Browse Articles

Myoepithelial carcinoma: A National Cancer Database study of demographic and socioeconomic factors.

e22590 Background: Myoepithelial carcinoma (MECA) is a rare malignant tumor arising from myoepithelial cells and documented across multiple anatomical sites, most commonly in the breast and salivary glands. Due to its low incidence, the epidemiology and clinical characteristics of MECA remain poorly understood. This study aims to use population-level datasets from the National Cancer Database (NCDB) to better characterize demographic distribution, tumor characteristics and treatment patterns for MECA. Methods: This study examined histologically-confirmed MECA cases (ICD-O-3 code - 8982) in the National Cancer Database (NCDB) from 2004–2020 (N = 336). Variables included age, sex, race, facility type, distance from facility, insurance, Hispanic status, educational attainment, Charleson-Deyo comorbidity score, survival rates, and treatment modalities. Descriptive statistical testing and regression analysis were used to assess demographic trends. Results: A gradual upward trend in the number of reported cases of MECA was observed over this study period (R² = 0.22). Women were disproportionately affected (70.5%), and the average age at diagnosis was 56.7 years. Most patients were White (82.1%) and non-Hispanic (89.3%), and the majority had a Charlson–Deyo score of 0 (78.9%). The most common primary site was the upper outer quadrant of the breast (12.5%), followed by the overlapping lesion of the breast (10.7%) and the vulva (5.4%). Nearly half were privately insured (47.0%), and 39.3% were covered by Medicare. Most patients lived in metropolitan counties (81.5%) and 40.5% were in the highest income quartile ($74,063 or more). Patients were most frequently treated at academic or research programs (39.2%) and comprehensive community cancer programs (32.2%). Many patients received surgical procedures (77.9%), followed by radiation therapy (36.6%). After surgery, 68.2% had no residual tumor, 3.3% had a microscopic residual tumor, 2.75% had an unspecified residual tumor, and 0.6% had a macroscopic residual tumor. Two-year survival was 79.4%, five-year survival was 66.5%, and ten-year survival was 52.0%. Conclusions: To our knowledge, this is the first NCDB analysis of myoepithelial carcinoma, demonstrating a clear predominance among women and identifying the upper outer quadrant of the breast as the most common primary site. This study also provides the first population-level assessment of socioeconomic factors in MECA, showing that patients most often reside in densely populated metropolitan areas and fall within the highest income quartile. These insights expand the limited epidemiologic understanding of MECA and highlight the need for further research on how demographic and socioeconomic factors influence diagnosis, treatment, and outcomes.

Association of pre-existing chronic kidney disease with in-hospital mortality and resource utilization among U.S. solid tumor hospitalizations: A National Inpatient Sample analysis, 2018–2022.

e23166 Background: Chronic kidney disease (CKD) is prevalent among patients with cancer and may adversely influence inpatient outcomes through baseline physiologic vulnerability and constraints on diagnostic and therapeutic management. Nationally representative estimates describing the inpatient impact of CKD among hospitalizations primarily for solid tumors remain limited. Methods: A retrospective, hospitalization-level cohort study was conducted using the Healthcare Cost and Utilization Project National Inpatient Sample (NIS), 2018–2022. Adult hospitalizations with a principal diagnosis of solid tumor malignancy were identified using ICD-10-CM diagnosis codes, excluding hematologic malignancies. Pre-existing CKD was defined by ICD-10-CM code N18* in any diagnosis position, including end-stage renal disease (ESRD; N18.6). Acute kidney injury (AKI; N17*) was assessed in sensitivity analyses. Survey-weighted analyses incorporated NIS discharge weights, hospital clustering, and stratification to generate nationally representative estimates. Outcomes included in-hospital mortality, length of stay (LOS), and total hospitalization charges as a proxy for inpatient resource utilization. Multivariable survey-weighted logistic regression adjusted for age, sex, race, median household income quartile, and primary payer. Results: An estimated 4,298,089 hospitalizations with a principal diagnosis of solid tumor malignancy were identified (95% CI 4,197,740–4,398,438). CKD was present in 11.84% of hospitalizations (95% CI 11.71%–11.97%), including ESRD in 0.98% (95% CI 0.95%–1.00%). In-hospital mortality was higher among hospitalizations with CKD compared with those without CKD (5.41% [95% CI 5.24%–5.58%] vs 3.88% [95% CI 3.76%–4.01%]; absolute difference 1.52%). Hospitalizations with CKD had longer mean LOS (7.14 vs 6.00 days) and higher mean charges ($103,602 vs $98,613). In sensitivity analyses excluding AKI, mortality remained higher among hospitalizations with CKD (3.07% vs 2.75%). After multivariable adjustment, CKD remained independently associated with increased in-hospital mortality (adjusted odds ratio 1.25, 95% CI 1.20–1.30; p < 0.001). Conclusions: In a nationally representative sample of U.S. hospitalizations primarily for solid tumors, pre-existing CKD was common and independently associated with higher in-hospital mortality and increased inpatient resource utilization, with persistence of mortality differences after exclusion of AKI. These findings underscore CKD as an important baseline risk marker in hospitalized oncology populations and highlight the need for kidney-adaptive, system-level inpatient care strategies.

Trastuzumab-deruxtecan for the management of leptomeningeal metastases from breast cancer.

e14033 Background: Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with an antibody drug conjugate such as trastuzumab-deruxtecan (T-DXd) may be beneficial in patients with leptomeningeal metastases (LM), with limited real-world data. Methods: We performed a retrospective review at the University of Texas MD Anderson Cancer Center for patients with LM and breast cancer in the past 5 years and found a total of 133 patients. We selected only cytology proven LM (33 patients) and then analyzed the patients that were treated with T-DXd after their LM diagnosis was made. Results: We analyzed 16 patients, all females. Median age of 49 years at LM diagnosis, with 50% white, and 93.8% non-Hispanic. Invasive ductal carcinoma was the histology in 68.8% of patients with 31.3% of invasive lobular carcinoma. All patients had brain metastases. Estrogen receptor (ER) was positive in 75% of patients, progesterone receptor (PR) was positive in 56.3%, HER2 was positive in 31.3%, and HER2 was low in 68.8%. Prior to receiving T-DXd 37.5% had received chemotherapy, and 25% had received endocrine therapy. LM directed therapy included whole brain radiation (43.8%), local radiation (37.5%), proton craniospinal radiation (18.8%), and intrathecal (IT) chemotherapy (18.8%). IT chemotherapy included topotecan with trastuzumab, cytarabine with trastuzumab, and topotecan alone. Response rate at first neuroaxis MRI after starting T-DXd was 66% (10 patients, two with complete response and 8 with partial response). Six patients were still on T-DXd at the time of our analysis, and 9 patients had died. Median time on T-DXd was 6.8 months (IQR: 2.7-12.0 months). Median time to LM diagnosis was 46.5 months (IQR 24.6-124.0 months). Eleven patients survived more than 6 months after LM diagnosis, and 8 over 12 months. Conclusions: Survival after LM diagnosis is increasing with novel therapy and our findings highlight the role of T-DXd even in the setting of low HER2. Our findings provide a single center experience in using trastuzumab-deruxtecan for LM in breast cancer patients.

Redefining lung cancer screening eligibility: Smoking duration vs. pack-years in a national VA cohort of nearly 1 million patients.

8004 Background: Lung cancer is the leading cause of cancer death in the US, yet current lung cancer screening (LCS) criteria based on tobacco pack-years (TPY) miss nearly half of all cases and are difficult to capture reliably in clinical practice. Tobacco smoking duration (TSD) is a simpler, more consistently measurable metric that may better identify high-risk individuals. We evaluated whether TSD improves lung cancer risk prediction compared with TPY in a unique real-world cohort of nearly 1 million patients. Methods: We conducted a retrospective cohort study of Veterans aged 50–80 in the Veterans Health Administration. The primary exposure was smoking history quantified as TPY and TSD; the primary outcome was 5-year lung cancer incidence (2021-2025). We compared risk-adjusted 5-year lung cancer incidence based on 2013 USPSTF guidelines (≥30 TPY, quit within 15 years), revised 2021 USPSTF guidelines (≥20 TPY, quit within 15 years), our proposed TSD criteria (≥20 TSD), and never-smoking. We further estimated the impact of switching to TSD-based eligibility on the theoretical number of missed lung cancer diagnoses (i.e., the proportion of lung cancers diagnosed in screening-ineligible individuals) and performed subgroup analyses across race and sex. Results: A total of 960,770 Veterans were included in the study, with 340,312 (35.4%) currently smoking, 304,589 (31.7%) formerly smoking, and 315,869 (32.9%) never smoking. The median (SD) age was 64.9 (9.6) years old. Most participants were male (n=876,215, 91.2%) and of white race (n=677,823, 70.6%). 341,061 (35.5%) qualified for 2013 TPY criteria, 437,803 (45.6%) qualified for 2021 TPY criteria, and 571,087 (59.4%) qualified for TSD criteria. Importantly, 127,604 (22.3%) individuals who met TSD criteria did not meet 2021 TPY criteria, suggesting that TSD criteria would increase the eligible screening population by 28.8%. The 5-year incidence of lung cancer was 0.95% (1.87% among 2013 TPY criteria; 1.73% among 2021 TPY criteria; 1.48% among TSD criteria; and 0.13% among never-smoking). The proportion of missed lung cancer diagnoses was 30.3% among 2013 TPY criteria, 17.1% among 2021 TPY criteria, and 7.5% among TSD criteria. Finally, eligibility was higher for TSD vs. TPY criteria in various subgroups, including among black individuals (percent of current or former smokers eligible for screening: 34.7% 2013 TPY; 54.0% 2021 TPY; and 83.7% TSD) and females (38.5% 2013 TPY; 55.1% 2021 TPY; and 83.7% TSD). Conclusions: In this nationwide VA cohort consisting of nearly 1 million Veterans, smoking duration performed at least as well as TPY in predicting lung cancer risk and substantially expanded screening eligibility with fewer missed cancers. TSD criteria were also associated with improved equity. These findings support revisiting national lung cancer screening guidelines to prioritize smoking duration over pack-years.

Characterizing the immune effects of enfortumab vedotin and pembrolizumab (EV+P) on peripheral blood mononuclear cells (PBMCs) in metastatic urothelial cancer patients (mUC).

4571 Background: Enfortumab vedotin improves response and outcomes over chemotherapy in mUC, with further benefit when combined with pembrolizumab. Although EV alone has limited immune-activating effects, we hypothesize that the combination of EV+P modulates peripheral T-cell activation states and correlates with clinical response. Methods: We conducted a retrospective analysis of mUC patients treated with EV+P at Memorial Sloan Kettering Cancer Center. PBMCs were isolated from patients on C1D1 and C2D1 of EV+P (n=33) and analyzed with a 32-color spectral flow cytometry panel. Immune subsets were compared between responders (complete [CR] or partial response [PR]) and non-responders (stable [SD] or progressive disease [PD]) using Wilcoxon rank sum test. Response was determined by a radiologist’s assessment of the best-overall response on EV+P according to RECIST v1.1. Results: Among 33 patients, median age was 71 years and 48% were male. 12.1% (4/33) received prior platinum chemotherapy and 18.1% (6/33) received prior PD-1/PD-L1 immunotherapy. The objective response rate was 67% (CR=10; PR=12); eight patients had SD and three had PD. At C1D1, CD8+ T cell frequencies did not differ by response. At C2D1 however, circulating CD8+ T cells were significantly higher in non-responders (p < 0.05). From baseline to C2D1, CD8+ T cells showed increased expression of CTLA4+ (p < 0.0001), Ki67+ (p < 0.01) and HLA-DR+ (p < 0.01), with higher expression of each marker at C2D1 significantly correlated with response (all p < 0.05, Table 1). At C2D1, CD4+ effector T cells showed increased expression of Ki67+ and HLA-DR+ (both p < 0.05), both significantly higher in responders (both p < 0.05). CD4+ regulatory T cells showed increased CTLA4+ (p < 0.001), Ki67+ (p < 0.01) and HLA-DR+ (p < 0.01) expression from C1D1 to C2D1, with significantly higher expression in responders (CTLA4+ p < 0.05, Ki67+ p < 0.0001, HLA-DR+ p < 0.001). Across all T cell subtypes, PD1+ expression significantly decreased (p < 0.05) from C1D1 to C2D1, but this decrease did not correlate with response. The frequencies of circulating memory CD8+ and CD4+ T cells did not change on treatment or correlate with response at either timepoint. Conclusions: EV+P induces early peripheral T cell activation in mUC, with increased expression of activation and proliferative markers in responders at C2D1. Ongoing studies are investigating correlation between TCR specificity, immune activation and responses to EV+P. Peripheral CD8+ T cell frequencies (median) at C1D1 and C2D1 from mUC patients on EV+P. CD8+ T Cell C1D1 C2D1 p-value C2D1 in Responders C2D1 in Non-Responders p-value CD8+ (%CD45+) 8.54 7.8 0.6 7.27 13.8 0.03 CTLA4+ (%CD8+) 1.15 3.94 0.0001 4.57 2.85 0.02 Ki67+ (%CD8+) 3.18 6.27 0.005 7.26 5.4 0.04 HLA-DR+ (%CD8+) 4.66 9.37 0.004 10.22 4.13 0.04 PD-1+ (%CD8+) 45.6 29.8 0.0005 28.7 31.5 0.48

Multi-omics and pan-cancer analysis revealed common molecular signatures to disclose multitargeted anticancer agents through network pharmacology approach

Cancer is characterized as a multifactorial disease due to their complex genetic and molecular mechanisms that often converge across tissue types. Shared oncogenic pathways can help us understand these functions and discover broad-spectrum therapeutics. Earlier, most studies focused on finding specific drivers for individual cancer types. However, researchers are now more interested in identifying common molecular patterns across different cancers and developing therapies that can target multiple pathways at once. This study aimed to understand the common oncogenic pathways between breast, ovarian and colorectal (BOC) cancers and identify possible multitargeted therapeutic drug molecules. To identify the common differentially expressed genes (DEGs), we analyzed three transcriptomic datasets and found a total of 128 DEGs. The protein-protein interaction (PPI) network study reveals the top-ranked, most significant hub targets, AURKA, CDK1 and CCNB1, as drug targets. Enrichment analysis with GO and KEGG pathways, as well as regulatory network (TFs and mRNAs) analysis, revealed common pathogenetic processes among BOC cancers. The AMG-900 exhibits the highest binding affinity scores of −10.8, −9.40, and −9.7 kcal/mol with the target proteins AURKA, CCNB1, and CDK1, respectively. The stability and structural flexibility of the selected protein-ligand complexes were validated by a large-scale (500 ns) molecular dynamics and MM-GBSA analyses, and the results indicate stable interactions for AURKA and CCNB1, while CDK1 showed comparatively reduced stability. The pharmacokinetic analysis revealed favorable drug-likeness and a manageable toxicity profile typical of anticancer agents. Therefore, the findings of this study propose that AMG-900 may serve as a promising multi-targeted candidate for further investigation in multi-target therapeutic strategies within precision oncology. Furthermore, these results require additional experimental (in vivo and in vitro) and clinical validation to confirm the potentiality and efficiency of this (AMG-900) lead compound.

A Bifunctional Descriptor Inspired by Electron‐Donating Ability for Regulating Dendrite Growth and Parasitic Reactions in Zinc‐Ion Batteries

ABSTRACT Aqueous zinc‐ion batteries (AZIBs) are promising alternatives to lithium‐based systems but are limited by dendritic growth and parasitic reactions at the Zn anode. Here, we introduce a bifunctional physicochemical descriptor ( Φ ) that evaluates hydrogen‐bond network strength in the electrolyte and interfacial adsorption strength at the electrolyte/electrode interface, capturing the respective tendencies of parasitic reaction and dendritic formation. This descriptor enables mechanism‐informed screening of amino acid additives and identifies l ‐tyrosine as an effective regulator. Multiscale characterizations show that trace l ‐tyrosine (1 mM) suppresses hydrogen evolution by restructuring the hydrogen‐bond network and promotes Zn(002)‐oriented deposition via interfacial adsorption. As a result, Zn||Zn symmetric cells exhibit prolonged stability, exceeding 4500 h at 1 mA cm −2 and over 12 000 cycles at 10 mA cm −2 , while MnO 2 ||Zn full cells retain 95.66% capacity after 500 cycles at 1 A g −1 . This work establishes a descriptor‐based framework for regulating dendrite growth and parasitic reactions and provides a rational strategy for electrolyte additive design in aqueous metal batteries.

Cytotoxicity assessment of propolis nanoparticles encapsulated in sodium alginate in the Vero cell line

Adoption of circular agricultural practices among small-scale farmers

Arylsulfatase L is a Golgi chondroitin sulfatase regulating skeletal development

Association of RNA-based immune gene expression with immunotherapy duration in advanced non–small cell lung cancer.

e20538 Background: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is commonly used to guide immunotherapy selection in advanced non–small cell lung cancer (NSCLC); however, its ability to consistently reflect tumor immune biology and treatment benefit remains limited. RNA-based immune gene expression profiling provides a complementary approach to characterize the tumor immune microenvironment using formalin-fixed paraffin-embedded specimens. We evaluated associations between RNA-based immune gene expression and duration of immunotherapy (IO) in advanced NSCLC. Methods: This retrospective biomarker study included patients with stage IV, non– EGFR , non– ALK NSCLC treated with immune checkpoint inhibitors. Tumor RNA expression profiling was performed using a multiplex, amplification-free gene expression assay quantifying 204 genes. Gene expression was analyzed as categorical variables (high expression defined as log 2 ≥1) and as continuous measures. The primary endpoint was duration of IO, defined as time from initiation of IO until progression of disease as documented by treating physician, initiation of alternative therapy, or death. Overall survival (OS) was evaluated as an exploratory secondary endpoint. Associations were assessed using univariate duration analyses, Kaplan–Meier methods, and Cox proportional hazards models. All tests were two-sided, and p<0.05 was considered significant. Analyses were exploratory and hypothesis-generating. Results: Sixty-one patients were included. Median duration of IO was 108 days (range, 7–2006). PD-L1 IHC categories (<1%, 1–49%, ≥50%) were not associated with IO duration (log-rank p=0.538). In contrast, multiple RNA-based tumor immune gene expression markers were significantly associated with duration of IO in Cox models (Table). Higher dichotomized (categorical) expressions of CDK6 , ERBB3 , MDM2 , PCSK9 , and STK11 were associated with shorter IO duration, whereas STK11 mutation status was not associated with IO duration. Of these genes, high CDK6 and PCSK9 expressions were also associated with worse OS. Conclusions: RNA expression profiling identified multiple biomarkers associated with IO duration and, for select genes, OS that were not captured by PD-L1 IHC or DNA-based mutation status. These findings suggest RNA-based assays may provide complementary biologic correlates of IO benefit in advanced NSCLC and warrant prospective validation. RNA Biomarker IO duration Hazard Ratio HR (95% CI) p Value OS HR p Value CDK6 3.25 (1.24-8.50) 0.017 28.86 (7.31-114.02) <0.001 ERBB3 2.19 (1.12-4.27) 0.022 0.70 (0.27-1.83) 0.767 MDM2 2.10 (1.08-4.08) 0.030 1.78 (0.79-4.01) 0.166 PCSK9 2.67 (1.16-6.13 0.021 3.64 (1.44-9.16) 0.006 STK11 2.57 (1.08 -6.12) 0.033 1.16 (0.40-3.33) 0.787

Timeliness of care and outcomes in thymic epithelial tumors: A single-center real-world cohort in Colombia (2015–2025).

e20175 Background: Thymic epithelial tumors (TETs) are rare malignancies, and real-world evidence from Latin America remains limited. We aimed to benchmark diagnostic and treatment intervals using United Kingdom National Health Service (NHS) waiting-time targets as operational analogs and to describe survival outcomes. Methods: Adult patients with pathologically confirmed TET diagnosed between 2015 and 2025 were included. Care intervals from first suspicious imaging to pathologic confirmation, treatment initiation, and surgery were evaluated using NHS-derived benchmarks (≤60 days), with an exploratory confirmation-to-systemic therapy target of ≤30 days. Overall survival (OS) and event-free survival (EFS) were estimated using Kaplan–Meier methods and stratified by histologic subtype. Results: The study population comprised 35 patients and was predominantly female (74.3%), with a median age of 58.4 years. Thymoma accounted for 80.0% of cases, while 11.4% had thymic carcinoma. 77.1% of patients were classified as Masaoka–Koga stages I–II. Surgical resection was performed in 31 patients (88.6%), achieving R0 margins in 93.5%. Thirty-day postoperative complications occurred in 9.7%, and there was no 30-day mortality. Median imaging-to-confirmation, imaging-to-treatment, and imaging-to-surgery intervals were 38 (IQR 14.5–97.5), 50 (IQR 15.5–89.5), and 38 (IQR 15–74) days, respectively. Median confirmation-to-systemic therapy time was 8 days (IQR 0–11). Overall survival was favorable, with a 5-year OS rate of 66%. Event-free survival declined over time, and differed significantly by histologic subtype (log-rank p < 0.001), with durable disease control in thymoma (1-, 3-, and 5-year EFS: 100%, 92%, and 74%). Conclusions: In this real-world cohort of patients with TET, care delivery met international benchmarks, with high complete resection rates, low perioperative morbidity, and no 30-day mortality. Survival outcomes were consistent with established histologic prognostic differences. These findings provide valuable real-world survival data for rare thoracic malignancies in Latin America and address a critical gap in regional evidence. Baseline characteristics, diagnostic features, and treatment patterns of patients with thymic epithelial tumors. Baseline characteristics, n=35 Age, median (IQR) 58.4 (54.67-68.29) Female, n (%) 26 (74.3%) Diagnosis Thymoma 28 (80.0%) Thymic carcinoma 4 (11.4%) Masaoka-Koga stage I–II 27 (77.1%) Care timeliness  Imaging-to-treatment, days, median (IQR) 50 (15.5–89.5) Imaging-to-surgery, days, median (IQR) 38 (15–74)

<i>TP53</i> variant allele frequency as a driver of survival in <i>TP53</i> -mutated acute myeloid leukemia.

e18508 Background: TP53 -mutated AML represents a challenging subtype with only 10-15% of patients achieving long-term survival. Determinants that best predict disease behavior remain incompletely defined. Methods: We conducted a retrospective cohort study of adults with TP53- mutated AML treated at the University of Kentucky from 2016-2025. TP53 alterations were characterized by number of mutations, allelic status, mutation type, hotspot status, and maximum variant allele frequency (VAF). TP53 maximum VAF was assessed as both continuous and categorical variables. Primary endpoints were CR/CRi (per ELN), RFS, and OS. Survival was analyzed using Kaplan-Meier, and associations were tested using Cox models. Results: Sixty-five patients with TP53 -mutated AML were identified, with median age of 64 years. 69% were male, 28% had prior MDS, and 23% had therapy-related AML. Complex karyotype was present in 89%, most commonly involving 5q (83%), 7q (68%), and 17p (63%). Co-occurring pathogenic mutations were uncommon: 52% lacking additional pathogenic variants, while 15% had IDH1/2 and 11% had DNMT3A mutations. TP53 alterations were predominantly multi-hit (81%), with 72% of patients harboring a single mutation, while 25% had two or more. Mutations types included missense-only (77%), hotspot missense (24%), and truncating variants (15%). Induction therapy was HMA/venetoclax in 45% and intensive chemotherapy for 31%. Among treated patients, the overall CR/CRi rate was 37%. Median OS of the entire sample was 6.0 months. HMA/venetoclax was associated with a significantly higher likelihood of achieving CR/CRi compared with intensive induction chemotherapy (63% vs. 11%, p=0.002), although RFS did not differ among responders. Achievement of CR/CRi was similar between those with TP53 VAF &lt;40% and ≥40% (42% vs. 33%, p=0.7) Factors independently associated with inferior OS included deletion 5q (HR 2.57, p=0.038), TP53 VAF ≥40% (HR 2.71, p=0.002), and increasing age (HR 1.38 per 10 years, p=0.016). Median OS for TP53 VAF &lt;40% was 12.8 months and 4.5 months for TP53 VAF ≥40%. After adjusting for age and allogeneic HSCT in multivariable analysis, TP53 VAF ≥40% remained independently associated with inferior OS (HR 2.50, p=0.006). Continuous modeling of TP53 VAF showed a dose-dependent relationship with OS. In contrast, type of TP53 mutation (truncating, splice-site, missense-only, or hotspot), allelic status, and number of TP53 mutations were not associated with response, RFS, or OS. Conclusions: These findings highlight substantial biological heterogeneity within TP53 -mutated AML. TP53 allelic burden, rather than mutation class, represents a strong prognostic indicator. &lt;40% (n 28) ≥40% (n 34) p-value Age (months) 66 (63-69) 63 (58 - 73) 0.3 Prior MDS % 36 21 0.3 tAML % 29 21 0.6 TP53 % Multihit 73 88 0.12 Muts - 1, ≥2 75, 25 74, 26 Truncating 15 15 Splice 11 6 Missense Only 75 79 Hotspot 30 18 Induction % &gt;0.9 HMA/Ven 46 44 Intensive 32 30

Neoadjuvant toripalimab combined with inetetamab, pertuzumab, and nab-paclitaxel in HER2-positive breast cancer (TORCH): A phase II trial.

e12658 Background: Incorporating immunotherapy into neoadjuvant therapy for HER2-positive breast cancer (BC) is an area of active investigation. Inetetamab is an engineered anti-HER2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). This phase II study evaluated the PD-1 inhibitor toripalimab combined with inetetamab, pertuzumab, and nab-paclitaxel in early or locally advanced HER2-positive BC. Methods: This single-center, single-arm study used a Simon's two-stage minimax design. Eligible patients received 6 cycles of neoadjuvant therapy: toripalimab 240 mg; inetetamab (8 mg/kg load, then 6 mg/kg); pertuzumab (840 mg load, then 420 mg); and nab-paclitaxel 125 mg/m² (days 1 and 8) — all Q3W, followed by surgery. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). With a historical tpCR rate of 45.5% and an expected rate of 65% (α = 0.05, β = 0.2), the design required 18 evaluable patients in stage I. If &gt; 8 achieved tpCR, the study would proceed to stage II (total N = 42). The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2500109920). Results: As of January 2026, 18 patients were evaluable at the stage I analysis, with a median follow-up duration of 5.9 months (95% confidence interval [CI]: 4.7-7.2). The objective response rate was 94.4% (17/18). Among 15 patients who underwent surgery, the tpCR rate was 66.7% (10/15) and breast pCR rate was 73.3% (11/15). No event-free survival (EFS) events or deaths were observed. Grade 3/4 treatment-related adverse events occurred in 6 patients (33.3%): neutropenia (n = 4), leukopenia (n = 3), elevated aspartate aminotransferase and (or) alanine aminotransferase (AST/ALT) (n = 3), and diarrhea (n = 1). Toripalimab was discontinued/postponed in 4 patients (22.2%) due to elevated AST/ALT (n = 3) or rash (n = 1). Conclusions: The combination of toripalimab, dual anti-HER2 blockade (inetetamab/pertuzumab), and nab-paclitaxel showed promising efficacy and manageable toxicity in the neoadjuvant setting for HER2-positive BC. These findings support further evaluation in randomized trials. Clinical trial information: No. ChiCTR2500109920.

Germline HLA class II diversity as a predictor of survival selectively in MHC-silenced gliomas.

2082 Background: CD4⁺ T cell help is central to durable anti-tumour immunity and predicts response to neoantigen vaccination. Antigen presentation to CD4⁺ T cells is governed by HLA class II molecules, yet the class II landscape in glioma remains poorly defined. Germline HLA diversity can influence immunity only if tumours retain antigen-presentation capacity. We hypothesised that the prognostic impact of HLA class II heterozygosity in glioma is conditional on tumour MHC-II expression. Methods: We performed germline HLA class II typing (DRB1, DQB1, DPB1) in 893 TCGA gliomas (388 glioblastoma, 505 lower-grade glioma) using a weighted consensus of four algorithms (HLA-HD, hla-genotyper, SOAP-HLA, Kourami). Tumour MHC-II expression was quantified using a nine-gene antigen-presentation signature. The primary analysis tested the interaction between germline heterozygosity and tumour MHC-II status on overall survival using multivariable Cox regression. Allele-level survival analyses were exploratory. Results: Gliomas showed extensive class II polymorphism (54 DRB1, 28 DQB1, 47 DPB1 alleles), with 35.9% of patients homozygous at one or more loci. The most frequent alleles were DRB107:01 (12.7%), DQB103:01 (20.7%), and DPB1*04:01 (38.7%). Germline heterozygosity was not prognostic in unstratified analyses (HR 1.04, 95% CI 0.83–1.32, p = 0.72). However, a significant interaction with tumour MHC-II expression was observed (p-interaction = 0.044). In MHC-II–low tumours, germline heterozygosity independently predicted improved survival (HR 0.71, 95% CI 0.52–0.97, p = 0.031), whereas no effect was seen in MHC-II–high tumours (p = 0.89). Tumour MHC-II expression itself was independently prognostic (p = 0.004). Exploratory allele-level analysis identified DRB1*03:01 (10.2%) as nominally associated with worse survival (median 23.7 vs 34.9 months, uncorrected p = 0.041). Conclusions: Germline HLA class II diversity influences survival in glioma only when tumour antigen presentation is impaired. Combined tumour MHC-II loss and limited germline diversity identify a biologically and clinically high-risk group with compounded antigen-presentation deficits. These findings have direct implications for neoantigen vaccine design and patient stratification, suggesting that restoration of antigen presentation may be required prior to immunotherapy in selected patients. The adverse association with DRB1*03:01 merits mechanistic investigation. Independent validation in 322 glioblastoma patients is ongoing.

Comprehensive clinical analysis of cervical clear cell adenocarcinoma: A real-world multicenter study.

e17525 Background: Cervical clear cell adenocarcinoma (CCAC) is a rare and aggressive malignancy for which evidence-based management strategies are lacking. This study aimed to characterize the real-world clinicopathological features, treatment patterns, and outcomes of patients with CCAC. Methods: We retrospectively analyzed clinical data from 553 patients diagnosed with CCAC between 1993 and 2024 across 26 tertiary hospitals in China. Clinicopathological features, therapeutic approaches, and survival outcomes were assessed. Patients were categorized according to the 2018 FIGO staging system into early-stage (IA1–IB2, IIA1), locally advanced (IB3, IIA2–IIB), lymph node metastasis (IIIC), and advanced-stage disease (IIIA, IIIB, and IV). The primary outcome was overall survival (OS) at 5 years. Treatment outcomes and prognostic factors were assessed using Kaplan-Meier curves and Cox-regression models. Results: A total of 553 patients were included, with a median age of 50 years (IQR, 39–58). Patients were often diagnosed at an early-stage (54.4%), with 5-year OS rates exceeding 90% and declining progressively with stage. Surgery was identified as an independent favorable prognostic factor (HR 0.34 [95% CI 0.12-0.95]). Among patients with early-stage disease, low-risk patients achieved favorable outcomes with surgery alone, whereas intermediate-risk patients demonstrated improved OS with adjuvant chemotherapy. In non–early-stage disease, combined treatment with surgery and radiotherapy was associated with the best survival outcomes in locally advanced and node-positive subgroups. Vaginal bleeding was the most common presenting symptom (83.9%). Regarding initial diagnostic evaluation, imaging showed the highest abnormality detection rate (82.2%), outperforming cytology (54.8%) and human papillomavirus (HPV) testing (17.9%). Conclusions: This study provides an up-to-date overview of CCAC, highlighting that surgery plays a central role in its management and the importance of individualized adjuvant therapies. In early-stage disease, surgery alone is appropriate for low-risk patients, whereas adjuvant chemotherapy may be considered for those at intermediate risk. In non–early-stage disease, incorporating surgery into multimodal treatment with (chemo)radiotherapy is associated with superior survival compared with non-surgical or surgery-alone approaches. The low detection rates of HPV and cytology testing underscore the limitations of standard cervical screening in CCAC and emphasize the critical role of clinical evaluation and imaging in symptomatic patients.

Time from diagnosis to treatment in multiple myeloma: A systematic review and meta-analysis.

e19539 Background: While delays in systemic therapy initiation adversely impact survival in various malignancies, the magnitude and clinical significance of the diagnosis-to-treatment interval in newly diagnosed multiple myeloma (NDMM) remain poorly characterized. This systematic review synthesizes global evidence on time to first treatment (TTFT) and its association with patient demographics and clinical outcomes in NDMM. Methods: A systematic search was designed and executed by a medical librarian across OVID MEDLINE, CINAHL, Scopus, and Cochrane databases through December 31, 2025. Eligible studies included cohort, registry, or observational designs reporting median TTFT in adults (≥ 18 years) with NDMM; smoldering myeloma was excluded. Following PRISMA 2020 guidelines, title/abstract screening and full-text review were performed. The primary outcome was the weighted pooled median TTFT. Pearson’s correlation coefficient (r) evaluated the relationship between study midpoint and TTFT, and Cohen’s d determined the effect size of differences between data sources. Risk of bias was assessed using the Aarhus Checklist. The study protocol was registered in PROSPERO (CRD420261290973). Results: From 4,878 initial records, 11 studies (119,626 patients) across six countries met the inclusion criteria and were analyzed. Most studies were US-based (n=8; 72%) and many utilized real-world EHR datasets (n=6; 55%), while the remainder utilized registry data (n=5; 45%). Frequently analyzed variables included age/sex (91%), geography (82%), and socioeconomic status (72%); fewer assessed comorbidities (55%), disease stage (36%), survival (36%), or high-risk cytogenetics (19%). The overall weighted pooled median TTFT was 55.9 days. A significant negative correlation was observed between study midpoint year and TTFT (r = −0.45, p = 0.04), indicating improving efficiency over two decades. However, registry-based cohorts demonstrated significantly longer TTFT compared to EHR cohorts (mean difference: 64.73 days; p = 0.0199; Cohen’s d = 1.43). Conclusions: This review identifies a global weighted pooled median TTFT of 55.9 days in NDMM. While systemic efficiency has improved (r=−0.45), the profound discrepancy between data sources (d=1.43) suggests that registry-based benchmarks may inaccurately reflect clinical reality. These findings challenge the reliance on large-scale abstracted databases for quality-of-care assessments. Furthermore, the lack of data on high-risk cytogenetics and survival outcomes represents a critical knowledge gap. Prospective studies are urgently required to establish evidence-based TTFT benchmarks that correlate treatment intervals with clinical outcomes and ensure equitable access.

Global development and validation of the Lung Cancer Prevention Score (LCPS): A quantitative framework linking policy strength, incidence, and outcomes across 40 countries.

10518 Background: Lung cancer is the leading cause of cancer worldwide. Despite advances in tobacco control, national prevention efforts remain fragmented. We developed and validated the Lung Cancer Prevention Score (LCPS), a 0–100 composite linking prevention policy strength with real-world outcomes for global benchmarking and equity tracking. Methods: Two LCPS models were created. Policy LCPS quantified 12 weighted domains: smoke-free laws, TAPS bans, ≥50% pictorial warnings, ≥75% excise tax, plain packaging, legal-age limits, e-cigarette control, LDCT screening, asbestos ban, radon plan, clean-cooking access, and occupational carcinogen controls. Data-Driven LCPS combined age-standardized incidence (ASIR), mortality (ASMR), mortality-to-incidence ratio (MIR), smoking prevalence, GDP, health expenditure, and HDI (normalized 0–1; higher = stronger prevention). Data from GLOBOCAN 2022, WHO GTCR 2023, World Bank, and UNDP HDR 2023 covered 40 countries (G20 + 20 others). Analyses included correlation, regression (adjusted for GDP, HDI), Bland–Altman agreement, and ROC AUC for MIR ≤0.60. Results: Among 32 complete datasets, Policy and Data-Driven LCPS correlated moderately (r = 0.31; 95% CI –0.04–0.60). Discrimination of favorable outcomes (MIR ≤0.60) showed AUC 0.68 vs 0.77. High-policy countries (≥75) had lower smoking (17%) and MIR (0.45) than those &lt;60 (27%, 0.65; p &lt;0.001). Policy LCPS inversely correlated with ASIR (r = –0.42; p = 0.004); Data-Driven LCPS showed a stronger link (r = –0.55; p &lt;0.001). Each 10-point LCPS-D increase predicted 2.4 fewer cases per 100 000 (β = –0.24 ± 0.07; p = 0.002). Results were consistent across income tiers. Conclusions: LCPS provides a validated, reproducible framework connecting prevention policy to measurable cancer burden. Data-Driven LCPS reflected performance most accurately, while Policy LCPS defined actionable tiers linked to lower smoking, incidence, and MIR. LCPS serves as a quantitative global benchmark for policy evaluation. Policy-driven lung cancer prevention score (LCPS-P) and data-driven lung cancer prevention score (LCPS-D): Domains and scoring weights. Component Type Wt Rule / Effect Smoke-free law P 1 Yes = 1 TAPS ban P 1 Yes = 1; Partial = 0.5 Pictorial ≥ 50 % P 1 Yes = 1 Excise ≥ 75 % P 1 Yes = 1 Plain pack P 0.5 Yes = 1 Legal age P 0.5 18–19 = 0.5; ≥ 21 = 1 E-cig reg P 0.5 Full/Prescr = 1; None = 0 LDCT screen P 2 Nat = 1; Reg = 0.5 Asbestos ban P 1 Yes = 1 Radon plan P 1 Yes = 1 Clean-cook &gt; 90 % P 1 Yes = 1 Occ carcinogen ctrl P 1.5 Yes = 1 ASIR D 1 Lower = better (1–scaled ASIR) ASMR D 1 Lower = better (1–scaled ASMR) MIR D 1 Lower = better (1–scaled MIR) Smoking prev D 1 Lower = better GDP D 0.5 Higher = better Health exp D 0.75 Higher = better HDI D 0.5 Higher = better Scoring — — Policy LCPS = Σ (weight×value)/12×100; Data LCPS = Σ (weighted norm)/Σ weights×100

Time to treatment initiation (TTI) and survival outcomes in metastatic extrapulmonary neuroendocrine carcinoma (EP-NEC).

e16323 Background: Advanced EP-NEC are typically treated with the combination of platinum plus etoposide. Despite therapy, outcomes remain poor, with reported median overall survival (OS) of 12-13 months. Early initiation of systemic therapy is commonly practiced given the aggressiveness; however, recent data from small cell lung carcinoma (SCLC) suggest that shorter TTI does not necessarily improve OS. The impact of TTI on outcomes in EP-NEC has not been well studied. Methods: We conducted a multicenter retrospective cohort study across three Mayo Clinic sites including adults with biopsy-confirmed stage IV EP-NEC diagnosed between 2005 and 2025. TTI was defined as days from pathologic diagnosis to initiation of first-line systemic therapy. A binary cutoff (≤14 vs &gt; 14 days) was determined using receiver operating characteristic (ROC) analysis, and TTI was also analyzed as a continuous variable. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method and evaluated using Cox proportional hazards models. Multivariable analyses adjusted for age, sex, ECOG performance status, presence of liver metastases, and first-line treatment strategy (chemotherapy alone vs chemotherapy plus immunotherapy). Results: Among 248 pts, median age was 61 years. Median OS for the cohort was 13.9 months (95% CI, 11.7–16.7), and median PFS was 5.7 months (95% CI, 5.3–6.3). Pts with TTI &gt; 14 days had longer median OS compared with those treated within ≤14 days (16.4 vs 10.1 months), with improved OS on unadjusted analysis (HR 0.69, 95% CI 0.50–0.96; p = 0.028), though this association was not statistically significant after multivariable adjustment (HR 0.74, 95% CI 0.53–1.05; p = 0.097). Pts with TTI &gt; 14 days also had longer median PFS compared with ≤14 days (6.5 vs 4.8 months), with improved PFS on unadjusted analysis (HR 0.67, 95% CI 0.51–0.88; p = 0.0038). On multivariable analysis, TTI &gt; 14 days remained independently associated with improved PFS (HR 0.75, 95% CI 0.56–1.00; p = 0.047). However, when analyzed as a continuous variable, TTI was not independently associated with OS (HR 0.99, 95% CI 0.98–1.00; p = 0.173) or PFS (HR 0.99, 95% CI 0.98–1.00; p = 0.089). Conclusions: In this multicenter cohort of pts with metastatic EP-NEC, earlier initiation of systemic therapy (≤14 days) was not associated with improved overall survival, and longer time-to-treatment was independently associated with improved PFS. However, when TTI was analyzed as a continuous variable, no statistically significant associations were observed, suggesting that the observed benefit with delayed treatment may reflect pt selection or clinical context rather than a direct biological effect. These findings may provide reassurance in scenarios where short delays are necessary—for biomarker testing or clinical trial enrollment—and highlight the need for further investigation in the era of precision oncology.

Identifying sex-specific symptom-based predictors of lung cancer risk using explainable machine learning.

e22575 Background: Lung cancer presents with a broad range of symptoms, many of which are nonspecific or atypical, contributing to delayed diagnosis. Symptom presentation and clinical recognition may differ between men and women, with important implications for diagnostic pathways. However, most symptom-based lung cancer risk models include sex only as a covariate, implicitly assuming similar symptom predictors across sexes. We evaluated sex-specific symptom predictors of lung cancer risk using explainable machine learning. Methods: We analyzed a publicly available lung cancer dataset comprising demographic characteristics and self-reported symptoms, including smoking status, respiratory symptoms, systemic features, and pain-related complaints (Biswas &amp; Nath, 2024). Patients were stratified by sex, and separate gradient-boosted decision tree models were trained for males and females. Model performance was evaluated using 5-fold cross-validated area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) were used to quantify and compare symptom-level contributions to lung cancer risk within sex-specific models. Results: Sex-stratified models demonstrated comparable discrimination for lung cancer risk prediction. Explainable feature attribution revealed marked differences in symptom importance between sexes. Among females, age was the most influential predictor, followed by a heterogeneous mix of respiratory and non-respiratory features, including cough, chronic disease burden, chest pain, fatigue, and swallowing difficulty; smoking contributed relatively less to overall risk prediction. In contrast, male risk prediction was dominated by respiratory symptoms—wheezing, cough, and shortness of breath—along with behavior-associated factors such as smoking, alcohol use, and peer pressure. Both the ranking and magnitude of symptom contributions differed substantially between male and female models. Conclusions: Symptom-level predictors of lung cancer risk differ meaningfully between men and women. Explainable machine learning identified a more heterogeneous, non-respiratory symptom profile among women, compared with predominantly respiratory-driven risk patterns in men. Incorporating sex-specific symptom models may improve early risk stratification and support timelier recognition of lung cancer, particularly in patients presenting with non-classic symptoms.