), but 40% of adherent non-English speakers still reported delays due to communication challenges. English proficiency (aOR 3.66, 95% CI 1.67–8.01, P=0.001) and earlier cancer stage (aOR 0.59, P=0.043) were associated with higher compliance. Conclusions: Limited English proficiency is independently associated with lower satisfaction and reduced treatment compliance in GU oncology care. Despite institutional language services, non-English speakers report communication gaps that impact care. These findings support incorporating linguistically tailored strategies to enhance equity in cancer communication and adherence.

Global landscape and trends of antibody-drug conjugates in oncology: A machine learning–driven decade-long informatics analysis.

e15038 Background: Antibody-Drug Conjugates (ADCs) are reshaping the treatment standard for a wide range of tumors. However, with the explosive growth of research in this field, it is difficult for researchers to fully grasp the current scientific landscape and future trends. Therefore, this study aims to provide a panoramic view of the global scientific landscape of ADCs in oncology over the past decade. Methods: This study retrospectively collected all relevant studies regarding the application of ADCs in oncology in the last decade. Through unsupervised clustering, all the studies were classified into five research clusters. Further, the emerging research cluster and the most impactful research cluster in the whole field were identified through time series analysis and impact analysis. Finally, through Walktrap algorithm, this study identified research directions that are highly relevant to the field but not yet deeply explored. Results: Quantitative statistical analysis revealed that the application of ADCs in oncology has a favorable development trend (Annual Growth Rate = 18.57%) and global collaboration (International Co-authorship = 28.32%) in the last decade. Through unsupervised clustering algorithm and semantic integration analysis, the application of ADCs in oncology was clustered into five research clusters: Cluster 1 (Basic and Translational Research of ADCs); Cluster 2 (Clinical Trials of ADCs in Hematologic Tumors); Cluster 3 (Clinical Trials of ADCs in Her2+ Breast Cancer); Cluster 4 (Clinical Trials of ADCs in Multiple Solid Tumors); Cluster 5 ( Balance of Clinical Efficacy and Safety of ADCs and its Biomarker Discovery). Further time-series analysis and impact analysis revealed that among these five clusters, Cluster 4 was the emerging cluster (Temporal Central Tendency = 2022.87, Research Effort Dispersion = 0.96) while Cluster 3 was the most impactful cluster (Average Citation = 28.97±26.16). More importantly, the Walktrap algorithm further revealed that “Breast Cancer, Her2, T-DM1, Prognosis” (Relevance Percentage [RP] = 90.9%, Development Percentage [DP] = 36.4%), “Antibody-Drug Conjugates, Cancer, Toxicity, Tumor Microenvironment” (RP = 81.8%, DP = 63.6%), “Brentuximab Vedotin, Hodgkin Lymphoma, CD30, Relapse” (RP = 72.7%, DP = 45.5%) are highly relevant to the field but still underdeveloped, suggesting that they hold noteworthy future research prospects. Conclusions: In conclusion, this study objectively and comprehensively presents the global scientific landscape, concerns, development trends, and future research directions of ADCs in oncology through machine learning-driven informatics analysis methods, providing an important reference for subsequent clinical trial design, decision-making, and in-depth research in this field.

Second primary malignancies (SPM) risk after CAR T-cell therapy: A real-world analysis.

e23445 Background: Chimeric antigen receptor (CAR) T-cell therapy is an engineered T-cell therapy that offers curative potential for patients with relapsed, refractory hematological malignancies. Due to utilization of viral vector-based transduction, genetic modification, and durable remissions in CAR-T responders, ongoing surveillance for second primary malignancies (SPMs) is imperative. This study aims to quantify the burden and characterize SPM subtypes using a large-scale, real-world database of patients treated with FDA-approved CAR T-cell products. Methods: We conducted a retrospective cohort study using de-identified data from the TriNetX Global Collaborative Network, and using ICD-10 codes identified patients with hematologic malignancies between January 1, 2018 and January 25, 2026. Exposure was defined by the administration of CAR T-cell therapy (identified via RxNorm codes), with the index event marked as the first infusion. To ensure the accuracy of SPM status, patients with a documented malignancy prior to the index window were excluded. The primary outcome was the incidence of SPMs, stratified into hematologic versus solid tumor categories. Incidence proportions were calculated within the cohort to assess relative risk. Results: The study cohort included 3,886 patients that were 38.55% female, 61.54% male and had a mean age of 60 ± 12 years. We identified 800 SPMs among the cohort; with a median follow-up of 380 days, the overall cumulative SPM risk was 20.6% (95% confidence interval [CI], 19.3–21.9%). In the distribution of SPM subtypes, hematologic malignancies accounted for the largest proportion (12.25%), followed by solid tumors (8.34%). Among hematologic SPMs, the most frequently observed were MDS/AML (7.6%), non-Hodgkin lymphoma (7.1%), plasma cell disorders (1.5%), and myeloproliferative neoplasms (0.3%). Among solid tumor SPMs, non-melanoma skin cancers (2.8%) were most common, followed by genitourinary (1.4%), gastrointestinal (1.1%), lung (0.9%), sarcoma/GIST (0.7%), and melanoma (0.5%), with breast, brain, thyroid, and gynecological malignancies collectively accounting for less than 1.5% of cases. Conclusions: This large-scale analysis demonstrates that the development of SPMs is a clinically relevant long-term complication of CAR T-cell therapy. The cumulative incidence rates particularly for myeloid neoplasms and skin cancers underscore the necessity for rigorous, lifelong oncological surveillance in this patient population. Demographic characteristics of cohort. Ethnicity Not Hispanic/Latino 3,208 (82.6%) Hispanic/Latino 221 (5.7%) Unknown 457 (11.7%) Race White 3,096 (79.7%) Black/African American 369 (9.5%) Asian 113 (2.9%) Other* 308 (7.9%) Region South 1,360 (35.0%) West/Northwest 1,866 (48.0%) Northeast 622 (16.0%) *Other races include American Indian/Alaska Native, Native Hawaiian or Other Pacific Islander, and unknown race categories.

Tumor treating fields in newly diagnosed glioblastoma: An updated systematic review and meta-analysis with geographic subgroup analysis.

e14087 Background: Tumor Treating Fields (TTFields) combined with temozolomide received FDA approval for newly diagnosed glioblastoma (ndGBM) in 2015. Since the last comprehensive meta-analysis (Ballo et al., 2023), substantial new evidence has emerged, including studies suggesting variable efficacy across geographic regions. No prior meta-analysis has provided pooled hazard ratios for progression-free survival (PFS). We conducted an updated systematic review and meta-analysis to evaluate overall survival (OS) and PFS outcomes with pre-specified geographic subgroup analyses. Methods: PubMed, SCOPUS, and EMBASE were searched through December 2025 following PRISMA guidelines (PROSPERO CRD420261292232). Comparative studies evaluating TTFields plus standard of care (SOC) versus SOC alone in ndGBM were included. Random-effects models estimated pooled hazard ratios. Geographic subgroups (Global, USA, Asia, Europe) were pre-specified. Publication bias was assessed using DOI plots with LFK index. Results: Twelve studies met inclusion criteria (n=5 new studies). TTFields significantly improved OS (HR 0.62, 95% CI 0.51–0.76, p<0.001; I²=70.7%) and PFS (HR 0.65, 95% CI 0.55–0.78, p<0.001; I²=62.7%). US-based studies demonstrated the most consistent benefit with minimal heterogeneity for both OS (HR 0.70, 95% CI 0.59–0.83; I²=0%) and PFS (HR 0.74, 95% CI 0.62–0.89; I²=10.7%). Asian studies showed significant but heterogeneous benefits (OS: HR 0.55, I²=88.2%; PFS: HR 0.59, I²=79.9%). LFK indices indicated no major publication bias (OS: −0.3; PFS: −1.6). Conclusions: This updated meta-analysis confirms TTFields survival benefit in ndGBM and provides the first pooled PFS hazard ratio estimate. US studies demonstrate highly consistent treatment effects. Regional heterogeneity in Asian populations warrants further investigation to optimize patient selection globally. Meta-analysis of overall survival and progression free survival by geographic subgroup. Subgroup N OS HR (95% CI) I² PFS HR (95% CI) I² Global 1 0.63 (0.53–0.76) — 0.63 (0.52–0.76) — USA 5 0.70 (0.59–0.83) 0% 0.74 (0.62–0.89) 10.7% Asia 5 0.55 (0.32–0.93) 88.2% 0.59 (0.41–0.86) 79.9% Europe 1 0.61 (0.39–0.95) — 0.64 (0.42–0.97) — Overall 12 0.62 (0.51–0.76) 70.7% 0.65 (0.55–0.78) 62.7% HR = hazard ratio; CI = confidence interval; OS = overall survival; PFS = progression free survival; N = number of studies. Test for subgroup differences: OS p=0.75; PFS p=0.55.

Cognition of apalutamide + ADT treatment responders versus non-responders.

5085 Background: LIBERTAS (NCT05884398) evaluates intermittent androgen deprivation therapy (ADT) with apalutamide monotherapy in metastatic castration-sensitive prostate cancer (mCSPC). ADT is known to affect cognitive domains such as visuospatial ability and executive function. However, links between cognition and treatment responses remain unclear. LIBERTAS offers an opportunity to examine this relationship in participants with mCSPC. Methods: All 410 participants received apalutamide and continuous ADT during the initial treatment phase, 144 without prior ADT exposure (ADT naive). Participants with PSA <0.2 ng/mL at 6 months were considered responders, otherwise they were non-responders. Cognition was assessed by two tasks from Cambridge Cognition’s CANTAB battery: Paired Associates Learning (PAL; visual memory) and Spatial Working Memory (SWM; executive function) at baseline (C1), 2 months (C3), and 4 months (C5). Outcomes included PAL First Attempt Memory Score (PALFAMS28, higher=better), PAL Total Errors Adjusted (PALTEA28, lower=better), and SWM Between Errors (SWMBE468, lower=better). At each visit, group differences were evaluated using the Mann-Whitney U test. Longitudinal change within and between groups were assessed using linear mixed effect models adjusted for age and testosterone. Results: At all visits, responders had higher PALFAMS28, lower PALTEA28, and lower SWMBE468 than non-responders in the entire sample (Table 1). In ADT-naïve participants, responders (N=100) had higher PALFAMS28 than non-responders (N=44) at C3 (10.48 ± 4.74 vs. 8.59 ± 5.00, p=0.01). SWMBE468 was lower in ADT-naïve responders than ADT-naïve non-responders at C1 (14.25 ± 9.12 vs. 19.30 ± 8.37, p=0.001) and C5 (15.42 ± 8.58 vs. 19.77 ± 11.06, p=0.01). Among all participants and within the ADT-naïve group, only the responders' performance changed over time: PALFAMS28 increased and PALTEA28 decreased from C1 to C5 and SWMBE468 increased from C1 to C3 (p <0.01). No significant time-by-group interaction emerged. Conclusions: Analyzed in retrospect, responders outperformed non-responders in visual memory and executive function at baseline and throughout initial treatment, maintaining a cognitive advantage. Though not tested, we hypothesize early cognitive performance could be considered among a constellation of clinical factors to prognosticate treatment response, support patient stratification and personalize treatment strategies. Clinical trial information: NCT05884398 . Significant differences between responders and non-responders. Measure Visit Responders (N=266): Mean ± SD Non-Responders (N=144): Mean ± SD P value PALFAMS28 C1 9.43 ± 4.53 8.18 ± 4.08 0.005 C3 9.78 ± 4.65 8.07 ± 4.30 <0.001 C5 10.16 ± 4.85 8.47 ± 4.80 0.003 PALTEA28 C1 28.52 ± 17.94 32.92 ± 17.83 0.02 C3 26.74 ± 17.90 31.90 ± 18.83 0.007 C5 25.74 ± 18.40 31.80 ± 20.00 0.004 SWMBE468 C1 15.26 ± 9.00 18.03 ± 7.95 0.008 C3 16.44 ± 9.08 18.73 ± 9.07 0.03 C5 14.79 ± 9.30 17.89 ± 9.83 0.004

Navigating the post–covalent bruton tyrosine kinase inhibitor (cBTKi) landscape in mantle cell lymphoma (MCL): Real-world insights on treatment patterns, discontinuation, and healthcare resource utilization (HCRU).

7058 Background: cBTKis have become standard therapy for relapsed/refractory MCL and are rapidly advancing to the first-line setting. However, real-world evidence on clinical and economic outcomes following cBTKi therapy is limited. Treatment patterns, time to treatment discontinuation (TTD), and HCRU were evaluated among patients (pts) with MCL previously treated with cBTKis. Methods: This retrospective observational study used claims data from the Symphony Integrated Dataverse (Jan 2020-Aug 2025) to identify adults with MCL who received a cBTKi in any line of therapy (LOT) and, following discontinuation, initiated another treatment. Post-cBTKi regimens were categorized as B-cell lymphoma 2 inhibitor (BCL2i), cBTKi, noncovalent BTKi (ncBTKi), chimeric antigen receptor T-cell therapy (CAR-T), chemo±immunotherapy (C±IT), and other. TTD and HCRU (outpatient/inpatient/other medical, reported per-patient-per-month [PPPM]), were assessed for regimens received post cBTKi. Results: Of 10,519 total US pts with MCL, 571 were previously treated with cBTKis and received a subsequent therapy (median age, 72.0 years; ≥65 years, 77%; male, 74%; White non-Hispanic, 67%; Medicare, 62%). Regimens received in a subsequent LOT after cBTKi included cBTKis (38%), ncBTKis (32%), C±IT (11%), BCL2is (9%; monotherapy 7%), CAR-T (2%), and other (8%). Median TTD was longest with cBTKis (365 days), followed by ncBTKis (206 days), and shortest with BCL2is (140 days). Mean HCRU PPPM was lowest with cBTKis (outpatient, 1.21; inpatient, 0.20; other medical, 1.07) and highest with CAR-T (outpatient, 10.63; inpatient, 1.89; other medical, 1.55). Conclusions: In this real-world analysis, pts with MCL who previously received cBTKis were most frequently re-treated with cBTKis, highlighting the need for novel treatment options in the post-cBTKi setting. TTD was greatest in pts who received cBTKis or ncBTKis and shortest in those treated with BCL2is. HCRU burden was lowest for pts who received cBTKis and highest for those treated with CAR-T. Further research, including an understanding of the reasons for re-exposure to cBTKis, is warranted to confirm these findings. TTD and HCRU by MCL treatment regimens received post cBTKi. Outcomes AllN=571 cBTKin=215 ncBTKin=182 C±ITn=62 BCL2in=53 CAR-Tn=12 Follow-up, median (IQR), days 294(118-628) 414(206-762) 189(89-453) 330(116-727) 256(70-844) 412(216-912) TTD, median (95% CI), days 222(181-281) 365(278-460) 206(173-304) 169(112-183) 140(100-315) NA HCRU, mean (SD), PPPM Outpatient 1.95 (2.82) 1.21 (1.61) 1.48 (2.19) 2.19 (2.65) 2.34 (2.70) 10.63 (5.05) Inpatient 0.34 (0.91) 0.20 (0.67) 0.33 (0.75) 0.29 (0.82) 0.43 (1.22) 1.89 (1.89) Other medical services 1.47 (2.62) 1.07 (1.93) 1.35 (2.54) 2.54 (3.59) 1.64 (2.82) 1.55 (1.70)

Prognostic impact of AXL expression in upper gastrointestinal cancer in MONSTAR-SCREEN-2: An international collaborative study between United States and Japan.

4032 Background: AXL, a receptor tyrosine kinase of the TAM family, promotes epithelial-mesenchymal transition (EMT) and tumor progression. Elevated AXL expression is reported as poor prognostic factor with immunosuppressive features in colorectal cancer (Karam Ashouri, et al. J Immunother Cancer. 2025). We investigated the prognostic impact of AXL expression and its associated molecular and tumor microenvironment (TME) features in upper gastrointestinal (GI) cancers. Methods: Treatment-naïve patients with gastric cancer (GC) and esophageal cancer (EC) enrolled in MONSTAR-SCREEN-2 with available RNA-seq data (Caris MI TumorSeek) were analyzed. AXL expression was dichotomized by median into high and low groups within each cancer type. Molecular alteration, including somatic mutations and copy number alterations, and expression of receptor tyrosine kinases, including FGFRs, VEGFRs, and EGFR were compared between groups. Overall survival (OS) was evaluated using Kaplan-Meier analysis and Cox proportional hazards models. Tumor microenvironment (TME) cell infiltration, assessed using xCell deconvolution and gene set enrichment analysis (GSEA) performed using Hallmark gene sets, was compared between AXL-high and AXL-low groups. Results: A total of 320 patients were analyzed (GC: n = 270; EC: n = 50). In GC, AXL-high patients were older than AXL-low patients (median 71 vs 66 years, p = 0.012), while no other baseline characteristics, including sex, histology, primary site, metastatic sites, microsatellite instability-high, and tumor mutation burden-high status, differed between groups. ARID1A mutations were enriched in AXL-high GC (p < 0.05), while CCNE1 amplification was associated with AXL-low (p < 0.05). Across both cancer types, AXL-high tumors exhibited significantly higher expression of FGFR1, VEGFR1-3, and MET (p < 0.01). In GC, AXL-high was associated with significantly shorter OS compared to AXL-low (median 12.9 vs 16.6 months; HR 1.44, 95%CI 1.03-2.02; p = 0.034). Similarly in EC, AXL-high showed worse OS compared to AXL-low (median 10.4 vs not reached; HR 2.46, 95%CI 1.08-5.62; p = 0.027). TME analysis revealed increased stromal scores, endothelial cells, M1/M2 macrophages, and regulatory T cells, along with higher expression of immune checkpoint molecules, including PD-L2 and CTLA4, in AXL-high tumors. GSEA showed enrichment of EMT, IFN-γ response, and PI3K/AKT/mTOR pathways in AXL-high GC. Conclusions: AXL overexpression is a prognostic biomarker in upper GI cancers, and is associated with worse survival and a distinct molecular and immune landscape characterized by EMT activation and immune-suppressive TME. These findings support AXL as a potential therapeutic target and warrant further investigation of AXL-targeted therapy in upper GI cancers.

AQP4 and MOG as definers of distinct autoantibody signatures in immune checkpoint inhibitor–induced optic neuritis.

12128 Background: Checkpoint blockade–induced optic neuritis (CBON) is a rare but vision-threatening immune-related adverse event with limited response to standard immunosuppression and no established diagnostic biomarkers. The humoral immune mechanisms underlying CBON remain poorly characterized, limiting early recognition and mechanistic understanding. Methods: We conducted a multicenter study integrating three independent CBON cohorts (n=25, 29, and 34) and 49 ICI-treated controls without neuro-ophthalmic complications, enrolled between January 2020 and June 2025. CBON cases were identified from a prospective biospecimen bank of >2,300 ICI-treated patients. Leveraging pre-ICI baseline, prodromal-phase, onset, and follow-up serum samples (>2,300 total samples), IgG autoantibodies against 25 neural surface antigens were assessed using cell-based assays. Longitudinal antibody dynamics and associations with clinical and oncologic features were evaluated. Results: Across 88 CBON patients, the autoantibody response was highly antigen-specific and dominated by aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). AQP4-IgG or MOG-IgG was detected in 32–48% of CBON cases across cohorts, while paraneoplastic, synaptic, and other neural autoantibodies were rare (<12%). AQP4-IgG and MOG-IgG were largely mutually exclusive, suggesting distinct immunologic subtypes of CBON. These antibodies were virtually absent in ICI-treated controls (0–2%). Longitudinal analyses demonstrated consistent seronegativity prior to ICI exposure, followed by seroconversion at symptom onset with persistent antibody titers during follow-up despite corticosteroid therapy, consistent with a sustained humoral immune response. Autoantibody status showed limited and inconsistent associations with demographic, oncologic, or clinical characteristics. Conclusions: CBON is characterized by a distinct, antigen-specific humoral immune response targeting AQP4 or MOG that emerges following ICI exposure. These findings support an ICI-triggered breakdown of immune tolerance and establish a serologic framework for CBON diagnosis and classification. Incorporation of AQP4-IgG and MOG-IgG testing may aid early recognition and risk stratification of visual immune-related adverse events during immunotherapy.

A national analysis of in-hospital outcomes following cytoreductive surgery with HIPEC.

e16497 Background: Cytoreductive surgery with hyperthermic intra-peritoneal chemotherapy (HIPEC) is an aggressive multi-modal treatment strategy used in carefully selected patients with peritoneal surface malignancies. The procedure combines extensive surgical debulking with intra-peritoneal circulation of heated chemotherapy to eradicate residual microscopic disease while limiting systemic toxicity. In this study, we examined in-hospital outcomes, healthcare resource utilization, and palliative and end-of-life care patterns associated with HIPEC using a nationally representative inpatient database. Methods: We conducted a retrospective cohort study using the National Inpatient Sample to identify adult hospitalizations for colorectal, ovarian, appendiceal, gastric, primary peritoneal, and secondary peritoneal malignancies. Hospitalizations involving HIPEC were compared with non-HIPEC cancer related admissions. Survey weighted multivariable logistic and linear regression models were used and adjusted for patient demographics, hospital characteristics, and Elixhauser comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included ICU admission, mechanical ventilation, central venous catheterization, vasopressor use, blood transfusion, length of stay, total hospital charges, palliative care consultation, and do not resuscitate (DNR) status. Results: Among approximately 3 million abdominal cancer related hospitalizations, 6,950 patients underwent HIPEC, most commonly for colorectal, ovarian, appendiceal, and peritoneal malignancies. After multivariable adjustment, HIPEC was associated with significantly lower in-hospital mortality (adjusted odds ratio [aOR] 0.11; 95% CI 0.05–0.24; p < 0.001). HIPEC was associated with higher utilization of critical care resources, including ICU admission (aOR 1.68), mechanical ventilation (aOR 1.77), central venous catheter placement (aOR 1.49), vasopressor support (aOR 2.67), and blood transfusion (aOR 1.44) (all p≤0.01). HIPEC was also associated with longer hospital stay (+2.60 days) and higher total charges (+$127,467) (both p < 0.001). Notably, HIPEC recipients were significantly less likely to receive palliative care consultation (aOR 0.11) or DNR orders (aOR 0.03) (both p < 0.001). Conclusions: In this large national cohort, HIPEC was associated with lower in-hospital mortality regardless of substantially increased critical care utilization, length of stay, and costs, suggesting a favorable short term survival benefit despite utilization of high intensity care. The low utilization of palliative and end-of-life care may reflect the highly selected nature of the population undergoing this procedure and a predominant intent of HIPEC as life prolonging therapy.

Machine learning–optimized multi-biomarker panel for discriminating lung cancer from LDCT-positive benign pulmonary nodules.

10539 Background: Accurate discrimination between lung cancer and benign pulmonary nodules remains a critical challenge in lung cancer screening, particularly among individuals with positive findings on low-dose computed tomography (LDCT). Blood-based biomarkers with proven biological relevance may improve risk stratification when integrated with advanced analytical approaches. Serum carcinoembryonic antigen (CEA), serum amyloid A (SAA), and osteopontin (OPN) are biomarkers reflecting tumor burden, host inflammatory response, and tumor microenvironmental activity, respectively. The discriminatory performance of these three biomarkers between healthy individuals and lung cancer patients has previously been validated in a cohort exceeding 2,000 subjects (ASCO 2025, Abstract #489322). Building on this foundation, the present study evaluates whether algorithmic integration of these biomarkers can improve discrimination of lung cancer within the clinically challenging population of LDCT-positive pulmonary nodules. Methods: Serum CEA, SAA, and OPN levels were quantified by ELISA in patients with histologically confirmed lung cancer and individuals with LDCT-positive benign pulmonary nodules. To enhance discrimination within this high-risk cohort, machine learning–based modeling was applied. Multiple analytical methods were evaluated, and a Random Forest classifier was selected to capture inter-marker correlations and non-linear biological relationships. The dataset was divided into independent training and validation cohorts. Diagnostic performance was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: In the LDCT-positive pulmonary nodule population, the machine learning–optimized three-biomarker panel demonstrated strong discriminatory performance. In the validation cohort, the model achieved an AUC of 0.879, with a sensitivity of 88.8% and a specificity of 83.3% for differentiating lung cancer from benign nodules. The algorithm consistently outperformed individual biomarkers and linear models, including in early-stage lung cancer. Conclusions: Application of machine learning to a biologically complementary three-protein biomarker panel significantly enhances discrimination of lung cancer within LDCT-positive high-risk pulmonary nodule populations. These findings support the clinical utility of this non-invasive approach as an adjunct to LDCT, addressing a key diagnostic gap in lung cancer screening and management.

Prognostic significance of imaging-detected extranodal extension (iENE) in pathological ENE-negative head and neck squamous cell carcinoma.

6079 Background: Advances in perioperative systemic therapy for head and neck squamous cell carcinoma (HNSCC) (e.g., KEYNOTE-689) have increased the need to tailor postoperative management, balancing oncologic benefit against toxicity and resource constraints. Imaging-detected extranodal extension (iENE) has been incorporated as a potential prognostic factor in the UICC TNM 9th edition. However, the prognostic impact of iENE among patients without pathological extranodal extension (pENE) remains unclear. We evaluated the association between iENE status and clinical outcomes in pENE-negative HNSCC. Methods: We retrospectively reviewed patients with HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx, radiologically suspected lymph node metastasis, and underwent primary surgery with neck dissection without adjuvant therapy, between 2012 and 2021. Eligible patients had pathologically confirmed lymph node metastasis, negative surgical margins, and no evidence of pENE. Preoperative iENE status was assessed by board-certified radiologists. Survival endpoints included event-free survival (EFS) and overall survival (OS). Patients were stratified into low-risk (non-candidates for adjuvant therapy) and intermediate-risk (candidates for postoperative radiotherapy alone) groups according to NCCN guidelines. Results: Of 3,771 screened patients, 133 met the eligibility criteria (low-risk: 20, intermediate-risk: 113), of whom 41 (30.8%) were iENE-positive. At a median follow-up of 60.6 months, iENE-positive patients demonstrated poorer outcomes than iENE-negative patients, including shorter EFS (5-year: 33.1% vs 55.4%; hazard ratio [HR], 1.69; p=0.029). The association between iENE positivity and inferior EFS was observed consistently across both risk strata. Overall survival also favored iENE-negative patients (5-year: 80.4% vs. 68.7%). On multivariate analysis, iENE positivity, ECOG Performance Status ≥1, and lower baseline serum albumin were independently associated with poorer EFS. Patients meeting none of the three factors had excellent outcomes despite omission of adjuvant therapy (5-year EFS: 69.8%, 5-year OS: 88.0%). Conclusions: iENE may help identify an unfavorable-prognosis subset among pENE-negative HNSCC patients. The study cohort predates the routine use of perioperative immunotherapy, and the generalizability of these findings in contemporary treatment settings requires prospective validation. Five-year EFS by iENE status: Overall and by risk group. Group iENE status 5y-EFS HR (95% CI) P-value ALL (n = 133) Positive 33.1% 1.69 (1.05-2.71) 0.029 Negative 55.4% Ref. Intermediate risk (n = 113) Positive 34.2% 1.57 (0.94-2.63) 0.08 Negative 51.9% Ref. Low risk (n = 20) Positive 28.6% 3.57 (0.85-15.04) 0.06 Negative 76.9% Ref.

Effect of a weight loss intervention (WLI) on quality of life (QOL) and symptoms in women with breast cancer: Results from the Breast Cancer Weight Loss (BWEL) trial.

12010 Background: BWEL (Alliance A011401; NCT02750826) is a Phase III trial that randomizes patients (pts) with stage II-III breast cancer and body mass index (BMI) ≥27 kg/m 2 1:1 to a 24-month (mo) lifestyle-based WLI + health education (HE) or HE alone. Here we report prespecified secondary outcomes of the impact of the WLI on patient-reported QOL and symptoms. Methods: The first 540 BWEL pts (randomized between 9/2016 and 7/2017) were included in this substudy that collected PROMIS 29 Profile 2.0 and Global Health scores at enrollment, 6 and 24 mos. Adjusting for baseline scores, mean physical function (predefined substudy primary outcome), global physical and mental health, fatigue and other scores were compared at 6 and 24 mos using analysis of covariance (ANCOVA). P-values <0.05 were considered significant. Positive differences in positive attributes (e.g., physical function) and negative differences in negative attributes (e.g., anxiety) represented better outcomes in the WLI arm. Results: At baseline, median BMI was 32.9 kg/m 2 (26.5 – 69.1), median age was 53 (25 - 78) years; 83.9% of pts were non-Hispanic White, 10.7% were Black and 5.9% were Hispanic. At 6 mos, the WLI (vs HE) arm had significantly better physical function (ANCOVA-based mean difference between arms 1.9 [95% CI 0.8, 3.0]; p<0.001), global physical health (2.0 [95% CI 0.9, 3.0]; p<0.001), global mental health (1.30 [95% CI 0.2, 2.4], p=0.03), social roles and activities (2.3 [95% CI 1.1, 3.6]; p<0.001), and fatigue (-1.7 [95% CI -3.1, -0.4], p=0.01) (Table). Improvements were generally maintained at 24 mos. Similar findings were seen in analyses using longitudinal mixed modeling. Conclusions: The BWEL WLI demonstrated QOL benefits for patients with breast cancer, resulting in significantly better physical function, global physical and mental health, and symptoms. Future analyses will evaluate which populations experienced the most benefit, as well as the relationships among QOL, symptoms, and weight loss. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820; U10CA180868; U10CA180863, CCS 707213; U10CA180888; UG1CA189858; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02750826 . Analysis of covariance-adjusted least squares means values at 6-mos adjusted for baseline scores. QOL/Symptom Attributes HE WLI Between arm difference (95% CI)* P value Physical Function 47.1 49.0 1.9 (0.8, 3.0) <0.001 Global Physical Health 46.2 48.1 2.0 (0.9, 3.0) <0.001 Global Mental Health 48.6 49.9 1.3 (0.2, 2.4) 0.03 Social Roles and Activities 52.7 55.0 2.3 (1.1, 3.6) <0.001 Anxiety 50.2 50.0 -0.2 (-1.6, 1.2) 0.77 Depression 47.5 47.5 -0.0 (11.2, 1.2) 0.96 Fatigue 50.6 48.9 -1.7 (-3.1, -0.4) 0.01 Sleep Disturbance 51.0 51.1 0.1 (-0.6, 0.8) 0.80 Pain Interference 51.3 50.3 -1.0 (-2.4, 0.4) 0.15 *Positive differences in positive attributes and negative differences in negative attributes favor WLI arm.

Assessing the role of oncologist type in shared decision-making for patients with metastatic breast cancer.

e13085 Background: Metastatic breast cancer (MBC) involves complex treatment plans, as patients and their oncologists must balance extending life with maintaining quality of life, within a landscape of rapidly increasing therapeutic options. Shared Decision-making (SDM), a collaborative approach between clinician and patient, underscores the importance of patient engagement in their treatment decisions. This patient-led study examined the relationship between seeing a breast specialist and perceptions of shared decision-making for people with MBC. Methods: We collected data using a self-administered survey developed by the Patient-Centered Dosing Initiative, a patient-led nonprofit working to bring real-life experience into cancer treatment decisions. Eligible participants were aged ≥18 years, US residents, with a self-reported history of MBC. Participants were asked whether their primary oncologist treated exclusively breast cancer patients (yes/no/I don’t know). They also rated their level of agreement on a 6-point (0 to 5) scale using the validated 9-item SDM-Q-9 instrument. We calculated the median (Med) and standard deviation (SD) of the summed SDM score (Min:0, Max: 45) and of individual SDM-Q-9 items (Min: 0, Max: 5), where higher scores indicated having a greater sense of SDM. We used Mann-Whitney U tests to compare medians between respondents who saw a breast specialist and those who did not. P values less than 0.05 were considered statistically significant. Results: There were 501 respondents with MBC with complete survey data. Participants had a mean age of 55 and 62.9% (n = 315) reported seeing a breast specialist. The overall median summed SDM-Q-9 was 40 (SD:15.2) and was statistically different (p = 0.043) between respondents who saw a breast specialist (Med: 42, SD: 15.7) and those who did not (Med: 37, SD: 14.2). For the specific SDM item “My doctor and I selected a treatment option together,” respondents who saw a breast specialist had significantly higher median SDM scores (Med: 5.0, SD: 1.6) than those who did not (Med: 4.0, SD: 1.5), (p = 0.011). For the SDM item “My doctor precisely explained the advantages and disadvantages of treatment options,” respondents who saw a breast specialist had significantly higher median SDM scores (Med: 5.0, SD: 1.4) than those who did not (Med: 4.0, SD: 1.4), (p = 0.008). Conclusions: Patients with MBC reported high levels of shared decision-making overall; however, patients treated by breast specialists reported significantly greater overall shared decision-making. The differences across several subdomains indicate that patients seeing breast specialists may be more involved in treatment selection and communication about treatment trade-offs. These differences identify potential system-level targets across different types of oncology practices to improve patient-centered, preference-concordant care in MBC.

Perspectives of oncology professionals on cancer care for displaced populations in Africa.

e13503 Background: Over 45.9M Africans are forcibly displaced, including over 35M Internally Displaced Persons and around 10 million refugees and asylum seekers. Despite this reality, the cancer care needs of these populations remain poorly addressed in research and policy. This mixed-methods study explored the continuum of cancer care for displaced populations in Africa from the perspective of oncology care professionals (OCPs). A study protocol was developed and ethical clearance obtained from Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Methods: A bilingual English/French online survey designed by the African Organization for Research and Training in Cancer, Special Interest Group on Cancer in Conflict and Displacement Settings was administered to OCPs between Jun-Nov 2025 capturing respondents' geographic location, the demographic characteristics of the displaced patients served, respondents’ professional experiences, perceived challenges, and comparative access and financial cost of cancer care for refugees and asylum seekers as compared to nationals. Data were analyzed using Excel and SPSS. Results: 130 responses were received from 18 African countries, with the highest representation from Uganda, Ethiopia, and Kenya, followed by Cameroon, Nigeria, and Burkina Faso. Incomplete responses and those not providing care to displaced populations were excluded and sixty seven responses were included. Over 60% of respondents worked in public cancer facilities, less than 10% and 30% in private, and mixed-type facilities successively. The number of patients treated by each respondent over the last 18 months was 1-20, the majority of whom were children under 18 years old and a higher percentage of patients were females. Breast cancer was the most common type of cancer, followed by cervical cancer, colorectal cancer, lymphoma, and leukemia. More than 50% of respondents indicated that refugees have equal access to care at no extra cost when compared to nationals. Only 25% respondents were aware of any additional support provided to refugee and asylum seeker patients by humanitarian organizations. A substantial majority of respondents (82%) did not receive any dedicated training in providing cancer care to displaced populations, and 88% indicated that such training is highly needed. Key barriers include socio-cultural, economic and psychological impact of displacement, late-stage presentation, high pressure on services, funding shortages, poor treatment adherence, limited service availability and referral challenges. Conclusions: Addressing the cancer care needs of displaced populations is a reality for OCPs in Africa, yet a deficit in relevant training persists. To enhance the quality of service and improve patient outcomes among these vulnerable populations, OCP training and bridging the cultural, financial and service gaps must be prioritized.

Designing a triple-negative breast cancer patient journey: A multi-stakeholder initiative to improve clinical pathways and communication in Italy.

e13507 Background: Triple negative breast cancer (TNBC) is associated with poor prognosis and complex management, requiring a dedicated and adequate care pathway. To address this need, Fondazione The Bridge and Bridge for Future-University of Pavia, in collaboration with AIOM (Italian Society of Clinical Oncology) and FAVO (Italian Federation of Voluntary Associations in Oncology), developed a patient-centered TNBC Patient Journey (PJ) for the Italian healthcare setting, to provide accessible information to all stakeholders who are not expert in the breast cancer care such as patients (pts), caregivers, patient associations, other healthcare professionals, healthcare managers and politicians. Methods: A multidisciplinary core group of 9 professionals, including a breast oncologist, radiologist, surgeon, geneticist, patient representative, health policy expert and health economist was established. Firstly, they analysed existing guidelines and care pathways present in literature. Secondly, additional professionals (psycho-oncologist, cardio-oncologist, nutritionist, gynaecologist, pathologist, nurse, plastic surgeon, radiation oncologist, general practitioner and specialist in bone, fertility, nuclear medicine, palliative care) from Breast Units (BUs) and pts’ associations were involved through structured interviews to identify best practices. Starting from these interviews, some key statements defining an optimal TNBC care pathway were selected and validated using a modified Delphi process. Besides, a National survey among Italian BUs was performed to assess the relevance of each statement and its real implementation in every BU. Finally, outcomes were translated into a PJ and a Vademecum. Results: From February 2024 to June 2025 the working group developed 2 main documents: a PJ, mainly addressed to pts and caregivers in a less technical language, and a Vademecum containing clinical explanations, best practices and gaps in pts care; this second tool was designed to provide a clear and deep information about the data reported in the PJ. The manuscripts have been enhanced with visual elements and colour images designed to facilitate reading and draw the reader’s attention. Both documents described the ideal journey of pts distinguishing different pathways in relation to BRCA1/2 status mutation (carriers vs non-carriers). The materials were disseminated nationally through online publication on the websites of involved organizations, printed distribution, press events and meetings with policymakers. Conclusions: This initiative highlights the feasibility and value of a multidisciplinary, co-designed approach to develop accessible, patient-centered tools in TNBC care. The PJ supported standardized and informed care while emphasizing the need for adaptable pathways in a rapidly evolving therapeutic landscape.

A phase III trial evaluating addition of adjuvant chemotherapy to ovarian function suppression + endocrine therapy in premenopausal women with pN0-1, HR+/HER2– breast cancer and Oncotype recurrence score ≤ 25 (OFSET): NRG-BR009.

TPS650 Background: The TAILORx and RxPONDER trials showed that recurrence score (RS) identifies many postmenopausal pts who do not benefit from addition of ACT to endocrine therapy (ET); however, RS also identifies subsets who do benefit (node-neg/high clinical risk/RS 16-20, node-neg/RS 21-25, and node-pos/RS ≤25). Most premenopausal pts in these trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR+/HER2– BC in SOFT/TEXT, we question whether the ACT benefit in TAILORx/RxPONDER was due to chemotherapy-induced OFS. To address this, we developed OFSET, a phase III clinical trial comparing OFS+ET to ACT+OFS+ET. Methods: We hypothesize that addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal pts with early-stage HR+/HER2– tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival, overall survival, distant recurrence-free interval, breast cancer-free interval, and health-related quality of life (HRQOL). Pts must be node-neg with RS 16-20 (plus high clinical risk), RS 21-25, or have 1-3 positive nodes with RS ≤25. Stratification is by nodal status/RS status (pN0 RS 16-25; pN1 RS 0-15; pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39; ≥40). Pts are randomized after surgery to either OFS+ET or ACT+OFS+ET. ET is an aromatase inhibitor (AI) per physician discretion; or tamoxifen if AI is not tolerated or if OFS is incomplete. Radiotherapy will be administered per protocol guidelines. An HRQOL sub-study will assess severe menopausal symptoms (measured by FACT ESS-19) and pain severity (PROMIS) between arms. Blood and tumor specimens will be collected for future research. We anticipate accrual of 3,960 pts in 7 yrs, 7 mos. Per NSABP B-28/RxPONDER data, 5-yr IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Per TAILORx data, 5-yr IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of pts to be pN0 and 44% pN1, and a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET v OFS+ET, with 1-sided α of 0.025 and 80% power, will require 380 IBCFS events, expected to occur ~11 yrs after study initiation. Accrual is 496/3,960 (from 8/2023 to 1/2026). NCT #: NCT05879926. Clinical trial information: NCT05879926 .

Inhomogeneous Strain‐Modulated Phonon Scattering Sustains Hot Electrons for Enhanced Enzymatic Therapy

ABSTRACT Enzymatic therapy holds potential as a tumor therapeutic approach, yet enhancing the catalytic activity of nanozymes remains a challenge in tumor cells. Here, we designed a strain‐engineered nanozymes (PWO) based on platinum (Pt) nanodots epitaxially grown on tungsten oxide (WO x ) nanoribbons, which introduced inhomogeneous lattice strain. The phonon spectrums reveal the different influences on acoustic and optical branches caused by inhomogeneous strain. Enhanced acoustic phonon scattering promotes elastic electron–phonon interactions, enabling hot electrons to retain energy as confined lattice heat rather than dissipating as bulk photothermal output. Consequently, the photothermal conversion efficiency of WO x decreased from 37.19% (unstrained) to 20.80% (strained), confirming the formation of confined lattice heat. Under the synergistic effect of confined lattice heat and contact potential difference, the activation energy of the enzymatic catalytic reaction was reduced by 51.30% due to hot electrons. Moreover, PWO caused damage to mitochondria and the cytoskeleton, leading to the eventual induction of apoptosis in tumor cells. These results elucidate the physical manifestation of electron‐phonon and phonon‐phonon scattering under inhomogeneous strain and provide a general strategy for improving nanozyme catalysis via hot‐electron regulation in enzymatic therapy.

Computational modeling in the optimization of lipid nanoparticles for efficient siRNA delivery: Design, molecular dynamics simulations, and experimental validation

Fast-acting covalent protein drugs

Dynamic Redox‐Active Self‐Assembled Monolayers Enable Robust Inverted Tin–Lead Perovskite Solar Cells

ABSTRACT Tin–lead (Sn–Pb) perovskites have quickly emerged as essential absorbers for narrow‐bandgap (NBG) perovskite solar cells (PSCs). However, their development is severely constrained by interfacial energy‐level misalignment and chemical instability at the buried interface. This mismatch induces charge extraction barriers, while the rapid oxidation of Sn 2 + creates deep trap states and detrimental p‐type self‐doping. Here, we propose novel redox‐active self‐assembled monolayers (SAMs) as functional hole‐transport layers (HTLs) using ferrocene (FC) derivatives, ferrocene acetic acid (FCAA) and ferrocene carboxylic acid (FCCA), showing better interfacial energetics and eliminating chemical defects via redox mediation. We found that the energy levels of FC‐based SAMs align more closely with the Sn–Pb perovskite, promoting efficient hole extraction. Moreover, the reversible FC/FC + redox process establishes a dynamic cycle, effectively suppressing the undesired oxygen‐ and light‐inducing metallic Pb 0 and oxidized Sn 4+ . FCAA, with a longer alkyl chain that enables stronger electron‐donating and redox properties, shows superior to FCCA, achieving a champion power conversion efficiency (PCE) of 23.8%, and retains 95.8% after 2000 hours of storage with significantly inhibited oxidized Sn species. This study proposes a novel functional HTL for Sn–Pb PSCs, providing a promising way for high‐performance and stable all‐perovskite tandem photovoltaics.