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Real-world outcomes of neoadjuvant chemo-immunotherapy in triple-negative breast cancer at a safety-net institution.

e12715 Background: The addition of immunotherapy to neoadjuvant chemotherapy for stage II-III triple negative breast cancer (TNBC) has been shown to significantly improve pathologic complete response (pCR) rates and patient survival. However, the applicability of these results to real-world populations with varying ethnic and socioeconomic backgrounds is unclear. We sought to evaluate neoadjuvant treatment outcomes of TNBC patients treated at a safety net institution in Los Angeles County (48% Hispanic.). Methods: This is a retrospective cohort study of patients with TNBC treated at a safety-net hospital between 2020 and 2025 who received neoadjuvant chemoimmunotherapy per KEYNOTE 522 regimen. Patients who did not receive surgery were excluded. Primary outcomes included pCR, primary refractory disease, and disease relapse. Outcomes were compared between Hispanic and non-Hispanic patients. An exploratory analysis evaluated the association between Ki-67 expression and treatment response. Overall rates of pCR, primary refractory disease, and relapse were calculated with exact 95% confidence intervals using binomial methods. Categorical outcomes were compared between groups using Fisher’s exact test. Ki-67 was compared across outcome groups (pCR vs no pCR, refractory vs responders, relapse vs no relapse) using the Wilcoxon rank-sum test. All analyses were two-sided, with statistical significance set at p < 0.05, and performed using R. Results: The overall pCR rate was 54.5% (12/22; 95% CI 32.2–75.6%). pCR rate in Hispanics was 47.1% (8/17) vs 80.0% (4/5) in non-Hispanics (p = 0.32). The overall primary refractory rate was 27.3% (6/22; 95% CI 10.7–50.2%) with 35.3% (6/17) in Hispanics vs 0% (0/5) in non-Hispanics (p = 0.27). Overall relapse rate was 9.1% (2/22; 95% CI 1.1–29.2%) with 11.8% (2/17) in Hispanics vs 0% (0/5) in Non-Hispanics (p = 1.00). Patients who achieved pCR had a higher Ki-67 vs those who did not (75% vs 60%, p = 0.14). Treatment refractory patients had a lower Ki-67 vs treatment responders (45% vs 70% p = 0.18). There was not enough data to calculate the association between relapse and Ki-67. Conclusions: KEYNOTE-522 established neoadjuvant chemoimmunotherapy as the standard of care in high risk early stage TNBC, demonstrating higher pCR rates (64.8%) than chemotherapy alone. However, Hispanics were underrepresented in the trial population. In our real-world cohort, the pCR rate was lower (54.5%) with Hispanics patients achieving pCR (47.1%) less frequently than non-Hispanics (80.0%). Rates of primary refractory disease and relapse were also higher among Hispanic patients. Interpretation of subgroup comparisons is limited by the small number of non-Hispanic patients. These findings highlight the need for further investigation and inclusion of ethnically diverse patient populations to better understand factors influencing treatment response and recurrence risk.

Utilizing large language models for lung cancer patient education compared to publicly available information.

9019 Background: The advent of the internet, social media, and more recently of large language model (LLM) platforms has led patients to seek information about cancer directly through digital sources. Complete, readable, and accurate information could reduce physician time clarifying information and increase patient self-activation, especially in low-resource environments. We evaluated the quality of publicly available information provided for the five most common lung cancer questions asked on the internet with information provided by the American Cancer Society (ACS), the National Cancer Institute (NCI), ChatGPT, and Gemini. We hypothesized that LLM platforms could produce readable and information quality equivalent to that found on nationally recognized websites. Methods: ChatGPT (OpenAI, logged-out version, accessed 12/14/25) was queried to determine the five most common questions patients with lung cancer ask. These question prompts were used to generate responses in ChatGPT (OpenAI, logged-out version, accessed 1/13/26) and Gemini (Google, version 3 Flash, 1/13/26). Additional passages were extracted from NCI and ACS patient education web pages, and all passages were de-identified and reformatted with links and references removed. The deidentified passages were evaluated by seven providers representing medical oncology (n=4), radiation oncology (n=1), surgical oncology (n=2), and onco-primary care (n=1) using Information Quality Grade, Global Quality Scale, Error Classification, Comprehensibility, and Confabulation. Readability was determined via Flesh-Kincaid grade level. Results: Readability was similar between passages, ranging from grade levels 6.9-8.2. LLM’s were rated higher on information quality with fewer total errors. Providers were able to discern LLM content in > 50% of the cases but considered human-generated content as LLM in about one third of cases. The most frequent error reported in LLMs was too little information (n=19) and in websites too much information (n=29). Conclusions: LLMs can provide more succinct high-quality information for patients with lung cancer compared to current publicly available websites. The information provided by LLMs is accessible to the public, with potential positive implications for low-resourced populations. Further research is urgently needed to understand the potential of LLMs to improve lung cancer outcomes, such as patient self-activation and adherence. Source Readability(Grade level)* Info Quality*(1 high - 4 low) Global Quality Scale*(5 high - 1 low) % Comprehensibility % Confabulation Total # of errors % Considered LLM ACS 7.8 1.7 3.7 75.0 7.5 28 30.6 NCI 8.2 1.9 3.1 75.0 7.5 43 35.3 ChatGPT 6.9 1.5 4.3 100.0 2.6 20 63.2 Gemini 8.1 1.5 4.4 52.3 2.6 19 64.1 *Averages across all 5 questions.

Safety and efficacy of APS03118, a next-generation RET inhibitor, in patients with non-small cell lung cancer (NSCLC): Results from a phase I clinical trial.

8617 Background: Acquired resistance to first-generation selective RET inhibitors (SRIs) remains a significant clinical challenge in the treatment of RET fusion-positive NSCLC. APS03118 is a next-generation, highly selective RET inhibitor also with additional potent inhibitory activity against YES1, a SRC family kinases. This Phase I study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of APS03118 treatment in patients with advanced RET fusion-positive NSCLC. Methods: This multicenter Phase I trial enrolled 108 patients, including 85 patients with NSCLC harboring RET aberrations. In the dose escalation stage (Ia), APS03118 was administered orally at doses ranging from 40 mg once daily to 120 mg twice daily (BID) 28 days a cycle in 29 patients with solid tumors. In the expansion stage (Ib), 79 patients received 80 mg BID and 100 mg BID, including 66 patients of NSCLC with RET fusions. Efficacy was assessed per RECIST v1.1 every 2 cycles (4 weeks/cycle). Safety was evaluated according to CTCAE v5. Molecular profiling was performed using next-generation sequencing on blood and, when available, tumor tissue. This report focuses mainly on the NSCLC cohorts, including treatment-naïve and previously treated patients with 1-4 lines of therapy, including six different SRIs, (e.g., pralsetinib and selpercatinib). Results: Out of 85 NSCLC patients (Ia+Ib), the Objective Response Rate (ORR) was 80% (confirmed) in 20 (20/22) evaluable treatment-naïve patients. The median Progression-Free Survival (mPFS) is not reached, with 10 patients up to or over the 16 cycles at the data cutoff date. In 22 (22/25) evaluable patients with prior systemic therapy not including the SRIs, the ORR was 55%. There were 38 patients in the cohort of prior SRIs treatment failure. Among 22 (22/26) evaluable patients without known bypass pathway mutations, ORR was 23% with 14 patients’ PFS up to or over 6 cycles and 10 patients up to or over 8 cycles (data cutoff date). Promising anti-tumor action was observed in the two patients with G810S and G810C mutations, who experienced tumor shrinkage of up to 50%. Grade ≥3 TRAEs occurred in 50.9% of patients. The most common AEs were creatine phosphokinase, AST and ALT elevation, which were reversible and mostly observed within cycle 1-3 and rarely after cycle 5. Dose reductions in 22.2%, and permanent discontinuation in 4.6%. Overall, APS03118 demonstrated a manageable and predictable safety profile. Conclusions: APS03118 shows highly promising clinical activity in both treatment-naïve and SRI failed NSCLC patients harboring RET fusions. Its survival benefit may result from potent inhibition of RET and YES1. The safety profile is manageable, characterized primarily by reversible enzyme elevations. Further development in NSCLC patients harboring RET fusion is warranted. Clinical trial information: NCT05653869 .

FAITH: Fatigue associated with immunotherapeutics—Analyzing patterns and associated factors during treatment.

e24065 Background: Fatigue is a frequent, multifactorial toxicity in patients receiving immune checkpoint inhibitors (ICIs), but its drivers and severity patterns remain poorly characterized in real-world practice. We analyse the incidence, attribution, and predictors of fatigue in this LMIC cohort, so that potentially preventable and reversible causes can be identified and addressed. Methods: We conducted a single-centre retrospective chart review of adults with solid malignancies who received ≥4 cycles of ICI therapy between January 2023 and December 2025. Demographic, clinical data, the highest CTCAE v5.0 fatigue grade per patient and contemporaneous clinical notes were reviewed. Descriptive analytics, Chi Square/Mann-Whitney U tests were used where appropriate and univariate analyses were used for exploratory screening. Results: 264 patients with solid malignancies who received ≥4 cycles of ICI therapy were included. Median age was 62 years (range 38–89), 42% were female, 83% with metastatic disease and 53% had ECOG PS-2. Treatment regimens included chemo–immunotherapy in 66%, tyrosine kinase inhibitor–ICI combinations in 22%, and ICI monotherapy in 12%. The most common malignancies were lung (22%), gastrointestinal & hepatobiliary (25%) and head and neck (14%). All-grade fatigue was reported in 90% of patients (n=238), with grade ≥3 in 69 (26%) patients. Median time to onset of worst-grade fatigue was comparatively shorter in the chemo–immunotherapy group (6 vs 8 weeks). On qualitative assessment, 90% patients reported a loss of appetite, 61% reported a new-onset sleep disturbance and only 31% engaged in exercise and physical activity. Overlapping etiologic attribution included chemo-immunotherapy (66%), hematologic causes requiring growth factors & transfusions (35%), dyselectrolytemia (26%), infections (23%), worsening comorbidities (18%) and endocrine irAEs (16%). ≥2 simultaneous contributing factors were identified in 15%. ICI related asthenia (diagnosis of exclusion) presented in 7% patients and responded to temporary treatment stoppage. Treatment was interrupted in 55% patients due to fatigue, and 35% could be restarted. 18% had a progression event on treatment. On univariate testing, chemoimmunotherapy, irAEs, cytopenias, age ≥65, ≥2 comorbidities, and poor sleep were associated with grade ≥3 fatigue (p<0.05). More than half of the patients had reversible causes, which included electrolyte disturbances, cytopenias, endocrine dysfunction, and infection. Conclusions: Systematic evaluation using a triage checklist of electrolyte, endocrine, infectious and hematological surveillance can help pinpoint causes of disproportionate fatigue. Earlier causal identification can avoid morbidities, unnecessary admissions and treatment interruptions, thus enabling better quality of life and facilitating better patient communication.

Structural inequities in ovarian cancer care: A national study of hospital utilization, costs, and outcomes.

e17607 Background: Racial disparities may affect the clinical outcomes in ovarian cancer. In this study we aimed to identify the racial disparities in United States hospital outcomes of patients with ovarian cancer. Methods: We performed a retrospective analysis of ovarian cancer-related hospital admissions using the 2022 National Inpatient Sample. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, & Other. Results: There were 12,397 ovarian cancer patients admitted in 2022, out of which 68.41% were whites, 11.72% African-Americans, 11.63% Hispanics, 4.60% Asian or Pacific Islanders, 0.60% Native-American & 3.04% were included in the minor groups. White patients had the highest mean age (65 years), while Hispanic & Asian/Pacific Islander patients presented at a younger age (57 years). There was no statistical difference in mortality rates among the different racial group (p-value 0.31). Most ovarian cancer hospitalizations occurred at large hospitals and teaching institutions, with higher teaching-hospital utilization among African-American (88.2%), compared with White patients (83.1%). Socioeconomic disparities were observed, as African-American (43.3%) & Native American (41.4%) patients were overrepresented in the lowest median household income quartile, whereas Asian/Pacific Islander patients were more frequently in the highest quartiles (Quartile 3–4: 78.8%). Discharge to home was most common across all groups (52.1–65.1%), while White (11.9%) & African-American (10.8%) patients had higher rates of discharge to skilled nursing facilities. Insurance status differed significantly, with Medicaid coverage more common among African-American (18.9%), Hispanic (26.3%), & Native American patients (20.6%), while Medicare predominated among White patients (57.7%) ( p < 0.001). African-American & Native American patients experienced longer hospital stays (7.3 and 7.5 days, respectively) compared with White patients (5.7 days) (p < 0.001). Total hospitalization charges were significantly higher among Hispanic, Asian/Pacific Islander, Native American, & Other racial groups, with the highest costs observed in Asian/Pacific Islander patients ($112,699), compared with White patients ($81,546) (p < 0.01). Conclusions: This national analysis demonstrates clear & clinically meaningful racial disparities in ovarian cancer hospitalizations. Minority patients present at younger ages, experience greater healthcare utilization, incur substantially higher hospitalization costs, & are disproportionately cared for in large, teaching hospitals while residing in lower-income communities. Urgent, targeted policy and system-level interventions are needed to address socioeconomic barriers, optimize care delivery, & advance equity in ovarian cancer outcomes.

Phase Ib evaluation of a recombinant overlapping peptide survivin immunotherapy: Safety, immunogenicity, and immune–clinical associations in advanced solid tumours.

2651 Background: Survivin (BIRC5) is a tumour-associated self-antigen broadly expressed in solid malignancies but subject to immune tolerance, limiting its value as an immunotherapy target. OVM-200 is a recombinant overlapping peptide (ROP) survivin immunotherapy designed to enhance antigen processing and presentation through both MHC class I and II pathways, thereby overcoming HLA restriction. A Phase Ia study established safety and the recommended regimen. Here we report novel Phase Ib data evaluating extended immunisation and immune–clinical associations. Methods: Phase Ib enrolled a total of 24 patients with advanced NSCLC, ovarian, or prostate cancer who had progressed on standard therapies. Patients received OVM-200 at the recommended regimen (2 mg) with extended immunisation schedules (3–11 immunisations). The primary endpoint was safety and the secondary endpoint was immunogenicity. Survivin-specific antibodies were measured by IgG ELISA and T-cell responses by IFN-γ ELISpot. Tumour response was assessed using RECIST 1.1, with best overall response (BOR) classified as stable disease (SD) or progressive disease (PD). Immune responses were analysed longitudinally and in relation to BOR. Results: The primary endpoint of safety was met, with OVM-200 well tolerated and no dose-limiting toxicities or treatment-related serious adverse events. Survivin expression was detected in tumour tissue in 17 patients prior to immunisation; however, baseline survivin-specific antibody and T-cell responses were low or undetectable, consistent with immune tolerance. The secondary endpoint of immunogenicity was achieved. Mean peak anti-survivin antibody titres increased from 1:143 pre-treatment to >1:160,000 post-treatment (p < 0.001), and mean peak T-cell responses increased from 211 to 859 net SFU/10⁶ PBMCs (p < 0.00001). Antibody responses were durable, rising through Days 113–169, whereas T-cell responses peaked at Day 57 and remained significantly above baseline. Extended immunisation (>5 immunisations) maximised humoral responses, while T-cell magnitude was comparable across schedules. Patients with BOR of SD showed higher and more sustained survivin-specific humoral and cellular immune responses than those with PD. Conclusions: Phase Ib results demonstrate that OVM-200 is safe and immunogenic, achieving both the primary safety and secondary immunogenicity endpoints. OVM-200 overcomes immune tolerance to survivin and induces durable humoral and cellular immune responses. The observed association between stronger immune responses and BOR of SD supports further clinical evaluation and rational combination strategies. Clinical trial information: NCT05104515 .

Outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with relapsed or refractory (R/R) mantle cell lymphoma (MCL): First real-world data from the CIBMTR.

7026 Background: Liso-cel, an autologous, CD19-directed CAR T cell product, demonstrated deep, durable responses with manageable safety in pts with R/R MCL in the MCL cohort of TRANSCEND NHL 001 (NCT02631044). In this study, we present the first report of real-world outcomes for pts with R/R MCL who received liso-cel, using data from CIBMTR. Methods: This retrospective study included pts in the US with R/R MCL who received commercial liso-cel from 05/2024 to 09/2025 with ≥ 1 postinfusion assessment reported to CIBMTR. Effectiveness outcomes included ORR, CR rate, duration of response (DOR), PFS, and OS. Safety outcomes included AEs of special interest, nonrelapse mortality (NRM), and death. Results are descriptive. Results: A total of 94 pts were eligible. Median age was 73 y (range, 46–85), 74% were male, 4% (4/92) had ECOG PS ≥ 2, and 65% (53/81) had ≥ 1 clinically significant comorbidity, with cardiac (31%), pulmonary (31%), and obesity (17%) being most common (> 10%). Largest nodal mass > 10 cm, indicative of bulky disease, was observed in 15% of pts (9/60), 31% had ≥ 2 extranodal involvement, and 5% had CNS involvement. Data on TP53 mutation status and Ki-67 score were limited. Median number of prior lines of therapy (including HSCT/cell therapy) was 4 (range, 2–12); 69% of pts (62/90) had refractory disease and 72% (67/93) received bridging therapy. At a median follow-up of 6.0 mo (95% CI, 5.9–6.2), ORR was 88% (95% CI, 80–94) with CR rate of 80% (95% CI, 70–87). Median DOR, PFS, and OS were not reached; 6-month DOR, PFS, and OS rates were 79% (95% CI, 55–91), 79% (95% CI, 68–87), and 92% (95% CI, 83–96.5), respectively. Any-grade (gr) cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome were reported in 65% (gr ≥ 3, 2%) and 37% (gr ≥ 3, 12%) of pts, respectively, with no gr 5 events. Clinically significant infections were reported in 23% of pts, gr 4 thrombocytopenia and/or neutropenia persistent at 30 days after infusion in 18%, and second primary malignancies in 5%, with skin malignancies being the most common. Gr 3/4 organ toxicity occurred in 1 (1%) pt, and none had tumor lysis syndrome. Nine (10%) pts died, including 6 (6%) due to PD. The NRM rate at 6 mo was 1% (95% CI, 0.1–5.4). Of the 36% of pts planned for outpatient infusion, 59% (20/34) were reported as being hospitalized postinfusion with a median (range) time to hospitalization and stay of 5.5 days (1–35) and 4.5 days (2–32), respectively. Conclusions: These results show that liso-cel is associated with high response rates in a broad population of heavily pretreated pts with R/R MCL with early signs of durable benefit and safety profile consistent with TRANSCEND NHL 001. While longer follow-up is needed, this supports the potential of liso-cel to address critical gaps for pts with limited treatment options, providing strong effectiveness and manageable safety.

First-line (1L) trastuzumab deruxtecan (T-DXd)–based regimens in advanced HER2-expressing gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): Safety results from DESTINY-Gastric03 (DG-03) Part 2 arms D and F, and Part 4.

4022 Background: T-DXd 6.4 mg/kg monotherapy is approved in several countries for advanced HER2+ (IHC 3+ or IHC 2+/ISH+) GC/GEJA after an indicated HER2-directed regimen. Early data have shown promising antitumor activity with 1L T-DXd + immunotherapy + chemotherapy for advanced HER2+ GCs. Here, we report an approximate time-matched analysis of safety results for DG-03 Part 2 arms D and F, and Part 4. Methods: DG-03 (NCT04379596) is a Phase 1b/2, open-label, multipart trial. Part 2 (arms A–F) enrolled patients (pts) with previously untreated advanced HER2+ (IHC 3+ or IHC 2+/ISH+) GC/GEJA/EA. Pts in arm D received T-DXd 6.4 mg/kg + pembrolizumab (pembro) + fluoropyrimidine (FP; 5-fluorouracil or capecitabine), and pts in arm F received T-DXd 5.4 mg/kg + pembro + FP. In Part 4, pts with previously untreated advanced HER2-expressing (IHC 3+, IHC 2+/ISH+, IHC 2+/ISH−, or IHC 1+) GC/GEJA/EA were enrolled and received T-DXd 5.4 mg/kg + rilvegostomig (rilve; a monovalent, Fc-reduced, bispecific IgG1 antibody against PD-1 and TIGIT receptors) + FP. HER2 status was based on local testing. Secondary endpoints included frequency of adverse events (AEs) and serious AEs. Results: As of Feb 15, 2023, Aug 19, 2024, and Oct 16, 2025, 43, 32, and 62 pts received treatment (Tx) in Part 2 arm D, Part 2 arm F, and in Part 4, respectively. Median (range) total duration of Tx for both T-DXd and pembro was 6.1 (0.5–13.3) months (mo) in Part 2 arm D, and 6.9 (0.7–10.3) mo for T-DXd and 7.5 (0.7–10.3) mo for pembro in Part 2 arm F. Median (range) total duration of Tx for both T-DXd and rilve was 6.5 (0.7–14.7) mo in Part 4. A summary of safety data is shown in the Table. Drug-related adjudicated interstitial lung disease (ILD)/pneumonitis events occurred in 2 pts (5%) in Part 2 arm D, no pts in Part 2 arm F, and 2 pts (3%) in Part 4. Conclusions: Results with T-DXd (5.4 mg/kg)–based regimens were generally consistent with the known safety profiles of each agent; no new signals were observed. Safety data support use of pembro/rilve as combination partners for T-DXd (5.4 mg/kg) in advanced HER2-expressing GCs. Clinical trial information: NCT04379596 . n (%) Part 2 arm D T-DXd 6.4 mg/kg + pembro + FP (n=43) Part 2 arm F T-DXd 5.4 mg/kg + pembro + FP (n=32) Part 4 T-DXd 5.4 mg/kg + rilve + FP (n=62) AEs 43 (100) 31 (97) 60 (97) Drug-related AEs* 40 (93) 27 (84) 55 (89) Grade ≥3 AEs 38 (88) 15 (47) 31 (50) Drug-related Grade ≥3 AEs* 33 (77) 11 (34) 24 (39) Serious AEs 25 (58) 12 (38) 22 (36) Drug-related serious AEs* 19 (44) 5 (16) 12 (19) AEs leading to discontinuation of any IP 16 (37) 7 (22) 7 (11) Drug-related AEs leading to death 4 (9) † 0 1 (2) ‡ *Assessed by the investigator as possibly related to any investigational product (IP); † ILD/pneumonitis (n=2), respiratory failure due to pneumonitis/pneumocytis jirovecii infection (n=1), febrile neutropenia (n=1); ‡ pneumonia.

Dose-escalation results from a phase I study of FZ-AD004, a TROP2-directed ADC, in patients with advanced solid tumors.

8523 Background: FZ-AD004 is an ADC (antibody-drug conjugate) targeting Trop-2 (trophoblast cell-surface antigen 2), an intracellular calcium signaling transducer overexpressed on many epithelial tumors. It delivers the topoisomerase inhibitor DXd. This first-in-human study evaluated the safety and efficacy in patients(pts) with advanced solid tumors, mainly in non–small-cell lung cancer (NSCLC). Methods: PTs with unresectable, treatment-refractory or relapsed solid tumors received FZ-AD004 intravenously on days 1 of 21-day cycles. The primary objectives were to determine maximum tolerated dose (MTD), safety, and tolerability; secondary objectives included efficacy, pharmacokinetics, and immunogenicity of FZ-AD004. Pts were eligible regardless of TROP2 level. Results: As of November 28, 2025, 22 pts were treated with ≥1 dose of FZ-AD004 (median age: 61.5 years [range from 45-75], male: 77.3%, EOCG PS 1: 100%, prior lines of anticancer treatment ≥ 2: 77.3%). Diagnoses included NSCLC (n=21) and SCLC (n=1). Doses evaluated were at 3.2 (n=3), 5.6 (n=3), 6.4 (n=3), 8.0 (n=4), 10.0 (n=3), and 12.0 mg/kg (n=6). No dose-limiting toxicity (DLT) was observed across all dose levels.19 pts (86.4%) discontinued (15 (68.2%) due to disease progression per RECIST v1.1). Treatment emergent adverse events (TEAEs) regardless of causality were reported in all of 22 pts (100%; 10 pts [45.5%] experienced ≥grade 3, 5 pts [22.7%] had serious adverse events). Treatment-related AEs (TRAEs) occurred in all pts (100%; grade ≥3 in 36.4%; serious TRAEs in 13.6%). Grade ≥3 TRAEs included stomatitis (13.6%), decreased lymphocyte count (9.1%), nausea (4.5%), hypokalemia (4.5%), and keratitis (4.5%).Among 12 efficacy-evaluable pts at doses ≥8.0 mg/kg, the objective response rate (ORR) was 50.0% and the disease control rate (DCR) was 83.3%. Responses were observed in pts harboring KRAS G12C (n=1), EGFR mutations (n=3), and without AGA mutations (n=2). The longest duration treatment was 11.4 months. Conclusions: FZ-AD004 demonstrated a manageable safety profile with no DLTs observed up to 12.0 mg/kg and promising antitumor activity in heavily pretreated NSCLC patients, particularly at doses of 8.0 and 10.0 mg/kg. These doses are being further explored in the expansion phase. Clinical trial information: NCT05914545 .

Mortality trends and disparities in prostate cancer with co-occurring cardiometabolic disorders among U.S. men aged ≥ 55 years, 1999–2024.

5061 Background: Prostate cancer (PCa) survivors are at significant risk for cardiometabolic disorders (CMD) including hypertension, diabetes, and cerebrovascular diseases which often act as competing causes of death. While PCa survival with CMD has improved but trends in deaths remain poorly characterized across demographic and geographic strata. This study evaluates longitudinal trends to identify success in management and remaining inequities in men aged ≥ 55. Methods: We analyzed U.S. mortality data (1999–2024) from the CDC WONDER database for men aged ≥ 55 years with PCa as the underlying cause of death (UCOD) and CMD as the multiple cause of death (MCOD). Age-adjusted mortality rates (AAMR) per 100,000 and joinpoint regression were used to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Stratified analyses were performed by race, census region, and urbanization. Results: A total of 151,108 deaths were identified (cumulative AAMR: 18.78). Overall mortality demonstrated a significant declining trend (1999–2024; AAPC: -2.48%, p < 0.001). Significant declines were observed across all racial groups. Black or African American men experienced the highest mortality burden but also the most rapid decline (AAPC: -6.01%, p < 0.001), narrowing the gap with White men (AAPC: -4.33%, p < 0.001). While all regions showed improvement, the Southern U.S. demonstrated the slowest rate of decline (AAPC: -4.13%, p < 0.001) compared to the Northeast, which saw the most substantial reduction (AAPC: -5.76%, p < 0.001). Recent trends (2019–2024) showed sharp decreases across regions, including the South (APC: -11.28%, p = 0.002). Declines were consistent across the rural-urban continuum. Micropolitan (non-metropolitan) areas showed a significant overall decline (AAPC: -1.72%, p < 0.001). However, segments of transient increase were noted between 2015–2020 in Medium Metro (APC: +3.77%, p = 0.004) and Large Fringe Metro (APC: +3.55%, p = 0.005) areas before resuming a downward trend. Conclusions: Mortality for prostate cancer with contributing cardiometabolic causes is significantly decreasing among U.S. men aged ≥ 55. The accelerated decline among Black men and in the Northeast reflects improvements in integrated oncological and cardiovascular care. However, the slower decline in the South and transient increases in specific metropolitan areas underscore the necessity for targeted cardio-oncology interventions. Continued focus on equitable access to cardiometabolic risk management is vital to sustaining these positive trends and eliminating geographic and racial disparities in PCa survivorship.

Transfer of care after virtual oncology second opinions.

e23212 Background: Virtual oncology second opinions have expanded access to subspecialty expertise, potentially reducing geographic and structural barriers to care. However, their impact on management decisions and transfer of care (TOC) remains poorly understood. We evaluated patient characteristics, diagnostic and treatment changes, and factors associated with TOC following virtual oncology second opinions at a large academic cancer center. Methods: This retrospective study included patients with an oncologic diagnosis who sought virtual second opinions at Stanford Cancer Institute (SCI) between January 2018 and December 2024. This study was approved by the Stanford Institutional Review Board. Collected variables included age, sex, zip code, oncologic diagnosis, year of consult, diagnosis change, whether there was treatment change, and transfer of care. Geographic distance to SCI, rurality (RUCA code), and social vulnerability index (SVI and subscales) were derived from zip codes. Statistical analyses were performed in R (version 4.5.1), using chi-squared tests for categorical variables and Mann-Whitney U tests non-normally distributed continuous variables. Results: Of the 3,669 patients in this cohort, 697 (19.0%) transferred their care to Stanford. This did not differ by age, sex, or rurality. Patients who transferred care were more likely to live in California (70.7% vs. 33.1%, p < 0.001) and live within 100 miles of SCI (59.8% vs 24.0%, p < 0.001). Overall, SVI and socioeconomic or household composition SVI subscales did not differ, while higher vulnerability in housing/transportation (21.1% vs 15.5%, p = 0.02) and racial/ethnic and language status SVI subscales (29.6% vs 17.1%, p < 0.001) were observed among those who transferred care (Table 1). There was no difference in rate of diagnosis change. Although major and minor treatment changes were more frequent among those who transferred care (54.4% vs 49.4%), this difference did not reach statistical significance. Conclusions: TOC after virtual oncology second opinions appears to be driven primarily by geographic proximity rather than demographics or diagnostic change, with higher social vulnerability observed among patients who transitioned care. Ongoing analyses will further characterize factors influencing TOC following virtual second opinions. Patient characteristics by transfer of care status. Transfer of Care N (%) Yes (N = 697) No (N = 2972) Average age (years) 57.8 56.6 Gender Female 375 (53.8) 1613 (54.3) Male 268 (38.5) 1146 (38.6) Other/Unknown 54 (7.7) 213 (7.2) California Residence 493 (70.7) 985 (33.1) Less than 100 miles from SCI 417 (59.8) 714 (24.0) High Social Vulnerability Index Subscales Socioeconomic Status 28 (4.0) 140 (4.7) Housing 29 (4.2) 152 (5.1) Race/Ethnicity & Language 206 (29.6) 507 (17.1) Housing & Transportation 147 (21.1) 462 (15.5) Diagnosis Change 47 (6.7) 212 (7.1) Treatment Change (major or minor) 379 (54.4) 1467 (49.4)

Real-world feasibility and tolerability of Pedmark for otoprotection in young adults receiving cisplatin for solid tumors.

e24189 Background: Cisplatin-induced ototoxicity is an irreversible toxicity that affects up to 90% of patients, with particularly profound consequences for young adults whose communication, education, and quality of life may be permanently impaired after treatment. As cancer survival improves, the need to preserve hearing and long-term function becomes critical. Pedmark (sodium thiosulfate) is the only FDA-approved agent for reducing the risk of cisplatin-induced hearing loss and is recommended for adolescents and young adults according to the NCCN guidelines. This study provides real-world data on its integration into adult oncology practice. Methods: This retrospective case series included nine patients aged 18–39 years with localized and disseminated solid tumors treated at a cancer center in 2024–2025. All patients received cisplatin-based chemotherapy with Pedmark administered six hours after cisplatin infusion. Supportive care included antiemetics (a combination of ondansetron, metoclopramide, olanzapine, and promethazine) and hydration. Outcomes assessed were feasibility of administration, Pedmark-related adverse events, and auditory symptoms. Results: All nine patients (testicular, cervical, germ cell, and head and neck cancers) received Pedmark without major complications or significant adverse events. Nausea was the most common adverse event (5/9 patients) and was effectively managed with antiemetics (ondansetron, metoclopramide, olanzapine, and promethazine) or infusion flow rate adjustments. One patient discontinued Pedmark at the recommendation of the clinical team following a self-limited episode of rigors. Importantly, no new-onset hearing loss or tinnitus was reported. There were no Cisplatin dose reductions, treatment delays, or other deviations from planned therapy. All patients completed their intended cancer treatment courses, demonstrating that Pedmark can be successfully integrated into routine Cisplatin regimens to reduce ototoxicity and improve survivorship outcomes. Conclusions: Preventing ototoxicity is critical for preserving long-term quality of life in young adults treated with Cisplatin. This real-world case series demonstrates that Pedmark can be feasibly incorporated into adult oncology workflows and does not interfere with Cisplatin-based treatment. These findings support the routine adoption of Pedmark for young adults to reduce the risk of Cisplatin-induced hearing loss and enhance survivorship outcomes.

BRIDGES: A phase 3 randomized trial of immediate postoperative cesium-131 tile-based radiation therapy followed by abbreviated chemoradiation for newly diagnosed glioblastoma (NCT07195591).

TPS2105 Background: Glioblastoma remains a lethal primary brain tumor with limited therapeutic progress and a persistent unmet clinical need. Standard management requires maximal safe resection followed by external beam radiation therapy (EBRT) with concurrent temozolomide (TMZ); however, the required 4–6-week postoperative healing interval before initiating EBRT creates a vulnerable window for rapid early progression (REP), defined as radiographic tumor progression occurring between surgery and the start of chemoradiation. REP is detected in more than half of patients and is associated with inferior survival. Tile-based radiation therapy (TBRT) with cesium-131 brachytherapy sources (GammaTile, GT Medical Technologies, Tempe, AZ, USA), offers a strategy to eliminate this treatment gap by immediately initialing localized radiation at the time of resection. A feasibility and safety study (NCT05342883) evaluating TBRT implantation following EBRT has been fully accrued and supports randomized evaluation. The BRIDGES study (NCT07195591) builds on this foundation. Methods: NCT07195591 is a prospective, randomized, open-label, multicenter, phase 3 trial to evaluate whether immediate postoperative TBRT followed by abbreviated EBRT with concurrent and adjuvant TMZ improves outcomes compared with standard postoperative EBRT with concurrent and adjuvant TMZ. Eligible adults must have newly diagnosed, radiographic suspicion of glioblastoma, can undergo maximal safe resection, possess a Karnofsky Performance Status score ≥70, and be candidates for standard chemoradiation. Key exclusion criteria include multifocal or disseminated disease, prior cranial radiation or chemotherapy, inability to receive TMZ, and medical comorbidities that would interfere with protocol treatment or follow-up. Patients are randomized 2:1 to receive either TBRT implantation followed by a shortened EBRT course with concurrent and adjuvant TMZ or standard postoperative EBRT with concurrent and adjuvant TMZ. Randomization is stratified by age, sex, prior sub-maximal safe resection, and size of pre-operative tumor. A stratified log-rank test using Kaplan–Meier methods will be done using the stratification factors will be implemented for the primary endpoint. Additional time-to-event endpoints will be analyzed using Kaplan–Meier methods and Cox proportional hazards models, and the analyses will follow the intent-to-treat principle. The trial has two pre-planned interim analyses. A Data and Safety Monitoring Board will oversee the trial and conduct periodic safety reviews. Four of the 766 planned patients have enrolled. Clinical trial information: NCT07195591 .

Comparing oncologists, a GPT-based model, and a SEER-based survival calculator for cancer prognostication.

1621 Background: Prognostic estimates guide cancer treatment planning and goals-of-care discussions. Clinicians often rely on population-based survival statistics (e.g., SEER), which may not reflect individualized risk. Large language models (LLMs) such as ChatGPT may offer more personalized estimates, but their performance relative to oncologists and population-based tools remains unclear. Methods: We conducted a retrospective comparative study of 205 adult cancer patients treated in a safety net cancer clinic. For each patient, one deidentified clinical note from the time of diagnosis was provided to a HIPPAA compliant instance of ChatGPT (GPT-4.1) and an oncologist unfamiliar with the patient. Both generated binary (alive/deceased) and probabilistic (0–100%) predictions of survival at 6 months, 1, 2, and 5 years. The primary endpoint was per-patient binary accuracy (0–4 correct timepoints) comparison between ChatGPT and the oncologist. Secondary outcomes (n=189) included Brier scores, and calibration metrics compared with oncologists and a publicly available SEER-based cancer-specific survival calculator (CancerSurvivalRates.com), and subgroup analyses by cancer stage. Significance testing used exact binomial methods for per-patient win–loss comparisons and paired nonparametric tests to compare probabilistic performance across methods. Results: Of the 205 patients, 25, 53, 53, and 74 were stages I, II, III, and IV, respectively. Gender was balanced (53% male). All surviving patients had at least 5 years of follow-up. Notes varied in final staging and treatment plans, as some patients were in their initial evaluation. In the primary analysis (N = 205), ChatGPT was numerically, not statistically, superior to the oncologist (52 vs. 41, p=0.299). In secondary analyses (n = 189), ChatGPT had superior overall accuracy with lower Brier scores at 1 year (p < 0.001) and 2 years (p = 0.030). Calibration analyses showed that at 5 years, ChatGPT achieved near-ideal reliability (calibration slope 1.018), whereas oncologists demonstrated overconfidence (slope 0.535). As expected, cancer specific survival by CSR was significantly higher than OS estimates from oncologists or ChatGPT. Stage-stratified analyses revealed oncologist superiority in Stage I disease (p = 0.036), while ChatGPT significantly outperformed oncologists in Stage IV disease at 2- and 5-year horizons (both p < 0.001). Conclusions: For a safety-net cancer clinic, using one unstructured note, ChatGPT demonstrated comparable or superior prognostic estimates for clinically relevant time points as compared to oncologists, particularly in long-term outcomes for advanced disease. Future studies should evaluate cancer specific survival and prognosis after or during treatment.

Unraveling the Crystal‐Field‐Mediated Cobalt Spin‐State Evolution for Electrocatalytic Ethylene Glycol Oxidation by In Situ X‐Ray Emission Spectroscopy

ABSTRACT The electrocatalytic oxidation of polyethylene terephthalate (PET) derived ethylene glycol (EG) into valuable formate and hydrogen represents a sustainable waste valorization strategy. Although cobalt‐based oxyhydroxides (CoOOH) have emerged as promising electrocatalysts for the ethylene glycol oxidation reaction (EGOR), achieving high product selectivity remains challenging due to incomplete understanding of reaction mechanisms. Herein, we developed a phosphorus‐doped P‐CoOOH catalyst, in which the heteroatom incorporation effectively triggers lattice distortion and electronic reconstruction. These synergistic effects collectively promote a spin‐state transition of cobalt centers from a low‐spin to a high‐spin configuration. Such electronic reconfiguration creates synergistic electron‐deficient Co and electron‐rich P sites, with non‐degenerate orbitals facilitating selective C─C bond cleavage during EGOR. The innovative application of in situ x‐ray emission spectroscopy (XES) and x‐ray absorption spectroscopy (XAS) dynamically captures spin‐state evolution and suggests the structure‐activity relationship between high‐spin Co 3+ electronic configuration and product selectivity. The optimized P‐CoOOH/NF electrode achieves a low potential of 1.26 V versus RHE at 10 mA cm −2 with a formate selectivity of 93.7%. Overall, this work highlights that spin‐state engineering offers an effective strategy for steering polyol electrooxidation pathways.

Green-synthesized Co₃O₄/bentonite nanocomposite as an efficient photocatalyst for methyl blue degradation in water

A renaissance in targeting the PI3K/AKT/mTOR pathway

Stable Energy‐Level Regulation of NiO <i> _x </i> for Efficient Deep‐Blue Perovskite LEDs

ABSTRACT NiO x offers tunable energy‐level via interfacial molecular modification, making it a promising hole injection layer for perovskite light‐emitting diodes (PeLEDs). However, conventional modifiers often detach during perovskite deposition, reverting energy‐level to the intrinsic state. While simply enhancing electron‐withdrawing strength can improve anchoring, it causes excessive energy‐level shifts. Here, we employ a multidentate anchoring strategy to enhance modifier adsorption stability on NiO x , preventing the regulated energy‐level from shifting back. These interactions correspondingly provide multiple charge‐transfer pathways, which effectively disperse the charge density and thereby mitigate the localized strong electron transfer that causes excessive energy‐level modulation. Specifically, tridentate anchor 4‐bromophenylphosphonic acid (BPA) engages in multiple Ni‐O coordination bonds, achieving a high adsorption strength of −6.47 eV and retaining over 95% surface‐coverage after polar solvent rinsing. Concurrently, multiple charge‐transfer pathways effectively distribute the electron‐withdrawing effect of ─PO 3 H 2 group, yielding favorable energy‐level alignment with a small barrier of less than 0.69 eV. We integrate this strengthened NiO x with pure‐halide quasi‐2D perovskites to fabricate deep‐blue PeLEDs. The obtained PeLEDs exhibit a champion external quantum efficiency (EQE) of 15.8% at 463 nm and a record‐low turn‐on voltage of 2.4 V. This approach also enables large‐area (3 × 3 cm 2 ) PeLEDs fabrication, with an EQE of 11.2%.

Rigid Flexible Pillaring via Synergistic Co‐Doping Stabilizes High‐Capacity Sodium Layered Oxide Cathode

ABSTRACT O3‐type layered oxide cathodes offer high energy density but suffer from interlayer gliding and oxygen release at elevated voltages, leading to rapid capacity fade. Here, we propose a rigid–flexible coupled pillaring strategy, where Mg/Li co‐doping offers a versatile route to achieve excellent performance at high voltage. This stems from rigid Mg─O pillaring that suppresses slab gliding, together with compliant Li─O buffering that smooths the in‐plane potential. In tandem, closed‐shell Mg/Li weakens TM─O eg* antibonding and downshifts the O‐2p band center, promoting a tempered, reversible anionic‐redox reaction, thereby avoiding the usual trade‐off in which improvements in durability come at the expense of capacity. Consequently, this pair redirects the high‐voltage response from P3→OP2 to a P3 solid solution, cutting c‐axis breathing to ∼1.7%, and the cathode delivers a capacity of over 160 mAh g −1 at 4.2 V, retains 80% after 500 cycles at 5C. Furthermore, the cathode is scalable to kilogram batches. With excellent coin and Ah‐scale pouch‐cell performance, it shows guidance of design and commercial promise for high‐voltage O3‐type cathodes.

Empirical analysis of adversarial robustness in 3D Gaussian Splatting under multi-view inconsistency attacks

Abstract 3D Gaussian Splatting has emerged as a promising technique for real-time novel view synthesis, achieving rendering quality comparable to neural radiance fields while enabling significantly faster inference. Despite its growing adoption in various applications including autonomous driving, robotics, and augmented reality, the adversarial robustness of 3D Gaussian Splatting remains largely unexplored. This paper presents a comprehensive empirical analysis of 3D Gaussian Splatting robustness against multi-view inconsistency attacks, which inject imperceptible perturbations into training images to disrupt the reconstruction process. We propose an adversarial attack framework that maximizes view-dependent inconsistencies while preserving visual imperceptibility through semantic-aware perturbation constraints. Our extensive experiments on the Mip-NeRF 360 dataset reveal that 3D Gaussian Splatting exhibits strong robustness to multi-view photometric inconsistency attacks, with quality degradation limited to less than one percent across standard metrics including Peak Signal-to-Noise Ratio, Structural Similarity Index, and Learned Perceptual Image Patch Similarity. We identify three key factors contributing to this robustness: multi-view averaging during optimization, the explicit Gaussian primitive representation, and the gradient-based optimization dynamics that naturally suppress view-dependent artifacts. These findings provide important insights for deploying 3D Gaussian Splatting in security-sensitive applications and suggest directions for developing more effective adversarial attack strategies.