Browse Articles

Quantifying the impact of protocol design on enrollment and dropout rates in breast cancer clinical trials.

11027 Background: Clinical trial enrollment can sometimes fail due to protocol design being overly complex, including procedures that are overly burdensome on patients and/or trial sites. Procedures that may be more logistically challenging or introduce higher risk (ex: radiation exposure in imaging procedures) can affect trial enrollment and patient retention. To better understand factors that optimize operational design of protocols, we evaluated breast cancer protocols to assess and quantify procedures that had the highest potential impact on enrollment and dropout rates. Objective: Our objective is to develop an algorithm that can predict enrollment and dropout rates by analyzing the procedures and procedure frequency included in protocol design. Methods: 42 breast cancer protocols (sourced from aggregated, anonymized Medidata Clinical Cloud data) from closed clinical trials conducted between 2010-2023 were utilized to train a predictive model. The model leveraged the procedure and schedule-of-activity data to capture the frequency of protocol-specified procedures as input features, and enrollment and dropout rates as outcome features. Model performance was assessed utilizing cross-validation. To assess the relative impact of individual procedures or groups of procedures on a protocol, a sensitivity analysis was performed by increasing each procedure’s frequency by 1 unit while holding all other variables constant and measuring the resulting percent change in predicted enrollment and dropout rates. Results: Analysis of selected protocols demonstrated that inclusion of Positron Emission Tomography (PET) Imaging was associated with a 10-23% reduction in enrollment rates. Genetic testing and analysis procedures were associated with enrollment rate decreases of up to 5%. In contrast, bone density imaging, abdominal and pelvic imaging, and increased tumor and biopsy procedures were associated with enrollment increase of up to 6%. With respect to retention, increased cardiac rhythm monitoring was associated with up to 10% reduction in dropout rates, while blood cell analysis, collagen biomarker testing, and quality of life questionnaires were each associated with dropout reductions of up to 8%, 8% and 5% respectively. Conclusions: Procedure requirements and frequency had a measurable impact on clinical trial enrollment and retention. Some procedures, such as PET scans, were associated with reduced enrollment; whereas other clinically relevant imaging procedures (i.e., DEXA bone density imaging, CT/MRI abdominal and pelvic imaging) and other tumor-related procedures, monitoring, and assessments were associated with improved enrollment and/or reduced dropout. These findings highlight opportunities to optimize protocol design by prioritizing procedures that improve the likelihood of recruitment and retention.

Efficacy analysis of high-dose-rate brachytherapy combined with total neoadjuvant therapy versus total neoadjuvant therapy alone.

e15663 Background: Colorectal cancer is the third most common tumors and the second leading cause of cancer-related deaths worldwide. Most patients are diagnosed with locally advanced rectal cancer (LARC), which is associated with high recurrence risks and low survival rates. The standard treatment for LARC is preoperative neoadjuvant chemoradiotherapy combined with total mesorectal excision (TME). However, only a small proportion of patients achieve pathological complete response (pCR) after treatment, and approximately 30% develop distant metastases following neoadjuvant therapy. How to strengthen or optimize the preoperative neoadjuvant therapy of LARC to benefit more patients is a critical focus of current clinical research. High-dose-rate brachytherapy (HDR-BT) offers the potential to deliver higher radiation doses to tumors while sparing surrounding tissues and organs from radiation damage. Limited studies have investigated the combination of total neoadjuvant therapy (TNT) with HDR-BT. This retrospective study aims to compare the efficacy and safety of TNT combined with HDR-BT versus TNT alone, with the goal of providing new insights into comprehensive treatment strategies for LARC patients. Methods: Patients with LARC who received neoadjuvant therapy in our hospital from May 2016 to July 2024 were retrospectively screened according to inclusion and exclusion criteria. Clinical information, neoadjuvant treatment regimens, and serological indexes were collected. Pathological staging, tumor regression grade, R0 resection status, overall survival (OS), disease-free survival (DFS), Recurrence-free survival (RFS), and incidence of adverse reactions were recorded. The efficacy and safety of the two groups were compared. Results: This study included a total of 86 patients, with 50 in the TNT group and 36 in the TNT+HDR-BT group. There was no statistical significance in the distribution of clinical characteristics, concurrent and consolidation chemotherapy regimens between the two groups. In the TNT+HDR-BT group, 11 patients (31.4%) achieved pathological complete response (pCR), which was numerically higher than 10.0% in the TNT group (P = 0.013). The median follow-up time in the TNT+HDR-BT group and the TNT group was 68.7 months and 56.7 months, respectively. 5 year DFS was 72.2% in the TNT+HDR-BT group and 59.8% in the TNT group (HR = 0.66, 95% CI 0.31-1.43, P = 0.292). 5 year RFS was 82.5% in the TNT+HDR-BT group and 67.2% in the TNT group (HR = 0.45, 95% CI 0.17-1.16, P = 0.091). 5 year OS was 87.9% in the TNT+HDR-BT group and 70.3% in the TNT group (HR = 0.34, 95% CI 0.11-1.04, P = 0.046). Conclusions: Compared with TNT, TNT combined with HDR-BT in the treatment of LARC patients significantly increased the proportion of pCR and showed a trend of better survival outcomes.

Regional trends in testicular cancer burden among adolescents and young adults (15–39 years), 1990–2023: A Global Burden of Disease analysis.

5030 Background: Testicular cancer is the most common solid malignancy in adolescent and young adult (AYA) males. Contemporary long-term regional trends in incidence and health loss among AYAs remain incompletely described. We quantified trends in testicular cancer burden among ages 15–39 years from 1990–2023 across World Health Organization (WHO) regions. Methods: Using annual Global Burden of Disease (GBD) estimates (1990–2023) for ages 15–39 years, we assessed trends in incidence, prevalence, deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs). For each WHO region and measure, we fit log-linear models (ln[rate] = β×year) and calculated annual average percent change (AAPC) as 100×(e^β−1), with 95% confidence intervals (CI) derived from the regression. Results: Incidence showed an upward trend in all regions, ranging from 0.62%/year in the African Region (95% CI 0.28–0.96) to 3.15%/year in the Eastern Mediterranean Region (2.98–3.33). Prevalence rose across regions, highest in the South-East Asia Region (6.04%/year, 5.82–6.26) and Eastern Mediterranean Region (5.22%/year, 5.09–5.34). Mortality trends varied across regions. Deaths declined in the Western Pacific (−1.69%/year, −1.99 to −1.39), Europe (−1.43%/year, −1.49 to −1.36), and Africa (−0.89%/year, −1.20 to −0.58), were stable in South-East Asia (−0.07%/year, p=0.44), and increased in the Americas (1.68%/year, 1.49–1.87) and Eastern Mediterranean (0.42%/year, 0.32–0.51). DALYs and YLLs followed similar patterns (declining in Europe/Western Pacific, rising in the Americas). Conclusions: From 1990–2023, testicular cancer incidence and survivorship-related burden increased across all WHO regions among AYAs, while mortality-related metrics improved in Europe/Western Pacific but worsened in the Americas and Eastern Mediterranean. These findings support urgent investigation of drivers of rising incidence and targeted strategies to reduce regional inequities in timely diagnosis and curative treatment for AYAs.

Real-world outcomes of axicabtagene ciloleucel in older versus younger adults with diffuse large B-cell lymphoma.

e19102 Background: Axicabtagene ciloleucel (axi-cel) has substantially improved outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, older adults are underrepresented in pivotal clinical trials, and real-world data describing long-term survival and treatment-related toxicity in patients aged 70 years and older remain limited. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network to evaluate adult patients with DLBCL treated with axi-cel. Patients were stratified by age at the time of CAR-T infusion (<70 vs ≥70 years). The primary outcome was all-cause mortality at 3 years. Secondary outcomes included acute respiratory failure (ARF) at 30 days and 1 year as a surrogate for severe treatment-related toxicity. Survival outcomes were assessed using Kaplan–Meier analysis, risk estimates, and Cox proportional hazards models. Propensity score matching was explored but was not feasible due to limited overlap in baseline characteristics between age groups. Results: A total of 818 patients treated with axi-cel were identified across 23 healthcare organizations, including 517 patients aged <70 years and 301 patients aged ≥70 years. At 3 years, mortality was significantly higher among patients aged ≥70 compared with those aged <70 (43.0% vs 33.1%; risk ratio [RR] 0.77, 95% CI 0.64–0.92; p=0.0046). Correspondingly, 3-year overall survival was lower in the older cohort (49.9% vs 60.7%; log-rank p=0.0236). On multivariable Cox regression, age <70 years was independently associated with improved overall survival (hazard ratio [HR] 0.77, 95% CI 0.61–0.97). Rates of acute respiratory failure were low and did not differ significantly between age groups. At 30 days, ARF occurred in 5.7% of patients aged <70 years and 6.2% of patients aged ≥70 years (HR 0.95, 95% CI 0.50–1.80; p=0.87). Similar results were observed at 1 year, with no significant age-based differences. Conclusions: In this large real-world analysis, older adults receiving axi-cel for DLBCL experienced significantly worse long-term survival compared with younger patients, while early severe respiratory toxicity was comparable between age groups. These findings support the feasibility of CAR-T therapy in carefully selected older adults but underscore the need for improved long-term outcomes and age-specific risk stratification strategies in this growing patient population.

Greening a chemotherapy day ward.

1567 Background: Cancer care is climate toxic and contributes to the triple planetary crisis which threatens human health and cancer care delivery. Despite this toxicity, sustainability guidelines in oncology are lacking. Our objectives are based on the sustainability touchpoints identified in previous research in our department. Study aims were to understand prescribing patterns, quantify plastic waste, and assess patients' and healthcare professionals' views on acceptability of proposed "green" strategies with the aim to develop a green prescribing checklist. Methods: A prospective review of systemic anti-cancer therapy (SACT) delivery at a tertiary oncology outpatient unit was performed. Variables collected included SACT regimen details, dosing interval extensions, supportive medication details and treatment value as rated by the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Daily plastic waste output was measured. Anonymous surveys of patients and healthcare professionals were developed using previously validated questionnaires and circulated among adult patients attending cancer services locally and cancer care professionals nationally. Survey domains included sustainability knowledge, perceived barriers/facilitators, and willingness to adopt sustainability measures such as oral therapy. Findings were reported using descriptive statistics. Institutional and ethical approval was received prior to study commencement. Results: Selected findings show 23% (n=200/864) of supportive medications were given intravenously (IV). There was widespread adoption of subcutaneous formulations and extended dosing intervals. Most regimens with ESMO-MCBS scores showed substantial clinical benefit. Each patient attendance generated a mean of 46 grams of plastic waste. Seventy-two healthcare professionals responded to the survey; 97% (n=70/72) agreed that climate change adversely impacted human health and 82% (n=59/72) agreed that sustainable practices can decrease the effects of climate change yet only 15% (n=11/72) reported routinely considering environmental impacts when prescribing. Barriers to sustainable practices included time 65% (n=47/72), inadequate training 61% (n=44/72) and lack of institutional support 63% (n=45/72). A total of 211 patients submitted responses; 91% (n=190/208) agreed that reducing environmental impact should be a priority for hospitals, and 82% (n=159/194) were in favour of oral medications over IV where appropriate. Conclusions: This study, integrating provider and patient perspectives, demonstrates support for sustainable practices in oncology, but ad-hoc current implementation of same. The findings will guide development of a green checklist informed by patients and prescribers, followed by implementation and re-audit. Patient-centred strategies can align high value cancer care with planetary health and fill the current gap in sustainable oncology practice.

Post-treatment cervical cancer surveillance cytology and recurrence outcomes in a large integrated healthcare system.

e17507 Background: Post-treatment cervical cancer surveillance strategies are used to facilitate timely detection of recurrence and commonly includes annual vaginal or cervical cytology, despite limited evidence of its clinical utility for detecting recurrence. This study aimed to determine whether abnormal post-treatment vaginal/cervical cytology was a risk factor contributing to cervical cancer recurrence and to identify additional independent predictors of recurrence. Methods: We conducted a retrospective cohort study using electronic health records of patients with cervical cancer between January 1, 2011, and December 31, 2020, in an integrated health system who completed at least two consecutive years of post-treatment surveillance. Recurrence rates were compared between patients with abnormal and normal cytology results using chi-square tests for categorical variables and ANOVA for continuous variables. Multivariate analysis was performed using logistic regression to identify independent predictors of recurrence and Cox proportional hazards regression with Fine and Gray competing risks modeling to estimate subdistribution hazard ratios for time to recurrence. Results: Among 365 patients, 52 (14.2%) experienced recurrence at a median of 1.9 years (IQR 1.3–3.9) post-treatment. Recurrence was associated with older age at diagnosis (median 51.5 vs 45.0 years, p<0.05), higher stage (I: 10.5%, II: 24.4%, III: 27.7%; p<0.01), and treatment type (surgery: 7.5%, concurrent chemoradiation therapy (CCRT): 23.9%, combined: 28.1%; p<0.001). Abnormal cytology was not significantly associated with recurrence (OR 1.1, 95% CI 0.6–2.0, p=0.78). In multivariate analysis, surgery followed by adjuvant chemoradiation remained a significant predictor compared with surgery alone (OR 4.4, 95% CI 1.8–10.9, p=0.001). A treatment intensity gradient from surgery alone through chemoradiation alone to combination therapy showed significant association with recurrence (p<0.001,effect size 0.26). Higher cancer stage at diagnosis and lymph node involvement were also significantly associated with recurrence (p<0.01), with an effect size of 0.19 for the former and 0.15 for the latter. Conclusions: Treatment modality was the strongest independent predictor of recurrence, reflecting higher baseline disease burden. Age, stage, and lymph node involvement define recurrence risk, not cytology.

Tumor-specific drivers of PD-1/PD-L1 inhibitor brand preference in NSCLC, melanoma, and renal cell carcinoma: A U.S. oncologist perspective.

e23229 Background: Multiple PD-1/PD-L1 inhibitors are approved across solid tumors with overlapping indications. Despite class-level similarities, real-world prescribing suggests tumor-specific brand preferences. This study evaluates how efficacy data, clinical familiarity, and access influence brand selection in non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC). Methods: A national mixed-methods study surveyed 102 U.S. hematologist-oncologists from academic (44%, n = 45) and community (56%, n = 57) practices across all U.S. regions (Nov–Dec 2025). A structured online questionnaire assessed brand utilization, sequencing, physician satisfaction, switching behavior, and perceived comparative benefit between pembrolizumab- and nivolumab-based therapies using Likert-type scales and utilization metrics. All participants met predefined screening criteria for patient volume and clinical practice time. Eight qualitative interviews explored drivers of brand choice, sequencing decisions, and switching rationale. Results: PD-1/PD-L1 use was brand-led and tumor-dependent. In 1L NSCLC, 54% identified pembrolizumab-based regimens as better suited than nivolumab, citing longer-term and more mature OS and PFS data, including trials beyond five years, and greater clinical familiarity. Pembrolizumab was favored by academic (61% vs. 2% nivolumab) and community oncologists (48% vs. 2%). In melanoma, brand preference was more balanced, with a modest preference for nivolumab (28% vs. 27%), driven by perceived flexibility in combinations and sequencing, despite higher reported use of pembrolizumab and its selection as preferred 1L monotherapy (55% vs. 35%). This pattern was consistent across practice settings (academic vs. community: pembrolizumab 60% vs. 51.8%; nivolumab 42.5% vs. 30.4%). RCC showed minimal brand differentiation, with 65% reporting pembrolizumab and nivolumab as equally appropriate. Decisions prioritized regimen context, risk stratification, and combination partners, though pembrolizumab was more often perceived as better suited overall (24% vs. 12%), consistent across academic (26% vs. 13%) and community settings (22% vs. 11%). Across tumors, OS and PFS were the most influential drivers (1L NSCLC: OS 93%, PFS 87%; melanoma: OS 91%, PFS 80%; RCC: OS 95%, PFS 92%), followed by toxicity (81%, 83%, 82%) and payer or formulary access (64%, 61%, 62%). About one-third reported switching inhibitors, most often due to insurance requirements or disease progression. Conclusions: PD-1/PD-L1 brand preference is tumor-dependent and shaped by evidence maturity and regimen approvals. These findings suggest preference reflects adherence to trial-informed standards of care rather than perceived drug superiority, while access and formulary pathways continue to play a meaningful secondary role in real-world use.

Initial safety and efficacy of A2B694, a logic-gated mesothelin (MSLN)–targeted Tmod chimeric antigen receptor T-cell (CAR T) therapy in patients with advanced solid tumors with HLA-A*02 loss of heterozygosity (LOH).

8579 Background: LOH may provide a means to target tumor versus normal cells, to augment the efficacy and safety of MSLN-targeted programs (Hecht et al. JCO . 2022). A2B694 is an autologous, logic-gated, Tmod CAR T therapy designed to improve tumor selectivity and decrease toxicity by integrating an MSLN CAR activator with an HLA-A*02 blocker (Hamburger et al. Mol Imm. 2020). Methods: The first-in-human, open-label, phase 1/2 EVEREST-2 (NCT06051695) study of A2B694 in patients with recurrent/metastatic MSLN-expressing cancers with tumor-associated HLA-A*02 LOH. The prescreening study BASECAMP-1 (NCT04981119) identifies eligible patients and cryopreserves leukapheresis product. Upon progression, A2B694 is manufactured and administered after lymphodepletion. Phase 1 primary objective: evaluate the safety and tolerability of A2B694 and identify a recommended phase 2 dose. Results: As of 05 January 2026, 13 patients were enrolled: 8 women/5 men, median age 59 years, 11 non-Hispanic White/2 Hispanic with unknown race. Tumor types included colorectal (n = 4), ovarian (n = 3), pancreatic (n = 3), non–small cell lung adenocarcinoma (NSCLC), gastro-esophageal, and mesothelioma (n = 1 each). A2B694 dose level (DL) groups were: DL1: 1×10 8 cells (n = 3), DL2: 2×10 8 cells (n = 4), DL3: 4×10 8 cells (n = 5), and DL4: 6×10 8 cells plus low-dose IL-2 (n = 1). Lymphodepletion prior to administration of A2B694 was well-tolerated, with expected, transient cytopenias. The only adverse event reported in more than 1 patient was grade 3 neutropenia. One patient had grade 3 ICANS and 1 patient had grade 1 CRS. There were no dose-limiting toxicities or new safety signals after up to 17 months follow-up. All 13 patients received A2B694, were efficacy-evaluable, and had A2B694 detected post-infusion in peripheral blood. While A2B694 was not detected in tumor biopsies collected in patients treated at DL1 (0/2), all patients treated at DL2-DL4 with available biopsies (3/3) had detectable A2B694 in the tumor microenvironment. A patient with KRAS G12V /STK11 co-mutated NSCLC who had progressed on carboplatin, pemetrexed, and pembrolizumab achieved a complete response (CR) at D90 post-infusion per RECIST 1.1 by central review and had a confirmed CR at D180. In addition, PET-CT scan and ctDNA on D190 demonstrated no evidence of disease. On D243, the patient had a CNS relapse, with an ongoing non-CNS CR per RANO-BM at D284. At M12, the patient's CT showed no new findings and persistence of A2B694 in the blood was confirmed by ddPCR. Conclusions: We report the first patient with NSCLC to have a CR after CAR T. Overall, A2B694 demonstrated manageable safety and tolerability in patients with advanced solid MSLN-expressing tumors with tumor-associated HLA-A*02 LOH. The maximum tolerated dose has not been reached; dose-escalation continues. Clinical trial information: NCT06051695 .

Association of NAB2–STAT6 distal fusion with risk level of metastatic disease and thoracic primary site.

11519 Background: Solitary fibrous tumors (SFTs) are defined by the NAB2–STAT6 gene fusion, but the clinical significance of these breakpoints remains incompletely understood. Although fusion breakpoint heterogeneity has been implicated in influencing biologic behavior, there are few studies linking variant location to outcomes. Recent genome analyses suggest that proximity based breakpoint clustering approaches can reveal driver loci, suggesting investigation of NAB2–STAT6 fusion breakpoints may be potential prognostic markers. Because individual variants are rare, we used a proximal vs distal breakpoint analysis to evaluate high-risk clinical features. In this study, we evaluated trends between the NAB2–STAT6 breakpoint and metastases, primary tumor location, and recurrence in a single-institution, retrospective cohort study. Methods: We performed an analysis of patients with SFTs treated at the Sylvester Comprehensive Cancer Center (n=48). Samples without pathology-confirmed NAB2–STAT6 fusions were excluded. Clinical variables included primary tumor site, size, stage, and recurrence. Molecular data was extracted from next-generation whole transcriptome and exome sequencing reports. Breakpoints were categorized by exon numbers. NAB2 breakpoints were considered proximal if they occurred before exon 6 and distal if they occurred at exon 6 or more distally. STAT6 breakpoints were considered proximal if they occurred at exon 6 or earlier and distal if they occurred at exon 16 or more distally. Associations were analyzed using Fisher exact tests. Results: Breakpoint patterns were significantly associated with metastatic presentation at diagnosis. Metastatic disease at the time of diagnosis was not observed in any patients with proximal STAT6 breakpoints (n= 29) but was present in 24% (n = 17) of those with distal STAT6 breakpoints (p=0.02). Additionally, metastatic disease occurred exclusively in tumors with distal NAB2 breakpoints (n=14, p=0.01). Breakpoint patterns were also associated with primary tumor sites. The majority of proximal STAT6 fusions were present mostly in thoracic cavity tumors (55%), while distal STAT6 fusions occurred mainly in tumors at non-thoracic sites (p=0.02). Among fusion subtypes, metastatic presentation was absent in ex4: ex2 tumors but observed in 31% of tumors with ex6: ex16/17 tumors (p=0.02). Distal STAT6 breakpoints also showed trends toward higher recurrence rates and grades as well as larger tumor sizes. Conclusions: Our study shows that NAB2–STAT6 distal fusion breakpoint patterns are associated with metastatic disease at diagnosis, non-thoracic primary tumor locations and more aggressive clinical features. These findings support the consideration of breakpoint patterns as part of molecular risk stratification and identifies a potential biomarker for SFT patients with a primary tumor who may benefit from chemotherapy.

Clinical outcomes and safety of central nervous system tumor patients in phase 1 trials: A single-institution experience.

e14047 Background: Central nervous system (CNS) tumors present unique therapeutic challenges due to limited drug penetration across the blood-brain barrier and the potential for neurologic toxicity. Historically CNS tumors have been underrepresented in early-phase clinical trials (CTs), limiting the data related to safety and efficacy of investigational therapies in this patient population. Methods: A retrospective study of patients with primary CNS tumors enrolled in phase 1 CTs was conducted at Miami Cancer Institute, between January 2018 and October 2024, included baseline demographic, clinical, treatment, and laboratory data. Outcomes assessed included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Survival outcomes were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results: A total of 46 patients with primary CNS tumors were enrolled in phase 1 trials (median age 53 years; 54.3% female; 43.5% non-Hispanic White). Most patients had KPS ≥80 (82.6%). Patients received targeted therapy alone (47.8%) or combination regimens (52.2%), with a median of 3.5 cycles administered (IQR, 2–8). Concomitant anti-epileptic drugs and steroids were used in 67.4% and 73.9% of patients, respectively. The ORR was 15.2% and DCR was 58.7%. Median PFS was 3.7 months (95% CI, 2.8–5.5) and median OS was 11.0 months (95% CI, 8.2–14.3). OS was shorter for KPS <80 vs ≥80 (5.3 vs 12.6 months; p=0.041). On multivariable analysis, ≥2 prior systemic therapy lines (HR 104.76; 95% CI, 7.71–1423.17; p<0.001) and concurrent steroid use (HR 15.61; 95% CI, 1.30–186.97; p=0.030) were associated with higher mortality. Grade 3-4 adverse events occurred in 69.6%. No treatment-related deaths were reported. Conclusions: Patients with primary CNS tumors can derive meaningful clinical benefit from participation in phase 1 trials. Survival outcomes were comparable to patients with other tumor types treated at our center during the same time frame. Baseline functional status, prior therapy exposure, and the need for concurrent steroids appear to identify higher-risk patients. These findings support continued and expanded inclusion of primary CNS tumor populations in phase 1 trials. Efficacy outcomes of all patients (n=46). Outcome/Metric Estimates PFS Median, months, (95% CI)6-month rate, %12-month rate, %24-month rate, % 3.7 (2.8-5.5)53.3 (40.6-70.1)25.5 (15.4-42.3)9.3 (3.7-23.5) OSMedian, months, (95% CI)6-month rate, %12-month rate, %24-month rate, % 11.0 (8.2-14.3)72.4 (60.2-87.0)46.9 (33.7-65.2)NA

Phase I study of [ ²²⁵ Ac]Ac-ETN029, a DLL3-targeted radioligand therapy, in patients with advanced DLL3-expressing solid tumors.

TPS3174 Background: Delta-like ligand 3 (DLL3) is an atypical Notch ligand that is highly expressed in small cell lung cancer (SCLC) and other neuroendocrine carcinomas, with minimal expression in normal adult tissues. [ 225 Ac]Ac-ETN029 ( 225 Ac-ETN029) is a novel, DLL3-targeted, macrocyclic peptide-based radioligand therapy (RLT) demonstrating potent antitumor activity in DLL3-positive, SCLC cell line–derived, xenograft mouse models. Here, we describe CESP359A12101 (NCT07006727), a global first-in-human phase 1 study evaluating 225 Ac-ETN029 in patients with selected advanced DLL3-expressing solid tumors. Methods: The primary objectives of the study are to assess the safety and tolerability of 225 Ac-ETN029 and to identify the recommended radioactive dose(s) of 225 Ac-ETN029 for further clinical evaluation. Secondary objectives are to assess the preliminary antitumor activity of 225 Ac-ETN029, characterize the pharmacokinetics (PK) and dosimetry of 225 Ac-ETN029, and characterize the safety, PK, dosimetry, and imaging properties of [ 111 In]In-ETN029 ( 111 In-ETN029). Study participants are expected to receive 4 cycles of 225 Ac-ETN029 at 6-week intervals, although a lower or higher number of cycles may be explored if deemed beneficial and safe. The study includes dose escalation and dose expansion parts. During dose escalation, increasing levels of administered activity per cycle will be assessed across cohorts. Dose escalation decisions will be based on a review of all available data, including safety, tolerability, dosimetry, PK, pharmacodynamics, and preliminary efficacy, and guided by the Bayesian logistic regression model using the escalation with overdose control principle. Dose expansion will begin once recommended radioactive dose(s) of 225 Ac-ETN029 for further clinical investigation have been determined. Eligible patients must be ≥18 years old; have locally advanced, unresectable, or metastatic disease measurable per RECIST v1.1; and be diagnosed with one of the following: (1) SCLC, (2) large cell neuroendocrine carcinoma (LCNEC) of the lung (escalation only), (3) de novo or castration-resistant, treatment-emergent, neuroendocrine prostate cancer (NEPC; expansion only), or (4) gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC; expansion only). Patients with SCLC, LCNEC, and GEP-NEC must have disease progression following, or intolerance of, ≥1 prior line of systemic therapy. Patients with NEPC and GEP-NEC must have ≥1 measurable lesion (per RECIST 1.1) demonstrating 111 In-ETN029 uptake higher than surrounding tissues on SPECT/CT as assessed by the investigator. Patients with prior DLL3-targeted therapy (except for SCLC) or prior RLT (except for NEPC) will be excluded. Patient enrollment began in October 2025. Clinical trial information: NCT07006727 .

Gender distribution of international cancer research funding.

e21018 Background: The Lancet Commission on women, power, and cancer recommends that women have equitable access to cancer research resources, leadership, and funding opportunities. To measure implementation of this recommendation, the International Cancer Research Partnership (ICRP) reviewed the proportion of funding for oncology research allocated to female principal investigators (PIs) globally, along with funders’ knowledge and use of PI gender data related to their programs. The ICRP is a network of 174 government and non-profit cancer research funding organizations across thirteen countries. Methods: The gender of PIs reported on 120,463 cancer research projects in the ICRP database funded between 2006 - 2022 was estimated using genderize.io, a name-to-gender algorithm. Descriptive and inferential statistics were used to identify differences in research projects led by male and female PIs, including stratifications by start year, funder organization country, PI country, cancer scientific outline code, cancer site, total funding amount, and career phase. An online survey of 29 multiple choice and free text questions was fielded to ICRP members with questions about whether and how they collect, report, and use gender information about their funded PIs. Results: Over 63% of funded cancer research in the ICRP database was led by a male PI, with 36% led by a female PI and the remaining 1% led by PIs reported as unknown or undisclosed gender. While there is evidence of modest growth of the percentage of female PIs over time, from 35% in 2006 to 41% in 2022, female PIs lead fewer than 50% of grants across nearly all domains of research and the dollar value of their grants is on average half that of male PIs. The gender differences are particularly stark in projects associated with later career stages and higher award amounts, suggesting differences in how male and female PIs advance in the cancer research workforce. Cancer research funders are increasingly aware of gender disparities in their funding portfolios, but most have not yet developed or implemented strategies in response. Conclusions: This study aligns with existing literature and bibliometric analyses and serves as a benchmark for future action for research funders and partners. We call on funders to collect and publicly report PI gender information of funded research projects, focus on stopping the “leaky pipeline” of female investigators in cancer research, and develop and implement strategies to increase equity in review and evaluation processes. Funding: Funded in part by NCI Contract No. 75N91019D00024.

Economic factors and screening practices in global lung cancer staging disparities: A systematic review.

e22500 Background: To assess the global distribution of lung cancer staging at diagnosis and explore the impact of economic disparities and screening practices on staging outcomes. Methods: The MEDLINE and Embase databases were systematically searched, supplemented by a review of gray literature and published cancer reports. Population- or hospital-based cancer registry reports on lung cancer staging at diagnosis were also included. The percentage of lung cancer stages in different countries was extracted and the distribution of stages, changes in stage incidence over time, and the impact of screening programs were examined Correlations between the Human Development Index (HDI), Social Development Index (SDI), and proportion of distant metastatic lung cancer were assessed. Subgroup analyses were conducted based on sex, age, tumor histology. Results: Among the 35 countries in the main analysis, the proportion of distant metastatic lung cancer ranged from 30.4% in Hungary to 81.2% in Brunei Darussalam, with a median of 50.8% (interquartile range: 44.8–59.2%). Higher HDI and SDI were not significantly associated with lower proportions of distant metastatic lung cancer (HDI: ρ = −0.19, 95% confidence level (CI): −0.50 to 0.15; SDI: ρ = −0.22, 95% CI: −0.51 to 0.13). In countries with lung cancer screening programs, the proportion of metastatic cases decreased in the United States (from 56.5% in 2004 to 48.5% in 2021) and England (from 54.7% in 2013 to 48.7% in 2021). Additionally, the United States and the Republic of Korea experienced an increase in early-stage incidence, while the United States saw a significant decline in late-stage incidence. Higher metastasis rates were observed in males, younger patients, and patients with small cell lung cancer. Conclusions: Significant global variations in lung cancer staging at diagnosis highlight the need for targeted strategies to enhance early detection and improve treatment outcomes, particularly in regions with a high incidence of metastatic disease.

Green synthesis and molecular-level mechanism of silver nanoparticles from Pandanus fascicularis (Keya) leaf extract with antibacterial activity

In Situ Regenerative Adduct Assisted p‐Type Doping of Organic Semiconductor

ABSTRACT Organic semiconductors (OSCs) are leading materials for next‐generation optoelectronic devices. Effective charge transport in devices often requires electronic doping of OSCs. Conventional methods using molecular dopants or metal salts often suffer from poor efficiency, undesirable side products, and require additives and prolonged incubation. Under device operational conditions, these undesirable side products and additives lead to degradation in device performance. Here, an in situ regenerative adduct‐assisted (IRAA) doping is presented, which is rapid, metal‐ion‐free, and requires no additives for dopant stabilization, enabling clean and efficient doping of various OSCs. Spectroscopic analyses reveal a self‐regenerating adduct as the active doping species. The simplicity of the doping method and the range of materials available open new avenues for the development of diverse electronic‐doping strategies, providing a scalable and universal approach to doping OSC‐based hole‐transporting layers for various types of optoelectronic devices, including halide perovskite solar cells.

AhR as a coupler of tryptophan metabolism to immune checkpoint regulation in breast cancer.

e12579 Background: Tryptophan (Trp) is an essential amino acid metabolized through the kynurenine, serotonin, and indole pathways. Dysregulation of Trp metabolism has been implicated in cancer progression. Several Trp-derived metabolites serve as ligands for the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that is critical to immune response and tumorigenesis. Although AhR is broadly expressed across breast cancer subtypes, its precise role in breast cancer remains unclear. Thus, investigating Trp metabolism in relation to AhR activation may provide novel insights into how the Trp-AhR axis interfaces with immune regulation in breast cancer. Methods: Serum samples were obtained from patients with breast cancer (n = 13) and age-matched individuals with fibroadenoma (n = 9). Eighteen Trp metabolites were quantified using ultra-high performance liquid chromatography. Differential metabolite levels were analyzed, followed by Pearson correlation analysis of individual metabolites relative to Trp to assess pathway-specific metabolic flux. To evaluate transcriptional regulation, RNA-seq data for key Trp-metabolizing enzymes and AhR were retrieved from The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma cohort. Correlation analyses were performed between AhR expression, Trp metabolic enzymes, and immune checkpoint–related genes. Results: Serum Trp metabolism was significantly altered in breast cancer compared with fibroadenoma. Trp levels were reduced, while cinnavalininate, 5-HIAA, and picolinic acid demonstrated the most pronounced differences. Correlation analyses revealed preferential engagement of the kynurenine and serotonin pathways in breast cancer. Consistent with serum metabolite profiles, TCGA analysis showed differential mRNA expression of key Trp-metabolizing enzymes in breast cancer relative to benign tumors. AhR expression was significantly reduced in breast cancer. Despite modest effect sizes, AhR expression positively correlated with multiple Trp metabolic enzymes, including IDO, HAAO, and MAO-A. Notably, AhR expression strongly correlated with immune checkpoint–related genes, including PD-L1, and CTLA-4 ligands (CD80, CD86). Conclusions: Trp metabolism is significantly disrupted in breast cancer and is coupled to altered AhR signaling. The association between AhR, Trp metabolic enzymes, and immune checkpoint gene expression highlights a previously underappreciated role for the Trp-AhR axis in immune regulation within the breast cancer microenvironment. Although preliminary, these results support further investigation of AhR-coupled Trp metabolism as a potential therapeutic target for immunomodulatory strategies in breast cancer.

Long-term outcomes of SINTART 1 and SINTART 2: Two phase II trials of multimodal treatments in patients with locally advanced sinonasal carcinomas.

6120 Background: Sinonasal carcinomas (SNCs) are rare malignancies with poor prognosis. Multimodal treatments including induction chemotherapy (ICT), surgery and radiotherapy (RT) - modulated by histology and response to ICT - are often used, aiming to improve oncological outcome in terms of local control and survival. Two phase II clinical studies published in 2023 assessed the role of ICT in SNCs, SINTART1 and 2 for resectable and unresectable tumors, respectively [PMIDs: 37164774, 37163806]. The current work aims at reporting the long-term follow-up (FUP) data for both trials. Methods: The FUP was updated as of January 2026 for patients enrolled in both clinical studies. Median FUP was estimated with reverse Kaplan-Meier method. The following survival times were analyzed with Kaplan-Meier method in each cohort: overall survival (OS), disease-free survival (DFS), loco-regional-free survival (LRFS), distant metastasis-free survival (DMFS). Results: The updated median (m) survival times (in months) with their 95% confidence intervals (CI) and the event rates are detailed in Table 1. Pooling together the 2 studies, 30% of patients (18/60) were alive at last follow-up. Conclusions: SINTART 1 and 2 represent, to date, the largest prospective cohorts with long-term survival data in SNCs. With a median FUP exceeding 9 years, these results provide a robust benchmark for ICT-based multimodal strategies in this setting. Survival outcomes remain consistent with the initial reports, indicating that prognosis is largely determined within the first 2-3 years, when most deaths occur (approximately 70%). The near-overlap of mDFS and mLRFS identifies loco-regional failure as the predominant pattern of recurrence. Moreover, the short interval between relapse and death underscores the limited opportunity for salvage. These findings collectively emphasize the need for more effective local-intensification approaches and novel systemic agents. Additional analyses are underway to identify prognostic and predictive factors. Clinical trial information: NCT02099175 ; NCT02099188 . Resectable (SINTART1)N=35 Unresectable (SINTART2)N=25 mFUP (95% CI) 108.26 (97.37-129.84) 103.22 (91.68-NR) mOS (95% CI)Events 37.53 (21.97-98.36)66% 27.07 (11.28-65.03)76% mDFS (95% CI)Events 26.25 (15.43-80.43)71% 17.1 (7.89-37.76)80% mLRFS (95% CI)Events 26.25 (15.43-80.43)71% 18.95 (7.89-39.05)80% mDMFS (95% CI)Events 34.47 (21.84-96.32)69% 26.88 (9.31-46.78)76%

An artificial intelligence–based framework for longitudinal risk prediction in patients with cirrhosis through trajectory modeling: A multi-center prospective study in time-series cohorts.

e16011 Background: Surveillance for hepatocellular carcinoma (HCC) in adults with cirrhosis relies on fixed-interval AFP testing and imaging examination, which are designed to detect established disease rather than predict its occurrence. Consequently, HCC is often diagnosed between surveillance visits or after progression beyond a clinically actionable stage. Thus, there is a need for approaches that prospectively predict HCC occurrence before clinical detection using routinely available data. Methods: We conducted a multicenter longitudinal study including retrospective model development, independent external validation, and randomized prospective interventional cohorts. Using routinely collected laboratory data, we developed the Temporal Estimation Model for Predicting Occurrence of HCC (TEMPO) to estimate individualized probabilities of HCC occurrence within predefined 6- and 12-month horizons. Model performance was assessed using AUC in development and validation cohorts. In the prospective cohort, participants were randomized 1:1 to TEMPO-guided or AFP-based surveillance (threshold 20 ng/mL). Sensitivity comparisons were performed after calibrating TEMPO to matched diagnostic specificity with AFP. Results: A total of 6,909 participants were included in the development cohort, 6,022 in the external validation cohort, and 4,408 in the prospective cohort. In the development cohort, TEMPO demonstrated strong discrimination for near-term HCC prediction, with AUCs of 0.937 (95% CI 0.923–0.950) and 0.895 (0.876–0.918) for the 6- and 12-month horizons, respectively. In the external validation cohort, corresponding AUCs were 0.921 (0.903–0.939) and 0.861 (0.838–0.885). In the prospective interventional cohort, after calibration to matched diagnostic specificity, sensitivity for incident HCC detection at 6 and 12 months was higher with TEMPO-guided surveillance than with AFP-based surveillance (0.93 and 0.80 vs. 0.59 and 0.50). Among participants with incident HCC, TEMPO-guided surveillance was associated with lower tumor burden at diagnosis, including a higher likelihood of single-tumor presentation (relative proportion 0.78, 0.65–0.94 at 6 months; 0.52, 0.34–0.79 at 12 months), smaller dominant tumor diameter (0.55, 0.41–0.69 at 6 months; 0.61, 0.47–0.77 at 12 months), a higher proportion of BCLC stage 0 disease (0.12, 0.06–0.25 at 6 months; 0.25, 0.10–0.60 at 12 months), and higher use of curative-intent treatments, including surgical resection (0.69, 0.52–0.91 at 6 months; 0.63, 0.42–0.94 at 12 months). Conclusions: TEMPO uses routinely collected baseline laboratory data to predict individualized probabilities of hepatocellular carcinoma occurrence within 6 and 12 months in adults with cirrhosis, enabling prediction of HCC before it becomes clinically detectable.

Understanding patient engagement with an oncology chatbot: Thematic and sentiment analysis of medical adherence.

e13705 Background: Oral oncology treatment is an effective option, but faces challenges of suboptimal adherence. Penny, an oncology support chatbot, was designed to enhance patients’ engagement and symptom management. While the parent pilot randomized controlled trial showed non-significant effects of the intervention on medical adherence, traditional qualitative analyses showed favorable user experiences. To better explain these discrepancies, we leverage large language models (LLMs) to extract latent emotional, thematic, and sentiment signals from patient interviews to understand how patients emotionally and behaviorally engaged with Penny during routine oral oncology treatment support over a 12-week period. Methods: Of the 38 patients randomized to the Penny arm, 19 completed semi-structured interviews. Latent Dirichlet Allocation (LDA) was applied to 4,835 cleaned words derived from a combined term frequency-inverse document frequency (TF-IDF) and bigram dataset of interview transcripts. Sentiment analysis using a BERT-based model was conducted on 1,089 cleaned interview sentences. Generalized linear mixed-effects logistic regression was used to examine fixed effects of sentiment polarity, medication user type, and adherence, with participant-level random effects. Results: Thematic analysis identified two medical adherence-related aspects: 1) Emotional support, such as anxiety reduction and confidence improvement in managing treatment; and 2) Routine practical assistance, such as reminders, symptom monitoring, and appointment coordination. A crude descriptive analysis showed that adherent patients had a significantly higher positive sentiment (29.1% vs. 20.4%, p = 0.012). Stratified descriptive analysis showed that prevalent users, defined as those already using the medication at enrollment, had higher positive sentiment towards Penny than newly prescribed users in both the adherence and non-adherence subgroups. This difference was statistically significant only among the adherent group (32.7% vs. 26.3%, p =0.033). The mixed-effects model showed no significant association between sentiment and medical adherence at the fixed-effect level, and the random effects had a low adjusted ICC (0.029). Conclusions: The study suggests that patient engagement with an oncology chatbot is associated with both emotional and practical support needs and treatment history. Higher positive sentiment among prevalent users suggests that prior medication experience may play an important role as an associated factor in patients' emotional response to digital support tools, with potential implications for medical adherence. The high variation within each patient indicates that adherence engagement is a dynamic, context-dependent process, which requires an implementation-focused, patient-centered strategy to better support oral oncology treatment. Clinical trial information: NCT04347161 .

Intraductal carcinoma of the prostate as a predictor of efficacy of olaparib combined with novel hormone therapy in metastatic castration-resistant prostate cancer.

e17063 Background: Intraductal carcinoma of the prostate (IDC-P) is a clinicopathological entity of prostate cancer characterized by increased homologous recombination repair deficiency (HRD). This study aimed to evaluate the predictive value of IDC-P for the efficacy of olaparib combined with novel hormonal therapy (NHT) in metastatic castration-resistant prostate cancer (mCRPC) after progression on NHT. Methods: A total of 64 consecutive patients treated with olaparib plus NHT after NHT progression were analyzed, including 33 IDC-P and 31 prostate adenocarcinoma (PAC) cases. Main outcomes included progression-free survival (PFS) and treatment change-free survival (TFS). Prostate-specific antigen (PSA) response, overall survival and adverse events were also evaluated. Additionally, paired blood and tissue samples from 187 PCa patients were analyzed to assess HRD scores. Results: After a median follow-up of 35.0 months, patients with IDC-P showed significantly longer PFS and TFS than those with PAC (PFS: 6.2 vs. 3.0 months, p < 0.01; TFS: 10.0 vs. 6.3 months, p < 0.01). Among BRCA1/2 mutated patients, IDC-P was associated with improved PFS and TFS (PFS: 9.8 vs. 3.0 months, p < 0.01; TFS: 11.3 vs. 10.2 months, p = 0.04). Multivariate analysis confirmed IDC-P as a predictor of better PFS and TFS after adjusting for BRCA1/2 mutation status. Additionally, IDC-P showed higher HRD scores than PAC in both BRCA1/2 mutated and non-mutated cohorts, potentially explaining its favorable response to olaparib plus NHT. Conclusions: IDC-P may serve as a predictor for the efficacy of PARPi-based therapy in mCRPC. Further large-scale and prospective validation is warranted Baseline characteristics of the mCRPC patients receiving olaparib plus NHT progression after NHT. Variable Overall,N = 64 1 PAC,N = 31 1 IDC-P,N = 33 1 p-value 2 Age (yrs, median (range)) 70 (62, 75) 71 (68, 77) 69 (61, 74) 0.07 Baseline PSA 0.7 <50 ng/ml 15 (23%) 8 (26%) 7 (21%) ≥50 ng/ml 49 (77%) 23 (74%) 26 (79%) ISUP >0.9 3 3 (4.7%) 2 (6.5%) 1 (3.0%) 4 11 (17%) 5 (16%) 6 (18%) 5 50 (78%) 24 (77%) 26 (79%) Metastatic burden 0.02 <5 20 (31%) 14 (45%) 6 (18%) ≥5 44 (69%) 17 (55%) 27 (82%) Visceral metastasis 9 (14%) 4 (13%) 5 (15%) >0.9 Progression-free interval of first-line NHT 10 (6, 14) 9 (6, 20) 10 (6, 13) 0.7 Pre-olaparib PSA 0.08 <50 ng/ml 34 (53%) 13 (42%) 21 (64%) ≥50 ng/ml 30 (47%) 18 (58%) 12 (36%) Number of treatment lines post-olaparib 0.8 0 34 (53%) 15 (48%) 19 (58%) 1 16 (25%) 9 (29%) 7 (21%) 2 10 (16%) 5 (16%) 5 (15%) 3 3 (4.7%) 1 (3.2%) 2 (6.1%) 4 1 (1.6%) 1 (3.2%) 0 (0%) BRCA mutation 31 (48%) 13 (42%) 18 (55%) 0.3 PSA: prostate specific antigen; ISUP: International Society of Urological Pathology; NHT: novel hormone therapy; IDC-P: intraductal carcinoma of the prostate; PAC: prostate adenocarcinoma.