Browse Articles

Mortality trends: Colorectal carcinoma associated with tobacco use as a cause of death in the United States—A CDC WONDER analysis (1999-2023).

e15659 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (U.S.) Tobacco use is a modifiable risk factor for CRC and can carry a 14-18% higher risk of CRC compared to non-smokers. Despite this recognized association, contemporary analyses examining long-term national trends and the relationship between tobacco use and CRC mortality remain limited. Methods: Mortality data were obtained from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database to assess colorectal cancer (CRC; International Classification of Diseases (ICD-10) codes C18–C20) and tobacco-related deaths (ICD-10 code F17) among adults aged ≥25 years in the United States. Annual age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the direct method and standardized to the 2000 U.S. standard population. Analyses were stratified by year, sex, race/ethnicity, and U.S. census region. Chronological trends in mortality were assessed using Joinpoint regression analysis to estimate average annual percent changes (AAPCs) and corresponding 95% confidence intervals (CIs). Statistical significance was defined as p value < 0.05. Results: From 1999–2023, 71,007 CRC deaths were linked to tobacco use. Overall AAMR rose from 0.13 in 1999 to 1.67 in 2023 (APC: 4.88; 95% CI: 3.60–7.04). Men were found to have higher AAMRs than women (1999: 0.21 vs 0.07; 2023: 2.39 vs 1.08). Racial and ethnic disparities were also evident. Non-Hispanic Whites had the highest mortality, followed by Non-Hispanic Blacks, then Hispanics/Latinos (2023 AAMRs: 1.94, 1.58, and 0.73, respectively). Marked regional variation was also observed, with the Midwest exhibiting the highest mortality rates since 2008 (2023 AAMRs: Midwest, 2.35; South, 1.77; West, 1.30; Northeast, 1.23 per 100,000). State-level variation was noted: North Dakota led in 1999–2020, Kentucky in 2021–2023, while California had the lowest rates. Conclusions: In this multivariate analysis from 1999-2023, tobacco use was shown to have significant impact on CRC mortality. The CDC-WONDER database demonstrated clear disparities by region, sex and ethnic backgrounds. Despite advancements in colorectal cancer screening and treatment, the rising burden of tobacco related CRC mortality underscores the persistent and preventable impact of tobacco use.

DOACs versus vitamin K antagonists for cancer-associated VTE: Updated systematic review and meta-analysis.

e23324 Background: Cancer-associated venous thromboembolism (VTE) remains a major driver of morbidity and mortality, and anticoagulant choice requires balancing recurrence prevention against bleeding risk. While low–molecular–weight heparin has historically been preferred, direct oral anticoagulants (DOACs) are increasingly used in routine practice, including in patients underrepresented in randomized trials (older age, mixed malignancy types, variable treatment status, and comorbidity burden). Therefore, we performed an updated systematic review and meta-analysis to clarify the effectiveness and safety of DOACs versus VKAs in adults with active cancer and VTE across contemporary clinical settings. Methods: We synthesized 10 comparative observational studies (retrospective cohorts and database-based analyses) enrolling adults (≥18 years) with active solid or hematologic malignancy and objectively confirmed VTE (deep vein thrombosis and/or pulmonary embolism) treated with DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) or VKAs (warfarin/other VKAs with INR-guided dosing, with or without initial parenteral anticoagulation). Primary outcomes were recurrent VTE and major bleeding; secondary outcomes included all-cause mortality. Random-effects models pooled adjusted hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) were reported. Heterogeneity was assessed using I², with leave-one-out sensitivity analyses. Results: Across 49,806 patients (DOACs: 22,817; VKAs: 26,989), DOACs were associated with lower adjusted recurrent VTE (HR 0.73, 95% CI 0.68–0.79; I² = 0.0%; prediction interval 0.59–0.91) and lower unadjusted recurrent VTE (RR 0.72, 95% CI 0.62–0.83; I² = 13.7%; prediction interval 0.59–0.87). DOACs also reduced adjusted major bleeding (HR 0.83, 95% CI 0.72–0.97; I² = 0.0%), though statistical significance was sensitive to omission of one large study. Adjusted all-cause mortality was lower with DOACs (RR 0.46, 95% CI 0.36–0.60; I² = 0.0%), but prediction intervals were wide, and results were influenced by individual studies. No clear funnel-plot asymmetry was observed. Conclusions: In adults with active cancer and VTE treated in real-world settings, DOACs were associated with reduced recurrent VTE and lower major bleeding compared with VKAs, with low heterogeneity across studies. Mortality estimates should be interpreted cautiously due to observational design and imprecision. Prospective comparative studies are needed to confirm survival effects and optimize anticoagulant selection in heterogeneous oncology populations.

Safety and antitumor activity of VRN110755, a brain-penetrant, selective EGFR inhibitor, in patients with EGFR-driven non–small cell lung cancer.

8623 Background: Third-generation EGFR tyrosine kinase inhibitors (TKIs) have improved outcomes in EGFR-mutant non–small cell lung cancer (NSCLC); however, acquired resistance, including EGFR C797S mutations, and central nervous system (CNS) progression remain major unmet medical needs. VRN110755 is an orally available, highly selective EGFR inhibitor designed to target a broad spectrum of EGFR mutations, including C797S, and has demonstrated robust brain penetration in preclinical models. Methods: This ongoing, open-label, multicenter Phase I/II study evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of VRN110755 in patients with EGFR-mutant NSCLC who progressed on prior third-generation EGFR TKIs and had no remaining standard treatment options. A dose-escalation phase (10–480 mg once daily) followed by protocol-defined backfill cohorts (80–400 mg) was conducted. Patients with stable, asymptomatic brain metastases and/or leptomeningeal metastases were eligible. This abstract reports data available at the time of analysis to characterize emerging safety, PK, and antitumor activity and to inform ongoing dose optimization and cohort expansion under protocol-defined safety monitoring. Early reporting was undertaken due to emerging systemic and intracranial activity in a population with high unmet medical need; enrollment and follow-up are ongoing. Results: As of January 18, 2026, 63 patients were enrolled. VRN110755 demonstrated dose-proportional PK. At 320 mg, target engagement (C trough /IC 50 ) against common EGFR mutations exceeded that of osimertinib 80 mg by approximately four-fold. Treatment-related adverse events were predominantly low grade (grade 1: 37%; grade 2: 20%; grade 3: 2%), with no dose-limiting toxicities observed; the most common event was grade 1 rash (16%). Low rates of diarrhea were reported, with no interstitial lung disease or clinically meaningful QTc prolongation observed to date. Among 38 response-evaluable patients treated at doses ≥160 mg following progression on prior EGFR TKIs, 7 (18.4%) achieved partial responses and 28 (73.7%) achieved stable disease, yielding a disease control rate of 92.1%; approximately half remained on treatment beyond 7.5 months, suggesting durable disease control. In patients with baseline EGFR C797S mutations (n=7), the overall response rate was 85.7% (6/7), with ctDNA clearance of C797S observed in 83.3% (5/6) of responders. Complete intracranial responses were observed in two patients, and a K p,uu,CSF of 2.0 was documented at the 160 mg dose. Conclusions: VRN110755 demonstrated favorable PK, a manageable safety profile, and encouraging systemic and CNS antitumor activity in heavily pretreated EGFR-mutant NSCLC, including C797S-positive disease, supporting continued clinical development. Clinical trial information: VRN110755_01.

Solvent‐Controlled Pathways Enable Structure‐Programmable Metal‐Organic Framework Membranes for Isomer Separation

ABSTRACT The separation of structurally similar aliphatic and aromatic isomers remains a critical industrial challenge, as their nearly identical sizes render conventional distillation highly energy‐intensive. Molecular‐sieving metal–organic framework (MOF) membranes offer an energy‐efficient alternative; however, reliably programming their growth pathways to achieve targeted pore architectures is difficult. Here, we report a solvent‐triggered pathway control strategy that directs distinct growth routes from a single vertically aligned Zn─Al layered double hydroxide (LDH) nanoarray template. In N , N ‐dimethylformamide (DMF), selective activation of LDH metal sites stabilizes the framework and guides a surface‐induced interstitial growth mechanism, yielding a dense Zn‐BODC membrane with ∼0.5 nm apertures for highly selective n‐hexane/2,3‐dimethylbutane (Hex/23DMB) separation. In water, rapid LDH dissolution triggers a complete template‐conversion pathway that replicates the honeycomb morphology, producing an Al‐BODC membrane with ∼0.7 nm pores capable of efficient para‐/ortho‐xylene (PX/OX) discrimination. These solvent‐defined pathways enable programmable microstructures and complementary separation performances. This work establishes a versatile platform for the rational design of ultramicroporous MOF membranes with tailored sieving properties for demanding isomer separations.

Transport of Eyring-Powell nanofluid flow over a Riga surface with binary chemical reaction and convective boundary condition effects

In vivo CAR T purchase spree continues with Lilly deal worth up to US$7 billion

Coordination‐Induced Reconstruction Optimizes Spatial Arrangements of Heterogeneous Yet Cooperative Sites to Boost Oxygen Reduction Kinetics

ABSTRACT Control over the spatial arrangement of heterogeneous yet cooperative sites is highly desirable yet challenging to enhance reaction kinetics. This study develops a coordination‐induced reconstruction (CIR) strategy that, under a chloride atmosphere, in situ converts Fe nanoparticles into FeN 4 Cl single atoms (SAs) and Fe atomic clusters (ACs) on nitrogen‐doped carbon (NC), enabling several SAs around single ACs with an average distance of about 0.86 ± 0.08 nm. This spatial arrangement constitutes heterogeneous yet catalytically cooperative interfaces, enabling an efficient cascade of proton generation, proton transport, and oxygen hydrogenation at favorable sites with suitable distances, as revealed by operando infrared spectra, kinetic isotope effect, local pH measurements, and theoretical calculations. Resultant FeN 4 Cl SAs ‐Fe ACs /NC remarkably enhances the oxygen reduction reaction (ORR) and steers it toward a 4‐electron pathway with an ORR half‐wave potential of 0.934 V, and robust stability for 50 000 cycles. The CIR strategy is effective for at least Ni‐ and Mn‐based systems.

A unified framework of information measures for complex linear Diophantine fuzzy sets with application to chronic kidney disease

Comparative analysis of hereditary cancer genetic testing programs in India and the US: Identifying disparities and guiding global program development.

e13531 Background: Identifying actionable pathogenic variants in hereditary cancer genes is critical to assess eligibility for targeted therapies and locate at-risk relatives. Currently, little is known about disparities and trends in patients seen in India and other LMICs (low/middle income countries) compared to the US. Creating and analyzing metrics allows researchers to identify, track and reduce these inequities. Most patients seen in the Indian program are cancer patients referred internally (by their oncologist within the same health system). Counseling and testing are performed by one genetic counselor and one oncologist using NCCN criteria. The American clinic sees internal referrals, external referrals, and high-risk unaffected patients. The clinic is staffed by multiple providers including three genetic counselors. Methods: Characteristics of patients seen in both centers from 2022-2024 were compared in this unique dataset. This data was reviewed to identify disparities and trends in genetic testing both across centers and over time. Results: Summary data is presented in the table below. Patient volumes at both centers increased significantly over time. In contrast to India, the majority of patients evaluated at the US center are now unaffected. Female patients represent over 80% of patients seen in both clinics. A personal or family history of breast cancer remains the most common reason for referral in both clinics. The percentage of pathogenic/likely pathogenic variants (P/LP) is markedly higher in the Indian patients tested. In the Indian clinic, referred patients are seen within two days, whereas wait times in the US clinic may be up to four weeks. Conclusions: These cross-national results provide real-world evidence of disparities in germline cancer genetic testing. Training additional genetics providers is critical to improving testing volume. In both nations, sex is the dominant disparity noted in genetic testing; special emphasis should be placed on identifying male patients who meet criteria for testing. Programs must also focus on testing eligible patients with cancer types other than breast cancer. Evaluating high-risk unaffected patients and emphasizing cascade testing will amplify the impact of genetic testing. When developing and expanding testing programs worldwide, our data can be used to preemptively address and reduce these inequities. Patient characteristics from MCCF (IN/India) & VOA (US) genetic clinics. Year 2022 2023 2024 IN total 149 168 272 US total 1661 1912 2534 IN % unaffected 21% 14% 8% US % unaffected 41% 44% 55% IN % female 83% 88% 90% US % female 82% 80% 80% IN personal/family history of breast cancer 54% 60% 59% US personal/family history of breast cancer 43% 41% 41% IN % P/LP variants 21% 20% 14% US % P/LP variants 11% 12% 12%

Simultaneous anthracycline-based chemotherapy and dual HER2 blockade in early-stage HER2-positive breast cancer: A retrospective analysis.

e12741 Background: Early-stage HER2-positive breast cancer represents a biologically aggressive subtype; however, outcomes have substantially improved with the introduction of HER2-targeted therapies. Anthracyclines have been considered a cornerstone of chemotherapy, but their role is increasingly being questioned. Recently, antibody–drug conjugates are being evaluated in clinical trials with the aim of redefining treatment standards in the early setting. However, some comparative concepts remain methodologically limited, particularly when anthracycline-based regimens are administered without concurrent HER2-targeted therapy and compared with modern regimens that include simultaneous HER2 blockade. From both a biological and clinical perspective, the concomitant administration of chemotherapy and HER2-directed treatment appears critical to maximize antitumor efficacy. Non-pegylated liposomal doxorubicin (Myocet) has been developed to reduce cardiotoxicity while preserving antitumor activity, offering a potential strategy for anthracycline-based approaches with an improved safety profile. Methods: We performed a retrospective analysis of 164 consecutive patients with early-stage HER2-positive breast cancer treated at the Department of Obstetrics and Gynecology, Medical University of Innsbruck between April 2013 and February 2022. Patients were routinely assigned to receive six cycles of a neoadjuvant regimen consisting of Myocet, docetaxel and dual HER2 blockade administered concurrently. Primary endpoint was pathological complete response (pCR) rates. Secondary endpoints included overall survival, disease free survival and cardiotoxicity. Results: A total of 164 patients were analyzed. Median follow-up was 8,38 years (Q1,Q3; 6,5, 10,08). The median age at diagnosis was 50,8 years (Q1, Q3; 42,7, 58,7). In our cohort, 56% of patients were pre- and 43% postmenopausal. Regarding hormone receptor (HR) status, 42% (69/164) were HR negative and 58% (95/164) HR positive. PCR rate was achieved in 81,1% (133/164) of patients. Patients exhibiting HR negative cancers showed pCR more often, 92,8% (64/69), compared to HR positive patients, 72,6% (69/95). Overall survival in our cohort was on median 90,4 months (Q1, Q3; 65,4, 110,2) and disease-free survival 83,2 months (Q1, Q3; 60, 106,5). Data regarding cardiotoxicity was available for 89% (146/164) of patients at the time of their operation and 90% (147/164) of patients at the end of their treatment. At both time points, two patients (1%; 2/146, 2/147) had a left ventricular dysfunction grade CTCAE 2 (LVEF 40-49% and LVEF reduction of > 10%). Conclusions: In our cohort providing real world data, simultaneous anthracycline-based chemotherapy and dual HER2 blockade in early-stage HER2-positive breast cancer was an effective treatment with a pCR rate of 81,1% and excellent cardiac safety.

Updated results of the phase 1 dose escalation and expansion study of alveltamig (ZG006), a trispecific T cell engager targeting DLL3/DLL3/CD3, as monotherapy in patients with refractory small cell lung cancer or neuroendocrine carcinoma.

8096 Background: Alveltamig (ZG006) is a uniquely designed T cell engager, targeting two distinct delta-like ligand 3 (DLL3) epitopes and CD3 and, thereby bridging tumor cells and T cells together and mediating T cell-specific killing of DLL3-expressing tumor cells such as small cell lung cancer (SCLC) or neuroendocrine carcinoma (NEC). Methods: This is a multi-center, open-label, phase 1 clinical study of ZG006 as monotherapy in patients with SCLC or NEC who failed or were intolerant to the standard therapies. A standard "3+3" design, with an accelerated titration approach for the first two lower dose levels was used during the dose escalation stage. Here we report the updated results of the efficacy and safety data from the phase I study. Results: In this phase I study, patients received ZG006 at 0.1 mg Q2W and escalated at 8 dose levels up to 100 mg Q2W (Wang Q et al, ASCO 2025). A step dose of 1 mg was implemented for higher dose groups starting from 10 mg Q2W. Dose expansion was conducted at dose levels of 10, 30, and 60 mg. A total of 31 patients with SCLC, including 4, 15, and 12 patients from the 10 mg, 30 mg, and 60 mg dose groups respectively, were included in the current efficacy analysis. The overall median follow-up time was approximately 16 months. The median age was 59 years (range, 45.0-72.0), the median number of prior treatment lines was 3 (range,1-4), 80.6% of the patients had received prior immunotherapy, and 90.3% had a baseline ECOG performance status score of 1. The confirmed objective response rate (ORR) assessed by an independent review committee (IRC) was 74.2%. The median duration of response (DoR) was 12.6 months, with 12-month DoR rate at 65.3 %. The estimated 12-month PFS rate was 50.5%. The median overall survival (OS) was not reached yet, however,the 12-month and 18-month OS rates approached 74.2% and 58.6% respectively. Consistent with prior report, the most common adverse events with longer follow-up included CRS, anemia and other conditions, with most being Grade 1 or 2 and occurring during the first two cycles. Overall, ZG006 was well-tolerated and the treatment related adverse events including CRS were manageable. Conclusions: With longer follow up from phase I study, ZG006 continued to demonstrate robust antitumor activity in the dose expansion cohorts including high ORR, longer DoR/PFS, and clinically meaningful survival benefits in patients with refractory SCLC. No new safety signal was encountered. These data support ongoing development of ZG006 as monotherapy and in combination with other modalities in SCLC. Clinical trial information: NCT05978284 .

Duffy-null status and cytopenias following BCMA-directed CAR T therapy in multiple myeloma.

7549 Background: Anti-BCMA chimeric antigen receptor T-cell (CAR T) therapies are highly effective in relapsed or refractory multiple myeloma (RRMM). The Duffy null phenotype, common among individuals of African ancestry and associated with lower baseline neutrophil counts, may influence hematologic toxicity following CAR T therapy. We evaluated outcomes of anti-BCMA CAR T by Duffy antigen status. Methods: We performed a retrospective analysis of 173 RRMM patients receiving ciltacabtagene autoleucel (cilta-cel; n=83) or idecabtagene vicleucel (ide-cel; n=90) between July 2021 and May 2025. Primary endpoints were PFS, OS, and response rate. Secondary endpoints included cytopenias and infections. Analyses were stratified by Duffy status and race/ethnicity and adjusted for age, prior therapies, and baseline ANC. Results: Cilta-cel: Duffy null patients (n=11, 13.3%) had comparable baseline characteristics to Duffy positive patients, except lower ANC (1.71 vs 2.44, p=0.01). Duffy null status was associated with prolonged neutropenia, with lower median ANC at day 30 (0.56 vs 1.77, p=0.005) and day 90 (1.06 vs 2.45, p=0.0002), and persistent grade ≥3 neutropenia at day 90 in 44.4% vs 4.3% (p=0.002). Infection rates were similar between groups (36.4% vs 41.7%, p=1.0). Response rates were high in both groups (100% vs 92%) and PFS did not differ significantly (HR 0.54, 95% CI 0.12–2.43, p=0.42), with a nonsignificant trend toward improved PFS among Duffy null patients after adjustment (HR 0.38, p=0.24). There were no significant differences in OS. Ide-cel: Duffy null status (n=16, 17.8%) was not associated with delayed cytopenia recovery (day 90 grade ≥3 neutropenia 33.3% vs 16.4%, p=0.2). Duffy null patients had higher infection rates (68.8% vs 39.2%, p=0.03) and a trend toward inferior OS (median 19.1 vs 40.4 months, log-rank p=0.11). These patients were more heavily pretreated (median 7 vs 5 prior lines, p=0.04); in multivariable analysis, prior lines of therapy predicted OS (HR 1.13, p=0.046) while Duffy status did not (HR 1.63, p=0.30). Response rates and PFS were similar between groups. Race/ethnicity alone was not associated with cytopenia recovery, infection rates, or survival. Conclusions: Duffy null status predicts severe, prolonged cytopenias following cilta-cel, without compromising efficacy or survival. Despite profound neutropenia, similar infection rates suggest benign cytopenia rather than true immunosuppression. Pre–CAR T Duffy phenotyping may prevent unnecessary neutropenia-directed interventions such as growth factors or stem cell boost. In ide-cel recipients, higher infection rates and inferior survival trends likely reflect heavier pretreatment and diminished marrow reserve. Future studies should evaluate Duffy status in earlier treatment lines and assess post-CAR T supportive care utilization by phenotype. Christen Dillard and Erneisha Brown contributed equally to this work.

Distinct immunogenomic features of cancers arising in solid organ transplant recipients.

10587 Background: Solid organ transplantation recipients (SOTRs) are at increased risk of cancer due to long-term immunosuppressive therapy to prevent organ rejection. However, the immunogenomic characteristics of cancers arising in SOTRs remain poorly defined, limiting evidence-based treatment decisions, particularly regarding immunotherapy. Methods: Next-generation sequencing (NGS) of tumor tissue for DNA (592-gene panel/whole exome) and RNA (whole transcriptome) was carried out at Caris Life Sciences for SOTRs (n=1,024) and individuals without a transplant matched by age, sex, and cancer type (10:1 ratio, n=10,240). Immune cell infiltration in the tumor microenvironment (TME) was estimated by quanTIseq. Interferon-gamma (IFN-γ) signaling was assessed by a 10-gene transcriptomic signature. Tumor mutational burden (TMB) was assessed by NGS. Microsatellite instability (MSI) was assessed by immunohistochemistry (IHC) and NGS, and PD-L1 expression by IHC. Among SOTRs treated with immunotherapy, overall survival was assessed from insurance claims and calculated from treatment initiation to last contact. Results: The median age at sample collection was 65 years, with kidney recipients comprising the majority of SOTR cases (59.6%). Non-small cell lung cancer (NSCLC) was the most common malignancy (18.5%), followed by colorectal cancer (CRC, 10.5%). For all tumors combined, SOTRs exhibited significantly reduced adaptive immune cell infiltration in the TME, including CD8 + T-cells (SOTR vs non-SOTR median: 0.11% vs 0.23%), regulatory T-cells (1.60% vs 2.10%) and B-cells (3.69% vs 3.91%); no significant differences were observed in innate immune cell fractions except for myeloid dendritic cells (0.64% vs 0.79%). While IFN-γ signatures were similar among all SOTRs and non-SOTRs, SOTRs had significantly lower IFN-γ for NSCLC and cutaneous squamous cell carcinoma (cSCC). Median TMB was significantly higher in SOTRs than non-SOTRs for NSCLC, colorectal cancer (CRC), pancreatic cancer, cSCC, melanoma, and esophageal cancer. MSI was more common in SOTRs overall (4.9% vs 1.9%; p<0.0001) and for CRC (15.8% vs. 6.8%; p <0.0001). PD-L1 positivity was less common in SOTRs than non-SOTRs (12.4% vs 18.6%; p=0.021). Finally, among SOTRs treated with immunotherapy, those with high TMB (≥10 mutations/Mb) tended to have better survival than those with low TMB (hazard ratio 0.79, 95%CI 0.47-1.34, p=0.374). Conclusions: Despite higher prevalence of tumors with high TMB and MSI for select cancer types, SOTRs had lower adaptive immune infiltration and IFN-γ signaling within the TME, likely reflecting the immunosuppressive anti-rejection treatment. Our findings highlight distinct immunogenomic features of transplant-associated cancers and provide biologic rationale for further study of immunotherapy strategies in carefully selected SOTRs.

Post-transplant outcomes stratified by induction therapy in patients with AML undergoing allogeneic transplantation.

e18572 Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option for patients with higher-risk acute myeloid leukemia (AML); however, transplant failure occurs in approximately 40% of cases, most commonly due to relapse. Post-transplant outcomes are influenced by multiple factors, but the impact of pre-transplant induction regimen remains unclear. Methods: We retrospectively analyzed adults with AML who underwent allo-HCT at our institution between January 2015 and January 2025. Patients were grouped by induction regimen prior to transplant into three cohorts: anthracycline plus cytarabine (anthracycline-based), hypomethylating agent plus venetoclax (HMA/VEN), and CPX-351. OS and RFS were calculated using Kaplan–Meier. Induction groups were matched using inverse probability of treatment weighting (IPTW) based on age, sex, ELN 2022 risk category, and conditioning regimen. Weighted Kaplan–Meier analyses were used to estimate OS and RFS. Statistical analyses were performed using R version 4.4.0. Results: A total of 144 patients were included. Median age was 57 years (IQR 43–64), and 53% were male. At transplant, 61% of patients were in first complete remission (CR1) and 22% in second complete remission (CR2). By ELN 2022 risk stratification, 22% had favorable-, 28% intermediate-, and 50% adverse-risk disease. One hundred patients (69%) received anthracycline-based induction, 34 patients (23%) received HMA/VEN, and 10 patients (7%) received CPX-351. Induction strategy differed significantly by ELN risk category. Patients with favorable- and adverse-risk AML were more likely to receive anthracycline-based induction compared with those with intermediate-risk disease (94% and 70% vs 46%, respectively; p<0.01). CPX-351 was used almost exclusively in patients with adverse-risk AML. Patients receiving anthracycline-based induction were younger (median age 55 years) than those treated with HMA/VEN or CPX-351 (both median age 61 years; p=0.017). Median follow-up from transplant was 66 months (IQR 43.3–NR). After IPTW adjustment, there was no significant difference in OS across induction regimens. Median OS was 101 months (95% CI 69–NR) for anthracycline-based induction, 91 months (95% CI 73–NR) for HMA/VEN, and 20 months (95% CI 16–NR) for CPX-351 (weighted p=0.20). In contrast, the CPX-351 group demonstrated inferior RFS, with a median RFS of 11 months (95% CI 5–15), compared with not reached for anthracycline-based induction and 50 months (95% CI 6.6–NR) for HMA/VEN (weighted p=0.04). Conclusions: In this retrospective analysis, pre-transplant induction regimen was not associated with differences in overall survival after allo-HCT. Patients receiving CPX-351 had a higher risk of post-transplant relapse after adjustment for ELN risk and other confounders. These findings should be confirmed in prospective clinical trials.

From pathophysiology to prognosis: An oncology curriculum for interdisciplinary palliative care specialists.

9026 Background: Integrating specialty palliative care (SPC) improves outcomes for patients with advanced cancer, yet effective collaboration requires a shared understanding of the clinical condition. Oncologists report that SPC professionals lack familiarity with new oncologic therapies and their implications for prognosis and decision-making—a gap that can hinder the quality and timing of communication amongst providers as well as goals of care conversations with patients and surrogates. Addressing this gap may enhance the value of SPC consultations and support more aligned co-management of patients with advanced malignancies. Objective: To design, implement, and evaluate an interdisciplinary oncology curriculum for SPC health science professionals (HSPs) at a single institution, with the goal of enhancing SPC’s knowledge and confidence in caring for patients with advanced solid-tumor malignancies. Methods: An informal needs assessment was conducted with oncologists and palliative care physicians to inform content development. The topics identified to discuss included oncologic terminology, therapeutics, side effects, and disease trajectories for breast, lung, colon, and pancreatic cancer. The curriculum comprised five synchronous virtual sessions delivered over five months. Sessions incorporated active learning strategies grounded in principles of Andragogy and Self-Determination Theory. Medical oncologists reviewed content and participated in sessions. Electronic flashcards were distributed to provide learners asynchronous background knowledge and for post-session reviews. A paired pre/post survey assessed knowledge (via 19 multiple-choice questions for physicians, APPs, and pharmacists) and SPC’s attitudes (via 5-point Likert scale). Results: Of 79 invited SPC HSPs across nine sites, 51 participated: 17 APPs, 26 physicians, 1 pharmacist, 7 social workers, and 1 chaplain. 87% of the participants attended at least 4 of the 5 curriculum sessions. 67% of the participants utilized the flashcards. Among the physicians, APPs, and pharmacists completing knowledge assessments (pretest n= 42, posttest n= 35), mean scores improved from 53.9% (SD 13.6) to 67.8% (SD 13.1), p < 0.001. Confidence in applying oncology concepts increased from 2.7 (0.8) to 3.5 (0.5), p < 0.001. Perceived importance of this education remained high throughout (pre 4.2 [0.6], post 4.1 [0.8], p = 0.609). Conclusions: This oncologist-informed curriculum significantly improved SPC’s oncology knowledge and confidence. By equipping specialty palliative care teams with stronger oncologic foundations, this curriculum offers a scalable approach to enhancing interdisciplinary collaboration—potentially improving consultation quality, communication, and shared decision-making for patients with advanced cancer.

CXCR2 expression in lung neuroendocrine neoplasms.

e20143 Background: The incidence of lung neuroendocrine neoplasms (NENs), which account for 1%-3% of all lung malignancies, has been increasing in recent years. Lung NENs range from low-grade typical carcinoid tumor, to intermediate-grade atypical carcinoid tumor, to aggressive high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). C-X-C Motif Chemokine Receptor 2 (CXCR2) is a G protein-coupled receptor for chemokine interleukin-8 (IL-8), and previous studies suggested that IL-8/CXCR2 pathway may drive the neuroendocrine cell differentiation; however, the expression levels and functional roles of CXCR2 in lung NENs have not been studied. Methods: The expression levels of CXCR2 in lung typical carcinoid (TC) tumors, atypical carcinoid (AC) tumors, and high-grade neuroendocrine carcinomas (HGNEC, including small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC)) were examined by immunohistochemistry using anti-CXCR2 antibody (clone 6C6, BD Biosciences). The immunostaining of CXCR2 was scored by pulmonary pathologists using the intensity of labeling (1 = weak, 2 = moderate, 3 = strong) and percentage of positive tumor cells (1–100%), with the product of these two parameters yielding an H-score (ranged from 0 to 300). The H-scores in three groups were compared using one-way analysis of variance (ANOVA) with multiple groups comparison, P ≤ 0.05 was considered statistically significant. Results: 25 TCs, 18 ACs, and 18 HGNECs (14 SCLC, 1 LCNEC, 3 SCLC and LCNEC combined) were examined. All TC and AC tumors were from resection specimens, the HGNEC group included 10 transbronchial biopsies and 8 resection cases. CXCR2 expression levels did not differ significantly between the TC and AC tumors (mean 182.2 versus 159.7, P = 0.5211), despite a slight reduction in the AC group. HGNECs showed significantly reduced CXCR2 expression compared to the TC (25.2 versus 182.2, P < 0.0001) and AC (25.2 versus 159.7, P < 0.0001) tumors. Using H-score ≤ 20 to define negative staining, 83% (15/18) HGNECs were negative for CXCR2 expression, while none of TCs and only 5.6% (1/18) of ACs showed negative staining. When compared HGNECs to all carcinoid tumors (TCs + ACs), CXCR2 loss demonstrated 83% sensitivity and 98% specificity for distinguishing HGNECs from carcinoid tumors. Conclusions: Our data indicates that pulmonary HGNECs lost CXCR2 expression in comparison to typical and atypical carcinoid tumors, although the underlying mechanism is not clear. CXCR2 might be a valuable diagnostic marker in distinguishing HGNEC from carcinoid tumor in challenging diagnostic scenarios for pathologists. Analysis of the correlation between CXCR2 expression and tumor clinicopathologic characteristics is underway.

Factors associated with treatment response and survival outcomes in plasmablastic lymphoma: A retrospective study in a predominantly Hispanic population.

e19099 Background: Plasmablastic lymphoma (PBL) is a rare, aggressive NHL with historically poor outcomes and a median overall survival (OS) of 9-15 months. We evaluated clinicopathologic characteristics and factors associated with response and survival in a predominantly Hispanic cohort of patients with PBL. Methods: We retrospectively analyzed 35 patients with pathologically confirmed PBL diagnosed between December 2012 and June 2025. Factors associated with response were assessed by chi-square and multivariable logistic regression. Survival outcomes were evaluated by Kaplan-Meier method with log-rank test and multivariable Cox regression. Results: Median age was 49 years; 85.7% were male, and 74.3% were Hispanic. Interim overall response rate (ORR) and complete response rate (CRR) with first-line therapy were 62.9% and 54.3%, respectively. On univariate analysis, female sex (p=.03) and LDH <220 U/L ( p <. 01) were associated with achieving CR. On multivariate analysis, LDH <220 U/L (OR .05, 95% CI .005–.54, p=.01) remained independently associated with CR after adjusting for ethnicity, age >40, ECOG >2, advanced stage, IPI ≥3, and Ki-67 >80%. With a median follow-up of 17 months, median progression-free survival (PFS) and OS were 20 and 60 months, respectively. Estimated 1-, 2-, and 5-year PFS were 59.3%, 49.2%, and 43.7%, and OS were 67.9%, 54.8%, and 46.0%, respectively. On univariate analysis, female sex (HR .29, 95% CI .09-.89, p=.03; HR .28, 95% CI .08-.96, p=.04) and achieving CR (HR .12, 95% CI .04-.34, p<.01; HR .11, 95% CI .04-.31, p<.01) were associated with improved PFS and OS. IPI ≥3 (HR 2.8, 95% CI 1.1-7.3, p=.03) and LDH ≥220 U/L (HR 2.7, 95% CI 1.0-6.9, p=.04) were associated with worse OS, but not PFS. On multivariate analysis, age >40 (HR 4.7, 95% CI 1.2-19.3, p=.03) was associated with worse PFS, but not OS. High/high-intermediate IPI scores (IPI ≥3; HR 7.4, 95% CI 1.2-47.1, p=.03; HR 12.7, 95% CI 1.4-118.6, p=.03) were independently associated with inferior PFS and OS, while achieving CR (HR .04, 95% CI .01-.38, p<.01; HR .03, 95% CI .003-.31, p<.01) was associated with improved PFS and OS, independent of LDH ≥220 U/L, interim response, disease stage, immunocompromised status, EBV status, CNS prophylaxis, radiation therapy, and autologous stem cell transplantation. Conclusions: In this predominantly Hispanic cohort, only half of patients achieved complete response following first-line therapy, with survival outcomes comparable to contemporary reports. Normal LDH at diagnosis was associated with higher CR rates, while high/high-intermediate IPI scores and failure to achieve CR after first-line therapy were associated with inferior survival. These findings underscore the need for more effective first-line treatment strategies to improve CR rates and long-term outcomes, particularly in patients with high-risk disease.

Healthcare utilization and end-of-life care in pancreatic cancer: A single-institution cohort study.

e23206 Background: Pancreatic cancer carries high symptom burden and frequent acute care use, yet real-world utilization and end-of-life care patterns are incompletely described. Methods: We conducted a retrospective cohort study of adults with pancreatic cancer treated at the Mitchell Cancer Institute (2018–2024) under institutional review board approval. Encounters from the tumor registry, electronic health record, and billing data included emergency department visits, hospitalizations, ICU admissions, hospice enrollment, palliative care consultation, and chemotherapy within 30 days of death. Total utilization was defined as the sum of encounters across settings. Early palliative care was defined as consultation ≥90 days before death or within 60 days of metastatic diagnosis. Utilization was summarized using medians (IQR) and compared by chemotherapy receipt using the Mann–Whitney U test. Results: Among 583 patients (median age 67 years; 51% male), 297 (50.9%) received chemotherapy and 210 (36.0%) died during follow-up. Median total utilization was 20 encounters [6.5–45]. Chemotherapy receipt was associated with higher utilization (39 [21–65] vs 7 [2–18], p < 0.001). ICU admission occurred in 49 patients (8.4%). Among decedents, hospice enrollment occurred in 94 (44.8%) and early palliative care in 46 (21.9%). Chemotherapy within 30 days of death occurred in 119 (56.7%), exceeding commonly used quality benchmarks ( < 20%). Conclusions: Care was characterized by high utilization and frequent intensive treatment near the end of life. Low hospice and early palliative care use highlight opportunities for earlier supportive care integration. Findings are limited by single-institution design and reliance on registry and billing data. Healthcare utilization and end-of-life care metrics. Measure Overall (N=583) Benchmark/Notes Age, median (IQR) 67 (58–73) Baseline Male sex, n (%) 298 (51.1) Baseline Total encounters, median (IQR) 20 (6.5–45) Chemo 39 vs 7; p<0.001 ICU admission, n (%) 49 (8.4) Care intensity Chemo ≤30d of death* 119 (56.7) QOPI <20% Hospice enrollment* 94 (44.8) QOPI >50% Early palliative care* 46 (21.9) — *Among decedents (N=210).

Clinical outcomes and cumulative cost of preventive surveillance versus treatment in Li–Fraumeni syndrome: Results from the European PREVENTABLE project.

10553 Background: Li-Fraumeni syndrome (LFS), caused by TP53 pathogenic variants, is one of the most severe hereditary cancer predisposition syndromes, characterized by very early cancer onset, broad tumor spectrum, and a high lifetime risk of multiple cancers. At the European level, no large-scale health economics study has compared LFS proactive cancer preventive management including intensive multiorgan surveillance and early cancer detection, with treatment approaches initiated after the first tumor occurs in individuals at high cancer risk. To address this gap, and within the European PREVENTABLE project, we evaluated healthcare pathways and cumulative costs of proactive prevention versus treatment in LFS European families. Methods: We retrospectively collected clinical data from 866 individuals from seven European countries (ERN GENTURIS centers), including 505 TP53 gene carriers (27% of whom were children) and 361 non-carrier family members. Based on multidisciplinary expertise, we developed a structured LFS care matrix, mapping patient clinical trajectories and clinical procedures across diagnosis, risk reduction strategies, surveillance and treatments. Costs were estimated using standardized French hospital tariffs, and data were collected via a GDPR-compliant digital tool interface developed by the PREVENTABLE consortium. Results: From 866 individuals, 155 were TP53 carriers without a prior cancer diagnosis at the time of genetic testing, defining the preventive arm. During follow-up (median 75 months; range 6–267), 20 individuals developed one or more cancers.The mean prevention cost per patient was €6,046.8 (range €451–€71,854.76). Among the 273 patients with a history of cancer prior to genetic testing, 109 had early-stage disease and 164 had advanced-stage disease (median follow-up 83 months; range 2–468). The mean treatment cost per patient was €53,906 (range €385.50–€440,760.93). Overall cumulative costs were €937,258 for prevention and €15,103,188 for treatment, including €5,245,915 for early-stage cancers and €9,857,273 for advanced-stage cancers. Preventive mastectomy was performed in 24% of women in either prevention or treatment groups. Conclusions: This first European cumulative cost analysis demonstrates that treatment costs for LFS far exceed prevention costs (9-fold), providing strong economic evidence in favor of early genetic diagnosis and preventive surveillance. These findings support public health decision-making and the harmonization of care pathways within the framework of precision medicine in Europe. Preventable is funded by the European Union (EU) under Grant nº 101095483.

A randomized phase II clinical trial of a fasting-mimic diet prior to chemotherapy to evaluate the impact on toxicity and efficacy.

e12522 Background: Fasting may help reduce the toxicity of certain chemotherapy drugs but a low calorie, low protein fasting-mimicking diet (FMD) may be more feasible than prolonged fasting. We evaluated whether the FMD will reduce chemotherapy toxicity when used with neoadjuvant or adjuvant chemotherapy in breast cancer (BC) or docetaxel chemotherapy in prostate cancer (PC). Methods: Patients were randomized (1:1) to FMD (arm A) consumed 3 days prior to and 24 hours after chemotherapy for 4 cycles, or regular diet (Arm B). Eligibility: BMI > 18.5. Exclusion: Insulin treated Diabetes Mellitus. Results: 121 subjects were accrued, PC, n = 25, BC n = 96. 99 subjects received 3 or more cycles of chemotherapy. 39 of 59 subjects in FMD arm, 66% completed 3 or more cycles of the FMD, whereas 47% were compliant with 4+ cycles. 7 BC and 1 PC patients in Arm A did not submit any FMD records, so, these 8 (14%) patients were counted among those who did not use the FMD. Rate of NHST during the first four chemotherapy cycles was 39% in Arm A compared to 35% in Arm B (p = 0.35), however grade 3+ NHST was 3% in in the FMD Arm (A) compared to 10% in Arm B (p = 0.08). Grade 2+ hematologic toxicity occurred in 5% of patients in FMD Arm (A) and 10% in Arm B (p = 0.17) and grade ≥3 hematologic toxicity observed in 3% in FMD Arm versus 6% in the control Arm (p = 0.22). Grade ≥2 nausea occurred in 7% of patients in FMD Arm (A) compared with 3% in Arm B (p = 0.19), while no grade ≥2 vomiting was reported in FMD Arm (A) compared with 2% in Arm B (p = 0.17). FMD-related toxicity among BC patients included grade 2+ nausea in 6%, with no grade 3–4 events; the highest grade 2+ toxicity was fatigue (9%). Among PC patients, grade ≥2 nausea was not observed; grade 3+ toxicities included fatigue (8%) and pain in extremity (8%), and one patient experienced grade 3 memory impairment (8%). In FMD Arm A, 10% of patients required chemotherapy dose reduction or hold compared to 3% in Arm B. Changes in QOL could not be determined due to missing data. Conclusions: FMD was safe and feasible in patients receiving chemotherapy for both breast and prostate cancer, although accrual was limited in the PC cohort. While the primary toxicity endpoint was not met, grade ≥3 toxicities were lower in patients receiving the FMD. Heterogeneity of chemotherapy regimens and incomplete accrual limited power to detect the prespecified difference. Analyses of compliance and the proportion of chemotherapy cycles completed with FMD may help inform future studies. Clinical trial information: NCT01802346 .