Browse Articles

Epidemiology of typical and atypical lung neuroendocrine tumors in a rural U.S. population.

e22631 Background: Lung neuroendocrine neoplasms comprise a heterogeneous group of tumors that include typical and atypical carcinoid tumors. These well-differentiated, low-grade malignancies are most diagnosed in the fifth to sixth decades of life, with atypical carcinoids often presenting 5-10 years later. Although prior studies have described demographic patterns, associations such as biological sex remains incompletely characterized, and data from rural populations are limited. We aimed to characterize sex-based and epidemiologic differences between typical and atypical lung neuroendocrine tumors in a rural U.S. population. In this rural cohort, lung neuroendocrine tumors demonstrated distinct sex-based patterns by histologic subtype, warranting validation in larger studies. Methods: This retrospective cohort study reviewed adult patients treated at Renown Regional Medical Center in Nevada between Jan 2020-Dec 2025 with a pathology-confirmed diagnosis of primary pulmonary typical or atypical lung carcinoid tumor. Demographic variables and clinical characteristics were collected under IRB approval. Descriptive statistics like Fisher’s exact test and Wilcoxon Rank-Sum were utilized to summarize the cohort. Results: A total of 43 patients were identified with typical or atypical lung carcinoids. Of the total patients, 35 (81%) had typical lung carcinoids, and 32 (74%) were female. 5 (11%) had an autoimmune disease all of which were females with typical carcinoid tumors, whereas no cases of autoimmune disease were observed among patients with atypical carcinoids. Of the atypical patients, 5 (63%) of the patients were male. Female sex was more common among patients with typical compared with atypical carcinoids (81% vs 38%; p = 0.02). The median age for typical carcinoids was higher (64.5 years) compared to atypical (50.5 years), though not statically significant (p = 0.10). Typical carcinoids occurred predominantly among White, non-Hispanic patients (31/34, 91%), whereas atypical tumors were more evenly distributed across racial and ethnic groups, though subgroup sizes were small. Conclusions: In a rural northern Nevada cohort, females comprised a higher proportion of patients with pulmonary neuroendocrine carcinoid tumors, suggesting a possible regional association. In addition, sex distribution differed by histologic subtype, with female predominance in typical and male predominance in atypical tumors. Although no established association between autoimmune disease and pulmonary carcinoid tumors exists, the clustering of autoimmune conditions among female patients with typical carcinoids in this cohort represents a hypothesis-generating observation that warrants further investigation. Future studies should evaluate whether this apparent female predominance persists across broader rural populations and explore potential environmental or biologic contributors.

Impact of pre-segmented regions on CT-based evaluation of the Peritoneal Cancer Index: A reader study

Objectives Accurate assessment of peritoneal tumour burden is crucial for treatment selection and prognosis. The Peritoneal Cancer Index (PCI), traditionally assessed by laparoscopy, is increasingly applied to imaging. This study investigates whether pre-segmented radiological PCI (rPCI) regions on CT improve interobserver variability, diagnostic accuracy, and user experience. Materials and methods This prospective, comparative reader study included nine contrast-enhanced CT scans from patients with peritoneal metastases of ovarian, gastric, or colorectal origin. Radiologists, surgeons, and gynaecologists independently scored rPCI on two scans: one with and one without pre-segmented rPCI regions shown as colour overlays. Interobserver variability, mean absolute error compared with surgical PCI (sPCI), and reader confidence were compared between both conditions. User experience was evaluated through structured feedback. Results In total, 82 clinicians from 19 countries participated in this study. Each CT was assessed 8–10 times with and without overlaid segmentations. Pre-segmented region overlays did not significantly improve interobserver variability (p = 0.123), PCI accuracy (mean absolute error, p = 0.374), or reader confidence (p = 0.593). However, with use of segmentations, rPCI values were closer to sPCI in 7 of 9 scans. In regions 9–12, the proportion of participants reporting moderate or high confidence increased from 48–53% without overlays to 59–63% with overlays. User feedback was positive, with 83% of participants reporting the tool as useful, 82% as easy to use, and 71% indicating they would use it in clinical practice. Conclusion Pre-segmented region overlays for CT-based rPCI assessment were positively received by clinicians. Although no statistically significant improvements in interobserver variability or accuracy were observed, the findings of this exploratory study support further evaluation in larger studies to determine their clinical value.

Atomic and electronic structures of natural and artificial rutile TiO2 grain boundaries

Grain boundaries (GBs) significantly influence the properties and applications of materials. Due to the advantages associated with GB design and structural characterization, artificial bicrystal GBs are frequently constructed as model samples to mimic the atomic structures and properties of naturally occurring GBs in materials. The question of whether artificial and natural GBs exhibit identical structures and properties has been a long-debated scientific issue. In this study, we fabricated artificial bicrystal (011) and (031) twin boundaries (TBs) in rutile TiO2 (R-TiO2) through solid-state diffusion bonding, while their natural counterparts were obtained from an R-TiO2 thin film prepared via pulsed laser deposition. We systematically investigated the atomic and electronic structures of both artificial and natural (011) and (031) TBs using aberration-corrected scanning transmission electron microscopy integrated with electron energy loss spectroscopy. The results demonstrated that the artificial bicrystal TBs possess precisely the same atomic and electronic structures as their natural counterparts. This study underscores that artificial bicrystal GBs serve as excellent model samples for investigating GBs.

Effect of silver nanoparticles synthesized from Stachytarpheta jamaicensis leaf extract on Macrotyloma uniflorum germination

Enhancing Heterogeneous Nucleation on Buried Interface for Efficient Antisolvent‐Free Inverted Flexible Perovskite Photovoltaics

ABSTRACT Self‐assembled molecules (SAMs) significantly boost the power conversion efficiency (PCE) of inverted perovskite solar cells (PSCs), yet their hydrophobicity impedes uniform large‐area perovskite film deposition, especially on flexible plastic conductive substrates. Herein, we propose an interface ionic engineering strategy to address this issue. Specifically, a multifunctional N‐(4‐Cyanophenyl)guanidine hydrochloride (NCGCl) salt with multiple hydrophilic functional groups is employed to modify the SAM layer to overcome the perovskite solution spreading problem. We demonstrate that the nitrile and guanidinium groups in NCGCl strongly interact with perovskite components, facilitating heterogeneous nucleation and defect passivation. Moreover, the π–π * stacking between the benzene rings in NCGCl and SAMs further strengthens the substrate‐perovskite interface bridging. Consequently, the antisolvent‐free processed PSCs on rigid and flexible substrates demonstrate champion PCEs of 26.89% (certified 26.64%) and 25.29%, respectively. We also fabricate 5 cm × 5 cm flexible mini‐modules, showing an impressive PCE of 22.28%, along with outstanding mechanical bending stability.

Harpagide attenuates cerebral ischemic injury by modulating mitochondrial calcium homeostasis associated with the AMPK–MCU axis

Abstract Mitochondrial calcium homeostasis may offer therapeutic benefits for ischemic stroke. Harpagide has been shown to inhibit mitochondrial calcium uptake, but the mechanism remains unclear. In this study, a male ICR mouse model of permanent middle cerebral artery occlusion (pMCAO)-induced focal cerebral ischemia and PC12 and SH-SY5Y cells exposed to oxygen–glucose deprivation (OGD) were used. Apoptosis, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and the ATP levels were measured to assess the neuroprotective effects of harpagide. DCFH-DA, JC-1, and Rhod-2A probes were used to analyze the mitochondrial function. RT-qPCR and western blot were used to determine the mitochondrial calcium uniporter (MCU), the apoptosis-inducing factor (AIF), Endo G, Cyt C, Caspase-3, and AMPK–MCU phosphorylation expression levels. Additionally, Longa scoring and triphenyl tetrazolium chloride (TTC) staining were used. Transmission electron microscopy (TEM) was used to examine the mitochondrial ultrastructural changes. An immunohistochemical analysis was conducted to detect the MCU expression in the temporal cortex. Harpagide attenuated OGD-induced cytotoxicity, as evidenced by reduced lactate LDH leakage, restored ATP generation, and ameliorated mitochondrial ultrastructural damage. Mechanistically, harpagide suppressed oxidative stress and alleviated mitochondrial calcium ([Ca 2+ ] mito ) overload, concomitant with modulated expression of MCU complex components and apoptosis-related proteins. These neuroprotective effects were linked to harpagide-mediated AMPK expression and subsequent preservation of mitochondrial bioenergetics and calcium homeostasis. Collectively, these findings position harpagide as a promising phytochemical candidate for ameliorating mitochondrial dysfunction in ischemic stroke, warranting further investigation into its precise molecular interactions with the AMPK–MCU axis.

Alkaline Leaching: A Facile Surface Activation Strategy to Improve the Reactivity of Air Electrodes for Solid Oxide Fuel Cells

ABSTRACT The energy conversion efficiency of solid oxide fuel cells is primarily governed by the performance of their air electrodes. Several surface modification techniques, including nanocatalyst decoration, surface coating, and acid etching, have been reported to enhance the performance of air electrodes. However, these approaches often face limitations in cost and time efficiency. In this study, we propose alkaline leaching as a straightforward and innovative strategy to activate the surface of mixed‐conducting oxides by selectively dissolving the A‐site cation during bias application in an alkaline solution. After 10 min of alkaline leaching, the surface of the PrBa 0.8 Ca 0.2 Co 2 O 5+δ electrode becomes cobalt‐rich and amorphous, recognized for its favorable impact on reactivity. As a result, when the surface‐modified electrode is used as the air electrode in a solid oxide fuel cell, it exhibits a 5.6 fold enhancement in catalytic activity, achieving an area‐specific resistance of 0.019 Ω cm 2 . Single cell measurements further demonstrate a 33 % increase in maximum power density, reaching 2.10 W cm −2 at 650°C. This work provides a strategic approach for engineering highly active oxide surfaces, leveraging a straightforward system operable at ambient pressure and room temperature, with broad applicability across diverse devices.

TRIM25 enhances hypoxia signaling by catalyzing K11-linked polyubiquitination and stabilization of HIF-α

Late line treatment in hormone receptor positive, her 2 neu positive metastatic breast cancer with fulvestrant, abemaciclib, and trastuzumab, including prolonged CNS control.

e14010 Background: Since trastuzumab was introduced in 1998, her 2 targeted treatment has become the standard of care. We have a wealth of targeted treatments that have been developed over the last two decades, including monoclonal antibodies, antibody drug conjugates and oral kinase inhibitors. Treatment of these cancers has been primarily directed at the her 2 neu biology. However, many of these patients also express hormone receptor activity as an additional target. Findings from the Pertain trial, monarcHER and the Patina trials support the inclusion of endocrine therapy as part of treatment. CNS metastases develop in a large portion of metastatic her 2 neu positive breast cancer patients and finding treatments that are effective in this setting is important. CDK4/6 check point inhibitors are routinely used in hormone receptor positive metastatic breast cancer. Abemaciclib (in combination with fulvestrant and trastuzumab) is listed as a category 2B option in hormone receptor positive and her 2 neu positive breast cancer in version 4.2025 NCCN breast cancer guidelines. Neither abemaciclib or fulvestrant are currently FDA approved in her 2 neu positive breast cancer. Methods: We present a limited case series of six patients who have undergone treatment for their metastatic breast cancer that have survived during the era of expanding her 2 targeted treatment options and describe an effective treatment with her 2 targeted treatment enhanced by endocrine therapy with fulvestrant and abemaciclib. This group of patients has had extensive treatment with an average of 9 systemic treatments (5 to 14) and in 2 patients with CNS involvement with 8 and 11 prior local treatments before starting this regimen. Both patients with CNS disease have had prior fam-trastuzumab deruxtecan-nxki as well as prior Her 2 Climb style treatment. After many lines of treatment we have seen a palliative benefit, including sustained control of CNS involvement. We will present in tabular form the treatments and duration of response and demonstrate effectiveness of targeting the estrogen receptor pathway in combination with her 2 neu targeting. Results: Systemic control was seen in these 6 patients after multiple lines of treatment, local and systemic with duration of response at 4 mo, 6 mo, 6 mo, 6 mo, 20 and 31 months. Conclusions: We analyze separately patients with CNS metastases finding prolonged benefit in 2 patients for 20 and 27 months after multiple systemic and local treatments had been used and failed to control CNS disease. In one of these 2 patients leptomeningeal disease was diagnosed in 2019, progressing on intrathecal and systemic treatments as well as multiple radiation treatments before stabilizing for 20 months when treated with this regimen. The other patient has had 31 months of CNS free progression on this regimen after 10 prior CNS interventions.

Standardized birth rates and access to assisted reproductive technology among female cancer patients in the United States.

12105 Background: Fertility after cancer is critically under-defined on a national scale, reflecting a substantial gap in survivorship care. We constructed a novel longitudinal dataset to describe 1) live births and 2) use of assisted reproductive technology (ART) among female cancer patients from 2004-2022. Methods: We linked population-based cancer registry data (2004–2018 in 12 states; 2004–2011 in California) with live birth certificates and the Society for Assisted Reproductive Technology database (2004-2022), which captures ~90% of ART cycles nationally, to create a dataset integrating oncologic characteristics, obstetric outcomes, and ART utilization. Female patients aged 15-45 at diagnosis of cancer were included. The primary outcome was the standardized birth ratio (SBR) >9 months after cancer diagnosis stratified by age, race/ethnicity, cancer site, stage, and receipt of systemic therapy calculated using Centers for Disease Control (CDC) general population birth rates from the 13 states. Secondary outcome was ART use after cancer diagnosis (≥1 autologous oocyte/embryo cryopreservation or embryo transfer cycles). Patients were categorized by expected fertility detriment, defined as pelvic malignancy and/or receipt of chemotherapy, hormone therapy, or abdominal/pelvic radiation. Associations with ART were evaluated with Cox proportional hazards models adjusted for age, cancer stage, insurance, and race/ethnicity. Person-years accrued from diagnosis date to first post-diagnosis birth/use of ART, death, age 51 (oldest age a post-cancer birth was observed), or December 31, 2022. The study was approved by the institutional review board. Results: 286,198 female cancer patients were included, with 25,586 babies born to 19,713 women over a mean follow up of 8.3 years. The overall SBR compared to the general population was 0.38 [0.36, 0.40], with lowest rates in gynecologic and breast cancers (0.22[0.18, 0.27], 0.26[0.23, 0.30]). 46.2% (n=9,110) of patients with births had thyroid cancer or lymphoma. Median time from diagnosis to birth was 3.27 years (2.00-5.27). Only 1.56% (n=5343) of the cohort used ART, with highest use among patients with breast cancer (n=2506, 46.9%). Expected fertility detriment was associated with higher hazard of ART use (aHR 2.37, 95% CI 2.20, 2.54), specifically cryopreservation (5.53[4.89, 6.26]). The 2022 live birth rate from our cohort (44.0%, 70/159) paralleled national trends (42.5%) reported from 457 fertility clinics by the CDC (p=0.69). Conclusions: The burden of infertility among reproductive-aged cancer patients is profound, with observed birth rates less than half that of the general population. Among patients who access ART, however, birth rates mirror those published by fertility clinics nationally. Despite this, ART services among cancer patients are underused, highlighting unmet needs in survivorship care delivery.

Comparison of chemotherapy–immunotherapy and chemoradiation in esophageal cancer: A TriNetX real-world evidence study.

e16116 Background: Although chemoimmunotherapy is widely used in esophageal cancer, real-world comparisons with standard chemoradiation are limited. We compared toxicity, healthcare utilization, and short- and long-term survival between chemotherapy plus immunotherapy without radiation (NCIT) and standard chemoradiation (NCRT). Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with esophageal cancer treated with fluoropyrimidine- and platinum-based chemotherapy plus immune checkpoint inhibitors without radiation (NCIT) were compared with patients receiving chemoradiation without immunotherapy (NCRT). Outcomes were assessed at 90 days, 6 months, 1 year, and 2 years following treatment initiation. Propensity score matching (1:1) was performed to balance age, sex, race, ethnicity, and baseline comorbidities. Outcomes included toxicities, healthcare utilization, hospice use, and overall survival. Results: A total of 8,166 patients were identified (NCIT: n = 1,902; NCRT: n = 6,264). After propensity score matching, 1,501patients were included in each cohort. In the matched population, the mean age was 70.0 years in the NCIT cohort and 70.1 years in the NCRT cohort, with similar proportions of male patients (77.5% vs 76.8%). At 90 days, NCIT was associated with lower rates of neutropenia (17.0% vs 19.8%; p = 0.048), thrombocytopenia (8.9% vs 11.1%; p = 0.039), emergency visits (22.5% vs 25.9%; p = 0.03), and inpatient hospitalization (29.1% vs 39.1%; p < 0.001), with no difference in early mortality or hospice utilization. Immune-mediated colitis occurred more frequently with NCIT at 90 days (3.7% vs 2.2%; p = 0.017) and remained consistently higher at 6 months, 1 year, and 2 years. While reduced inpatient utilization persisted through 2 years, survival outcomes differed over time. Mortality was similar at 90 days and 6 months, borderline higher with NCIT at 1 year (39.4% vs 35.9%; p = 0.05), and significantly higher at 2 years (49.6% vs 43.6%; p = 0.001). Median overall survival was shorter with NCIT (416 vs 615 days), with increased risk of death (HR 1.22, 95% CI 1.10–1.35; log-rank p < 0.001). Conclusions: Chemotherapy–immunotherapy without radiation is associated with improved early tolerability and reduced healthcare utilization but shows inferior long-term survival compared with chemoradiation. These findings suggest a potential delayed survival disadvantage and underscore the importance of radiation-based multimodal therapy in esophageal cancer. Interpretation is limited by the lack of histologic subtype data, a key determinant of treatment selection and outcomes, underscoring the need for prospective studies that incorporate tumor histology.

H.O.P.E. (Hematology/Oncology Practical Education): A pilot curriculum.

e21007 Background: Patients with hematologic malignancies are living longer than ever before, due to advances in diagnostic tools, the development of novel therapies, and enhanced supportive care. Evidence suggests that clinicians without specialized training in hematology and/or oncology often feel underprepared to care for this population. This pilot curriculum aims to equip these caregivers with a practical, high-yield framework for approaching commonly encountered complications in this cohort. Methods: This curriculum was piloted with internal medicine residents enrolled in their residency program’s Hospital Medicine Track, first-year Hematology/Oncology fellows, and Intensive Care Unit Advanced Practice Practitioners (APPs). Participants completed a survey assessing their comfort level in managing various complications associated with hematologic and oncologic disorders. They received one-page educational summaries on these high-yield topics and then engaged in a case-based discussion that was designed to reinforce the key concepts outlined in the review sheets. Finally, participants completed a post-session survey to assess its impact. Results: A total of 18 physicians and APPs participated in this pilot study. The review documents and case-based discussion led to an increase in comfort in caring for patients with these complications (Table I). Conclusions: This pilot study demonstrated that concise one-page educational summaries, paired with case-based discussions, effectively increased participants’ comfort in managing hematologic and oncologic complications. Building on this preliminary success, we aim to broaden this program’s reach to include additional physicians and advanced practice providers who work as hospitalists or nocturnists or in the emergency medicine and pulmonology/critical care spaces, locally, nationally, and internationally. As specialists, it is our duty and privilege to educate our colleagues in managing this vulnerable population. We are hopeful that, in doing so, our cancer patients will receive optimal care regardless of their care team and location. Subsequent iterations of this initiative will assess durability, patient safety, and improved quality of care. Comfort level in complication management. Pre-Session (N=18, mean on 1-5 scale) Post-Session (N=15, mean on 1-5 scale) CRS 2.16 3.99 ICANS 2.05 3.79 GVHD 2.05 3.66 Neutropenic Fever 3.49 4.33 Transfusion Reactions 2.72 4.00 Complications of acute leukemia* 2.16 3.93 Engraftment Syndrome 1.66 3.46 Scale: 1: Very Uncomfortable​; 2: Somewhat Uncomfortable​; 3: Neither Comfortable nor uncomfortable; 4: Somewhat Comfortable​; 5: Very Comfortable​. CRS: Cytokine Release Syndrome; ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome. *Includes: Disseminated Intravascular Coagulation, Tumor Lysis Syndrome, Hyperleukocytosis, Differentiation Syndrome.

Impact of genomic subtype on intracranial outcomes in treatment-naive <i>EGFR</i> -mutant NSCLC with osimertinib (IGnITE).

2020 Background: Osimertinib is the standard first-line therapy for EGFR -mutant NSCLC with brain metastasis (BM); however, alteration-specific patterns of CNS failure and mortality in treatment-naive patients remain poorly defined. Methods: We assembled an international muti-institutional cohort of TKI and radiation-naive EGFR -mutant NSCLC patients with BM treated with first-line osimertinib, with or without upfront stereotactic radiosurgery (SRS) (within 2 months of BM diagnosis). The primary endpoint was time to CNS progression. Time-to-event outcomes were analyzed using the Kaplan-Meier method. Multivariable hazard ratios (MHR) were estimated using Cox proportional hazards models. Fine and Gray hazard models were used for endpoints with competing risks. Results: From 2016-2024, 470 patients from 11 institutions were identified with the following alterations: exon 19 deletion (57%), L858R mutations (33%), and atypical/uncommon mutations (9.6%). Median follow-up was 25.6 months (IQR, 14.7-41.3 months). At 24 months, the cumulative incidence of CNS progression was 30% for exon 19 deletions, 47% for L858R mutations (MHR 1.68, p&lt;0.001), and 76% for atypical mutations (MHR 4.33, p&lt;0.001). Atypical alterations experienced markedly shorter time to local failure (MHR 4.88, p&lt;0·001). Compared to exon 19 deletions, L858R (MHR 1.73, p=0.001) and atypical alterations (MHR 2.86, p&lt;0.001) were associated with shorter time to distant CNS progression. L858R was also associated with higher risk of leptomeningeal disease (MHR 2.49, p=0.001). At 24 months, cumulative incidence of neurological death was 4.6% for exon 19 deletions, 7.8% for L858R, and 9.1% for atypical alterations (p=0.023). Upfront SRS was associated with improved CNS outcomes, with greater benefit for patients in L858R and atypical alterations. Conclusions: In the largest multi-institutional study of treatment-naive EGFR -mutant NSCLC with BM treated with first-line osimertinib, EGFR alteration subtype was an independent determinant of CNS progression, defined patterns of CNS failure, and identified patients most likely to benefit from treatment intensification with SRS.

A phase 3 study of revumenib plus venetoclax/azacitidine in adults with newly diagnosed <i>NPM1</i> -mutated or <i>KMT2A</i> -rearranged acute myeloid leukemia ineligible for intensive chemotherapy (EVOLVE-2/HO177/AMLSG35-24/ACT-HOV-AML-002).

TPS6600 Background: Optimal treatment for patients (pts) with acute myeloid leukemia (AML) unfit for intensive chemotherapy (IC) remains challenging and depends on pt and disease characteristics and pt preference. In AML with a nucleophosmin-1 mutation ( NPM1 m) or lysine methyltransferase 2A ( KMT2A ) rearrangement ( KMT2A r), menin-KMT2A fusion proteins upregulate HOX/MEIS gene expression, resulting in hematopoietic differentiation arrest and leukemogenesis. Revumenib is a first-in-class, oral, potent, and selective inhibitor of the menin-KMT2A interaction. In the phase 1/2 AUGMENT-101 study (NCT04065399), revumenib monotherapy demonstrated clinically meaningful response rates and was generally well tolerated in pts with relapsed/refractory NPM1 m AML or KMT2A r acute leukemia. To further improve outcomes, combination regimens are being studied as front-line therapy for newly diagnosed (ND) pts. In the phase 1b Beat AML study (NCT03013998), revumenib plus venetoclax/azacitidine (VEN/AZA) demonstrated deep responses in pts ≥60 years (y) of age with ND NPM1 m or KMT2A r AML. EVOLVE-2 will assess whether revumenib plus VEN/AZA prolongs overall survival (OS) and improves complete remission (CR) rates in pts with ND NPM1 m or KMT2A r AML ineligible for IC. Methods: EVOLVE-2 is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT06652438/EU-CT 2024-512733-32-00). Eligible pts are ≥75 y of age (18–74 y with comorbidities), have ND AML with centrally confirmed NPM1 m or KMT2A r (excluding KMT2A partial tandem duplications/deletions), are ineligible for IC, and are AML treatment-naive. Pts will be randomized 1:1 to revumenib or placebo in combination with VEN/AZA and stratified by age (&lt;75 vs ≥75 y), genotype ( NPM1 m vs KMT2A r), and region (Europe vs Australia vs United States). In Cycle (C) 1, VEN is given daily on Days (D) 1–28 and AZA daily on D1–7, ± revumenib twice daily on D1–28. In C2+, responders (per 2022 European LeukemiaNet criteria) may adjust VEN based on remission status/count recovery. Treatment continues until disease progression, unacceptable toxicity, pt withdrawal, or death. The dual primary endpoints are OS and CR rate. Key secondary endpoints include event-free survival and rate of CR/CR with partial hematologic recovery (CRh). Other endpoints include rates of CRh and CR/CR with incomplete hematologic recovery (CRi), measurable residual disease (MRD) negativity (CR, CR/CRh, CR/CRi with MRD negativity), time to/duration of response, adverse events, time to hematopoietic recovery, and incidence of platelet and red blood cell transfusions. Overall, 448 pts will be enrolled. As of January 27, 2026, the study is open to enrollment. Clinical trial information: NCT06652438 .

Implementing a centralized navigator-led and AI-assisted platform to improve lung cancer screening rates and early detection: A 6-year health system analysis.

109 Background: Despite the known mortality benefits of low-dose computed tomography (LDCT) for lung cancer screening (LCS), national uptake remains stagnant (~15-20%). Significant barriers include primary care burden and geographic disparities in rural areas. This study evaluates the impact of a centralized navigation model combined with AI-assisted electronic health record (EHR) alerts on LCS rates and stage distribution within a large integrated health system. Methods: We conducted a retrospective analysis of LCS performance across a 16-hospital system (OSF HealthCare) from 2019 to 2025. The intervention included: 1) centralization of LCS navigators to manage registries and scheduling, and 2) implementation of AI-assisted EHR alerts to identify eligible high-risk patients. Outcome measures included absolute LDCT volume, system-wide screening rates, and AJCC staging at diagnosis. Benchmarks were derived from American Lung Association (ALA) national and state (Illinois) data. Results: The system-wide LCS screening rate increased from 18.2% in 2020 to 42.8% in 2025, significantly outperforming the projected 2025 US national average (19.5%) and the Illinois state average (20.8%). Absolute screening volume nearly doubled, rising from 2,257 scans in 2019 to 4,108 in 2025. Notably, the program demonstrated high resilience during the 2020 COVID-19 pandemic, maintaining 98.5% of prior-year volume compared to a 5% national decline. Early-stage detection (Stage I) showed the greatest improvement in rural facilities, with some centers seeing a +21% increase in Stage I diagnoses over the study period. Conclusions: A centralized, technology-enabled navigation model effectively doubles the national benchmark for lung cancer screening uptake. By removing administrative burdens from primary care and utilizing AI-assisted EHR alert system to close the "eligibility gap", this model provides a scalable blueprint for improving early cancer detection and addressing rural health inequities. OSF HealthCare lung cancer screening performance vs. national benchmarks (2020–2025). Year OSF Annual LDCT Volume OSF Screening Rate (%) National Screening Rate (%)* Performance Gap (Percentage Points) 2020 2,223 18.2% 14.5% +3.7% 2021 2,647 21.4% 14.8% +6.6% 2022 3,280 27.8% 15.5% +12.3% 2023 3,406 33.6% 16.0% +17.6% 2024 3,522 38.2% 18.2% +20.0% 2025 4,108 42.8% 19.5% +23.3% *National benchmarks based on American Lung Association "State of Lung Cancer" annual reports and CDC/ACS prevalence estimates.

Dissecting metastatic castration-resistant prostate cancer using regulatory network analysis of tumor transcriptomes.

5074 Background: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by profound clinical and biological heterogeneity, including variable dependence on androgen receptor signaling, frequent genomic instability, lineage plasticity, and highly divergent clinical outcomes. Despite the widespread use of genomic profiling and expression-based signatures, robust patient-level risk stratification and biologically grounded disease subtyping remain limited. We hypothesized that inference of transcriptional regulatory programs underlying tumor state, integrated with genomic and clinical features, would improve prognostication in mCRPC. Methods: We analyzed genomic, transcriptomic, and clinical data from mCRPC tumors in the Stand Up To Cancer (SU2C) cohort. A transcriptional regulatory network was reverse-engineered using the latest version of the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe3) and transcriptional regulator activity was inferred using Nonparametric analytical Rank-based Enrichment Analysis (NaRnEA). We constructed a novel prognostic machine learning model using a random survival forest integrating regulatory activity features, canonical genomic alterations, and clinical variables. Results: Samples were stratified by RNA-sequencing library preparation method into polyA-purified (training, n=150) and exon-capture (testing, n=100). Our model demonstrated strong and statistically significant performance in both the training cohort (out-of-bag Cox PH p=4.63×10⁻⁸, AUROC = 0.7711) and the independent test cohort (Cox PH p=2.92×10⁻⁵, AUROC = 0.7413). The most informative features included inferred activities of key transcriptional regulators implicated in proliferation, lineage programs, and neuroendocrine differentiation (E2F1, MYC, SOX2, AR, REST), canonical genomic alterations relevant to mCRPC biology (AR, TP53, RB1, FOXA1, APC, PI3K pathway), and select clinical variables (prior therapy, Gleason score, age, metastatic site). Our model also outperformed several widely used gene expression signatures (AR, NEPC, Cell Cycle Progression, RB1 Loss). Regulatory activity–based analyses also revealed substantially greater biological structure and cluster coherence than gene expression–based analyses in subsequent analyses, highlighting distinct and clinically aggressive regulatory states in this dataset. Conclusions: Integrating regulatory network–inferred transcriptional programs with genomic and clinical features enables robust, independently validated prognostication in mCRPC that outperforms widely used expression-based signatures. This approach exposes clinically relevant biological heterogeneity underlying aggressive and treatment-resistant disease states and provides a framework for improved risk stratification in advanced prostate cancer.

Advancing health equity in oncology: Virtual collaborative behavioral health engagement and outcomes among Medicaid-insured and BIPOC patients.

1552 Background: Depression and anxiety are common among patients with cancer, yet access to behavioral health care remains limited, particularly for Medicaid-insured and racially minoritized populations. We evaluated reach, baseline symptom burden, and longitudinal outcomes of a virtual collaborative behavioral health program embedded within community oncology. Methods: We conducted a retrospective cohort study of patients referred to a virtual collaborative behavioral health program (Cerula Care) across community oncology practices from 2024–2026. Outcomes included representation of Medicaid-insured and BIPOC patients among those initiating care, baseline symptom burden assessed by PHQ-9, GAD-7, and FACT-G7 stratified by insurance (Medicaid vs commercial+Medicare) and race/ethnicity (BIPOC vs White), and longitudinal symptom change during program participation. Independent t-tests were used for between-group comparisons, and paired t-tests were used for within-patient comparisons. Results: Between program launch and data cutoff, 1,400 patients were referred by oncology providers; 850 consented and scheduled an intake, and 631 completed intake and initiated behavioral health care. Among 631 patients initiating behavioral health care, 43.5% identified as BIPOC (36.5% Black) and 18.7% were Medicaid-insured, indicating a strong reach into populations historically underserved by behavioral health services. Baseline symptom severity was significantly higher among Medicaid-insured compared with commercial+Medicare patients across all measures, indicating clinically meaningful greater symptom burden. Baseline severity did not differ by race/ethnicity. Improvements in depression, anxiety, and quality of life were observed over time. Between-group differences in symptom improvement by insurance or race were not statistically significant, though Medicaid-insured and BIPOC patients showed directionally greater PHQ-9 and FACT-G7 improvement, and Medicaid-insured greater GAD-7 improvement. Patient-reported experience indicated high acceptability (Net Promoter Score 88); 60% reported improved oncology visit adherence and 61% improved adherence to non chemotherapy medications. Conclusions: Embedding virtual collaborative behavioral health in community oncology was associated with high reach among Medicaid-insured and BIPOC patients. Medicaid-insured patients entered care with greater symptom burden yet experienced symptom improvements comparable to commercially ensured and Medicare patients, with similar outcomes across racial/ethnic groups. These findings support collaborative care as a scalable strategy to expand access to behavioral health services and promote equitable supportive oncology care.

Study on the correlation between gut microbiota and metabolite, brevifolincarboxylic acid, and liver injury caused by third-generation EGFR-TKIs in lung adenocarcinoma.

e20552 Background: For patients with non-small cell lung cancer (NSCLC) who are treated with third-generation EGFR-TKIs, drug-induced liver injury (DILI) is a common adverse reaction that affects the therapeutic outcome. The gut microbiota and metabolites may participate in the occurrence of DILI through the gut-liver axis. Methods: From the clinical samples, 41 patients with lung adenocarcinoma who received first-line treatment with third-generation EGFR-TKI from April 2021 to April 2023 were enrolled in this study. According to the presence or absence of DILI, they were divided into DILI group (group D, n = 18) and N group (n = 23). Fecal metagenomic sequencing and untargeted metabolomics analysis were used to compare the differences in gut microbiota composition and metabolites between the fecal samples of patients with DILI at the time of DILI (Doccur group) and at baseline (Dbase group). The CCK-8 assay, LDH kit, colony formation experiment and flow cytometry were used to investigate whether BA could enhance the inhibitory effect of osimertinib on hepatocytes. Establish an mouse model of oxaliplatin-induced liver injury, and investigate the regulatory effects of BA on liver tissue pathology, serum liver enzymes (ALT/AST/LDH), and inflammatory factors.The TLR4/MyD88/NF- κB signaling pathway was analyzed through transcriptome sequencing, Western blot and ELISA. Results: The diversity of the intestinal flora in DILI patients was significantly reduced, while the abundance of Bacteroides / Faecalibacterium species increased, and the abundance of Clostridium decreased; the level of metabolite Brevifolincarboxylic acid（BA） was significantly downregulated.BA pre-treatment can reverse the hepatocyte toxicity induced by osimertinib (inhibiting apoptosis, reducing LDH release, and improving proliferation ability). BA intragastric administration alleviates liver tissue inflammatory damage in mice, significantly reducing serum levels of ALT/AST/LDH as well as inflammatory factors (IL-6/IL-1β/TNF-α). BA may exert liver-protective effects by inhibiting the activation of the TLR4/MyD88/NF- κB signaling pathway. Conclusions: By regulating the TLR4/MyD88/NF- κB signaling pathway, BA alleviates liver damage induced by third-generation EGFR-TKIs, providing a new target for the prevention and treatment of DILI based on the intestinal-liver axis.

Comparative safety and efficacy of venetoclax-combination therapies versus obinutuzumab-combination therapies in chronic lymphocytic leukemia: A systematic review and meta-analysis.

e19028 Background: Chronic lymphocytic leukemia (CLL) treatment has changed substantially with targeted therapies that achieve superior outcomes compared with traditional chemoimmunotherapy. Venetoclax, a BCL-2 inhibitor that promotes apoptosis, and obinutuzumab, a type II anti-CD20 monoclonal antibody that induces direct cell death and enhances antibody-dependent cellular cytotoxicity, are increasingly used in CLL patients and are generally well-tolerated. However, comparative evidence on their effectiveness remains limited. We conducted a systematic review and meta-analysis of randomized controlled trials to assess efficacy and safety. This analysis addresses existing evidence gaps and aims to support more informed clinical decision-making in CLL management. Methods: A systematic literature search (2010–2026) was conducted using the MeSH terms “BCL2 Inhibitors,” “type II anti-CD20 monoclonal antibody,” “Obinutuzumab,” “Venetoclax,” and “CLL.” Screening across PubMed (412), Google Scholar (1,236), and the Cochrane Library (128) identified 1,776 records. After duplicate removal and screening, six randomized controlled trials were included, while editorials, reviews, case reports, and guidelines were excluded. Eligible studies comprised RCTs and observational studies comparing venetoclax-based versus obinutuzumab-based regimens. Pooled effect sizes were estimated using random-effects models, with heterogeneity assessed via the I² statistic. Risk of bias for RCTs was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the review was conducted in accordance with updated PRISMA guidelines. Results: Six randomized controlled trials comprising 2,184 patients were included in this systematic review and meta-analysis. The primary outcomes were progression-free survival (PFS), undetectable minimal residual disease (uMRD), and mortality. Venetoclax-based regimens demonstrated significantly improved PFS compared with obinutuzumab-based therapies (RR = 1.95; 95% CI, 1.16–3.27; p = 0.01). The pooled analysis showed a higher uMRD rate in the venetoclax arm, but the difference was not statistically significant (RR = 1.63; 95% CI, 0.91–2.90; p = 0.10). Venetoclax-based therapies were associated with reduced mortality (RR = 0.71; 95% CI, 0.59–0.85; p = 0.0003) with no heterogeneity (I² = 0%). Secondary outcomes, including grade 3–4 adverse events (RR = 1.07; 95% CI, 0.94–1.23; p = 0.30) and neutropenia (RR = 0.92; 95% CI, 0.78–1.08; p = 0.31), showed no significant differences between the groups. Conclusions: Venetoclax-based therapies improved progression-free survival and reduced mortality compared with obinutuzumab, providing clinically relevant evidence to guide CLL treatment decisions, though larger studies are needed to confirm these findings.

Surufatinib plus KN046 and chemotherapy as first-line treatment for advanced pancreatic ductal adenocarcinoma: Updated results and biomarker analysis from a phase 1b/2 trial.

4198 Background: In China, gemcitabine (G) and nab-paclitaxel (nP) remain the standard first-line (1L) therapy for patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC). Our previous report (Wang W, et al; 2025 ASCO) showed that the add-on of surufatinib (S, multi-kinase inhibitor) and KN046 (K, bi-specific PD-L1/CTLA-4 antibody) to GnP chemotherapy provided enhanced anti-tumor activity in advanced PDAC. Here we present the updated results and findings from a biomarker analysis. Methods: In this single-arm, phase 1b/2 trial (NCT05832892), eligible pts with treatment-naïve advanced PDAC received oral S (200~250 mg, once daily), intravenous K (5 mg/kg, on day 1) and GnP (G 1000 mg/m 2 , nP 125 mg/m 2 , on days 1 &amp; 8) at 21-day cycles till disease progression or intolerable toxicity. The primary efficacy endpoint was ORR per RECIST 1.1; secondary endpoints included DCR, PFS, OS and safety; efficacy-predictive biomarkers were exploratory endpoints. Results: Overall, 31 pts were enrolled with a median age of 56 years (range 40–74) and a predominant male gender (74.2%). Distant metastasis was present in 28 (90.3%) pts and 24 (77.4%) had liver metastasis (LM) at baseline. Best overall responses included 4 CR, 18 PR, and 6 SD. The ORR was 71.0% (95% CI 52.0–85.8) and DCR was 90.3% (95% CI 74.2–98.0). As of Dec 25, 2025, with a median follow-up of 15.9 months, median PFS was 8.2 months (95% CI 6.1–not estimable [NE]). Median OS was 18.0 months (95% CI 13.8–NE) with a 12-month OS rate of 68.2% (95% CI 50.8–91.6). Baseline LM was correlated to significantly worse PFS (8.0 vs NE months, log-rank P = 0.02), though no significant impact on ORR (73.9% vs 62.5%, P = 0.66), DCR (91.3% vs 87.5%, P = 1.00) or OS (13.8 vs NE, log-rank P = 0.12) was observed. Among the 27 pts who received ≥4 cycles of treatment, 22 (81.5%) and 19 (70.4%) experienced a decline in CA199 and CA125 from baseline, respectively, while fewer (37.0%) had CEA declined. A ≥50% decline in CA199 was correlated to significantly improved PFS (10.3 vs 8.1 months, log-rank P = 0.01) and a trend towards improved OS (NE vs 11.1 months, log-rank P = 0.11), as compared to a milder decrease or increase in CA199; Such correlation was not observed for CA125 or CEA. Treatment-related adverse events (TRAEs) occurred in 29 (93.5%) pts, of whom 14 (45.2%) experienced Grade ≥3 events, with hypertension (12.9%), neutropenia (12.9%), and thrombocytopenia (9.7%) being the most frequently observed. No treatment-related serious adverse events or deaths occurred. Conclusions: S plus K and GnP demonstrated consistently encouraging efficacy and manageable safety in 1L treatment of advanced PDAC. Early and sharp decline in CA199 may predict more favorable survival benefit. Analyses in genetic profile and its impact on clinical outcome will be carried out in future, and investigations in larger population are warranted. Clinical trial information: NCT05832892 .