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Genomic biomarkers of sensitivity to bipolar androgen therapy (BAT) in metastatic castration-resistant prostate cancer (mCRPC).

5064 Background: In most cases, mCRPC remains driven by persistent androgen receptor (AR)-signaling. BAT has shown benefit in a subset of patients (pts) with mCRPC through multiple mechanisms of action, including modulation of AR activity, induction of DNA double-strand breaks and cell cycle arrest. There is a need for predictive biomarkers to identify patients most likely to benefit from BAT. Methods: This retrospective multicenter study included pts with mCRPC treated with BAT who had undergone tumor genomic profiling up to one month prior to BAT initiation. Somatic alterations were correlated with PSA50 response rates (≥50% decline in PSA from baseline), time to treatment failure (TTF) and overall survival (OS). PSA50 associations were assessed using Fisher’s exact test and logistic regression. Time-to-event outcomes were analyzed using Kaplan–Meier and Cox models. Independent predictors were evaluated using multivariable logistic regression and Cox models. Results: We identified 104 pts for inclusion. The median age was 72 years and 49.4% of pts presented with metastases at diagnosis. PSA50 was achieved in 39.4% overall. Median TTF and OS were 3.7 (95% CI: 3.0–4.9) and 28.5 (95% CI: 23.5–35.1) months, respectively. AR amplification, TP53 alterations and double-hit tumor suppressor alterations involving TP53 / RB1 / PTEN were all strongly associated with better PSA50 (Table). In multivariable analysis (MVA), AR amplification (OR 4.00, 95% CI 1.23–13.01; p = 0.021) and TP53 alterations (OR 5.18, 95% CI 1.71–15.71; p = 0.0037) remained independently associated with PSA50 In survival analyses, AR ligand-binding domain mutations that reduce testosterone binding affinity (low-affinity AR-LBD mutations: L702H, W742C, T878A/S) were linked to shorter TTF and remained independently associated in MVA (HR 2.19, 95% CI 1.15–4.18; p = 0.017), together with metastatic disease at diagnosis (HR 1.82, 95% CI 1.17–2.84; p = 0.008). Conclusions: Distinct genomic alterations are associated with sensitivity to BAT in mCRPC patients. AR amplification, TP53 alterations and TP53/RB1/PTEN double-hit status were all associated with increased likelihood of PSA response, while low-affinity AR-LBD mutations identify patients at risk for early treatment failure. These findings are in line with prior studies and support genomic profiling to refine patient selection for BAT. PSA50 TTF OS OR (95% CI) P value HR (95% CI) P value HR (95% CI) P value TP53 alterations 5.3 (1.9–15.4) 0.002 0.7 (0.4-1.1) 0.100 1.8 (1.0-3.3) 0.067 Double hit (TP53, RB1, PTEN) 4.4 (1.4–13.6) 0.013 0.8 (0.5-1.3) 0.313 1.7 (0.9-3.2) 0.115 AR amplification 4.6 (1.7–13.0) 0.003 0.7 (0.4-1.1) 0.110 0.9 (0.5-1.7) 0.809 Low affinity AR-LBD mutations 0.4 (0.1-1.5) 0.231 2.6 (1.4-4.6) 0.002 1.9 (0.9-3.89) 0.076 DDR alterations 0.6 (0.2-1.3) 0.210 1.3 (0.8-2.0) 0.223 1.6 (1.0-2.6) 0.057

Real-world evaluation of a deep learning–based serial CT imaging biomarker with variable thoracic and abdominopelvic coverage in metastatic colorectal and kidney cancers.

e15512 Background: Early on-treatment biomarkers that predict overall survival may benefit treatment decisions and clinical trial evaluations, particularly when tumor-burden changes are weakly associated with survival, such as with immune-based therapies. Deep learning applied to routinely acquired CT may capture prognostic signal beyond tumor size, but real-world scans vary in anatomic coverage. We evaluated the real-world generalizability of a serial deep learning CT biomarker across abdominal malignancies and variable anatomic imaging. Methods: Serial CT response score (Serial CTRS) is a fully automated deep learning biomarker that predicts overall survival (OS) using baseline and early on-treatment CT scans. Serial CTRS previously demonstrated improved OS prediction compared to tumor-sized based metrics when trained on thoracic CT scans from advanced non-small cell lung cancer (aNSCLC) patients. In the present study, Serial CTRS was expanded to use thoracic, abdominal, and pelvic CT images as available, trained using real-world aNSCLC data (1,178 patients; 16,790 CT series). Serial CTRS, generalized for variable anatomical coverage, was retrospectively applied to two real world cohorts with abdominal primary cancers: 92 patients with metastatic renal cell and other kidney cancer treated with immune checkpoint inhibitors (RCC cohort) and 76 patients with metastatic colorectal cancer treated with chemotherapy (CRC cohort). Serial CTRS was generated using pretreatment scans paired with follow up scans within 28 to 120 days from treatment start. Prognostic performance of Serial CTRS was assessed using OS concordance index (C-index) and area under the receiver operating characteristic curve (AUROC) of landmark OS at 6, 12, and 24 months. Results: In the RCC cohort, Serial CTRS demonstrated a C-index of 0.76 (95% CI: 0.68-0.85), and AUROCs of 0.86 for OS6 (95% CI: 0.76-0.95), 0.82 for OS12 (95% CI: 0.70-0.93), and 0.77 for OS24 (95% CI: 0.65-0.89). Five of the 92 RCC patients did not have thoracic scan coverage. In the CRC cohort, Serial CTRS demonstrated a C-index of 0.65 (95% CI: 0.56-0.73), with AUROCs of 0.78 (95% CI: 0.59-0.96) for OS6, 0.72 (95% CI: 0.58-0.87) for OS12, and 0.67 (95% CI: 0.55-0.79) for OS24. Twenty-nine of the 76 CRC patients did not have thoracic scan coverage. Confidence intervals for all metrics excluded 0.5, consistent with non-random prognostic performance. Conclusions: Serial CTRS demonstrated prognostic associations with OS in metastatic kidney and colorectal cancer cohorts. The ability to automatically derive prognostic signal from CT imaging with variable anatomic coverage supports generalization of Serial CTRS to real-world clinical settings. Further studies, including comparisons with tumor-size based metrics, are underway to better quantify the potential utility of Serial CTRS.

First-in-human phase I/II study of EN002-gel, a first-in-class drip inhibitor, in non-melanoma skin cancer and actinic keratosis.

e21567 Background: The high global incidence of skin cancer severely impairs patients' quality of life and even poses a life-threatening risk. Traditional therapies carry severe local adverse reactions, long treatment courses and high recurrence rates. EN002 is a novel anticancer compound we developed based on the novel anticancer targets, DNA Replication-Initiation Proteins (DRIPs) that we have established. It selectively induces apoptosis of cancer cells but not normal cells and can eradicate tumors in mouse xenograft models. Phase II clinical study of EN002 gel for non-melanoma skin cancer (NMSC) and precancerous lesions in China and Australia is near completion, with an emphasis on actinic keratosis (AK) which is a common precancerous skin lesion with a risk of developing into skin cancer. Methods: This is a multicenter, multiple-arm, partially randomized, open-label, Phase I/II clinical study to evaluate the safety, tolerability and efficacy of EN002-gel in the treatment of adult patients with AK or NMSC including basal cell carcinoma (BCC), Bowen's disease (BD), and low-risk squamous cell carcinoma (SCC). In Phase I, dose escalation was performed using the BOIN design, encompassing six dose levels from 0.008 to 0.12 mg/cm², and 0.06 mg/cm² was confirmed as the recommended Phase II dose (RP2D). Two dosing frequencies at the RP2D are under investigation in Phase II: each dosing cycle consists of either 11 once-every-other-day doses or 14 once-daily doses, both with a 5-day drug-free period preceding the next cycle. Treatment duration was up to three cycles for patients with AK, and six cycles for patients with NMSC. Patients underwent 28-day and 56-day follow-up periods after the last dose for Phase I and Phase II, respectively. Results: Drug-related adverse events were predominantly Grade 1 or 2 local cutaneous reactions at the application sites, with no drug-related serious adverse events reported. In Phase I, lesions exhibited varying degrees of clearance with no disease progression observed. In the ongoing Phase II study, among the first 20 evaluable AK patients (Olson grades 1-3; 1-7 lesions on the face and/or limbs per patient) who completed the study, 90% (18/20) achieved complete lesion clearance either at the end of treatment or during the follow-up period. Among six evaluable patients with one or more BD lesions who completed the study, 66.7% (4/6) attained complete clinical clearance. Significant tumor shrinkage was also observed in patients with BCC and SCC, although complete clearance has not been achieved to date. Conclusions: The Phase I/II studies provided clinical evidence of a favorable benefit-risk profile of a novel topical therapy for patients with BD, BCC, SCC or AK, who represent unmet medical needs. Phase II drug treatment for AK is expected to be completed in May 2026 and new results will be presented at this meeting. Clinical trial information: China-CTR20221021; also Australian-ACTRN12623001219673.

Impact of advanced pneumatic compression devices and usual care on psychosocial outcomes in head and neck cancer survivors with lymphedema.

6109 Background: Head and neck cancer (HNC)-associated lymphedema impairs quality of life (QOL) in survivors, affecting body image, self-management efficacy, work productivity, and psychosocial functioning. Data supports therapist guided lymphedema therapy (TGLT) and technologies such as advanced pneumatic compression devices (APCD) reduce swelling. There is a lack of data on psychosocial and QOL outcomes. This randomized clinical trial compared psychosocial outcomes of TGLT and APCD in treatment-naïve HNC survivors with symptomatic lymphedema over 6 months. Methods: Participants (N=236) with HNC-associated lymphedema were randomized 1:1 to receive either TGLT (117) or APCD (119) for 6 months. Psychosocial outcomes were assessed at baseline, 2, 4, and 6 months using validated instruments: the Work Productivity and Activity Impairment Questionnaire (WPAIQ), Perceived Medical Condition Self-Management Scale (PMCSMS), Body Image Quality of Life Inventory (BIQLI), and Linear Analog Self-Assessment (LASA) for QOL. Longitudinal mixed-effects models evaluated within- and between-group changes over time. Results: Both treatment groups experienced improvements in psychosocial outcomes over time. Self-management efficacy improved in both arms. The APCD group demonstrated significantly greater self-efficacy managing lymphedema at 6 months (p=0.004). Work and activity impairment decreased in both groups, with no significant between-group differences. BIQLI scores improved across timepoints in both arms, reflecting enhanced body image-related QOL. LASA scores for overall QOL and emotional, physical, and spiritual well-being also improved similarly in both groups. No significant time-by-treatment interactions were observed, indicating comparable trajectories of psychosocial recovery. Conclusions: Both TGLT and APCD were associated with meaningful improvement in psychosocial outcomes, including self-management efficacy, body image, and QOL, among HNC survivors with lymphedema. APCD offers ongoing access to a convenient, home-based treatment which may enhance fidelity and self-efficacy through ongoing instrumental support. These findings underscore the value of accessible, patient-centered lymphedema interventions to enhance survivorship care. Future research should explore long-term adherence, cost-effectiveness, and integration of psychosocial support into treatment pathways. Clinical trial information: NCT04797390 .

Survival and hematologic outcomes in prostate cancer patients with radiation cystitis receiving hyperbaric oxygen therapy: A propensity-matched analysis.

e17138 Background: Radiation cystitis is a common complication in prostate cancer patients receiving radiotherapy. Hyperbaric oxygen therapy (HBOT) is used to manage radiation-induced bladder injury, but its impact on hematologic parameters and survival outcomes is unclear. A prospective study in patients receiving HBOT reported no changes in hematological indices but called for more robust evidence. Given its effects on angiogenesis and tissue oxygenation, there has been theoretical concern that HBOT could influence tumor biology and cancer progression, although clinical data remains limited and inconclusive. We evaluated survival and hematologic outcomes in patients receiving HBOT versus matched controls. Methods: We conducted a multi-center retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with prostate cancer receiving HBOT within one month of diagnosis of radiation cystitis were compared to those not receiving HBOT. Propensity score matching was done using demographics, co-morbidities, prior prostate cancer therapies including radiotherapy and hormonal therapy, metastases, gross hematuria, baseline labs and prior blood transfusion. Outcomes were compared up to one year at 3 monthly intervals. Significance was set at p < 0.05. Results: After matching, 1,068 patients were included in each cohort. There was no difference in survival at 1-3, 3-6, 6-9 or 9-12 months (Hazard ratio, p values- 0.8,0.65; 0.59,0.33; 0.76,0.2; 1.14,0.7). Baseline hematologic indices were comparable between the matched cohorts with a standard mean difference of < 0.1. No differences were observed at 1–12 months. HBOT was associated with significant gross hematuria at 1–3, 3–6, and 9–12 months. Blood transfusion was infrequent post index event precluding meaningful analysis. Subgroup analysis was done based on metastases. Metastatic and non-metastatic sub-groups included 207 and 854 patients resepctively. Survival could not be assessed for sub-groups because of insufficient event counts before and after propensity matching, however there were no differences in labs between cohorts. In metastatic patients, gross hematuria did not significantly differ at any interval (all p > 0.05). In non-metastatic patients, HBOT was associated with significant gross hematuria at 1–3, 3–6 months and 9-12 months. Conclusions: HBOT does not affect survival or hematologic parameters up to one year. It is associated with higher gross hematuria at several intervals, whereas some intervals, including all in the metastatic subgroup, were not significant. This may indicate that HBOT is being chosen for patients with significant gross hematuria (sicker population). Overall, these findings support similar survival and the hematologic safety of HBOT in prostate cancer patients with radiation cystitis.

Prediction of lymphovascular invasion in breast carcinoma using MRI-based radiomics: A systematic review and meta-analysis.

e12560 Background: Lymphovascular invasion (LVI) correlates with poor breast cancer prognosis, indicating metastatic progression status. Detection of LVI prior to surgery is clinically challenging. This meta-analysis evaluates the diagnostic value of MRI radiomics in detecting LVI in breast cancer patients. Methods: Studies were retrieved from 4 databases: PubMed, Scopus, Embase, and Web of Science. Eligible studies were those with radiomics models derived from machine learning algorithms, and studies using clinical-only models were excluded. Data regarding LVI status, feature selection, machine learning models, and diagnostic performance were extracted from externally validated testing cohorts. The pooled effect size was analyzed using the inverse-variance method, and a funnel plot was generated to assess publication bias. HSROC curves were generated using Bayesian estimation. This project was prospectively registered with PROSPERO (CRD420251186235). Results: 23 studies comprising 2,167 cases were included in the meta-analysis. The pooled area under the curve (AUC) for detecting LVI was 0.76 (95% CI 0.71 - 0.80) on random-effects model. Heterogeneity was noted among the studies (I 2 = 33%). Conclusions: Integration of MRI radiomics serves as a valuable clinical tool in determining LVI in breast cancer patients, aiding clinicians in earlier decision-making. It demonstrates potential as a noninvasive adjunct to enhance preoperative assessment and guide better treatment plans.

Admission acuity and inpatient outcomes among hospitalizations for pancreatic cancer in the United States, 2018–2022.

e16352 Background: Pancreatic cancer is associated with high morbidity and frequent hospitalization. National data describing the association between admission acuity and inpatient outcomes in pancreatic cancer hospitalizations remain limited. Methods: A serial cross-sectional analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations with a principal diagnosis of pancreatic cancer were identified. Admission acuity was classified as elective or non-elective. Outcomes included in-hospital mortality (primary), length of stay (LOS), and hospitalization cost estimated using cost-to-charge ratios. National estimates accounted for survey weighting, clustering, and stratification. Survey-weighted multivariable logistic regression evaluated factors independently associated with in-hospital mortality, adjusting for admission type, age, sex, race, payer, neighborhood income quartile, hospital teaching status, and calendar year. Results: From 2018–2022, an estimated 188,750 pancreatic cancer hospitalizations were identified nationally. Overall, 69.6% of hospitalizations were non-elective. In-hospital mortality was higher among non-elective than elective admissions (6.30% vs 3.44%), with longer LOS (7.97 vs 6.47 days) and lower mean hospitalization costs ($21,217 vs $41,231). In adjusted analyses, elective admission was independently associated with lower odds of in-hospital mortality compared with non-elective admission (adjusted odds ratio 0.55, 95% CI 0.41–0.73; p < 0.001). Conclusions: Among pancreatic cancer hospitalizations, non-elective admission was associated with substantially higher inpatient mortality and longer length of stay independent of patient and hospital characteristics. These nationally representative findings provide benchmarking data for admission acuity as a marker of inpatient risk in pancreatic cancer.

National patterns of overtreatment in low-risk and undertreatment in high-risk prostate cancer and associated survival impact.

e17027 Background: Guidelines recommend active surveillance for low-risk prostate cancer and definitive therapy for high-risk disease. We evaluated national patterns of risk-misaligned care and the survival consequences of undertreatment. Methods: National Cancer Database prostate cancer cases diagnosed from 2010–2022 were analyzed. Low-risk disease was defined as clinical T1–T2, Grade Group 1, and PSA < 10; overtreatment was definitive treatment vs active surveillance or no treatment. High-risk disease was defined as Grade Group ≥4, PSA ≥20, or clinical T3–T4; undertreatment was no definitive local therapy or incomplete definitive therapy. Multivariable logistic regression evaluated factors associated with misalignment. Overall survival (OS) among high-risk patients was assessed using multivariable Cox regression. Results: Among low-risk patients (N = 124,562), overtreatment occurred in 40% of cases. Overtreatment was more common among young men (adjusted odds ratio [aOR] 0.982; p < 0.001) and less common at academic centers (aOR 0.414; p = 0.015). Compared with White men, odds of overtreatment were lower among Black men (aOR 0.946; p = 0.002) and Asian men (aOR 0.827; p < 0.001), with additional variation by education and region (all p < 0.001). Among high-risk patients (N = 318,532), undertreatment affected 27.3% of patients and was more common among older men (aOR 1.061; p < 0.001). Compared with White men, undertreatment was higher among Black men (aOR 1.479; p < 0.001) and lower among Asian patients (aOR 0.863; p < 0.001) (overall race p < 0.001). Compared with private insurance, undertreatment was higher in Medicaid (aOR 2.038; p < 0.001) and uninsured patients (aOR 2.649; p < 0.001), and slightly lower with Medicare (aOR 0.931; p < 0.001) (overall insurance p < 0.001). Multiple comorbidities were associated with higher undertreatment (≥2 vs 0: aOR 1.252; p < 0.001). Facility type was not independently associated (p = 0.490), while region remained significant (overall p < 0.001). In the survival cohort (high risk) (N = 338,919), undertreatment was associated with substantially worse OS (HR 2.745, 95% CI 2.706–2.784; p < 0.001), adjusted for age (HR 1.056; p < 0.001), race (p = 0.001), insurance (p < 0.001), comorbidity (p < 0.001), income (overall p < 0.001), education (overall p < 0.001), and facility region (overall p < 0.001). Conclusions: Low-risk overtreatment remains common nationwide and varies across patient and health-system factors. In high-risk disease, undertreatment affects over one-quarter of patients and disproportionately impacts Black men and those with Medicaid or no insurance. Undertreatment confers a nearly threefold mortality hazard (adjusted HR 2.75; p < 0.001), highlighting a major national quality gap and the urgent need for system-level interventions to ensure equitable, guideline-concordant delivery of definitive therapy.

Efficacy and safety of Meilian Fuxin liquid for radiation-induced oral mucositis in head and neck cancer: A multicenter randomized clinical trial.

12145 Background: Radiation-induced oral mucositis (RIOM) is common during head and neck radiotherapy ( > 90% incidence), and 40–70% of patients develop severe oral mucositis (SOM; WHO grade 3–4), which markedly impairs quality of life and may lead to radiotherapy interruptions. Given the limited effective therapies and the lack of evidence-based standard of care, we assessed the efficacy and safety of MeiLianFuXin Liquid ( Periplaneta americana extract) for reducing SOM incidence. Methods: This multicenter, randomized, double-blind, placebo-controlled phase II trial was conducted across 7 hospitals in China from June 12, 2024, through October 31, 2025. Eligible patients (18–80 years) had non-metastatic head and neck cancer planned for radiotherapy (planned total dose ≥60 Gy), with cisplatin as the only allowed concurrent agent. Following investigator-confirmed WHO grade 1 oral mucositis, patients were randomized (1:1:1) via a centralized interactive web response system (IWRS) using a dynamic minimization algorithm to receive low-dose MeiLianFuXin Liquid, high-dose MeiLianFuXin Liquid, or a matched placebo. The study drug was administered three times daily until 14 days post-radiotherapy. The primary endpoint was SOM incidence. Adjusted proportion differences were estimated using logistic regression. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: In the full analysis set (FAS), 215 patients received treatment (low-dose, n = 72; high-dose, n = 72; placebo, n = 71). The incidence of SOM was 22.2% (95% CI, 13.3 to 33.6) in the low-dose group, 29.2% (95% CI, 19.0 to 41.1) in the high-dose group, and 43.7% (95% CI, 31.9 to 56.0) in the placebo group. Compared with placebo, adjusted proportion differences were −22.5% (95% CI, −37.3 to −7.8; P = .0042) for the low-dose group and −16.4% (95% CI, −32.2 to −0.5; P = .0463) for the high-dose group. Adverse events and serious adverse events were generally similar across groups. Conclusions: To our knowledge, this is the first randomized, double-blind, placebo-controlled trial of a traditional Chinese medicine for RIOM showing that MeiLianFuXin Liquid reduces SOM incidence versus placebo with a favorable safety profile. These findings support MeiLianFuXin Liquid as a promising treatment strategy to mitigate RIOM. Clinical trial information: ChiCTR2400084288.

Real-world outcomes of triplet therapy with hypomethylating agent, venetoclax, and FLT3 inhibitor versus doublet therapy in FLT3-mutated acute myeloid leukemia.

e18532 Background: FLT3-mutated acute myeloid leukemia (AML) is associated with inferior outcomes, particularly among older or medically unfit patients treated with hypomethylating agent (HMA)-based regimens. While HMA plus venetoclax has become a standard backbone, the real-world benefits and safety of adding an FLT3 inhibitor beyond clinical trials remain incompletely defined. We evaluated short- and intermediate-term outcomes of triplet therapy compared with doublet therapy in a large real-world cohort. Methods: Using the TriNetX global research network (111 healthcare organizations), we identified adults (≥18 years) with FLT3-mutated AML treated between January 2017 and January 2025. Patients received either triplet therapy (HMA + venetoclax + FLT3 inhibitor [gilteritinib, midostaurin, sorafenib, or quizartinib]) or doublet therapy (HMA + venetoclax). Propensity score matching (1:1) was performed using >20 baseline variables, yielding 459 patients per cohort. Outcomes included all-cause mortality, tumor lysis syndrome (TLS), acute kidney injury (AKI), and sepsis at 90 days and 1 year. Survival was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Results: After propensity matching, 459 patients in the triplet cohort and 459 patients in the doublet cohort were included in the 90-day and 1-year mortality analysis. At 90 days, mortality occurred in 26.1% of patients treated with triplet therapy versus 28.8% with doublet therapy, HR 0.87; 95% CI 0.68-1.11; p = 0.27. Mortality at 1 year occurred in 50.8% of triplet-treated patients compared with 57.3% of doublet-treated patients. In the Kaplan-Meier analysis, the median overall survival was 293 days in the triplet cohort versus 228 days in the doublet cohort. Triplet therapy was associated with a statistically significant reduction in mortality on Cox proportional hazards modeling (HR 0.81; 95% CI 0.67-0.96; log-rank p = 0.017). No significant differences were observed in rates of TLS, AKI, or sepsis between groups at 90-days or at 1 year. TLS occurred in 7.7% of triplet-treated patients versus 9.2% of doublet-treated patients (HR 0.77; 95% CI 0.46-1.29; p = 0.32). AKI occurred in 28.5% versus 26.0%, respectively (HR 1.05; 95% CI 0.76-1.47; p = 0.77), while sepsis occurred in 26.2% versus 23.9% (HR 1.03; 95% CI 0.75-1.41; p = 0.38). Conclusions: In this large real-world analysis of FLT3-mutated AML, triplet therapy incorporating a FLT3 inhibitor was associated with a significant improvement in 1-year overall survival compared with HMA plus venetoclax alone, without an apparent increase in toxicity. These findings support the real-world feasibility and potential benefit of FLT3 inhibitor-based triplet regimens and complement emerging prospective data, particularly in older or unfit populations underrepresented in clinical trials.

Improving cancer outcomes through equity: Interventions tailored for Hispanic families.

e13556 Background: People of Hispanic and Latino/a/x ethnicity (collectively referred to here as “Hispanic”) who are living with cancer and other serious illnesses experience well-documented inequities in care, including poorer pain and symptom management compared to White patients. To identify what has been shown to improve these outcomes, we conducted a systematic literature review to inventory, describe, and categorize health care interventions that have been tested to enhance the care experiences of Hispanic patients with cancer and their family caregivers. Methods: We conducted a targeted literature search using (a) PubMed for peer-reviewed studies and (b) gray literature sources, including news reports, organizational publications, and dissertation archives. The PubMed strategy combined three concept areas: (1) cancer and serious illness; (2) Hispanic or Latino/a/x populations; and (3) domains of the care experience, such as symptom burden, psychosocial needs, communication, and caregiver support. Additional eligible studies were identified through PubMed’s “Similar Articles” and “Cited By” features. Interventions were excluded if they were implemented outside the United States or if they targeted individuals without a current cancer or serious illness diagnosis (e.g., advance care planning interventions for healthy older adults). For all included studies, we extracted data on study design, sample size, clinical setting, population characteristics, and reported outcomes. Descriptive statistics were generated to summarize the scope and features of the interventions. Results: We identified 70 interventions aimed at improving the care experience for Hispanic patients living with serious illness. Nearly half (40%) were developed specifically for patients with cancer or their caregivers. These interventions have been implemented across diverse clinical sites in the United States, with two designed exclusively for pediatric oncology populations. Across the intervention landscape, we found efforts targeting 14 distinct domains of need, with the largest proportion focused on reducing caregiver burden (29%) and improving patient symptom management. Common intervention strategies included culturally tailored educational or outreach materials, provision of structured psychosocial support, and incorporation of bilingual clinicians or trained medical interpreters to strengthen communication and care coordination. Conclusions: Efforts to enhance care quality for this population are underway nationwide, with the most commonly targeted areas being caregiver burden and patient physical distress. Oncology leaders and policymakers should prioritize adapting and disseminating proven interventions to meet the needs of their local Hispanic patient populations.

Ziziphus nummularia-derived silver nanoparticles show potent anticancer activity against triple-negative breast cancer cells

Versatile Nano‐Crosslinker Enhanced Injectable Hydrogel Toward Rapid Hemostasis and Efficient Trauma Repair

ABSTRACT Uncontrolled traumatic hemorrhage, often complicated by infection and poor healing, accounts for over 30% of trauma‐related deaths worldwide. Injectable hydrogels with robust multi‐bond crosslinked networks, integrating fluidity and in situ stability, are promising for efficient hemostasis, but their crosslinkers’ relatively single structures limit the multifunctionality required for effective trauma management in resource‐scarce environments. Herein, a new class of versatile ε‐polylysine grafted manganese dioxide (EPL‐ g ‐MnO 2 ) nano‐crosslinkers is synthesized to construct an injectable hydrogel (i.e., OSEG hydrogel). Driven by EPL‐ g ‐MnO 2 , OSEG hydrogel rapidly achieves stable wet adhesion and efficient hemostasis in critical injuries (e.g., 24.9 s in a rabbit model of cardiac hemorrhage) via imine, hydrogen, and ionic bonds, which form a robust and multifunctional crosslinked network upon full gelation. In the microenvironment of traumatic wounds, OSEG hydrogel undergoes accelerated degradation to further expose EPL‐ g ‐MnO 2 and spermidine, thereby providing sufficient antibacterial and pro‐healing effects. As a result, OSEG hydrogel achieves a bone volume/total volume 3.3 times that of commercial hemostat SURGIFLO in a rat model of infected cranial defect. This work may inspire the design of advanced injectable hydrogels for synergistic trauma management.

Cervical cancer epidemiology in high-income nations (1990-2023): Three decades of prevention success and emerging disparities.

e17532 Background: Cervical cancer rates and deaths have dropped significantly in high-income countries after the start of organized screening programs and the rollout of human papillomavirus (HPV) vaccines. Still, the impact of the disease varies by region. Recent changes in epidemiology indicate a need to review long-term trends and the effectiveness of prevention efforts in these areas. Methods: We looked at data from the Global Burden of Disease (GBD) 2023 study for 59 high-income countries and territories (sociodemographic index greater than 0.80). We focused on outcomes such as incidence, mortality, disability-adjusted life years (DALYs), and age-standardized rates. We divided the analyses by age (15–49 years, 50 years and older) and by time period: pre-vaccination (1990–2006), early vaccination (2007–2015), and widespread vaccination (2016–2023). We used joinpoint regression to assess trends over time and to find significant changes. Results: In 2023, high-income regions reported about 45,200 to 52,800 new cervical cancer cases. This accounted for 12.8% of global cases, even though these regions only make up 16% of the global female population. Age-standardized incidence rates were between 6.2 and 7.8 per 100,000, showing significant regional differences. Nordic countries had the lowest rates at 3.1 to 3.8 per 100,000, while Central and Eastern Europe had rates more than double that, highlighting gaps in HPV vaccine coverage and screening access. Annual deaths ranged from 13,500 to 15,900. Age-standardized mortality rates declined by an average of 2.8% per year since 1990, which is a greater decline than the global average. Cervical cancer caused 485,000 to 612,000 DALYs, with nearly three-quarters due to early deaths. Incidence fell slightly before vaccination began, increased after the introduction of vaccines, and showed the steepest decrease after 2016 as vaccinated groups moved into higher-risk age ranges. Conclusions: High-income countries have made significant strides in reducing the burden of cervical cancer. However, major differences remain across regions and populations. Improving HPV vaccine uptake, expanding primary HPV-based screening, and enhancing access for underserved groups are crucial steps toward eliminating cervical cancer.

Dynamic, tumor-agnostic ctDNA analysis for MRD detection and longitudinal monitoring in pleural mesothelioma: The Janus-seq academic workflow.

e20065 Background: Pleural mesothelioma (PM) is an aggressive thoracic malignancy with poor prognosis and limited tools for sensitive, real-time disease monitoring. Tissue biopsies are often invasive, difficult to obtain, and may not reflect tumor heterogeneity, while radiological imaging frequently detects progression late, particularly in patients with minimal residual disease (MRD). Circulating cell-free DNA (cfDNA) offers a minimally invasive alternative to capture systemic tumor burden; however, most assays are tumor-informed and require matched tissue, limiting scalability in PM. Tissue-independent and longitudinal monitoring strategies are urgently needed. Methods: Janus-seq is an in-house developed, multimodal, tumor-agnostic liquid biopsy workflow based on shallow whole-genome sequencing (sWGS). We applied Janus-seq for longitudinal monitoring in 23 PM patients enrolled in the prospective ONC/OSS-02/2020 monocentric clinical trial. From a single plasma sample, tumor fraction (TF), somatic copy number alterations (SCNAs), and fragmentomic profiles (FP) were simultaneously assessed. Targeted sequencing of 178 cancer-related genes was performed on the same cfDNA preparation to detect emerging single nucleotide variants (SNVs) without tumor tissue. Serial samples were analyzed to evaluate dynamic ctDNA changes and their association with radiological progression. Results: TF was quantifiable in 97.6% of plasma samples. FP discriminated PM patients from healthy controls ( p=0.01 ) and remained informative in TF-negative samples, supporting its value in low-shedding disease. TF and FP were moderately correlated (r²=0.56), indicating complementary biological signals. Longitudinal analysis showed that TF increases ≥20% anticipated radiological progression by up to 13 months, enabling early MRD detection. Plasma–tissue concordance was limited for SCNAs (58.1%) and SNVs (30.5%), highlighting ctDNA’s ability to capture systemic tumor heterogeneity. Serial profiling identified emerging actionable alterations, including PTCH1 , FGFR4 , and NOTCH3 . Conclusions: Janus-seq provides a sensitive, non-invasive, and tissue-independent strategy for MRD detection and longitudinal monitoring in PM. By integrating TF, FP, SCNAs, and SNVs from a single blood draw, this workflow enables early progression detection, captures clonal evolution, and supports clinical decision-making. Key implications include tumor-agnostic MRD detection without tissue, anticipation of progression months before imaging, and identification of emerging actionable mutations. Overall, Janus-seq represents a robust academic liquid biopsy approach with potential to improve patient management and advance precision medicine in thoracic oncology.

Association of immune-mediated hepatitis with immune checkpoint inhibitor regimens in advanced hepatocellular carcinoma.

e16200 Background: Immune checkpoint inhibitors (ICIs) are standard for unresectable/advanced hepatocellular carcinoma (HCC); however, immune-mediated hepatitis (IMH) remains a clinically relevant toxicity in patients with underlying liver disease. Prior safety analyses often pool heterogeneous tumor types or report nonspecific transaminase elevations, limiting HCC- and regimen-specific risk estimation. We evaluated IMH across contemporary ICI regimens in advanced HCC. Methods: Phase II–III trials and relevant meta-analyses of ICI-containing regimens in unresectable/advanced HCC were reviewed. IMH was defined as trial-reported immune-related hepatitis or hepatic adverse events of special interest managed under immune-toxicity frameworks (when specified). Outcomes included any-grade and grade ≥3 IMH, corticosteroid use, treatment discontinuation, and fatal IMH. Regimens were categorized as ICI monotherapy, dual immune checkpoint blockade (IO–IO), or ICI plus anti-VEGF or tyrosine kinase inhibitor therapy (IO–VEGF/IO–TKI). Results: Across meta-analyses focused on primary liver cancers, pooled IMH incidence was ~2.0% (any grade) and ~1.3% (grade ≥3). Trial-level immune-hepatic toxicity reporting was most detailed for IO–IO and IO–VEGF/IO–TKI regimens. In HIMALAYA (STRIDE; IO–IO; n = 388), IMH occurred in 7.5%, with grade ≥3 events in 4.4%; corticosteroids were required in reported IMH cases, 2.3% discontinued therapy, and 0.8% experienced fatal IMH. Additional first-line trials informing regimen-class risk included IO–IO (CheckMate 9DW), IO–VEGF (IMbrave150; ORIENT-32; camrelizumab plus rivoceranib), IO–TKI (COSMIC-312; LEAP-002), and ICI monotherapy (CheckMate 459; RATIONALE-301; KEYNOTE studies). Overall patterns suggest higher IMH risk with IO–IO, intermediate risk with IO–VEGF/IO–TKI, and lower risk with monotherapy; however, cross-trial comparisons are limited by heterogeneity in immune attribution. Conclusions: IMH risk in advanced HCC appears regimen-class dependent, with the most clinically significant signal observed with dual checkpoint blockade. Standardized reporting of immune-attributed hepatic events is needed to support actionable risk stratification. Immune-mediated hepatitis across ICI regimens in advanced hepatocellular carcinoma. Regimen Key trials Any-grade IMH (%) Grade ≥3 IMH (%) Notes IO–IO HIMALAYA; CheckMate 9DW 7.5 / NR 4.4 / NR Steroids; 2.3% d/c; 0.8% fatal IO–VEGF IMbrave150; ORIENT-32; camrelizumab+rivoceranib NR NR Immune attribution variable IO–TKI COSMIC-312; LEAP-002 NR NR IMH not consistently separated ICI mono CheckMate 459; RATIONALE-301 Low Low Lower immune-hepatic toxicity Abbreviations: IMH = immune-mediated hepatitis; IO–IO = dual immune checkpoint blockade; IO–VEGF = ICI + anti-VEGF; IO–TKI = ICI + tyrosine kinase inhibitor; NR = not reported; d/c = discontinuation.

A phase I trial evaluating an optimized B7-H3xCD3 T cell engager for treatment of solid cancer.

TPS2667 Background: T cell-based immunotherapy has revolutionized oncological treatment of various malignancies. However, many patients still do not respond to immunotherapy, and long-term remissions remain rare, particularly in solid tumors. B7-H3 (CD276) is overexpressed in multiple cancer entities on both tumor cells and tumor microenvironment, the latter facilitating access of effector cells into the tumor site as prerequisite for success of therapeutically targeting solid cancers. To address the high medical need of patients with colorectal cancer (CRC), breast cancer (BC), penile cancer as well as bone and soft tissue sarcoma, we developed and validated a CD276xCD3 T cell engager (TCE) termed CC-3. CC-3 mediated pronounced antitumor activity in vitro and displayed the expected long half-life and potent antitumor activity in murine models using immunocompromised mice adoptively transferred with human effector cells with regard to prevention of lung metastasis and flank tumor growth as well as elimination of large established tumors (Zekri et al, Mol Ther, 2023). Methods: This is an ongoing open label, multi-center phase I clinical trial evaluating CC-3 in patients with metastatic CRC, BC, penile cancer as well as bone and soft tissue sarcoma. Key eligibility criteria include diagnosis of progressive metastatic disease and exhaustion of standard of care. The trial comprises a dose escalation part to determine the maximum tolerated dose followed by a dose expansion part to define the recommended phase II dose and collect first signs of efficacy. During the dose escalation, initially an accelerated titration design with single patient cohorts is employed. Here, each patient receives a fixed dose level (starting with 50µg for the first patient). Dose levels are increased by up to 100%, based on the decision of a safety review committee (SRC). Upon occurrence of adverse events (AEs) grade ≥2, dose limiting toxicity (DLT), or reaching a dose level of ≥800µg, treatment switches to a standard 3+3 dose escalation design. After maximum tolerated dose (MTD) is determined, defined as no more than one of six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to treatment according to RECIST 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations. At present, the accelerated titration phase employing cohorts 1 - 4 has been completed without DLT; likewise, in the so far completed cohorts 5-8 of the standard titration phase, no DLT was observed. Enrollment to cohort 9 began in May 2025. Clinical trial information: NCT05999396. Clinical trial information: 2022-503084-15-00.

Overall survival of first-line amivantamab plus lazertinib in atypical <i>EGFR</i> -mutated advanced non-small cell lung cancer (NSCLC): Updated results from the CHRYSALIS-2 study.

8501 Background: Patients with atypical EGFR -mutated advanced NSCLC have worse long-term outcomes with EGFR-targeted therapies than classical exon 19 deletion/L858R mutations (c EGFR ). Afatinib, approved for atypical EGFR -mutated NSCLC, showed a median overall survival (OS) of 19.4 months among 38 participants (pts) with atypical EGFR- mutations globally (Yang Lancet Oncol 2015). Amivantamab (ami)-based regimens are approved across multiple lines of therapy in different settings for c EGFR and exon 20 insertion (Ex20ins)-mutated advanced NSCLC. In MARIPOSA, first-line (1L) ami plus lazertinib (ami-laz) significantly prolonged OS vs osimertinib (HR, 0.75; P =0.005) in c EGFR -mutated NSCLC. In an earlier report of 49 pts with atypical EGFR -mutated advanced NSCLC who received 1L ami-laz, objective response rate (ORR) was 57%, median response duration was 20.7 months, median progression-free survival (PFS) was 19.5 months, and OS was still immature (Tomasini JCO 2025). Here we report OS data with longer follow-up for pts with atypical EGFR -mutated NSCLC who received 1L ami-laz. Methods: Cohort C of the global, phase I/Ib CHRYSALIS-2 study (NCT04077463) enrolled pts with atypical EGFR mutations, excluding Ex20ins and co-mutations with c EGFR , who were previously untreated or had ≤2 prior lines of therapy, which may have included a 1 st /2 nd -generation EGFR TKI. All enrolled pts received intravenous ami-laz. The primary endpoint was ORR by investigator per RECIST v1.1, which has been previously reported. Here we report OS, a key secondary endpoint, in the treatment-naïve population (n=49). Results: As of Oct 31, 2025, the median follow-up was 31.3 months (range, 0.1–53.2). The median OS was 41.0 months (95% CI, 27.7–not estimable), with 55% alive at 3 years and 46% alive at 4 years. As of data cutoff, 20% (10/49; 6 were confirmed responders and 4 had stable disease) of pts were still ongoing 1L treatment (range, 2.5–4.4 years), with 7 pts receiving ami treatment for &gt;3 years. Safety profile was consistent with prior reports; no additional safety signals were identified with longer-term follow-up. Among pts whose disease had progressed and discontinued 1L treatment, 71% (20/28) received subsequent therapy. The most common subsequent regimens included platinum-based chemotherapy agents (55%). Conclusions: 1L treatment of atypical EGFR -mutated advanced NSCLC with ami-laz resulted in a clinically meaningful median OS of nearly 3.5 years. Many pts were able to stay on 1L treatment long term, with 20% still ongoing. Ami-laz has now shown substantial survival benefit in both 1L c EGFR- and atypical EGFR- mutated disease. The recently FDA-approved subcutaneous formulation of ami may further simplify the overall treatment experience for this regimen. Clinical trial information: NCT04077463 .

A novel Bayesian approach for assessing associations between ECOG performance status (ECOG-PS) and patient-reported outcomes (PROs) in patients with gastric or gastroesophageal junction (GC/GEJC) adenocarcinoma: Post hoc analysis from the RATIONALE-305 trial.

e16044 Background: Oncology clinicians rely on ECOG-PS to guide trial eligibility and monitor disease impact, yet it provides only a limited, clinician-rated view of a patient’s functional status and is subject to inter-rater variability. We previously demonstrated that, at baseline (pretreatment), patients with ECOG-PS 1 had significantly worse patient-reported GHS/QoL, lower physical functioning, and greater pain compared with those with ECOG-PS 0. Here, we present a novel time-varying Bayesian approach to quantify the probability that longitudinal changes in ECOG-PS track PRO trajectories during treatment in patients with first-line GC/GEJC from the RATIONALE-305 trial. Methods: Bayesian hierarchical regression models with patient-level trajectories were used to estimate longitudinal ECOG-PS–PRO associations. Seven EORTC QLQ-C30 domains (GHS/QoL, physical and role functioning, fatigue, pain, constipation, and diarrhea) plus the EQ-5D VAS were analyzed. ECOG-PS was modeled as a continuous, time-varying predictor, with coefficients reflecting the expected PRO change per 1-level ECOG-PS change over time (eg, 0 to 1, 1 to 2, or 1 to 0). Posterior probabilities and 95% credible intervals (CrIs) were estimated for ECOG-PS and for treatment effects comparing tislelizumab + chemotherapy (T+C) versus placebo + chemotherapy (P+C). Results: 532 patients with longitudinal ECOG-PS and PRO assessments were analyzed. Lower (better) ECOG-PS was strongly and positively associated with better longitudinal PRO scores in five of seven QLQ-C30 domains—GHS/QoL, physical and role functioning, fatigue, and pain—as well as the EQ-5D VAS. For ECOG-PS, the 95% CrIs for fatigue (1.67, 4.46), pain (0.73, 3.15), physical functioning (2.36, 4.40), GHS/QoL (2.92, 5.89), and EQ-5D VAS (2.40, 4.72) were above 0, with corresponding posterior probabilities ≥99.9%, indicating a very high probability of ECOG-PS–PRO alignment over time independent of treatment. After adjusting for ECOG-PS, treatment effects favored T+C versus P+C for GHS/QoL (95% CrI [−4.88, −0.01]; posterior probability 97.6%) and pain (95% CrI [−5.09, 0.14]; 96.8%), indicating treatment-driven improvements independent of ECOG-PS. Conclusions: Longitudinal improvements toward lower (better) ECOG-PS levels were strongly associated with more favorable PRO trajectories, while treatment with T+C conferred additional improvements in GHS/QoL and pain beyond what was reflected by ECOG-PS. These empirical findings support incorporating PROs alongside ECOG-PS to give clinicians a more complete view of baseline functional and symptom burden, improve patient-centered monitoring, and strengthen trial eligibility and stratification. Clinical trial information: NCT03777657 .

Cancer screening and site-specific mortality in adults aged ≥ 65 years: A systematic review.

e23182 Background: Cancer screening in older adults is often guided by age-based policies; however, increasing life expectancy may extend the potential window of benefit for selected individuals beyond ages recommended in current guidelines. We evaluated whether recommended cancer screening tests are associated with reductions in site-specific cancer mortality among older adults. Methods: We conducted a systematic review of studies assessing breast, colorectal, and prostate cancer screening and site-specific mortality in adults aged ≥65 years. PubMed/MEDLINE, Embase, and Scopus were searched for studies published from 2016 to 2025. Grey literature searches and manual reference screening identified additional records. Two reviewers independently screened titles/abstracts and full texts using Covidence, with disagreements resolved by consensus. Eligible studies included cohort studies and post-hoc analyses of randomized screening trials evaluating screening modalities such as mammography, colonoscopy, fecal occult blood test (FOBT/FIT), stool DNA testing, sigmoidoscopy, virtual colonoscopy, or prostate-specific antigen (PSA) testing, and reporting cancer-specific mortality outcomes. Given substantial clinical and methodological heterogeneity, results were summarized using narrative synthesis. Results: Four studies were included: three observational cohort studies and one post-hoc analysis of a randomized screening trial evaluating colorectal or prostate cancer screening in adults aged ≥65 years. Three studies of colorectal cancer screening reported reductions in colorectal cancer–specific mortality, with hazard ratios ranging from 0.34 to 0.58. Two studies also demonstrated reduced colorectal cancer incidence, including a prospective cohort study showing a 56% reduction (HR 0.44; 95% CI 0.33–0.57). Evidence suggested greater benefit for distal colorectal cancers. One U.S. Medicare-based study of annual prostate-specific antigen screening reported reduced prostate cancer–specific mortality, corresponding to approximately 2.3 fewer deaths per 1,000 men aged 67–74 years. No eligible studies of breast cancer screening met inclusion criteria. Overall risk of bias was moderate. Conclusions: Among adults aged ≥65 years, available observational evidence suggests that colorectal cancer screening is associated with substantial reductions in cancer incidence and cancer-specific mortality, while prostate cancer screening is associated with more modest mortality benefits that vary by age and comorbidity burden. These findings support individualized cancer screening decisions in older adults based on life expectancy, comorbidity, and patient preferences. Interpretation is limited by study heterogeneity and reliance on observational data. Further randomized and pragmatic studies are needed to better define the balance of benefits and harms in this population.