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Phase 1 trial of a KRAS G12V/HLA-A*11:01–restricted TCR-engineered T-cell therapy in advanced solid tumors.

2542 Background: KRAS G12V is a prevalent oncogenic driver in solid tumors, particularly pancreatic cancer (PC), occurring in approximately 20-30% of patients (pts). Advanced solid tumors harboring this mutation carry a poor prognosis and limited treatment options following standard chemotherapy. This phase 1 study evaluates a novel TCR-engineered T cell (TCR-T) therapy derived from a naturally occurring, KRAS G12V/HLA-A*11:01–restricted T cell receptor (TCR) isolated from patient tumor-infiltrating lymphocytes. Methods: This open-label, single-arm, dose-escalation phase 1 trial assessed the safety, tolerability, and preliminary efficacy of autologous TCR-T cells in pts with advanced solid tumors. Eligible pts had confirmed KRAS G12V mutation and HLA-A*11:01 positivity. Using a standard 3+3 design, autologous T cells were transduced with a lentiviral vector encoding the TCR and a CD8 co-receptor. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed by a single infusion of TCR-T cells at either 5×10⁹ (DL1) or 1×10¹⁰ (DL2) cells, with adjunctive interleukin-2. Results: As of January 2026, 8 pts were enrolled; of whom 6 (median age 69.5 years, ECOG PS 1) received the planned infusion, including pts with colorectal cancer (n = 2), pancreatic cancer (n = 3), and endometrial cancer (n = 1). All pts had liver or lung metastases and > 2 metastatic sites. No dose-limiting toxicities (DLTs) or grade ≥3 treatment-related adverse events (TRAEs) were observed. The treatment was generally well-tolerated; the most common (≥50%) treatment-emergent adverse events (TEAEs) were pyrexia, cytokine release syndrome (CRS), neutropenia, anemia, and thrombocytopenia. Grade 1-2 CRS occurred in 4/6 pts and resolved without sequelae. No immune effector cell–associated neurotoxicity syndrome (ICANS) was observed. TCR-T cells peaked in peripheral blood at a median of day 4 (range, 1–10), with a median peak expansion of 61,863 copies/µg DNA (range, 40,394–80,824). The objective response rate (ORR) was 50.0% (3/6), with a disease control rate (DCR) of 83.3% (5/6). In the pancreatic cancer subset, the ORR was 66.7% (2/3) and the DCR was 100%. Conclusions: This KRAS G12V/HLA-A*11:01–restricted TCR-T therapy demonstrated a favorable safety profile and encouraging preliminary antitumor activity in advanced solid tumors. Notably, a high response rate was observed in heavily pretreated pancreatic cancer patients, supporting further clinical development of this novel cellular therapy. Clinical trial information: NCT06767046 .

Stratification of cardiovascular complications with immunotherapy.

e24004 Background: Immune checkpoint inhibitors (ICIs) are used to treat various malignancies and have expanded the therapeutic landscape. However, their use is linked with adverse drug reactions (ADRs), including cardiovascular toxicities. Prior studies have examined the relationship between ICIs and cardiac ADRs, but risk stratification among individual agents and regimens is limited. A pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) was done to evaluate disproportionate reporting of cardiovascular ADRs across ICIs, ICI classes, and combination regimens. Methods: FAERS is a database used for post-marketing surveillance. PD-1 inhibitors (pembrolizumab, nivolumab, cemiplimab), PD-L1 inhibitors (atezolizumab, durvalumab, avelumab), CTLA-4 inhibitors (ipilimumab, tremelimumab), and combination regimens (nivolumab/ipilimumab, durvalumab/tremelimumab) were evaluated. Cardiovascular ADRs assessed were atrial fibrillation, atrial flutter, atrioventricular block, myocarditis, pericarditis, pericardial effusion, cardiac arrest, and congestive heart failure (CHF). The Reporting Odds Ratio (ROR) was used to determine if these reports represented a significant signal in the FAERS database. 95% confidence intervals (CI) and p-values were calculated to assess the significance between each drug/combination and a cardiac ADR. P-values were significant (≤ 0.05), unless stated otherwise. ROR=(positive reports with drug/negative reports with drug)/(positive reports without drug/negative reports without drug). An ROR >1 is considered a potential signal for an ADR. Results: (Table 1) Combination ICI therapy demonstrated overall elevated CHF signals (ROR 1.37, 95% CI 1.39-1.67)- durvalumab/tremelimumab had an ROR of 17.90 (95% CI 14.27–22.45) and nivolumab/ipilimumab had an ROR of 4.52 (95% CI 3.83–5.33). Durvalumab/tremelimumab demonstrated the highest overall cardiac signal with ROR 2.30 (95% CI 1.98–2.68). Combination therapy also had disproportionate atrial fibrillation reporting (ROR 1.37, 95% CI 1.19–1.57). All monotherapy classes showed significantly lower CHF reporting: PD-1 (ROR 0.65, 95% CI 0.57-0.74), PD-L1 (ROR 0.61, 95% CI 0.48-0.78, and CTLA-4 (ROR 0.52, 95% CI 0.39-0.70). Conclusions: ICI-associated cardiotoxicity is strongly regimen-dependent- with combination therapy, particularly durvalumab-tremelimumab, showing the highest cardiac signals. Heightened cardiovascular surveillance should be considered for patients receiving combination regimens. Combination ADR signals. Drug/Class Total ADRs ROR, CI (Afib) ROR, CI (myocarditis) ROR, CI (CHF) ROR, CI (total) Nivolumab/ipilimumab 28388 - 1.32 (1.19-1.46) 4.52 (3.83–5.33) - Durvalumab/tremelimumab 2710 - 3.3 (2.70-4.03) 17.90 (14.27–22.45) 2.30 (1.98–2.68) Combination (all) 31098 1.37 (1.19–1.57) 1.52 (1.39-1.67) 5.89 (5.14-6.75) 1.13 (1.06-1.21)

HERTHENA-Breast04: A phase 3, randomized, open-label study evaluating the efficacy and safety of patritumab deruxtecan (HER3-DXd) versus treatment of physician’s choice in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) unresectable locally advanced or metastatic breast cancer.

TPS1149 Background: There is an unmet therapeutic need for patients with HR+/HER2− metastatic breast cancer who experience disease progression and recurrence after first-line standard of care treatment with a CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET). The main therapy options, for those patients who are not considered suitable for additional ET-based therapy, are chemotherapy and antibody-drug conjugates (ADCs). Human epidermal growth factor receptor 3 (HER3) is overexpressed in HR+/HER2− breast cancer and is associated with poor prognosis and drug resistance. Patritumab deruxtecan (HER3-DXd) is a novel ADC composed of a fully human anti-HER3 IgG1 antibody linked to a cytotoxic topoisomerase I inhibitor via a stable tetrapeptide-based linker that is selectively cleaved within tumor cells. In the phase 2 ICARUS-Breast01 study, HER3-DXd showed clinically meaningful antitumor activity and manageable safety in patients with HR+/HER2− advanced breast cancer who progressed on CDK4/6i treatment and 1 line of chemotherapy. The phase 3, multicenter, open-label, HERTHENA-Breast04 study (NCT07060807) evaluates efficacy and safety of HER3-DXd monotherapy vs treatment of physician’s choice (TPC) in participants with HR+/HER2− advanced breast cancer after progression on 1 line of CDK 4/6i treatment. Methods: Participants must be aged ≥18 y and have centrally confirmed HR+/HER2− (per most recent ASCO/CAP guidelines: HER2 IHC 0 or 1+ or IHC 2+/in situ hybridization negative) unresectable locally advanced or metastatic breast cancer. Participants must have experienced disease progression or recurrence following prior treatment with a CDK4/6i and ET and must be eligible for at least 1 TPC option, as determined by the investigator. Participants must have measurable disease per RECIST v1.1 and ECOG PS of 0 or 1. Participants who have received prior chemotherapy or are candidates for an additional line of ET-based therapy in the advanced setting are ineligible for the study. Participants are randomized 1:1 to Arm 1 or 2, with ~500 participants assigned to each arm. Participants in Arm 1 will receive HER3-DXd 5.6 mg/kg IV on day 1 Q3W, and participants in Arm 2 will receive TPC consisting of 1 of the following options: paclitaxel, nab-paclitaxel, capecitabine, liposomal doxorubicin, or trastuzumab deruxtecan. Treatment will continue until disease progression, unacceptable toxicity, or participant withdrawal. The dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints are ORR and DOR per RECIST v1.1 by BICR, safety, and patient-reported outcomes. Imaging assessments occur Q6W from randomization through week 60 and Q12W thereafter. Enrollment began in 2025. Clinical trial information: NCT07060807 .

Utility of sacubitril/valsartan in the prevention of cancer therapy–related cardiac dysfunction (CTRCD) in patients receiving cardiotoxic chemotherapy agents: A systematic review and meta-analysis.

e24038 Background: Cancer therapy–related cardiac dysfunction (CTRCD) is a recognized adverse effect of cardiotoxic chemotherapy agents like anthracyclines and HER2-targeted therapies. Neurohormonal blockage utilizing ACE inhibitors and beta blockers has been studied before. The efficacy of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, for primary prevention of CTRCD is still undetermined. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was done to identify randomized controlled trials evaluating the cardioprotective effects of Entresto compared with placebo in cancer patients receiving chemotherapy. Studies reporting cancer therapy-related cardiac dysfunction (CTRCD) or hypotension were included. Data were pooled using a random-effects model in RevMan Version 5.4. Risk ratios (RR) and risk differences (RD) with 95% confidence intervals (CI) were calculated for dichotomous outcomes. Heterogeneity was assessed using the I² statistic and Chi² test. Results: Three randomized trials including 352 patients were analyzed for CTRCD. Pooled RD showed that sacubitril/valsartan significantly reduced the absolute risk of CTRCD compared with placebo (RD = −0.19; 95% CI −0.28 to −0.11; p < 0.00001; I² = 24%), corresponding to an approximate number needed to treat (NNT) of 5. The pooled RR was not statistically significant (RR = 0.44; 95% CI 0.15–1.32; p = 0.14; I² = 70%), reflecting substantial heterogeneity in relative effects across studies. For hypotension, two trials including 252 patients reported events. Entresto significantly increased the risk of hypotension (RR = 3.64; 95% CI 1.23–10.79; p = 0.02; I² = 0%), indicating a consistent adverse effect across studies. Conclusions: This study shows that sacubitril/valsartan may be useful in cardio protection, but it is essential to consider the heterogeneity and the high incidence of hypotension when choosing this drug, as more research is needed to check its safety profile.

Efficacy and safety of intrathecal chemotherapy in <i>EGFR</i> -mutant non–small cell lung cancer with leptomeningeal metastases: A systematic review and meta-analysis.

e20700 Background: Leptomeningeal metastases (LM) are a particularly challenging complication of EGFR-mutant non–small cell lung cancer (NSCLC) and are often associated with rapid neurologic decline. Intrathecal (IT) chemotherapy is frequently used in this setting, but its efficacy and safety have not been well defined. We conducted a systematic review and meta-analysis to assess neurologic response and treatment-related toxicity associated with IT chemotherapy in EGFR-mutant NSCLC with LM. Methods: We performed a PRISMA-guided search of MEDLINE, EMBASE, Cochrane CENTRAL, and targeted grey literature to identify prospective and retrospective studies reporting outcomes of IT chemotherapy in EGFR-mutant NSCLC with LM. Quantitative analyses were restricted to studies with extractable endpoints. Neurologic response and grade ≥3 toxicity were pooled using random-effects generalized linear mixed models with logit transformation. Heterogeneity was assessed using I² and τ². Prespecified sensitivity analyses examined neurologic response by route of administration (lumbar puncture vs Ommaya reservoir), concomitant EGFR-TKI use, and study design or era. Results: Four studies comprising 76 patients reported extractable neurologic response data. The pooled neurologic response rate was 81.9% (95% CI, 64.0%–92.0%), with moderate heterogeneity (I² = 63.4%, p = 0.04). Grade ≥3 toxicity was reported in three studies (n = 59), with a pooled incidence of 11.8% (95% CI, 3.2%–34.9%) and substantial heterogeneity (I² = 71.3%, p = 0.03). Myelosuppression was the most frequently reported severe adverse event, and no consistent signal of severe neurologic toxicity was identified. Exploratory sensitivity analysis suggested higher neurologic response in LP-treated cohorts compared with mixed LP/Ommaya cohorts; however, this finding was driven by a single small study and is likely influenced by limited sample size and selection bias and should be considered hypothesis-generating only. Neurologic response was otherwise consistent across study designs and eras. Stratification by concomitant EGFR-TKI use was limited by incomplete reporting. Median overall survival was variably reported and ranged from approximately 7 to 12 months. Conclusions: In EGFR-mutant NSCLC with leptomeningeal metastases, IT chemotherapy is associated with a high pooled neurologic response and relatively uncommon severe toxicity, although heterogeneity across studies remains substantial. The observed neurologic benefit appears consistent across study designs and is more likely related to underlying EGFR-sensitive disease biology than to a definitive effect of route of administration. These findings support further prospective evaluation of IT chemotherapy as part of multimodal treatment strategies in this high-risk population.

Alcohol-related hospitalizations among patients with cancer in the United States: Trends and associated risk factors.

10624 Background: Alcohol consumption is associated with an increased risk of developing multiple cancers and has been linked to higher cancer-related mortality. Alcohol dependence and harmful alcohol use may also compromise oncologic care and worsen the clinical course. However, little is known about the prevalence and outcomes of alcohol-related hospitalizations among patients with cancer. Methods: We analyzed trends and risk factors of alcohol-related hospitalizations among adults with cancer using the National Inpatient Sample database for the years 2016-2021. Alcohol-related admissions were identified using ICD-10 codes for intoxication, withdrawal, alcohol-induced mood and psychotic disorders, and other alcohol-induced disorders. Prevalence estimates were adjusted using discharge-level weights to represent national data. Linear and multivariate logistic regression were used to assess trends in alcohol-related admissions and associations with sociodemographic and clinical characteristics. Results: Among 12,027,846 non-elective hospitalizations for patients with cancer, 15,205 (0.13%) were alcohol related. From 2016 to 2021, we observed an average increase of 185 admissions per year (from 2130 to 3200, P = 0.009). After adjusting for all non-elective hospitalizations in cancer patients, the linear time trend in alcohol-related admissions increased by an average of 0.008% per year ( P &lt;0.001). When stratified by diagnosis type, alcohol withdrawal was the leading cause of alcohol-related admissions (69.4%), followed by alcohol intoxication (22.2%). Factors associated with alcohol-related admissions included male sex, younger age, white race, rural residence, housing instability, opioid use disorder, mood and psychotic disorders (Table 1). Conclusions: Alcohol-related hospitalizations are rare among patients with cancer but have shown a significant upward trend in recent years. The factors linked to alcohol-related admissions in this population mirror known risk factors for harmful alcohol use among non-cancer patients. Further research is needed to improve alcohol use disorder screening, prevention, and management strategies for patients with cancer, particularly in high-risk populations. Multivariable predictors of alcohol-related hospitalizations in cancer patients. Characteristics Alcohol-related hospitalizationOdds Ratio (95% CI) SexFemaleMale 1 (reference)3.18 (2.90-3.47) Age category, years18-2930-4950-69&gt;70 1.72 (1.18-2.53)5.96 (5.11-6.94)4.25 (3.78-4.79)1 (reference) Race/ethnicityWhiteBlackHispanicAsianOther 1 (reference)0.57 (0.51-0.66)0.51 (0.43-0.60)0.15 (0.10-0.26)0.67 (0.56-0.81) Hospital locationUrbanRural 1 (reference)1.29 (1.11-1.50) Housing instability 5.84 (5.00-6.84) Opioid use disorder 2.37 (2.01-2.81) Depressive disorder 3.51 (3.23-3.82) Psychotic disorder 1.27 (1.01-1.61)

Epidemiology of head and neck cancers in Syria: An analysis from the national oncology center.

e18122 Background: Epidemiological data on head and neck cancers (HNC) in conflict-affected regions like Syria are scarce. This study aims to address this gap by analyzing the demographic and clinical characteristics of patients newly diagnosed with HNC at Syria's principal oncology referral center. Methods: We conducted a retrospective, using data from Al-Bairouni University Hospital, Syria’s national cancer center, which serves an estimated 65-70% of the country’s oncology patients. The study included all consecutive patients with newly diagnosed, primary head and neck cancers (including malignancies of the thyroid, glottis, nasopharynx, oral cavity, and other related sites) between January 1 and December 31, 2024. Clinico-demographic data were abstracted from medical records, including age at diagnosis, sex, governorate of residence, smoking status, primary tumor site, histopathological grade, and clinical stage at presentation. Institutional ethical approval was obtained prior to data collection. Results: A total of 664 patients were diagnosed with head and neck cancers during the study period in 2024 (Table 1). Across this year, a consistent female predominance was observed (52.41%). The average age at diagnosis was 52.2 years, 51.20% of patients were smokers, and 24.40% of all cases had advanced/metastatic disease at diagnosis. Thyroid (311) and Glottis (144) were the most common Head &amp; Neck cancers. The highest patient loads originated from Aleppo (17.02%) and Rural Damascus (12.80%), followed by Damascus (11.75%). Notably, patients from more distant governorates, such as Deir ez-Zor (7.53%) and Al-Hasakeh (11.45%), accounted for a significant proportion of head and neck cancers presenting to our center. Chi-square tests confirmed significant associations between cancer type and disease stage (p&lt;0.001) and between smoking and high-grade tumors (p&lt;0.01). Logistic regression identified smoking as a key predictor of advanced stage (OR=2.1) and high-grade disease (OR=2.8), with nasopharyngeal cancer showing particularly high risk. ANOVA revealed significant age differences across cancer subtypes (p&lt;0.001), with advanced-stage patients being significantly older. Conclusions: Syria’s first national head and neck cancer dataset identifies high smoking rates and late-stage presentation, highlighting key needs for prevention and earlier diagnosis to inform regional policy. Diagnosis 2024 Cases Average Age Male Sex (%) Smokers (%) High grade Advanced/Metastatic at diagnosis Thyroid 311 46.1 16.72% 28.30% 4.47% 20.27% Glottis 144 60.4 86.11% 89.58% 77.78% 29.60% Nasopharynx 50 49.2 78.00% 56.00% 86.36% 59.09% Mouth, Gum, tonsils and tongue 83 57.1 57.83% 59.04% 63.08% 40.85% Skin and lip 63 62.9 71.43% 63.49% 44.23% 13.33% Others (bones, small ear, nose, eye, and lymph node) 13 52.2 61.54% 46.15% 53.85% 30.77%

Impact of structured oncologist-led home visits on psychological distress and resilience in patients with solid tumors undergoing chemotherapy: A comparative study.

12089 Background: Psychological distress is prevalent among patients receiving chemotherapy. Home-based supportive interventions have the potential to address early psychosocial needs; however, data regarding their impact on both distress and resilience remain limited. Methods: Between March 1 and December 1, 2025, chemotherapy-naïve patients with solid tumors were invited to participate in a home-based supportive care study. Patients who opted for the intervention received a structured home visit by a medical oncologist following each of the first two chemotherapy cycles. These visits included patient-led discussions where the oncologist addressed questions regarding disease staging, prognosis, treatment protocols, and anticipated side effects. Before each chemotherapy cycle, patients completed self-reported assessments of psychological distress and resilience. Distress was measured using the Distress Thermometer (scale 0–10), with scores ≥4 categorized as high distress. Resilience was evaluated using the 10-item Connor-Davidson Resilience Scale, a unidimensional instrument where items are rated on a 5-point Likert scale. Higher scores indicate greater resilience. The control group consisted of patients who did not receive home visits; they completed the same assessments during routine clinic visits. In both cohorts, breast, lung, and colorectal cancers were the most frequent diagnoses. Distress and resilience outcomes were analyzed within each group across three time points using Cochran’s Q and Friedman test. Results: The intervention group included 66 patients (12 male, 54 female) with a mean age of 58 years (SD ±13.58). The proportion of patients reporting high distress decreased progressively: 72.7% at baseline, 53.0% after the first visit, and 45.5% after the second visit ( p &lt; 0.001). Mean distress scores also declined significantly from 4.91 ± 2.79) at baseline to 3.55 ± 2.71) and 3.53 ± 2.59) following the first and second visits, respectively (p &lt; 0.001). In contrast, mean resilience scores remained stable (30.26 ±7.06, 29.95 ± 8.82, and 28.24 ± 12.12; p = 0.72).The control group included 145 patients (39 male, 106 female) with a mean age of 58 years (SD ± 12.58). In this group, the prevalence of distress remained relatively stable across the three assessments: 66.2% at baseline, 57.9% at the second assessment, and 56.6% at the third (p = 0.074). Mean distress scores showed minimal variation: 4.45 ±, 4.08 ±, and 4.09 ±, respectively (p = 0.163). Mean resilience scores exhibited a downward trend from 30.19 ± 7.74) to 27.03 ± 12.20) and 25.52 ± 13.21), though this did not reach statistical significance (p = 0.076). Conclusions: This study demonstrates that oncologist-led home visits during the early stages of chemotherapy can significantly reduce psychological distress in cancer patients while preserving resilience.

Advances in supercapacitor technology: Materials, design, and emerging applications

Adaptive Throat‐Sieving Gate in a Metal Azolate Framework Enabling Synergistic Equilibrium‐Kinetic Separation of Propylene and Propane

ABSTRACT Developing porous adsorbents for propylene/propane (C 3 H 6 /C 3 H 8 ) separation faces the challenge of integrating high adsorption capacity with fast adsorption kinetics. Herein, we address this challenge through precise pore control in a slightly flexible metal azolate framework NUM‐27a, enabling synergistic equilibrium‐kinetic separation of C 3 H 6 /C 3 H 8 . The periodically expanded throat gate enables effective impeding the diffusion of C 3 H 8 , while a large pocket‐shaped cavity decorated with exposed oxide groups facilitates exceptional C 3 H 6 capture at low pressures. Specifically, NUM‐27a achieves exceptional low‐pressure C 3 H 6 capture (89.61 cm 3 cm −3 at 0.1 bar) and a record C 3 H 6 packing density (310.0 g L −1 at 0.01 bar). Kinetic analysis further reveals effective diffusion coefficient for C 3 H 6 is 1.57 × 10 −4 s −1 at 298 K. Gas‐loaded single crystal X‐ray diffraction analysis coupled with computational simulations elucidate that the intrinsic pore geometry underpins the unique adsorption and separation performance. Breakthrough experiments validate the outstanding separation performance of NUM‐27a for C 3 H 6 /C 3 H 8 mixtures. Moreover, the great stability, recyclability, and low‐cost precursors of NUM‐27a underline its potential as a reliable adsorbent for C 3 H 6 /C 3 H 8 separation. The work unveils the adaptive throat‐sieving gate strategy with optimal separation performance for challenging gas separations.

Immune checkpoint inhibitors and molecular targeted agents with or without transarterial chemoembolization in unresectable hepatocellular carcinoma with first- or lower-order portal vein tumor thrombosis: A target trial emulation framework.

e16293 Background: The optimal treatment for unresectable hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) remains controversial, especially for first- or lower-order (vp1-2) PVTT. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTA) with or without TACE as first-line treatment for advanced HCC with vp1-2 PVTT. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with MTA plus ICI (TACE-MTA-ICI) or only MTA plus ICI (MTA-ICI) from June 2018 to December 2024. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS) and progression-free survival (PFS), secondary outcomes included, objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT06881446. Results: Among 1834 patients included in the analysis, 1148 (62.6%) patients received TACE-MTA-ICI treatment, and 686 (37.4%) patients received MTA-ICI treatment. The median follow-up time was 24.2 months and 23.3 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-MTA-ICI group exhibited a significantly improved median OS (27.4 months [95% CI: 26.3–30.7] vs 20.1 months [18.2–23.0]; P &lt; 0.0001; adjusted hazard ratio [HR] 0.64 [95% CI: 0.55–0.75]). Median PFS was also longer in TACE-MTA-ICI group (13.3 months [12.3–14.3] vs 9.4 months [8.2–10.4]; P &lt; 0.0001; HR 0.66 [0.58–0.75]) per modified Response Evaluation Criteria in Solid Tumours (mRECIST) and (13.0 months [12.3–14.4] vs 9.1 months [8.1–10.4]; P &lt; 0.0001; HR 0.66 [0.59–0.76]) per RECIST version 1.1. A higher ORR was observed in TACE-MTA-ICI group per mRECIST (69.7% vs 41.7%, P &lt; 0.0001) and per RECIST version 1.1 (49.3% vs 32.2%, P &lt; 0.0001). Grade ≥3 adverse events occurred in 391 patients (34.1%) in TACE-MTA-ICI group and 208 patients (30.3%) in MTA-ICI group. Conclusions: This nationwide multicenter study supports TACE combined with MTA and ICI as first-line treatment for advanced HCC with vp1-2 PVTT, demonstrating improved survival benefit and acceptable safety profile.

HPV vaccination rates in New Mexico and future directions for promoting the HPV vaccine among young adults.

e22540 Background: The Human Papillomavirus (HPV) is the most common sexually transmitted infection in the U.S. and is attributed as a cause for cervical, penile, vaginal, vulvar, anal, and oropharyngeal cancers. Vaccination is an effective cancer prevention strategy and the Advisory Committee on Immunization Practices recommends HPV vaccinations for everyone between 11-26 years of age. Despite these recommendations, national rates have been consistently low (compared to other recommended vaccines) and very little research exists around HPV vaccination in New Mexico (NM). Methods: We used a mixed methods study design (i.e. sequential explanatory) to first describe NM’s HPV vaccination rates and second, identify strategies to improve vaccination rates. Results: Findings from NM Statewide Immunization Information System data show that in 2021, 47.62% of individuals between 13-17 years have received at least one dose (of the recommended two or three doses) of the HPV vaccine. National Immunization Survey Teen data show that in 2021, individuals between 13-17 years that received at least one dose of the HPV vaccine was 80.9% for New Mexico and 76.9% for the United States. To explore challenges and opportunities to improve vaccination rates in NM, we conducted interviews with clinical and community partners, supplemented with a comprehensive literature review. Conclusions: Key findings from our study include: (1) Compared to the national data, practice based data from NMSIIS reveal several opportunities for improving vaccination rates specifically for primary care providers and clinics; 2) Clinical and community partners noted building trust in communities, implementing educational interventions, and repeated reminders for the community to improve vaccination rates; (3) Given the limited research on 18-26 year olds, future research needs to be directed at examining attitudes and beliefs among young adults to inform the design of socio-behavioral interventions targeting vaccination uptake and exploring communication strategies to help young adults make informed decisions around HPV vaccinations.

Global context modeling with vision transformers for MRI-based classification of brain tumors.

e14003 Background: Brain tumors represent a heterogeneous group of neoplasms with widely variable prognosis and treatment strategies. Magnetic resonance imaging (MRI) is the cornerstone of brain tumor diagnosis and classification, yet interpretation is challenged by tumor heterogeneity, infiltrative growth patterns, and overlapping radiologic features across tumor subtypes. Convolutional neural networks (CNNs) have demonstrated strong performance in automated MRI analysis but rely primarily on localized receptive fields, which may limit modeling of long-range spatial relationships essential for characterizing tumor extent, edema, and mass effect. Vision Transformers (ViTs) introduce a fundamentally different paradigm by leveraging self-attention to capture global contextual dependencies across entire images. We evaluated a ViT-B/16 model for automated diagnosis and classification of brain tumors on MRI. Methods: We analyzed publicly available, curated brain MRI datasets, comprising gliomas and non-glioma brain tumors with expert annotation and histopathologic correlation. Multisequence MRI images were standardized, augmented, and split into training and validation cohorts using stratified sampling. A Vision Transformer B/16 model pretrained on ImageNet was fine-tuned for multi-class brain tumor classification. Input images (224×224) were partitioned into non-overlapping 16×16 patches and embedded into a token sequence augmented with positional encodings and a learnable class token. The architecture employed 12 transformer encoder blocks with multi-head self-attention and feed-forward layers, enabling global contextual modeling across tumor and peritumoral regions. Model performance was assessed using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUROC). Results: The Vision Transformer achieved robust diagnostic performance across brain tumor classes, with overall accuracy exceeding 90% and AUROC greater than 0.90. Attention-based global modeling improved discrimination of infiltrative tumors and lesions with heterogeneous signal characteristics, reducing misclassification commonly observed with convolutional approaches. Performance remained stable across MRI sequences and tumor morphologies, supporting generalizability. Conclusions: Vision Transformer–based modeling enables accurate and interpretable diagnosis and classification of brain tumors by capturing long-range spatial context beyond localized feature extraction. Although computationally more intensive than CNNs, ViT architectures offer complementary strengths for complex neuro-oncology imaging tasks and warrant further prospective evaluation to support clinical decision-making and treatment planning.

Real-world effectiveness of disitamab vedotin plus PD-1 inhibitor versus platinum-based chemotherapy as postoperative adjuvant therapy in high-risk upper tract urothelial carcinoma: A comparative study.

4611 Background: Currently, gemcitabine–platinum combination chemotherapy represents the standard adjuvant regimen following radical surgery for high-risk upper tract urothelial carcinoma (UTUC), as it reduces the risk of disease progression in approximately half of all patients. Nevertheless, a substantial proportion of patients are ineligible for this standard regimen due to post-surgical complications like renal insufficiency. Disitamab vedotin (DV), an antibody–drug conjugate targeting HER-2, has recently been shown to yield superior outcomes in advanced urothelial carcinoma when combined with PD-1 inhibitor immunotherapy. Therefore, based on real-world data, this study aims to evaluate the efficacy of the DV plus PD-1 inhibitor versus standard gemcitabine–platinum chemotherapy in the operative adjuvant treatment of UTUC. Methods: A retrospective cohort analysis was conducted using data from UTUC patients at Peking University Cancer Hospital between January 2015 and June 2025. The study included UTUC patients diagnosed as pT 2–4a N 0 M 0 , who received either 4–6 cycles of DV combined with PD-1 inhibitors or gemcitabine–platinum (cisplatin or carboplatin selected based on postoperative renal function) combination chemotherapy. The primary endpoint was disease-free survival (DFS), the key secondary endpoint was treatment-related adverse events (TRAEs). Results: A total of 105 UTUC patients were enrolled, with a median follow-up of 45.7 months. Of these, 34 patients were treated with DV combined with PD-1 inhibitors (DV group), and 71 patients received chemotherapy. Compared with chemotherapy, the DV plus PD-1 inhibitor significantly prolonged DFS, with a hazard ratio of 0.29 (95% CI 0.09–0.98; P = 0.047). The estimated 3-year DFS rates were 83.1% (95% CI 66.8–100.0) in the DV group and 64.9% (95% CI 54.3–77.7) in the chemotherapy group. Regarding safety, grade ≥ 3 TRAEs occurred more frequently in the chemotherapy group than in the DV group (36.6% vs. 12.9%), mainly comprising hematologic toxicities. Conclusions: Disitamab vedotin combined with PD-1 inhibitor immunotherapy might improve DFS compared with standard chemotherapy as adjuvant therapy for UTUC. Supported by favorable efficacy and safety outcomes, this combination represents a promising postoperative treatment option. Participants’ and tumour characteristics. Total (n=105) DV group (n=34) Chemotherapy group (n=71) P value Age(years)，median(IQR) 63 (56.5-63) 65 (57-69) 63 (56-70) 0.848 Sex, n (%) Male 56 (53.3) 16 (47.1) 40 (56.3) 0.372 Female 49 (46.7) 18 (52.9) 31 (43.7) Pathological T stage pT2 37 (35.2) 11 (32.4) 26 (36.6) 0.453 pT3 58 (55.2) 18 (52.9) 40 (56.3) pT4 10 (9.5) 5 (14.7) 5 (7.0) Nodal stage N0 95 (90.5) 33 (97.1) 62 (87.3) 0.225 N1 5 (4.8) 0 (0) 5 (7.0) N2 5 (4.8) 1 (2.9) 4 (5.6)

Advancing equity in clinical trials through decentralized methodology: A national position statement.

e23022 Background: Regional/Rural and socially disadvantaged populations continue to face persistent barriers to clinical trial participation. For research to truly improve health outcomes, equity must be central to the strategy. Decentralised Clinical Trials (DCTs) offer a critical solution by providing flexible delivery approaches that reduce participant burden, thereby improving recruitment and retention among diverse populations. However, a significant gap remains: while international agencies such as the FDA and EMA explicitly support these approaches, consolidated recommendations for routinely integrating DCT elements into study protocols, as a standard approach, are non-existent. Bridging this gap is essential to operationalise equity in research and healthcare. Methods: The Clinical Oncology Society of Australia (COSA), a peak national body representing multidisciplinary cancer care professionals, conducted extensive consultations with commercial sponsors, trial sites, researchers, and patients. These discussions informed of a national approach to integrate DCT methodology into all clinical trial protocols. COSA subsequently developed a position statement mandating inclusion of DCT options in trial design. Results: The position statement provides clear guidance and sets expectations for embedding components of a DCT in protocols. A set of wording that could be inserted into the protocol was also provided which was adapted from a phase 1, FDA and EMA approved commercial sponsor study ( ClinicalTrials.gov ID NCT06188702 ). The statement considers the need for flexibility in the level of uptake and application, based on the trial design, site capability, operational expertise, and compliance with local laws. It reinforces COSA’s foundational principle of equitable and inclusive engagement for all individuals, regardless of geography or background. Conclusions: Embedding DCT methodology into clinical trial protocols is critical to addressing participation inequities and improving cancer outcomes. COSA’s position statement establishes a national framework aligned with international best practice, supporting broader access and accelerating progress toward inclusive, patient-centered research. Importantly, the statement applies regardless of whether the protocol is commercially or academically driven.

Triple M syndrome following immune checkpoint inhibitors: Clinical features and mortality drivers of a severe irAE.

e23431 Background: Triple M overlap syndrome (TMOS) is a rare but lethal immune related adverse event (irAE) characterized by the concurrent development of myositis, myasthenia gravis, and myocarditis, with reported mortality rates up to 60%. Despite the severity, data on the incidence, treatment and outcomes remain quite limited. This study evaluates a single center cohort enriched for a Hispanic population to identify major clinical risk factors associated with TMOS. Methods: We conducted retrospective analysis of patients diagnosed with TMOS following ICI therapy between January 2022 and December 2025 at University of Miami. Cases were identified through multidisciplinary clinical services and confirmed by electronic health record review. TMOS was defined as the concurrent presence of myocarditis, myositis, and myasthenic features temporally associated with ICI exposure. Demographic and clinical data were abstracted and summarized descriptively. Logistic regression analyses were performed to evaluate clinical variables associated with mortality. Analyses were conducted using R version 4.5.2. Results: Out of 12 patients with TMOS, 83% were male, and 50% were Hispanic White with mean age 71 years. Most patients had good baseline performance status (ECOG 0-1). TMOS occurred early after ICI exposure (median 1 prior dose), 67.% patients had received nivolumab (single agent, 33%) or with ipilimumab combination (33%). All patients received high-dose corticosteroids, with concurrent use of IVIG (67%) and plasmapheresis (58%). New cardiac arrhythmias (3 complete heart block, 1 ventricular tachycardia) occurred in 50% of patients and all TMOS-related deaths. All fatal cases had preserved LV function on echocardiography. Median time from symptom onset to treatment initiation was 10 days. ICU admission was required in 58% of cases with TMOS related mortality rate of 33%. Multivariate logistic regression analysis showed new-onset arrhythmia was associated with increased odds of death (p = 0.016). Conclusions: In our study, TMOS was early-onset, highly lethal, with a strong male predominance. Nivolumab exposure and new-onset cardiac arrhythmias were strongly associated with mortality, suggesting a cardiac-driven phenotype. Delays in pre-hospital recognition persisted despite rapid and aggressive inpatient treatment. Earlier recognition, optimized treatment, and biomarker identification are needed to improve outcomes. Clinical characteristics of TMOS cases. Variable ICU Admission (n = 7, 58%) Mortality (n = 4, 33.3%) Age, mean ± SD (years) 69.0 ± 9.3 71.0 ± 9.9 Male sex, n (%) 7 (100%) 4 (100%) Non-Hispanic White ethnicity, n (%) 4 (57.1%) 3 (75.0%) ECOG performance status, median (IQR) 0 (0-1) 0 (0-1) Acute-onset cardiac arrhythmia, n (%) 6 (85.7%) 4 (100%) Time to treatment initiation, median (IQR), days 8 (3-12) 8 (2-21) ICI doses prior to TMOS onset, median (IQR) 1 (1-1) 1 (1-5)

Comparative real-world outcomes of tarlatamab and lurbinectedin in relapsed extensive-stage small cell lung cancer.

8100 Background: Extensive stage small cell lung cancer is an aggressive malignancy with rapid progression and poor survival after relapse following platinum-based chemotherapy. Tarlatamab, a DLL3 directed bispecific T cell engager, demonstrated a significant overall survival benefit compared with physician’s choice of chemotherapy, including lurbinectedin, in the phase 3 DeLLphi 304 trial. However, access to tarlatamab remains limited in routine clinical practice, and lurbinectedin continues to be commonly used in the post platinum setting. As a result, real world data comparing the effectiveness and toxicity of these agents are needed to better inform treatment decisions for patients with relapsed small cell lung cancer. Methods: We conducted a retrospective cohort study using the TriNetX Research Network, a federated, de-identified electronic health record database. Adults with lung cancer who received platinum-based chemotherapy or immunotherapy as first-line treatment and subsequently initiated tarlatamab or lurbinectedin as second-line therapy between January 1, 2020 and November 1, 2025 were included. Propensity score matching was then performed and overall survival was evaluated using Kaplan–Meier methods. Secondary outcomes included immune- and treatment-related adverse events, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS/ICE), and corticosteroid use. Results: After 1:1 propensity score matching, both groups had 133 patients each with good balance across demographics, comorbidities, metastatic burden, prior therapies, and baseline laboratory. At 1 year, mortality was 33.1% with tarlatamab versus 72.2% with lurbinectedin (absolute risk reduction 39.1%, 95% CI 28.1–50.1; p &lt; 0.0001), with improved 1-year survival probability (59.2% vs 17.1%) and superior overall survival (HR 0.46, 95% CI 0.32–0.66; log-rank p &lt; 0.0001). The survival benefit persisted at 2 years, with median survival of 417 days versus 149 days and survival probabilities of 47.4% versus 15.9%, respectively (HR 0.48, 95% CI 0.34–0.68; p = 0.0015). Tarlatamab was associated with higher corticosteroid use (56.4% vs 33.8%, p = 0.0002) and immune-mediated toxicities, including cytokine release syndrome in 45.1% (grade 1: 23.3%, grade 2: 13.5%) and ICANS/ICE in 17.3%, with no grade 4–5 events. Conclusions: In this propensity score–matched analysis, tarlatamab demonstrated a significant and durable overall survival advantage over lurbinectedin, with an approximately 50% relative reduction in the risk of death at both 1 and 2 years based on hazard ratios. While tarlatamab was associated with higher rates of expected immune-mediated toxicities, including CRS and ICANS, events were predominantly low-grade, supporting a favorable benefit–risk profile in this heavily pretreated metastatic population.

Characterizing spatial tumor architecture and ECM recapitulation using an EO771 syngeneic TNBC model.

e13133 Background: Triple-negative breast cancer (TNBC) remains an aggressive malignancy with limited therapeutic options and high rates of treatment resistance. Increasing evidence indicates that therapeutic response is strongly influenced by tumor microenvironment (TME) architecture, including extracellular matrix (ECM) composition, spatial organization, and tumor-stroma interactions that regulate drug transport, mechanotransduction, and immune infiltration. While syngeneic models (such as EO771) are widely used to understand therapeutic response due to their immunocompetent context, the extent to which these systems recapitulate the spatial tumor architecture and ECM organization observed in patient TNBC remains poorly defined. Quantitative, spatially resolved assessments of ECM recapitulation across human and syngeneic TNBC models are limited, representing a critical step toward better understanding the tumor biology and optimizing clinical treatment strategies. Methods: Primary human TNBC specimens (n = 14) and EO771 (also referred to as E0771 in literature) syngeneic TNBC tumors (n = 3) were analyzed using quantitative spatial tumor mapping. Human specimens were formalin-fixed, paraffin-embedded tissues; syngeneic tumors were generated by orthotopic implantation of EO771 cells into the mammary fat pad of C57BL/6 mice and harvested at matched tumor burden. Dual-stain histology was performed to visualize collagen (Picrosirius Red) and glycosaminoglycans (Alcian Blue). Whole-slide brightfield images were acquired (10x resolution) and analyzed using an automated, blinded computational pipeline to extract ECM features including collagen area fraction, peripheral versus intratumoral localization, GAG content and distribution, and collagen:GAG ratio. Identical analytical parameters were applied across all specimens. Results: Human TNBC specimens exhibited heterogeneous ECM distribution with notable intratumoral collagen and GAG presence, whereas EO771 tumors showed more uniform ECM and collagen was concentrated at the peripheral tumor margin. Quantitative metrics, including collagen area fraction and localization indices, highlighted these spatial differences, with human TNBC demonstrating higher intratumoral ECM heterogeneity compared with the syngeneic model. Conclusions: These data characterize distinct patterns of spatial tumor architecture and ECM organization in human TNBC versus a syngeneic mouse model of the disease, supporting further evaluation of a recapitulation gap and its implications for therapeutic response modeling. Quantitative spatial mapping may inform selection and refinement of preclinical models to better reflect human TME features relevant to therapy resistance phenotypes, and support the integration of human-relevant new approach methods (NAMs) to complement established translational research frameworks.

Tumor CTR1 expression and longitudinal serum copper assessment in breast cancer patients treated in the neoadjuvant setting.

e12629 Background: Copper is an essential nutrient required for energy production, antioxidant defense, and connective tissue maturation, yet has emerged as a metabolic vulnerability in cancer. CTR1 ( SLC31A1 ), the high-affinity copper importer, mediates cellular copper uptake, and its upregulation may signal increased copper demand in tumor cells. The dynamics of copper regulation across tumor growth, aggressiveness, and treatment resistance remain poorly defined in breast cancer. We investigated whether CTR1 expression and systemic copper changes reflect a coordinated tumor-systemic copper axis. Methods: A retrospective dataset of 1632 breast cancer patients receiving neoadjuvant chemotherapy was analyzed to compare CTR1 gene expression between responders and non-responders across molecular subtypes and tumor grades. Findings were extended to a prospective neoadjuvant cohort in which paired pre- and post-treatment serum copper levels were measured. △Copper (post–pre change) was correlated with subtype, grade, response, and tumor size. Results: CTR1 expression was significantly higher in triple-negative breast cancer (TNBC) non-responders than responders ( P = 0.0021), particularly in grade 3 tumors ( P = 0.0035), with no difference in luminal subtypes. In the prospective cohort, △Copper was positive predominantly in TNBC and strongly grade-dependent: all grade 3 TNBCs exhibited copper elevation post-therapy, whereas all grade 2 TNBCs showed negative △Copper ( P = 0.034). The only relapse in the cohort, a TNBC non-responder, exhibited persistently positive △Copper at follow-up and relapse, whereas non-responders from other subtypes showed near-zero or negative △Copper ( P = 0.011). Baseline serum copper was higher in patients with smaller (clinical T1) versus larger (T2–T3) tumors ( P = 0.033). Conclusions: Parallel CTR1 upregulation in tumors and systemic copper elevation post-therapy suggest a coordinated copper mobilization program in high-grade TNBC. These integrated retrospective and prospective findings link copper transport to therapy response and tumor aggressiveness, highlighting copper biology as a potential therapeutic axis in breast cancer.

Prevalence and prognostic value of Claudin 18.2 expression in pancreatic ductal adenocarcinoma.

4188 Background: Although Claudin18.2 expression (CLDN18.2) has been investigated in pancreatic ductal adenocarcinoma (PDAC), prevalence and prognostic significance remain inconsistent. This study evaluated both the prevalence and prognostic value of CLDN18.2 expression in PDAC. Methods: CLDN18.2 expression was assessed by IHC on FFPE tumor samples from 201 patients with PDAC enrolled in the BIOPAC study (NCT03311776) between Jan 2013-Feb 2024. Staining was performed using the Ventana CLDN18 (43) CE IVD Assay (Roche Diagnostic Solutions). All slides were independently scored by two pathologists, with discrepancies resolved by consensus. Positive expression was defined as moderate (+2) or strong (+3) staining in ≥75% of tumor cells. Patients with non-metastatic disease were excluded from the survival analysis to reduce prognostic confounding. OS and PFS were evaluated using Kaplan-Meier estimates, log-rank tests, and multivariable Cox models adjusted for stage, age, sex, chemotherapy type, diabetes, ECOG performance status, Body Mass Index, and Charlson Age-Adjusted Comorbidity Index. Associations with clinicopathological variables were evaluated using Mann-Whitney U, χ², or Fisher’s exact tests with Bonferroni correction (p &lt; 0.05 considered significant). Results: Of 201 patients, 56 had non-metastatic disease and 145 had metastatic disease. Positive CLDN18.2 expression was detected in 54 tumors (27% overall): 14 (25%) non-metastatic and 40 (28%) in metastatic cases. In patients with metastatic disease, the median OS was 9.9 months (95% CI, 6.7-12.8) in the CLDN18.2 positive group and 6.3 months (95% CI, 4.9-8.5) in the negative group, with a significant difference as demonstrated by log-rank test (p = 0.009). CLDN18.2 positivity was associated with improved OS in univariate analysis (HR = 0.60; 95% CI 0.41-0.89; p = 0.010) but was not statistically significant after adjustment for covariates (HR = 0.69; 95% CI 0.47-1.02; p = 0.064). A similar pattern was observed for PFS, with median PFS of 6.0 months (95% CI, 3.6-7.6) in the CLDN18.2 positive group and 4.1 months (95% CI, 3.4-5.3) in the negative group (log-rank p = 0.036). The unadjusted association between CLDN18.2 positivity and longer PFS (HR = 0.67; 95% CI 0.46-0.98; p = 0.037), was not maintained after multivariable adjustment (HR = 0.67; 95% CI 0.43-1.03; p = 0.066). No significant associations were identified between CLDN 18.2 expression and clinicopathological variables after correction for multiple testing. Conclusions: CLDN18.2 was expressed in 27% of PDAC tumors. While its association with OS and PFS was not statistically significant after adjustment for clinical covariates, its prevalence in metastatic cases highlights its potential relevance as a therapeutic target in PDAC. Ongoing validation in an expanded cohort may further clarify the prognostic and predictive significance of CLDN18.2 expression.