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Real-world outcomes in triple negative breast cancer (TNBC) in patients with residual disease after neoadjuvant therapy (NEOCAPE).

e12680 Background: Although adjuvant capecitabine may improve outcomes among patients with residual triple-negative breast cancer (TNBC) after neoadjuvant therapy, its real-world effectiveness and treatment selection patterns remain uncertain. Methods: Adults with TNBC (ER/PR ≤10%, HER2-) treated with ≥1 cycle of neoadjuvant therapy between 2014 and 2024 and ≥6 months follow-up after surgery were included. Patients with inflammatory disease or prior anti-HER2/endocrine therapy were excluded. Pathologic stage was defined by the AJCC 8th edition. Distant relapse-free survival (DRFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox regression was conducted in the contemporary cohort to adjust for pathologic stage and neoadjuvant regimen. Results: A total of 188 patients met eligibility criteria. Median age was 54 years (IQR 44-65), and all patients were female. Residual disease (RCB I-III) was present in 123 patients (65.4%), of whom 62 (50.4%) received adjuvant capecitabine. Compared with patients who did not receive capecitabine, treated patients had significantly greater residual disease burden (RCB II-III: 95% vs 70%, p = 0.001) and higher pathologic stage (AJCC II-III: 63% vs 38%, p = 0.013). The median time from surgery to capecitabine initiation was 90.5 days (IQR 76.0–112.3), and 37.1% initiated therapy within 12 weeks. Median cumulative dose was 882 mg/m² (IQR 761-1000) over 7 cycles (IQR 6–8); dose reductions and delays occurred in 46.8% and 29.0%, respectively, most commonly due to toxicity (61.1%). Median follow-up was 42 months (95% CI 37-47). Three-year DRFS was 56.8% in the capecitabine group vs 87.2% in the non-capecitabine group (p = 0.014), and 3-year OS was 69.4% vs 88.4%, respectively (p = 0.024). In multivariable analysis restricted to patients treated from 2017 onward (n = 112; 29 DRFS events, 25 OS events), adjuvant capecitabine was not independently associated with improved outcomes (DRFS: HR 2.48, 95% CI 0.98-6.33, p = 0.057; OS: HR 2.05, 95% CI 0.78-5.40, p = 0.145). Higher pathologic stage remained independently associated with worse DRFS (stage III vs I: HR 3.84, 95% CI 1.27-11.64, p = 0.017) and OS (stage III vs I: HR 4.17, 95% CI 1.32-13.23, p = 0.015). Conclusions: Use of adjuvant capecitabine in routine practice was strongly influenced by residual disease burden and pathologic stage, indicating that treatment selection was driven primarily by perceived recurrence risk rather than standardized criteria. The inferior outcomes observed in unadjusted analyses therefore, most likely reflect confounding by indication rather than treatment harm or lack of efficacy. Future integration of molecular phenotype data may further refine post-neoadjuvant risk stratification and help identify biologically defined subgroups most likely to benefit from adjuvant capecitabine.

Final results of a phase II study of utidelone capsule, the first solid oral microtubule stabilizer, in metastatic breast cancer patients.

1105 Background: Attempts to develop oral microtubule inhibitors have not made significant progress in decades. Utidelone is a novel microtubule inhibitor insusceptible to P-glycoprotein, enabling higher oral bioavailability and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for metastatic breast cancer (mBC) in China in 2021; utidelone capsule (UTD2) is the first solid oral formulation of microtubule stabilizer in clinical stage globally. Our previous phase I study of UTD2 showed promising activity with no DLTs being observed in late line metastatic solid tumors, and 75 mg/m 2 /d*5 was recommended as monotherapy dose (ASCO 2025). PopPK analysis indicated that AUC of UTD2 of 75 mg/m 2 /d reached 80%-125% of the AUC of UTD1. The absolute bioavailability of UTD2 vs. UTD1 was 35.1%. Here we report the final results of a phase II study of UTD2 in combination with capecitabine (CAP) in mBC. Methods: This is a single-arm, multi-center phase II trial. The key inclusion criteria included patients with metastatic breast cancer, refractory to anthracycline or taxane treatment, ≤ 4 lines of prior chemotherapy, ECOG score of 0-1 and an expected survival of ≥ 12 weeks. Eligible patients received UTD2 at 60mg/m 2 /d*5 in combination with CAP at 1000mg/m 2 bid*14 in a 21-day cycle. The primary endpoint was ORR; the secondary endpoints included PFS and safety. Results: By data cutoff on October 8, 2025, the recruitment had been completed. 50 mBC pts were enrolled with 72% of HR+/HER2-, 24% of TNBC, and 2% of HR+/HER2+. Twenty-one (21) pts (42%) had received ≥3 lines of treatment. 100% of the patients had received taxane or anthracycline and 86% had visceral metastases. Forty-four (44) pts were evaluated for efficacy with the best responses of 27 PR and 12 SD. The confirmed ORR was 52.3% (95%CI 36.7, 67.5) and DCR was 88.6% (95%CI 75.4, 96.2). Median PFS was 8.25 (95%CI 5.36, 10.58) months and median DoR was 7.62 months (95%CI 4.17, NE) (median treatment cycles was 9.0), demonstrating better efficacy than UTD1 +CAP (ORR 40.4%, CBR 53.9%, PFS 7.72 months, Lancet Oncol 2017) in mBC pts. The most prominent ≥ Grade 3 TEAEs was diarrhea (28%). However, the incidence of peripheral neuropathy (PN) was significantly decreased compared with UTD1+CAP (Grade 3 PN only 2% vs 25.1%) while maintaining the characteristic of low hematological toxicity (only 10% for both ≥ Grade 3 Neutropenia and Leukopenia). Treatment related discontinuations occurred in only 2 pts (4%). Conclusions: This study demonstrated excellent efficacy of UTD2+CAP in mBC pts. The safety profile with significantly decreased PN and low hematological toxicity highlighted another advantage of this regimen. Utidelone capsule is anticipated to dramatically improve medication convenience and enhance patient compliance. Clinical trial information: NCT05700084 .

SIGNAL-ER-101: Signatera-guided CDK4/6 inhibitor therapy in breast cancer.

TPS648 Background: The monarchE and NATALEE trials showed that the addition of a CDK4/6 inhibitor (CDK4/6i; abemaciclib or ribociclib) to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in patients with ER+/HER2- high-risk and high-intermediate risk early breast cancer (eBC), including those with node-positive disease and select high-risk node negative tumors. However, the absolute benefit was modest (monarchE: 6.4% at 4 years; NATALEE: 3.3% at 3 years) suggesting that while a subset of patients derive benefit, many high-risk patients will not recur following ET alone. Improved strategies are needed to more precisely identify patients most likely to benefit from adjuvant CDK4/6i. Circulating tumor DNA (ctDNA) is an established biomarker of molecular residual disease (MRD) in eBC; its detection is associated with a significant risk of recurrence, and lack of detection with highly sensitive assays is associated with excellent prognosis. The SIGNAL-ER-101 trial evaluates whether tumor informed ctDNA detection during post-surgical adjuvant therapy can identify ER+/HER2- patients at highest risk of recurrence who are most likely to benefit from the addition of a CDK4/6i to standard-of-care (SOC) adjuvant ET and avoid overtreatment in patients who are likely to benefit with ET alone. Methods: SIGNAL-ER-101 is a Natera-sponsored prospective, open-label, single-arm, multicenter phase II treat-on-MRD study that aims to enroll 725 patients with intermediate-risk, stage II ER+/HER2- eBC who have undergone surgical resection and have no prior exposure to a CDK4/6i. Patients will be enrolled before receipt of any planned chemotherapy and/or radiation and within 6 months of initiating ET. Personalized, tumor-informed ctDNA testing will be performed using the Signatera Genome assay (Natera, Inc.), developed from archived tumor tissue and matched normal DNA to detect tumor-specific variants in plasma. Patients who are ctDNA-positive at baseline will be initiated on adjuvant CDK4/6i (ribociclib or abemaciclib) plus ET for a minimum of two years. Patients who are ctDNA-negative will receive ET alone and undergo MRD surveillance with ctDNA testing every three months. Upon detection of ctDNA during surveillance, patients will undergo staging scans to exclude distant metastatic disease prior to the addition of CDK4/6i therapy to ET. Selection of the specific CDK4/6i and ET will be at the discretion of the treating physician based on available SOC adjuvant therapy options. Patients will be followed for up to nine years to assess outcomes, including the study primary endpoint (iDFS) and key secondary endpoints (e.g., overall survival). The primary endpoint will be met if 4-year IDFS is non-inferior to that from NATALEE (3% non-inferiority margin: 93.9% vs 90.9%), aiming to evaluate whether ctDNA-guided treatment preserves efficacy while reducing over-treatment. Recruitment is expected to begin in March 2026. Clinical trial information: NCT07214532 .

Information needs of breast cancer patients in a Brazilian capital city.

e13636 Background: Breast cancer is one of the most common cancers among women worldwide and in Brazil, influenced by genetic and lifestyle factors. Adequate clinical information during diagnosis and treatment is essential for patient-centered care, as informational access and understanding directly affect decision-making, coping, and treatment adherence. Objectives: To characterize informational satisfaction among people with breast cancer receiving outpatient treatment and to identify the resources used to obtain health-related information. Methods: This descriptive–exploratory study used a mixed-methods approach. Adults with confirmed breast cancer, recently diagnosed or undergoing treatment, were included. Data were collected through interviews using a sociodemographic questionnaire, the EORTC QLQ-INFO25, and a semi-structured interview to explore informational experiences and satisfaction. Results: Forty-two women with breast cancer were analyzed, most receiving care in the private sector and with high educational levels. The mean EORTC QLQ-INFO25 score was 62.3, reflecting overall good informational satisfaction. Most participants reported understanding the treatment plan, potential adverse effects, and recommended actions for acute events, and felt comfortable discussing concerns with the healthcare team, particularly physicians. Nevertheless, approximately half reported unmet informational needs. Identified gaps included management of specific side effects (hair loss, mucositis), sexual and gynecological health, nutrition, and information regarding patient rights and supportive services. Digital sources were frequently used in addition to healthcare professionals. Conclusions: Although overall informational satisfaction was high, clinically relevant gaps remain in key supportive care domains. The frequent use of digital resources underscores the need for standardized, accessible, and evidence-based educational materials to strengthen outpatient breast cancer care.

Impact of a centralized APP-led peer-to-peer program on patient access, provider burden, and institutional revenue.

1549 Background: Prior authorization (PA) and peer-to-peer (P2P) requirements impose a significant administrative burden on oncology clinicians, contributing to burnout and care delays. At our Comprehensive Cancer Center, internal data showed frontline Advanced Practice Providers (APPs) and oncologists spent unsustainable hours on insurance denials. To mitigate clinical fatigue and optimize workflows, we launched a centralized initiative transitioning P2P responsibilities from frontline clinicians to a specialized APP team. Methods: Following a successful pilot project, a centralized P2P program was established for outpatient diagnostic imaging denials. Based on early success, the program expanded to include outpatient medication-related denials. A dedicated APP team utilized standardized workflows, documentation, and formal escalation pathways to manage all outpatient P2P referrals. Program performance was evaluated on these metrics: 1) Access to Care: Measured by completion rate, authorization turnaround time (TAT) and pre-authorized status at arrival. 2) Provider Burden: Assessed by administrative hours reclaimed from frontline staff and qualitatively via a provider satisfaction survey. 3) Institutional ROI: Evaluated via denial overturn rates and net reclaimed revenue from authorized billable services. Results: Centralization markedly improved operational efficiency. The program achieved a clear increase in P2P completion rate from 80% provider-led baseline to 99% by centralized team. This coupled with a reduction in TAT for both imaging and medication authorizations, increased the percentage of patients arriving with pre-authorized status by 12% in the first two years. Overturn rates and positive disposition for initial denials rose to 85% or greater compared to the provider-led baseline of 78%. Frontline clinicians reported a substantial decrease in daily administrative tasks, facilitating increased patient-facing hours and improved work-life integration. Financially, the program demonstrated a robust ROI by securing authorization for high-cost services previously denied and providing payer trend data to inform broader managed care strategies. Conclusions: Centralizing P2P responsibilities within a dedicated APP team is a multidimensional solution that extends beyond revenue recovery. This model effectively mitigates provider burnout, optimizes patient flow, and protects clinical capacity. As oncology practices face increasing complexity in 2026, this scalable model offers a vital roadmap for balancing financial health with workforce sustainability.

Effect of on-treatment dose adjustments on the efficacy of enfortumab vedotin and pembrolizumab (EVP) in advanced urothelial carcinoma (aUC): A UNITE analysis.

4565 Background: EVP is the preferred 1 st -line regimen for patients (pts) with aUC. EV-related toxicities are often managed with dose adjustments, such as reductions and holds. Analysis of EV monotherapy trials showed consistent survival outcomes despite dose adjustments. We hypothesized that on-treatment EV dose adjustments would not impact survival in these pts. Methods: Pts with aUC treated with EVP in the multisite UNITE study were analyzed. Early dose reductions (DR) and holds were defined as occurring < 9 weeks from EVP start, with the remainder classified as late. Pts with DR at treatment start were excluded. Survival endpoints were progression-free survival (PFS) and overall survival (OS) from EVP start, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (≥ 75 vs < 75), ECOG performance status (0-1 vs 2-3), Hgb level (< 10 vs ≥ 10) and liver metastases (present vs not). A time-dependent covariate was used to reduce immortal time bias. Complementary MVA landmark analyses were performed, aligned to the total number of treatment cycles received, with six analyses from cycles 2 to 7. Results: 360 pts from 17 sites were included (median age 70; 78% Caucasian; 76% male; 27% upper tract primary; 35% histology subtype component; 17% with liver metastasis; 78% frontline); median follow-up was 11.7 months (95% CI [10.79, 13.08]). Median number of cycles was 6 in pts with DR and 3 with no DR. Early DRs (100 pts [28%]) and holds (18 pts [5%]) were most commonly due to rash (28% of all early DRs and holds). Late DR (75 pts [21%]) and holds (50 pts [14%]) were most commonly due to neuropathy (52% of all late DRs and holds). Pts with early or late DR had longer PFS and OS vs those who did not (Table); however, there was no significant PFS or OS difference with dose hold vs no hold (PFS HR 0.65, 95%CI (0.40, 1.05), p = 0.08; OS HR 0.70, 95%CI (0.39, 1.27), p=0.24). In landmark analyses, about 50% of pts had DR; no significant difference in PFS or OS was observed at most landmarks, except for longer OS in the DR cohort at cycle 4 (HR 0.53, 95% CI (0.29, 0.98), p = 0.042) and cycle 5 (HR 0.43, 95% CI (0.19, 0.99), p = 0.048). Conclusions: In this real-world retrospective analysis, EVP efficacy was maintained despite DR and dose holds. Survival difference noted in the time-dependent analyses were not consistently reproduced in landmark analyses, suggesting exposure-related selection bias rather than causal effect. Prospective studies are warranted to validate these hypothesis-generating findings. Association of EV DR with PFS/OS (time-dependent analyses). Early DR Late DR DR vs no DR outcomes UVAHR (95% CI), p MVAHR (95% CI), p UVAHR (95% CI), p MVAHR (95% CI), p PFS 0.50 (0.35, 0.72), <.001 0.56 (0.38, 0.84), 0.005 0.32 (0.21, 0.49), <.001 0.36 (0.23, 0.57), <.001 OS 0.51 (0.32, 0.79), 0.003 0.57 (0.35, 0.92), 0.022 0.26 (0.15, 0.45), <.001 0.31 (0.17, 0.55), <.001

DXC006, a first-in-class CD56-targeting antibody-drug conjugate, in advanced solid tumors: A first-in-human, phase I dose escalation clinical trial.

3000 Background: DXC006 is an antibody-drug conjugate of a humanized anti-CD56 antibody linked to the topoisomerase I inhibitor CPT113 with DAR=4 through a cleavable peptidyl bis-linker by CrossConju technology. DXC006 demonstrated strong antitumor activity in vivo and in vitro , here we report the safety and preliminary efficacy of first-in-human phase I trial of DXC006. Methods: Patients with metastatic/locally advanced solid tumors after at least one line of systemic standard therapy were enrolled. For dose escalation (D-ESC), DXC006 was administered intravenously at doses of 1.2, 2.4, 4.8, 6.0mg/kg Q2W or 6.0, 7.2 mg/kg Q3W with BOIN design and 3+3 design. A subset of pts was enrolled into dose-expansion (D-EXP) at recommended dose regimen. The primary objectives were to evaluate the safety and tolerability (dose limiting toxicities, DLTs; maximum tolerated dose, MTD) of DXC006. Results: Data cutoff at December 26 th , 2025, 72 patients were enrolled and received at least one dose(D-ESC n=16,D-EXP n=56)，including SCLC (n=44), lung adenocarcinoma (n=11), lung squamous cell carcinoma (n=3), neuroendocrine neoplasm (n=14). No DLTs occurred and MTD was not reached. D-EXP was carried out at 4.8mg/kg Q2W and 6.0mg/kg Q3W regimens. Treatment related adverse events (TRAEs) rate (all grade/≥G3) was 97.2% and 27.8%, TOP5 most common TRAEs (all grade/≥G3) were decreased appetite (54.2%/0%), nausea (52.8%/0%), anemia (48.6%/20.8%), asthenia (37.5%/1.4%), sensory disturbance (33.3%/0%). No interstitial lung disease (ILD) was observed. TRAEs led to dose interruption/discontinuation were observed in (23.6%/1.4%) of the patients. RP2D is 6.0mg/kg Q3W. Totally, 59 patients were eligible for efficacy analysis. For all patients, the objective response rate (ORR) and disease control rate (DCR) were 52.5 % and 81.4% (including confirmed and pending confirmation PR); for SCLC patients, were 69.4% and 91.7%; for lung adenocarcinoma, were 45.5% and 72.7% (details in table). Encouraging anti-tumor activity was observed for DXC006 treatment in SCLC at 2nd line (ORR 85.7%, confirmed 64.3%). PK, PD and PFS results will be updated in the upcoming meeting. Conclusions: DXC006 demonstrated a manageable safety profile and adequate tolerability, and showed encouraging efficacy in pretreated advanced solid tumors, especially in SCLC. Clinical trial information: NCT06224855 . Small cell lung cancer Small cell lung cancer（2nd Line） Neuroendocrine Neoplasm Lung Adenocarcinoma Lung Squamous cell carcinoma N 36 14 10 11 2 Median prior treatment line (range) 2(1, 6) 1(1, 1) 2(1, 6)　 2(1, 3)　 5(5, 5)　 cPR 14 9 1 4 0 PR 25 12 1 5 0 SD 8 2 6 3 0 PD 3 0 3 3 2 ORR % (95% CI) 69.4 (53.1, 82.0) 85.7 (60.0, 96.0) 10.0 (1.8, 40.4) 45.5 (21.3, 72.0) 0.0 DCR % (95% CI) 91.7 (78.2, 97.1) 100 (78.5, 100) 70.0 (40.0, 89.2) 72.7 (43.4, 90.3) 0.0

Mental health and malignancy: Real-world associations between early-onset hormone-related cancers and mental illness.

11173 Background: Although progress has been made in reducing overall cancer incidence, early-onset cancers have continued their troublesome rise. Similarly, the incidence and/or prevalence of psychiatric disorders has increased, particularly among young adults. Mental illness may influence cancer development, however, real-world evidence linking mental illness to early-onset hormone-related cancers is limited. Methods: We conducted a real-world, retrospective cohort study using the TriNetX United States Research Database, a federated network of de-identified electronic health records from over 70 healthcare organizations, to examine this association. Adults aged 18–50 years with at least one of five pre-determined core mental illnesses, including generalized anxiety disorder (GAD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bipolar disorder, and schizophrenia, were compared with same-aged individuals without any of the core mental illnesses. A five-year lookback period was used from January 25th, 2021 to January 25th 2026 and propensity score matching was used to adjust for confounders. Incidence of early-onset cancers diagnosed were then assessed during five-year follow-up. Sensitivity analyses required a ≥ 1-year lag between mental illness diagnosis and cancer onset. Results: 2,911,432 patients were identified as having a core mental illness, whereas 21,439,614 patients were identified as not having any core mental illness. All-cause mental illness was associated with an increased risk of developing early-onset breast cancer (RR 2.253, CI 2.149-2.362, p < 0.0001), uterine cancer (RR 1.711, CI 1.515-1.934, p < 0.0001), and ovarian cancer (RR 1.984, CI 1.790-2.198, p < 0.0001). Associations with early-onset prostate cancer and testicular cancer did not meet thresholds for statistical significance. Within the subgroup analysis, GAD was associated with an increased risk of developing early-onset breast cancer (RR 2.565, CI 2.398-2.742, p < 0.0001), uterine cancer (RR 1.534, CI 1.278-1.841, p < 0.0001) and ovarian cancer (RR 1.736, CI 1.492-2.019, p < 0.0001). MDD was associated with early-onset breast cancer (RR 2.380, CI 2.161-2.622, p < 0.0001), uterine cancer (RR 2.089, CI 1.625-2.685, p < 0.0001), and ovarian cancer (RR 1.983, CI 1.591-2.472, p < 0.0001). Bipolar disorder was associated only with early-onset breast cancer (RR 1.415, CI 1.244-1.610, p < 0.0001). OCD and schizophrenia had no statistically significant associations. Conclusions: In this large, real-world cohort study, all-cause mental illness, GAD, and MDD were associated with an increased risk of early-onset hormonal cancers more commonly affecting female patients. These findings suggest that mental health represents a potential modifiable risk factor in early-onset, hormone-related cancers and warrants further investigation.

Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-03 study of participants (pts) with previously untreated metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) vs chemotherapy (chemo).

1001 Background: In ASCENT-03, first-line (1L) SG led to a clinically meaningful improvement in PFS vs chemo (median, 9.7 vs 6.9 months [mo]; hazard ratio [HR], 0.62; 95% CI, 0.50-0.77; P < .0001) in previously untreated pts with mTNBC who were not candidates for PD-(L)1 inhibitors. Since overall survival data are immature, PFS2 can be used to assess long-term benefit as it accounts for the impact of initial and subs tx, including trial crossovers. We report PFS2 and subs tx from ASCENT-03. Methods: Pts (N = 558) were randomized 1:1 to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin); primary end point was PFS by blinded independent central review (BICR). Eligible pts in the chemo group could receive 2L SG provided on study via crossover following BICR-verified progressive disease or in any subs line commercially; other subs txs per local practice were also permitted. PFS2 was defined as the time from randomization to the first documented progression on next-line therapy per investigator assessment or death due to any cause, whichever occurred first. Results: Median follow-up for OS was 13.2 mo; 75 (27%) pts remained on study treatment in the SG group (n = 279) and 39 (14%) in the chemo group (n = 279). Of the 204 pts in the SG group who discontinued tx, 126 received any subs tx, the most frequent of which were platinum chemo (40%), taxanes (29%), and gemcitabine (19%). Of 240 pts in the chemo group who discontinued tx, 179 received any subs tx, the most frequent of which were SG (82%), capecitabine (16%), platinum chemo (9%), and trastuzumab deruxtecan (9%). Median (95% CI) PFS2 was 18.2 mo (15.9-not reached [NR]) in the SG group and 14.0 mo (12.5-17.4) in the chemo group (stratified HR, 0.70; 95% CI, 0.55-0.90). PFS2 rates are in the Table. Median (95% CI) time to first subs tx was 11.2 mo (10.0-13.0) and 7.9 mo (7.2-9.0) for SG and chemo, respectively; median (95% CI) time to second subs tx was 17.3 mo (15.2- NR) and 16.6 mo (13.6-18.5). Conclusions: PFS2 was improved in the SG group compared with the chemo group despite crossover tx, with most pts who initiated subs tx in the chemo group receiving SG. The benefit of first-line SG is clinically relevant and sustained until the next line of therapy, which further supports SG as a potential new standard of care in pts with previously untreated mTNBC who are not candidates for PD-(L)1 inhibitors. Clinical trial information: NCT05382299 . SG Chemo Pts with PFS2 events, n/N (%) 114/279 (41) 143/279 (51) Median PFS2 (95% CI), mo 18.2 (15.9-NR) 14.0 (12.5-17.4) Stratified HR a (95% CI) 0.70 (0.55-0.90) Stratified log-rank nominal P -value a .0051 PFS2 rate (95% CI), % 12 mo 71 (65-76) 59 (53-65) 18 mo 52 (45-59) 41 (33-48) a SG vs chemo.

Obesity paradox in gastrointestinal cancer patients on immunotherapy: A retrospective multi-institutional US cohort study.

11016 Background: Obesity is a well-established risk factor for different types of cancers, including gastric cancers. However, emerging research suggests its association with improved survival outcomes in cancer treatment, a phenomenon referred to as "the obesity paradox". Recent literature demonstrates this paradoxical effect in cancer patients receiving immunotherapy. We explored this effect across various types of gastrointestinal (GI) malignancies. Methods: De-identified data from the TriNetX database were used to identify adult patients (age > 18 yrs) with GI malignancies (hepatocellular, colorectal, pancreatic, upper GI (gastric and esophageal) who received immune checkpoint inhibitors (ICIs) between 2013 and 2025. Propensity score matching was performed to balance cohorts by demographics, comorbidities, ECOG and albumin level. The primary outcome was 5-year all-cause mortality, compared between patients with obesity (BMI ≥ 30 kg/m²) and those with normal BMI (18–24.9 kg/m²). The secondary outcome was the incidence of ICI-related adverse events (irAEs). Kaplan–Meier was used for time-to-event outcomes, differences were assessed using the log-rank test, and Cox proportional hazards using the TriNETx platform. Results: After propensity score matching, 4,956 patients were included in each cohort. Mean baseline characteristics were comparable between cohorts. The BMI > 30 cohort had BMI(kg/m2) 35.4 ± 5.4, albumin(g/dl) 3.54 ± 0.61, and mean ECOG 0.68 ± 0.96 while the normal BMI cohort had BMI 22.8 ± 4.5, albumin 3.48 ± 0.62, and mean ECOG 0.67 ± 0.83. Obesity was associated with significantly improved all-cause mortality compared with the normal BMI group (26.8 months vs 13.9 months; hazard ratio [HR], 0.7 [0.67-0.74]). Survival probabilities at 1 year (63.7% vs 52.6%), 3 years (46.2% vs 31.9%), and 5 years (39.1% vs 25.4%) were higher in the BMI ≥ 30 kg/m² cohort compared with the normal BMI cohort. Among GI cancer subtypes, the strongest associations between obesity and improved survival were observed in colorectal (HR 0.67 [0.62-0.72]) and pancreatic cancers (HR 0.66 [0.56-0.76]), with more modest effects seen in hepatocellular (HR 0.78 [0.72-0.84]) and upper GI cancers (HR 0.71 [0.62-0.80]). There were no significant differences between cohorts in the incidence of pneumonitis (HR 1.12 [0.80-1.57]), GI (HR 1.07 [0.98-1.17]), thyroid (HR 1.05 [0.97-1.14]), or cutaneous (HR 1.10 [0.99-1.23]) irAEs. Conclusions: In this analysis of 9,912 patients with GI malignancies treated with immunotherapy, higher BMI was associated with improved survival. Confounding by disease burden was partially addressed through adjustment for ECOG and albumin. These findings may reflect obesity-related immune modulation, as preclinical studies suggest leptin-mediated upregulation of PD-1 expression. However, further prospective studies are needed to validate and define these results

Pilot study of allostatic load, area deprivation, and race in endometrioid endometrial cancer.

e17631 Background: Area Deprivation Index (ADI) is a validated neighborhood-level metric of socioeconomic disadvantage. High ADI has been linked to worse healthcare outcomes, including in cancer populations. Similarly, high allostatic load (AL)—a biomarker reflecting the cumulative biological damage resulting from chronic socioenvironmental stress—has been linked to increased cancer risk, poorer survival, and membership within marginalized communities. We hypothesized that AL may be one mediator for the reported association of high ADI with adverse cancer outcomes, as well as racial disparities in cancer outcomes. This pilot study aimed to evaluate, within a sociodemographically diverse cohort of early stage endometrioid endometrial cancer (EEC) patients, the relationship of AL with ADI and race. Methods: Patients were identified using one institution’s IRB-approved database with electronic medical record and cancer registry information. Patients diagnosed with stage I-III EEC between 2008 and 2025 who had all AL variables available between 12 months prior to and 6 months after diagnosis were included. AL was calculated using a standard method assessing systolic and diastolic blood pressure, body mass index, heart rate, leukocyte count, alkaline phosphatase, blood glucose, creatinine, blood urea nitrogen, and albumin. Values closest to diagnosis date were used. Patients received 1 point per biomarker in the high-risk quartile: ≥75th percentile for all markers except albumin, for which ≤25th percentile was used. Points were summed to generate total AL scores. Spearman’s correlation measured the association of AL with continuous national ADI rank. Wilcoxon test compared AL by Black versus White race. Results: 220 patients met criteria. Of these, 26.8% identified as Black and 68.6% as White. 17.7% of patients resided within the most disadvantaged ADI quartile 4, 35% in ADI quartile 3, and 33.6% in quartile 2. Total AL was positively associated with national ADI rank (ρ = 0.18, p = 0.009). In contrast, total AL did not have a significant association with Black versus White race. At last follow-up, 21 (9.5%) patients had recurrence, an insufficient sample size for examining the relationship of AL and cancer outcomes. Conclusions: In this sociodemographically diverse, histologically uniform cohort, AL was associated with ADI but not race. These results suggest that the relationship of ADI with cancer outcomes may, in part, be mediated by AL. Our results also indicate race may be an oversimplified proxy for physiologic stress, which may be better represented by more comprehensive measures of health vulnerability. Together, these findings highlight the contribution of structural and environmental factors to biologic damage. Further studies integrating AL, ADI, and their effects on oncologic outcomes are needed to better inform equity-focused strategies addressing adverse outcomes in vulnerable populations.

Knowledge and uptake of HPV vaccination among Hispanic women and vaccine-eligible children.

e17531 Background: Despite the advent of effective and affordable prevention methods, disparities in HPV-related cancers persist in Hispanic populations. This disparity has been related in part to lack of knowledge and access, whereas ASCO, AACR and other national organizations have jointly endorsed strong support for HPV vaccination in order to eradicate HPV-related cancers. Thus, we evaluated HPV vaccination knowledge and uptake among women and their children in an urban, largely immigrant Hispanic community. Methods: Hispanic women aged 21 and older were administered intercept surveys in their preferred language (Spanish or English) by trained interviewers from 2015-2018 at community sites across east Los Angeles. Standardized questions were used to assess cervical cancer knowledge and HPV vaccine uptake of participants and their children aged 9-26, if applicable. Results: Respondents (n = 770, mean age = 47.4) disproportionately spoke Spanish at home (88.7%) and were uninsured (25.2%). Among respondents, 61.5% had heard of the HPV vaccine. Of these, 59.4% had heard about it through a healthcare provider, 36.4% through TV and 13.9% from family and friends. Only 7.8% of respondents, 25.1% of their sons and 45.8% of their daughters aged 9-26 had received at least one dose of the HPV vaccine. Further, only 28.1% of women interviewed endorsed knowing what causes cervical cancer, of whom only 52.4% attributed the main cause of cervical cancer to HPV, STIs or sexual activity. Conclusions: Our findings support that healthcare providers remain the primary source of information on HPV vaccination, with substantial gaps in knowledge and uptake of the HPV vaccine in this sample compared to the national average. Gender disparities in HPV vaccination observed in this sample may reflect differences in provider counseling, with boys being less likely to receive the vaccine despite AAP and CDC recommendations for HPV vaccination of all adolescents and young adults (AYAs). In the context of growing vaccine hesitancy, our results highlight the important role of clinicians in providing evidence-based education and ensuring equitable vaccine uptake to eradicate HPV-related cancers. HPV vaccine uptake among participants and their children aged 9-26. % Participants Have you received the HPV vaccine: Yes 7.8 60/770 Among participants with HPV vaccine-eligible children (aged 9-26), # of doses that children have received Males 0 doses 74.8 98/131 1 dose 5.3 7/131 2-3 doses 19.8 26/131 Females 0 doses 54.3 70/129 1 dose 7.8 10/129 2-3 doses 38.0 49/129

Drivers of non-evaluable imaging timepoints in oncology clinical trials.

e23021 Background: Robust imaging data are critical to endpoint determination in oncology clinical trials and regulatory decision-making. Blinded independent central review (BICR) provides imaging assessments but is inherently dependent on site-acquired imaging data. A common limitation across oncology trials is the occurrence of non-evaluable (NE) timepoint responses (TPRs), which may delay response or progression responses, lead to censoring, and complicate endpoint analysis. NE TPRs occur when BICR radiologists are unable to assign an overall response category at a scheduled on-study timepoint (TP) due to incomplete or uninterpretable imaging data. Contributing factors include missing required imaging, incomplete anatomic coverage, inadequate imaging technique, motion or other image-degrading artifacts, or disease-related assessment constraints. The frequency and drivers of NE TPRs are expected to vary by response criteria and imaging modality; however, few studies have characterized NE TPR causes across oncology imaging frameworks. We hypothesized that NE TPRs in BICR are driven by a limited set of recurrent factors that differ by response criteria and imaging modality. Methods: We analyzed BICR-assessed imaging TPs from oncology clinical trials employing RECIST 1.1, PCWG3, and Lugano criteria. NE TPRs were identified at the TP level and categorized by contributing factors, including missing required imaging, incomplete acquisition or anatomic coverage, and image quality limitations. TP component data (target, non-target, bone, spleen, and metabolic elements) were evaluated to determine the cause of NE responses. Results: A total of 62,798 imaging TPs were analyzed (RECIST 1.1 n = 37,344; PCWG3 n = 21,002; Lugano n = 4,453). NE TPRs occurred in 3.5% (n = 1,317) of RECIST 1.1 TPs, driven predominantly by NE target assessments (93.3%). Missing required imaging accounted for 69.9% of RECIST NE TPRs. In PCWG3 trials, 3.6% (n = 761) of TPs were NE, commonly due to NE bone response (77.5%), with missing bone scans (65.0%) and missing cross-sectional imaging (28.5%) as primary drivers. In Lugano trials, metabolic NE TPRs (n = 738, 16.6%) were more frequent than anatomic NE TPRs (n = 76, 1.7%). PET imaging NE TPRs were largely attributable to missing PET imaging (n = 680, 92.1%), whereas CT imaging NE TPRs were uncommon. Conclusions: Across RECIST 1.1, PCWG3, and Lugano criteria, NE TPRs were uncommon but consistently driven by a limited set of recurrent factors, primarily missing or incomplete required imaging rather than image quality limitations or disease-related constraints. Differences in NE drivers reflected the modality dependencies inherent to each response criteria. Systematic classification of NE reasons may inform protocol design, imaging acquisition compliance, and proactive data checks, supporting consistent endpoint evaluation and methods to reduce NE imaging TPs in oncology clinical trials.

Effectiveness of CAR-T cells engineered with TGF-βr/IL-9R domain-swapped chimeric receptor and membrane-bound IL-2 for treatment of CEA+ solid tumors.

e14502 Background: Despite recent progress, CAR-T therapy for solid tumors remains limited by poor infiltration, an immunosuppressive tumor microenvironment (TME), and inadequate pro-survival signaling. Existing strategies, including TGF-β blockade or IL-2 supplementation, cause substantial non-target toxicity. Here, we engineered domain-swapped chimeric receptor (DSCR) that convert TGF-β’s immunosuppressive signals into T cell proliferative/survival signals. Screening identified TGF-βR/IL-9R DSCR, composed of TGF-βR extracellular and IL-9Rγ intracellular domains, which triggers STAT5 phosphorylation and activate the IL-9 pathway. Integration of TGF-βR/IL-9R DSCR with mbIL-2 further generated Super-empowered CAR-T cells (SE-CAR), which preserve effector phenotype, promote boosts expansion, and enhance antitumor efficacy in solid tumors. Methods: We first assessed the activation status and expansion capability of SE-CAR T cells. Serial killing assays were subsequently performed to evaluate SE-CAR T cell durability by measuring their capacity for repeated tumor target elimination. On this basis, we evaluated SE-CAR-T cells’ tolerance and responsiveness to TGF-β1 in a mimicked TME. Moreover, the supernatant of each round was used to detect the release of cytokines. Finally, the in vivo expansion and antitumor efficacy of SE-CAR T cells were validated in cecal and lung orthotopic tumor models, rectal and gastric cancer subcutaneous models. Results: SE-CAR cells significantly increased the proportion of phosphorylated STAT5 in response to TGF-β1 (42.00 ± 10.71 vs 8.33 ± 3.40) %. Moreover, SE-CAR T cells exhibited superior serial killing and proliferative capacity compared with control CAR-T cells (8 vs 5 rounds). Similarly, SE-CAR T cells showed higher cytokine secretion at 5th sequential stimulation (30448 pg/mL vs 11505 pg/mL). Furthermore, SE-CAR T cells retained proliferative capacity and exhibited enhanced cytotoxicity activity in response to TGF-β1. Then, we further evaluated the antitumor efficacy of SE-CAR in four xenograft mice models. At 14 days post CAR-T cell infusion, the SE-CAR T cells exhibited significantly higher CAR copy numbers than control CAR-T cells (Table1). In addition, the tumor fluorescence curves also showed that SE-CAR T cells possess more prominent antitumor efficacy in vivo . Conclusions: These preclinical studies highlight the promise of SE-CAR as a next-generation multifunctional CAR-T modality, with the capacity to preserve effector phenotype, boost T-cell fitness and expansion, and improve TME tolerance for the treatment of CEA+ solid tumors. Mouse model CAR T SE-CAR T / Days Mean ± S.D. cecal orthotopic tumor model D14 944±1681 52516±81593 lung orthotopic tumor model D14 25951±10825 233744±65929 rectal cancer model D14 5697±9237 185814±170118 gastric cancer model D14 899±960 30214±30259

Enhancing oncology board exam readiness through a longitudinal review curriculum.

9031 Background: Due to the rapid pace of medical advancements in cancer care in recent years, passing the medical oncology board exam is a challenging task, with an average failure rate of 8% for first-time test takers since 2020 (American Board of Internal Medicine – ABIM). A needs assessment performed within our large academic Hematology/Oncology (H/O) fellowship program revealed that only a modest majority of fellows felt adequately prepared for medical oncology and malignant hematology board exam topics (53% and 63%, respectively). To improve fellow satisfaction, confidence, and exam performance, we developed a longitudinal board review curriculum that ran parallel to standard didactics. Methods: From August 2024 to May 2025, H/O fellows at The Ohio State University participated in a structured, longitudinal board review series covering medical oncology and malignant hematology topic areas. Faculty led monthly Zoom sessions focused on rapid content review and interactive question practice aligned with high-yield concepts per the ABIM Oncology exam blueprint. Questions from existing board review materials were utilized in session creation. Fellows completed pre- and post-surveys assessing satisfaction with the curriculum and confidence across 20 oncology topic domains using a 5-point Likert scale. Attendance and In-Training Exam (ITE) scores were collected. Analyses included descriptive statistics, correlation, and effect size testing. Results: Survey response rates (n = 29) were 72% (pre) and 86% (post). Agreement that the curriculum adequately prepared fellows for medical oncology and malignant hematology content on the board exam increased from 53% to 79% and 63% to 92%, respectively. Fellow confidence improved in all 20 topic domains, with an average increase of 0.57 on a 5-point Likert scale. Paired analysis of individual ITE scores could be performed in 19 fellows and demonstrated a mean gain of +58 points from 2024 to 2025. Larger improvements were observed among those who attended ≥50% of the 2024-2025 board review sessions (Cohen’s d ≈ 0.85). A moderate positive correlation was also identified between pre-ITE session attendance and the magnitude of the score increase for an individual fellow (r = 0.47). Notably, the correlation between attendance and change in ITE score held true for both second and third-year fellows. Conclusions: The implementation of a longitudinal, structured oncology board review series for H/O fellows at our institution improved trainee satisfaction with their preparation and confidence regarding all testable topic areas. Furthermore, improvements in ITE scores pre- and post-intervention were more robust in fellows with higher session attendance, regardless of fellowship year. This intervention strategy offers a model for other fellowship programs, H/O or otherwise, seeking ways to improve board exam readiness for their fellow-level learners.

Real-world clinical outcomes of neoadjuvant pembrolizumab among patients with early-stage triple-negative breast cancer (esTNBC) in a US community oncology setting.

e12630 Background: In the KEYNOTE-522 trial, neoadjuvant pembrolizumab plus chemotherapy (P+C) improved pathological complete response (pCR) and long-term survival compared with chemotherapy alone among patients (pts) with early-stage triple-negative breast cancer (esTNBC), with 64.8% achieving pCR and 5-year event-free survival of 81.3% and overall survival of 86.6%. However, clinical outcomes following pembrolizumab initiation in routine clinical practice remain incompletely characterized. This study aimed to describe long-term real-world clinical outcomes among pts initiating pembrolizumab following its U.S. Food and Drug Administration approval in July 2021. Methods: Electronic medical record data from The US Oncology Network identified adult patients with Stage II-III TNBC with documented surgery between 07/01/2021-08/31/2022, who were followed through 07/31/2025. Pts who received pembrolizumab in the neoadjuvant setting were selected. Pt characteristics and provider-documented pCR were described, and survival analysis results were stratified by pCR status. Real-world event-free survival (rwEFS) was assessed from neoadjuvant treatment initiation date to recurrence, progression, or death. Results: There were 182 pts eligible for the study. The majority (99%) of pts received P+C for first neoadjuvant regimen and pembrolizumab monotherapy in the first adjuvant regimen (85%). Overall, 56% (n=102) of pts achieved pCR. Pts with and without pCR were of similar age (median 53 yrs) and duration of follow-up (38 mths), but a higher proportion of pts with pCR had an ECOG of 0 (pCR:46%; no pCR:35%). Overall, median 3-year rwEFS was 87% in the overall population. 3-year rwEFS was significantly better among pts who achieved pCR compared to non-pCR pts (98% vs. 73%, p<0.001). Conclusions: In this real-world cohort of patients with esTNBC treated with neoadjuvant pembrolizumab, favorable 3-year event-free survival outcomes were observed, with significantly improved rwEFS among patients who achieved pathological complete response. These findings highlight the importance of timely access to neoadjuvant pembrolizumab following esTNBC diagnosis. Overall (N=182) pCR (N=102) no pCR (N=80) Age, median (yrs) 53 53.5 53 Follow-up, median (mths) 38.5 38.8 37.9 ECOG 0 at baseline, N (%) 75 (41.2) 47 (46.1) 28 (35.0) Stage III at diagnosis, N (%) 67 (36.8) 36 (35.3) 31 (38.8) 3-year rwEFS, % (95%CI) 87.1 (81.3,91.3) 98.0 (92.4,99.5) 73.1 (61.7,81.6)

DSE-YOLO11: Dynamic feature adaptation for key traffic element detection in complex road scenes

Accurate detection of key traffic elements in complex road scenes is critical for autonomous driving and intelligent transportation systems. However, existing lightweight detectors often suffer from missed detections under small targets, large-scale variations, and cluttered backgrounds. To address these challenges, we propose DSE-YOLO11, a RAD-oriented lightweight adaptation of YOLO11n that integrates DynamicConv, SlimNeck, and EMA in a stage-wise collaborative manner. The main contribution lies not in introducing entirely new primitive modules, but in developing a task-specific integration strategy for improving detection robustness in complex road scenes. Specifically, a dynamic convolution-based backbone improves local feature modeling and representation of irregular and small-scale targets. A lightweight neck strengthens cross-scale feature interaction while reducing redundant fusion overhead. Additionally, an efficient attention mechanism suppresses background interference and enhances responses to key regions. Experiments on the RAD dataset show that DSE-YOLO11 improves recall from 0.744 to 0.811 and mAP50 from 0.810 to 0.856, while maintaining 2.96M parameters and 7.1 GFLOPs. These gains are practically meaningful because they indicate fewer missed detections of small, low-contrast, and safety-relevant traffic elements in complex road scenes. Additional experiments on BDD100K provide preliminary external support, although broader validation is still needed.

Life‐Cycle‐Integrated Molecular Design of Hindered Phenylene Biacetal Epoxies for Practical Recyclable Composite Applications

ABSTRACT Carbon‐fiber reinforced polymer (CFRP) composites are central to lightweight wind‐energy infrastructure but suffer from poor end‐of‐life circularity due to permanent epoxy thermoset matrices. Here we present a life‐cycle‐integrated molecular design strategy for circular epoxy resins based on a hindered phenylene biacetal architecture, overcoming the longstanding industrial trade‐offs between scalable synthesis, processability, high in‐service performance, chemical recyclability, and long‐term stability. The resins are prepared through one‐pot scalable synthesis (≥200 g), producing liquid monomers compatible with vacuum‐assisted resin infusion molding (VARI) with processing windows exceeding 60 min at 55°C. The resulting networks exhibit strong thermal–mechanical properties ( T g = 119°C–136°C, tensile strength ≥72 MPa) and significantly improved impact resistance (+83% vs. commercial bisphenol A epoxy), together with excellent durability, including negligible creep at 180°C and stable properties after prolonged hygrothermal aging (60°C/90% RH, 32 days). Dormant dynamic acetal linkages enable weak‐acid‐triggered deconstruction at room temperature, allowing 100% nondestructive carbon‐fiber recovery and >80% recovery of high‐purity monomeric precursors. Artificial‐intelligence‐assisted life‐cycle assessment indicates a 45%–56% reduction in cradle‐to‐grave CO 2 emissions compared with conventional CFRP disposal, with a total resource reutilization/upcycling rate exceeding 92%. This platform provides a practical pathway toward circular structural composites for net‐zero infrastructure.

Corrigendum to “Synthesis and anticoagulating potentials of chitosan nanoparticle from cuttlebone of Sepiella inermis (Orbingy, 1848)” [Next Nanotechnol. 8 (2025) 100227]

Non‐Engineered Physiologically Modulated Nanovesicles Augment Antitumor Immune Responses via Dual‐Pathway T Cell Activation

ABSTRACT The therapeutic efficacy of cancer vaccines is critically contingent upon CD8 + T cell‐mediated antitumor immunity, but the effectiveness is hindered due to insufficient T cell activation. Inspired by the close interplay between cellular physiological states and immunoregulatory functions, we propose ASCENT, a nanovaccine platform integrating nanovesicles derived from activated platelets and senescent tumor cells to naturally co‐present antigens and co‐stimulatory molecules, thereby enabling dual‐pathway T cell activation. Specifically, senescent tumor cells promote antigen presentation via upregulated major histocompatibility complex‐I (MHC‐I) molecules, whereas activated platelets increase the surface expression of CD40L and OX40L, thereby enhancing immune activation. Thus, without genetic or chemical engineering, ASCENT can effectively stimulate CD8 + T cells through both antigen self‐presentation and dendritic cell‐mediated antigen presentation, ultimately eliciting robust immune responses. This non‐engineered, physiologically modulated nanovaccine exhibits broad‐spectrum antitumor activity while simultaneously inducing durable systemic immune memory to effectively suppress tumor recurrence and metastasis. Overall, the ASCENT nanovaccine provides new perspectives on rational vaccine design, emphasizing the importance of engaging both direct and indirect T cell activation in reinforcing cancer immunotherapy.