Browse Articles

Real-world outcomes of atezolizumab versus durvalumab in extensive-stage small cell lung cancer.

e23393 Background: Advent landmark trials, IMpower133 and CASPIAN, demonstrated improved median progression-free survival (PFS) and overall survival (OS) among those treated with chemotherapy and atezolizumab or durvalumab, respectively, over chemotherapy alone in ES-SCLC. Two retrospective single-center academic studies demonstrated improved OS with durvalumab compared to atezolizumab, and no PFS difference. In our study, we included academic and community treated patients using an intent-to-treat approach to evaluate treatment efficacy in a real-world population. Methods: Our retrospective real-world cohort study compared adults with ES-SCLC who received ≥ 1 cycle of first-line platinum-etoposide with atezolizumab or durvalumab from January 1, 2018 to December 31, 2025 at the University of Vermont Medical Center (UVM) and affiliate community centers. The study was developed, reviewed by UVM IRB, and exempt from full review, prior to data extraction. Patients identified from chart review. Demographic, clinical, treatment variables, immune-related adverse events (irAE), survival outcomes were collected via manual chart review. To reduce confounding, propensity score matching was performed on baseline labs, demographics, performance status, and treatment setting. Patients with incomplete data were excluded. Missing values were addressed using multiple imputations. Progression was determined by radiographic/clinician assessment. OS was time from first-line treatment start to death; PFS was time from treatment start to progression/death. OS and PFS were analyzed using the Kaplan Meier method and Cox proportional hazards model. Fisher’s test was used to compare baseline characteristics and irAE. Results: Of 96 patients, 78 remained after matching (39 per group). Baseline characteristics were balanced except for treatment setting, where academic practice favored durvalumab (p = 0.019). There was no significant difference in OS between atezolizumab and durvalumab (9.96 vs 11.61 months; hazard ratio [HR] 1.07; 95% CI 0.62–1.84; p = 0.80). PFS was also similar between groups (6.61 vs 4.41 months; HR 1.22; 95% CI 0.73–2.04; p = 0.44). Rates of irAE were comparable (n = 8 vs n = 9, p = 0.66). Conclusions: In this real-world analysis of patients with ES-SCLC, no significant difference in OS, PFS, or irAEs were observed between atezolizumab- and durvalumab-based first-line therapy. Limited by the imbalanced treatment setting, these findings support clinical equivalence between regimens and suggest treatment selection may be guided by institutional preference, access, or patient-specific factors. Larger multicenter studies are warranted to confirm these findings. Matched cohort outcomes. Outcome Atezolizumab Durvalumab Effect Estimate p-value Median OS, months 9.96 11.61 HR 1.07 (95% CI 0.62-1.84) 0.80 Mean PFS, months 6.61 4.41 HR 1.22 (95% CI 0.73–2.04) 0.435 irAEs, n 8 9 - 0.66

Disparities in statin prescription for secondary prevention of atherosclerotic cardiovascular disease in a Midwestern lung cancer screening population.

e13723 Background: Heart issues are a leading cause of death among lung cancer patients. Statins can effectively reduce patients’ risk of cardiovascular-related death, but they are not equally prescribed across demographic subgroups. Little is understood about the use of statins among patients facing both atherosclerotic cardiovascular disease (ASCVD) and potential lung cancer. We aimed to quantify the prevalence of statin prescription for secondary ASCVD prevention among patients seeking lung cancer screening (LCS) and assess whether disparities exist. Methods: A cross-sectional, retrospective analysis was conducted of patients who underwent LCS in the Midwest from 2022-2023. Analysis was limited to patients ages 50-80 with a history of ASCVD. Variables included race/ethnicity, sex, age, cardiovascular history, and statin prescription status. Log binomial regression models were used to calculate prevalence ratios for statin prescription across race, sex, and Medicare-eligibility subgroups. Results: The prevalence of statin prescription among LCS patients with ASCVD was 70.9% (n=10,536). Black patients had a significantly higher prevalence than White patients (PR=1.09, CI=1.06-1.12); this remained true when stratifying by sex and Medicare eligibility. Female patients – specifically White, Medicare-eligible females – had a significantly lower prevalence compared to their male counterparts (PR=0.97, CI=0.95-0.99). There was no difference in prevalence between Black female and Black male patients, regardless of Medicare eligibility. Conclusions: The prevalence of secondary statin prescription among LCS patients is high but varies significantly by race and sex. Whereas race-based disparities in statin prescription appear to be closing, sex-based disparities remain salient, especially for elderly White female patients. LCS represents a valuable opportunity to identify and address gaps in ASCVD prevention. Prevalence ratios and 95% confidence intervals for statin prescription across select race and sex subgroups overall and stratified by age. Comparison Overall PR (95% CI) 50-64 PR (95% CI) 65-80 PR (95% CI) Black (ref = White) 1.09 (1.06, 1.12)* 1.13 (1.07, 1.18)* 1.08 (1.04, 1.12)* Female (ref = Male) 0.97 (0.95, 0.99)* 0.98 (0.94, 1.03) 0.97 (0.94, 0.99)* Black male (ref = White male) 1.06 (1.02, 1.11)* 1.12 (1.04, 1.20)* 1.07 (1.02, 1.11)* Black female (ref = White male) 1.08 (1.04, 1.12)* 1.10 (1.03, 1.12)* 1.04 (0.98, 1.09) White female (ref = White male) 0.95 (0.93, 0.98)* 0.97 (0.92, 1.02) 0.95 (0.92, 0.98)* Black female (ref = Black male) 1.01 (0.96, 1.06) 0.99 (0.91, 1.07) 1.03 (0.97, 1.09) *Significant. 1 Abbreviations: CI = confidence interval, PR = prevalence ratio, ref = reference.

A phase 1, first-in-human study of DS5361, a small-molecule, nonsense-mediated mRNA decay (NMD) inhibitor in patients with advanced/metastatic solid tumors (parts 1 and 2).

TPS2680 Background: Despite the profound impact of immune checkpoint inhibitors (ICIs) on the treatment of patients with advanced or metastatic solid tumors, only a small proportion of patients experience meaningful responses, underscoring the need for novel therapies to maximize clinical benefit. High tumor mutational burden (TMB-H) and high microsatellite instability (MSI-H) are associated with improved efficacy of ICIs due to an increase in neoantigens, tumor-specific peptides displayed on tumor cell surfaces that are critical for antitumor immune responses. mRNAs harboring premature termination codons, including neoantigenic transcripts derived from frameshift mutations, are recognized and degraded by NMD. DS5361 is a potentially first-in-class, orally available, small-molecule inhibitor targeting the serine/threonine kinase SMG1, a key component of the NMD mechanism. DS5361 is designed to activate antitumor immunity by increasing neoantigen expression and, when administered in combination, to enhance ICI efficacy. Methods: DS5361-061 (NCT07182591) is a Phase 1, first-in-human, open-label, multicenter study (N≈66 for Parts 1 and 2) of DS5361 as monotherapy (Part 1) and in combination with pembrolizumab (Part 2). Patients must be adults, have measurable disease per Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1), and have an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with advanced or metastatic TMB-H and/or MSI-H solid tumors who are unable to tolerate standard treatment or have disease that is refractory to standard treatment, or for which no such treatment is available, will be enrolled across both parts. The primary objectives in Parts 1 and 2 (dose escalation) are to evaluate the safety and tolerability, and determine the maximum tolerated dose, of DS5361 as monotherapy in Part 1 and in combination with pembrolizumab in Part 2, and/or determine the recommended dose(s) for expansion in combination with pembrolizumab (Part 2 only). Safety endpoints include dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include objective response, disease control, and duration of response, all assessed by the investigator per RECIST 1.1, as well as pharmacokinetics. Enrollment is ongoing. Clinical trial information: NCT07182591 .

A global phase 1/2a trial of SHR-A1904, a CLDN18.2-targeting ADC, in advanced solid tumors expressing CLDN18.2.

e15018 Background: SHR-A1904, a novel CLDN18.2 targeted ADC, showed promising antitumor activity in pretreated CLDN18.2-positive gastric/gastroesophageal junction cancer (GC/GEJC) in a China-only phase 1 trial (Nat Med. 2025; NCT04877717). Here, we report a 2-part multicenter global study assessing SHR-A1904 in patients (pts) with CLDN18.2-expressing advanced solid tumors (NCT05277168). Methods: During dose escalation (DE), pts with CLDN18.2-expressing (H score ≥1 by central lab IHC) advanced relapsed or refractory (R/R) solid tumors were enrolled to receive SHR-A1904 at 0.6–6.0 mg/kg (Q3W IV) in an i3+3 design. During dose optimization (DO), pts with CLDN18.2-positive (≥50% of cells with 2+ or 3+ staining) advanced R/R GC/GEJC were enrolled to receive SHR-A1904 at 6.0 and 8.0 mg/kg. The primary endpoints were DLT and safety in DE, and efficacy and safety in DO. Exploratory subgroup analyses in Asians vs non-Asians were done at 3.6 mg/kg (the minimal effective dose) or higher. Results: As of Dec 1, 2025, 51 pts were enrolled from Australia, South Korea, the United States, and Moldova, including 41 with GC/GEJC, 9 with pancreatic cancer, and 1 with lung adenocarcinoma. 42 pts received SHR-A1904 at 3.6 mg/kg or higher, 24 of whom were Asian. All pts had prior therapy (≥2 lines, 72.5%). The median follow-up was 6.7 mo (range, 0.2–27.9). During DE, 1 DLT (grade 3 vomiting) occurred at 6.0 mg/kg. Among all pts, TRAEs were reported in 48 (94.1%) pts; the most common were nausea (66.7%), vomiting (52.9%), and fatigue (23.5%). Grade ≥3 TRAEs and serious TRAEs occurred in 21 (41.2%) and 9 (17.6%) pts. No TRAEs led to death. In Asians, TRAEs and Grade ≥3 TRAEs occurred in 22 (91.7%) pts and 11 (45.8%) pts; in non-Asians, TRAEs and Grade ≥3 TRAEs occurred in 17 (94.4%) pts and 9 (50.0%) pts. Overall, ORR, DCR, and CBR (CR + PR + SD ≥24 weeks) were 25.5%, 58.8%, and 33.3%, respectively. The median PFS, OS, and DoR were 2.8 mo (95% CI, 1.7–5.4), 9.8 mo (95% CI, 6.7–15.2), and 5.7 mo (95% CI, 2.8–NR), respectively. Exploratory subgroup analyses by race are shown in Table. After a single dose, C max and AUC of SHR-A1904 increased with the dose except the 4.8 mg/kg group. The mean t 1/2 of SHR-A1904 is around 4.3–7.2 days. Conclusions: SHR-A1904 showed tolerable safety and promising antitumor activity in pretreated CLDN18.2-expressing advanced solid tumors. Furthermore, exploratory subgroup analyses by race support global development of SHR-A1904 in both Asians and non-Asians. Clinical trial information: NCT05277168 . Efficacy summary. Overall (N=51) Asians (N=24) # Non-Asians (N=18) # ORR 25.5 (13; 14.3–39.6) 20.8 (5; 7.1–42.2) 44.4 (8; 21.5–69.2) DCR 58.8 (30; 44.2–72.4) 66.7 (16; 44.7–84.4) 66.7 (12; 41.0–86.7) CBR 33.3 (17; 20.8–47.9) 20.8 (5; 7.1–42.2) 66.7 (12; 41.0–86.7) DoR, mo 5.7 (2.8–NR) 8.5 (2.9–NR) 5.7 (2.8–NR) PFS, mo 2.8 (1.7–5.4) 2.8 (1.5–5.4) 9.7 (1.9–NR) OS, mo 9.8 (6.7–15.2) 9.8 (5.2–NR) 15.2 (9.0–NR) Data are % (n; 95% CI) or median (95% CI). # at 3.6 mg/kg or higher.

Integrated proteogenomic profiling to reveal prognostic subtypes and actionable targets in adenoid cystic carcinoma.

6067 Background: Adenoid cystic carcinoma (ACC) is a rare head and neck malignancy characterized by highly variable clinical outcomes and a lack of validated biomarkers to guide risk stratification or therapeutic decision-making. Despite a generally low tumor mutational burden, patients frequently experience late recurrence and distant metastasis, underscoring the need for biologically informed prognostic models. Existing genomic and transcriptomic classifiers have failed to adequately explain this heterogeneity. We therefore performed integrated multi-omic profiling to define biologically grounded prognostic subtypes and clinically actionable biomarkers in ACC. Methods: We established a multi-omics cohort of 55 surgically resected ACC tumors, including salivary gland–derived and pulmonary ACC, with matched adjacent normal tissues. Whole-exome sequencing, RNA sequencing, quantitative proteomics, and phosphoproteomics were performed. Cross-omics concordance and driver-anchored pathway effects were assessed. Transcriptomic and proteomic data were integrated using Similarity Network Fusion (SNF) to derive molecular subtypes. Prognostic proteins were evaluated using Cox regression. Targeted quantitative mass spectrometry was applied for orthogonal validation and for quantifying antibody–drug conjugate (ADC) targets and pathway stoichiometry. Results: ACC exhibited a low-mutational genomic landscape but profound proteomic and phosphoproteomic remodeling, with systematic activation of replication, cell-cycle, chromatin remodeling, and receptor tyrosine kinase–adhesion pathways, accompanied by suppression of immune-associated signaling. Driver effects were more consistently captured at the protein level than at the RNA level, indicating a proteome-driven tumor biology. SNF-based multi-omic integration identified three molecular subtypes with significantly different disease-free survival (DFS; log-rank P=0.0064), outperforming the conventional ACC-I/II classifier. These subtypes formed a biological continuum defined by metabolic robustness and cell-cycle competence. A compact three-protein signature independently stratified DFS. Quantitative profiling demonstrated broad and functionally relevant expression of ADC targets, including TROP2 and B7-H3, and identified ratio-based functional indices (e.g., IGF2/IGF1R and TP63/NOTCH1) associated with risk groups. Conclusions: ACC is a proteome-driven malignancy in which post-transcriptional regulation and signaling stoichiometry dominate clinical behavior. Integrated multi-omic analysis redefines ACC prognostic architecture and yields quantitative, translatable biomarkers that may inform precision risk stratification and therapeutic strategies in this rare head and neck cancer.

Genetic signatures of CNS relapse in DLBCL patients profiled with next-generation sequencing (NGS).

7016 Background: CNS relapse of DLBCL is a devastating event with median survival <6 months. While the overall incidence is low (~5%), various factors impact the risk of CNS relapse including CNS-IPI, cell-of-origin (COO), and MYC rearrangement. Recent studies using NGS have defined DLBCL genetic subgroups with distinct biology. The MCD and C5 subgroups, defined by LymphGen and DLB class , respectively, have a shared genetic signature characterized by MYD88 L265P and CD79B mutations, immune evasion, and extranodal tropism with enrichment in CNS lymphomas. We investigated the impact of MCD/C5 signature on the risk of CNS relapse in a large cohort of DLBCL patients (pts) profiled with NGS. Methods: We performed a retrospective analysis of 155 DLBCL pts treated with chemoimmunotherapy and profiled with the UCSF500 NGS panel, which includes 529 genes and copy number data. FISH was performed to evaluate for MYC , BCL2 and BCL6 rearrangements. Pts with CNS involvement at diagnosis were excluded. Data were extracted from medical records including demographics, WHO-HAEM5 diagnosis, COO per Hans algorithm, CNS-IPI, and treatment history. LymphGen and DLB class subtypes were determined using online classifiers incorporating NGS and FISH data. We identified LymphGen and DLB class subtypes enriched in pts with CNS relapse. We performed univariable and multivariable analysis (MVA) (Cox proportional hazards model) to assess the impact of COO, CNS-IPI, and genetic signature on the cumulative incidence (CI) of CNS relapse. Results: The median age was 61. 60% were male, 57% non-Hispanic white, 21% Asian, 16% Hispanic, and 3% Black. DLBCL subgroups included DLBCL-NOS (60%), transformed DLBCL (15%), Richter transformation (8%), high-grade B-cell lymphoma (HGBCL)-double hit (5%), primary mediastinal LBCL (4%), DLBCL, post-transplant (3%), HGBCL-NOS (3%), and T-cell histiocyte-rich LBCL (2%). 67% were stage III-IV, 51% non-GCB type, and 21% high-risk CNS-IPI. LymphGen subtypes included EZB-MYC- (26%), ST2 (12%), MCD (9%), EZB-MYC+ (7%), BN2 (7%), N1 (3%), and composite cases (3%); 34% were unclassifiable. DLB class subtypes included C1 (13%), C2 (3%), C3 (52%), C4 (8%), and C5 (11%); 14% were not classified given <50% confidence in assignment. Median follow-up was 30 months. 18 pts experienced CNS relapse; these cases were enriched for MCD and C5 subtypes (28% each). The 2-year CI of CNS relapse in pts with MCD and/or C5 subtypes (N=21) was 20.4% vs. 6.4% in non-MCD/C5 cases (HR 3.46, p=0.007). Notably, 3 MCD/C5 pts had late CNS relapse (>3 years from diagnosis). In MVA, MCD/C5 signature was an independent risk factor for CNS relapse (HR 4.51, 95% CI 1.42-14.32, p=0.011) along with MYC rearrangement (p=0.036) and non-GCB COO (p=0.028). Conclusions: In this heterogeneous DLBCL cohort, MCD/C5 genetic signature was an independent risk factor for CNS relapse. Incorporation of CNS-active agents should be prioritized for this subgroup.

Clinicopathologic features of South African colorectal cancer patients by HIV status in a retrospective cohort study.

3658 Background: Colorectal cancer (CRC) is increasing among people living with HIV. South Africa (SA) has the largest HIV-infected population in the world. Data characterizing the features of CRC among HIV patients in SA is limited. We compared the clinicopathologic features of CRC patients in SA by HIV-status. Methods: A retrospective cohort of CRC patients was identified using a database of histologically confirmed CRC patients seen at one of four referral hospitals in KwaZulu-Natal, SA between 2000 and 2024. Confirmed HIV-positive patients were randomly matched (1:2) with patients without HIV based on age at CRC diagnosis, year of CRC diagnosis, race, and tumor location. Additional clinical data was extracted through retrospective review of medical records. Chi-squared tests were used to compare features by HIV-status. Results: We identified 106 CRC patients with confirmed HIV-positive status and matched them with 155 CRC patients with confirmed HIV-negative status and 57 CRC patients with unknown HIV-status (assumed to be HIV-negative for analysis). At the time of CRC diagnosis, HIV-positive patients had an average duration of infection of 5.2 years and a mean baseline CD4 count of 451 cells/mm 3 . 72.6% of HIV patients were on antiretroviral therapy. HIV-status was not associated with duration of symptoms prior to CRC diagnosis (cohort mean 9.6 months; p-value = 0.687). HIV-positive patients were more likely than HIV-negative patients to present with metastatic disease (40.6% vs 28.8%, p-value = 0.035) and to have poorly differentiated tumors (13.9% vs 4.5%, p-value = 0.011). HIV-status was not associated with the rate of curative-intent treatment initiation (62.1% of non-metastatic patients received stage-appropriate treatment; p-value = 0.199) or palliative-intent systemic therapy (81.7% of metastatic patients received systemic therapy; p-value = 0.105). Conclusions: In SA, CRC patients with HIV are more likely than patients without HIV to present with high grade tumors and metastatic disease. This suggests a more aggressive tumor biology in this population. A comparison of overall survival by HIV-status will be presented at ASCO 2026. Future studies will compare the CRC tumor microenvironment by HIV-status in a subset of patients. Clinicopathologic features of colorectal cancer patients in South Africa by HIV-status (2000-2024). HIV-Positive(n = 106) HIV-Negative(n = 212) Total(n = 318) p-value Tumor Site 1.000 Colon 43 (40.6%) 86 (40.6%) 129 (40.6%) Rectal 63 (59.4%) 126 (59.4%) 189 (59.4%) Stage at Diagnosis 0.090 Early (I-IIa) 11 (10.4%) 32 (15.1%) 43 (13.5%) Locally Advanced (IIb-IIIc) 52 (49.1%) 119 (56.1%) 171 (53.8%) Metastatic (IVa-IVc) 43 (40.6%) 61 (28.8%) 104 (32.7%) Tumor Grade 0.040 Well Differentiated 2 (2.5%) 4 (2.6%) 6 (2.6%) Moderately Differentiated 66 (83.5%) 143 (92.9%) 209 (89.7%) Poorly Differentiated 11 (13.9%) 7 (4.5%) 18 (7.7%) Unknown 27 58 85

Targeting MAT2A-mediated metabolic pathways: A novel strategy for non-small cell lung cancer therapy.

e20711 Background: Methionine adenosyltransferase 2A (MAT2A) links metabolic reprogramming with epigenetic regulation by producing S-adenosylmethionine (SAM) in the methionine cycle. The regulatory mode of MAT2A in metabolic reprogramming of non-small cell lung cancer (NSCLC) is still unclear. The current efficacy of MAT2A inhibitors is limited, and further exploration is needed to improve their effectiveness. Methods: We systematically characterized the metabolic reprogramming of MAT2A rewiring in NSCLC cell lines treated with siRNA targeting MAT2A or inhibitor AG-270 using proteomics and metabolomics, supplemented by targeted metabolomics, RT qPCR, and ATAC seq, in order to characterize MAT2A-rewired metabolic reprogramming and identify potential combination strategies. Results: Knockout and inhibition of MAT2A significantly disrupt fatty acid biosynthesis, cholesterol metabolism, glycolysis, and transsulfuration pathway. In fatty acid biosynthesis, MAT2A affects the expression of key genes FASN and SCD, as well as the levels of key metabolites palmitic acid (PA) and oleic acid (OA), as exogenous PA reverses the cell growth inhibition caused by AG-270.In cholesterol metabolism, MAT2A regulates biosynthesis and efflux, binding AG-270 to liver X receptor agonists to promote cholesterol efflux and enhance anti-tumor efficacy. In energy metabolism, MAT2A affects glycolysis by regulating HIF1A. GLUT1 inhibitors that inhibit glucose uptake exhibit a synergistic effect when combined with AG-270. In the sulfur conversion pathway, MAT2A transcriptionally regulates the key enzyme CBS involved in cysteine biosynthesis. The combination therapy of AG-270 and inhibitors targeting genes upregulated by AG-270, such as PHGDH and SLC7A11, shows a synergistic effect. The former produces serine through cysteine biosynthesis, while the latter mediates cysteine uptake. Conclusions: Overall, our research findings confirm that MAT2A is a critical regulatory factor in NSCLC metabolism and propose a reasonable combination strategy to enhance the efficacy of MAT2A inhibitors.

Cardiotoxicity and mortality trends in chemotherapy-treated breast cancer patients before and during the COVID-19 pandemic.

e24013 Background: The Coronavirus Disease 2019 (COVID-19) pandemic caused widespread disruptions in breast cancer screening, diagnosis, and treatment delivery, raising concerns about downstream impacts on treatment-related morbidity and mortality. While excess mortality during the pandemic has been documented in the general population, its implications for cancer, particularly those exposed to potentially cardiotoxic chemotherapy remain insufficiently characterized. This study evaluates whether cardiotoxicity and mortality outcomes among breast cancer patients treated during 2019–2022 differed from prior years. Methods: We conducted a retrospective cohort study within Kaiser Permanente Southern California (KPSC), including adults (≥18 years) diagnosed with primary breast cancer from 2007–2022 who received ≥1 cycle of cytotoxic chemotherapy. Cardiotoxicity and mortality outcomes were compared across four periods: 2007–2010, 2011–2014, 2015–2018, and 2019–2022 (reference, representing the COVID-19 period) based on year of chemotherapy initiation. Proportional hazards models adjusted for demographic factors, tumor characteristics, smoking status, and pre-existing cardiovascular disease (CVD) conditions or risk factors. Cardiotoxicity was defined as either congestive heart failure (CHF), cardiomyopathy, or major adverse cardiac/cardiovascular events (MACE). Mortality analyses evaluated all-cause, cancer-specific, and CVD-specific deaths. Results: Among 12,302 chemotherapy-treated patients, cardiotoxicity rates during 2019–2022 were comparable to those in all pre-pandemic periods, with no significant increases in CHF, MACE, or cardiomyopathy. In contrast, mortality outcomes were consistently worse in earlier periods (Table 1). All-cause mortality was elevated in 2007–2010 (HR 1.16, 95% CI 1.00–1.36), and cancer-specific mortality was markedly higher in 2007–2010 (HR 1.97, 1.65–2.35), 2011–2014 (HR 1.56, 1.31–1.87), and 2015–2018 (HR 1.31, 1.09–1.56). CVD-related mortality was also higher in 2007–2010 (HR 1.70, 1.32–2.21) and 2011–2014 (HR 1.41, 1.09–1.83). Conclusions: We observed no increase in chemotherapy-associated cardiotoxicity or cause-specific mortality during the 2019–2022 COVID-19 period compared with earlier years. Cardiotoxicity rates, including CHF, MACE, and cardiomyopathy, remained stable, and all-cause, cancer-specific, and CVD-specific mortality were not elevated. These findings suggest that continuity of oncology and cardio-oncology care can be maintained even during major healthcare disruptions. Hazard ratios for CHF, MACE, cardiomyopathy. Year Quartiles CHF MACE Cardiomyopathy 2007-2010 0.92 (0.71-1.20) 1.09 (0.95-1.23) 1.02 (0.76-1.38) 2011-2014 1.00 (0.78-1.28) 1.04 (0.91-1.20) 0.89 (0.66-1.19) 2015-2018 0.99 (0.78-1.25) 0.96 (0.84 -1.10) 1.09 (0.83-1.45)

Finite element analysis of particle weight fraction & size effects in graphene-silicon carbide reinforced aluminium nanocomposites

Why it’s time to bin recommendation letters in science job applications

Three‐Dimensional Garment Architectures for Tactile Embodied Intelligence

ABSTRACT Sensory‐neuromorphic computing endows wearable devices with capabilities of environmental perception and active service, acting as a pivotal driver for the revolution in human–computer interaction. However, its implementation in textile electronics is hampered by incompatibility between conventional electronic device structures and the fabric‐woven manufacturing methodology. Here, we demonstrate a tactile‐neuromorphic interface integrating a textile‐type resistive random‐access memory (RRAM) array for constructing human–machine sensing‐computing interactive systems. The 3D stacked TiO 2 /Ti 3 C 2 T x textile RRAM exhibits an order‐of‐magnitude reduction in switching voltage (85 mV) compared to prevailing counterparts, ultra‐stable resistive switching over 10 3 operation cycles with ultralow 1.15% LRS coefficient of variation, ideal for actualizing weavable neuromorphic computing. An all‐textile integrated near‐sensor computing system, featuring monolithically co‐integrated pressure sensor and RRAM arrays, demonstrates quasi‐linear conductance modulation under pressure stimuli, allowing for the embedded computation‐memory nodes knitted into garment textiles to achieve in situ tactile processing for contactless vehicular maneuvering. This work demonstrates the potential to integrate an embedded sensing‐logic‐memory electronic device into smart textiles, propelling a transformative paradigm shift in human–machine interaction.

Registry-based machine learning in Sezary syndrome: Assessment of prognostic signal and age-masked racial inequities.

e22615 Background: Sézary syndrome (SS) is a rare leukemic cutaneous T-cell lymphoma with limited contemporary population data on survival, disparities, and prognostication. Methods: SEER-22 identified adults with first primary SS (ICD-O-3 9701/3), 2000–2021 (N = 403). Overall survival (OS) was evaluated by Kaplan–Meier and Cox models adjusting for age, sex, calendar year, SEER Summary Stage, and county-level socioeconomic status (SES). To evaluate machine learning (ML)–based registry risk stratification, we split the cohort by diagnosis year into training and held-out test sets and trained four survival models using identical covariates: multivariable Cox, elastic-net Cox, random survival forest, and gradient-boosted Cox. Model performance was evaluated using Harrell’s C-index, time-dependent Uno AUC (12/36/60 months), calibration, and Brier score. Results: Median age was 68; 77% were White and 19% Black. Black patients were younger at diagnosis (46.8% < 60 vs 25.4% in Whites; p = 0.0009). Median OS was 48 months; 1- and 5-year OS were 83.2% and 42.7%. Median OS was 37.0 months in Black patients versus 49.0 months in White patients (Other/Unknown: 36.0 months). Survival improved in 2011–2021 compared with 2000–2010 (median OS 56.0 vs 39.5 months; 12-month OS 87.5% vs 75.7%; 60-month OS 48.4% vs 35.0%). Racial OS was similar at 12 months (83.9% Black vs 82.9% White) but diverged thereafter. In Cox models, the crude Black vs White hazard ratio (HR) was 1.19 (0.86–1.63) but increased after age/sex/era adjustment; in the fully adjusted model, Black race remained independently associated with higher mortality (HR 1.61, 95% CI 1.14–2.27; p = 0.007), along with age (per decade HR 1.38, 95% CI 1.23–1.53; p < 0.001), while stage/SES were not. Time-windowed analyses suggested excess hazard beyond the first year. In the SS test set, all ML approaches demonstrated near-chance discrimination (C-indices ~0.5; low Uno AUCs) with minimal improvement in calibration. By contrast, applying the same modeling pipeline to a substantially larger SEER mycosis fungoides cohort yielded strong discrimination (C-index ~0.84). Conclusions: SS survival has improved modestly in the modern era but remains poor. Younger age at diagnosis masks inequity in unadjusted analyses; adjusted models reveal persistent longer-term mortality disadvantage for Black patients. Routine registry variables provide limited prognostic signal for SS, underscoring the need for biomarker- and treatment-sequence–enriched datasets to enable actionable risk stratification and address disparities.

Impact of COVID-19 mRNA vaccines on survival outcomes in patients with solid tumors receiving immunotherapy: A large-scale retrospective study.

2637 Background: Immune checkpoint inhibitors (ICIs) became the cornerstone in the treatment of solid tumors. While personalized cancer vaccines have yet to overcome complex scalability and manufacturing challenges, preclinical data suggests SARS-CoV-2 mRNA vaccines prime innate immunity, potentially enhancing ICI efficacy. A study by Grippin et al. evaluated the use of mRNA vaccine in NSCLC and melanoma patients receiving ICI and showed improved median and three-year overall survival (OS). We conducted a multicenter retrospective study to determine if this survival benefit extends across a broader range of ICI-treated solid tumors. Methods: Using the TriNetX global network, we identified adults (≥18) with solid tumors (NSCLC, melanoma, colorectal, hepatobiliary, gallbladder, gastric, bladder, pancreatic, renal, breast, head and neck, and esophageal) who received ICI treatment. The experimental group received SARS-CoV-2 mRNA vaccine within 100 days of ICI initiation; controls received no mRNA vaccine from 100 days pre-index through follow-up. Exclusion criteria: COVID-19 infection within 100 days and through the follow-up period. 1:1 propensity score matching (PSM) balanced demographics and comorbidities. Primary endpoint was median OS, including tumor-specific subgroup analyses. Survival was assessed via Kaplan-Meier and log-rank tests. Results: After PSM, we had 15,374 matched patients (7,687 per group). Vaccination within 100 days of ICI was associated with improved median OS (1,421 vs 667 days; HR 0.63; 95% CI 0.60-0.66; p<.001). Benefit was observed in 10 of 12 tumor types. Strongest effects were in NSCLC (n=7,350; HR 0.64), melanoma (n=2,684; HR 0.61; landmark survival 62.1% vs 50.3%), hepatobiliary (n=1,428; HR 0.64), colorectal (n=1,068; HR 0.67), gastric (n=792; HR 0.68), bladder (n=1,398; HR 0.63), pancreatic (n=240; HR 0.65), renal (n=1,996; HR 0.64), head and neck (n=964; HR 0.68), and esophageal (n=828; HR 0.63). No significant benefit was seen in breast (n=1,412; HR 0.85) or gallbladder cancer (n=58; HR 0.88). Conclusions: SARS-CoV-2 mRNA vaccination within 100 days of ICI therapy was associated with improved survival across solid tumors. These results suggest off-the-shelf RNA therapeutics may be scalable, cost-effective enhancers of cancer immunotherapy. Prospective studies are needed to confirm these findings and define the impact of universal mRNA strategies.

Phase II single-arm trial of low-dose capecitabine in patients with advanced breast cancer.

TPS1159 Background: Capecitabine is approved for use in both the adjuvant and metastatic settings of breast cancer. The clinical activity of capecitabine was established at the maximum tolerated dose of 1000–1250 mg/m² given on days 1–14 of a 21-day cycle. As seen with other cytotoxic agents, dose escalation may lead to increased toxicity without clear efficacy benefit, while lower, fixed-dose capecitabine maintains antitumor activity with fewer adverse effects, including diarrhea, hand–foot syndrome, mucositis, and neutropenia. This approach is especially important for older and frail patients, who are more vulnerable to toxicity and underrepresented in trials. Methods: This single-arm, open-label phase 2 study aims to evaluate the anti-tumor effect of continuous daily oral low-dose capecitabine at 1500mg in 40 patients aged 60 years or older, and/ or considered frail at any age (ECOG 0-2). Frailty is defined by the investigator as an individual at greater risk of complications and poorer outcomes with systemic therapy, secondary to a lower physiologic reserve and higher comorbidities and functional deficits. Eligible patients include those with HER2-negative unresectable or metastatic breast cancer (hormone positive or triple negative) with measurable disease, who have progressed on at least 1 prior line of therapy. Major exclusion criteria include HER2-positive breast cancer, severe hepatic or renal failure, inability to swallow pills, and uncontrolled CNS/ leptomeningeal disease. Patients will be evaluated for toxicity every 4 weeks and for response every three cycles using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Therapy will be continued until evidence of disease progression or unacceptable toxicity. The primary objective is the clinical activity of daily low dose capecitabine by overall response rates (ORR) per RECIST. The secondary objectives include progression-free survival (PFS), overall survival (OS), and determining the safety and tolerability of daily low dose capecitabine using the Common Terminology Criteria for Adverse Events (CTCAE) v.6.0. Exploratory analyses include evaluating quality of life, measurement of sarcopenia, geriatric assessment using the CARE (Cancer and Aging Resilience Evaluation) tool before registration and at the end of treatment, and evaluating adherence to capecitabine. Simon's two-stage minimax design will be used with a type I error rate of 0.05 and power of 80%. The null hypothesis response rate of 10% will be tested against a one-sided alternative response rate of 25%. In the first stage, 22 patients will be accrued. If there are 2 or fewer responses in the first 22 patients enrolled, the study will be discontinued. The trial was approved by the Institutional Review Board at the University of Alabama at Birmingham (UAB) and has been accruing since February 2025. 8 of the planned 40 patients have been enrolled. Clinical trial information: NCT06105684 .

A network analysis of symptoms in women with metastatic breast cancer undergoing systemic therapy.

e13107 Background: Women with metastatic breast cancer (MBC) experience various concurrent symptoms during cancer treatment that impact quality of life. Previous studies identified symptom clusters, but findings were inconsistent, and the interactome of these co-occurring symptoms remain unclear. Network analysis is a novel approach to identify and visualize interconnected relationships between multiple symptoms. We sought to explore the symptom network among core cancer symptoms in women with MBC receiving systemic therapy. Methods: Women with MBC (N = 209) were recruited between February and September 2024, from Yale Smilow Cancer Center and five MBC patient advocacy groups in the U.S. Participants completed the MD Anderson Symptom Inventory (MDASI) measuring 13 core cancer symptoms: pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting and numbness/tingling. Symptom severity was rated from 0 (not present) to 10 (most severe). We conducted a symptom network analysis by estimating a mixed graphical model via elastic-net regularized neighborhood regression. The estimated symptom network properties were examined by analyzing centrality indices: strength (weight of direct connection between symptoms), closeness (influence of symptoms on other symptoms), and betweenness (bridges of symptoms to one or more symptoms). Results: Of 209 women, 76.6% identified as White and 65.1% had HR+/HER2- breast cancer, with an average age of 50.1 years (SD = 14.1). The average time since MBC diagnosis was 4.4 years (SD = 3.9). The mean symptom score was 3.9 (SD = 2.2) with fatigue (mean = 5.8, SD = 2.7) and disturbed sleep (mean = 5.1, SD = 3.1) rated as the most severe symptoms. The network analysis illustrated three distinct subnetworks: neurological symptoms (“fatigue-drowsiness”), gastrointestinal symptoms (“nausea-lack of appetite-vomiting”), and psychological symptoms (“distress-sadness”). Shortness of breath (strength = 0.88, closeness = 0.01, betweenness = 35) demonstrated the highest centrality indices, and connected to lack of appetite, vomiting, dry mouth, numbness/tingling, and difficulty remembering. Conclusions: Network analysis revealed interconnected symptom patterns. In addition to well-recognized symptom clusters such as fatigue-sleep disturbance, shortness of breath may function as a key connector symptom. Future research is needed to determine the role and contribution of shortness of breath in overall symptom burden among women with MBC.

Updated efficacy results from the phase I cervical cancer cohort of BAT8008, a TROP-2–directed antibody-drug conjugate, in patients with advanced cervical cancer.

5507 Background: BAT8008 is a novel antibody-drug conjugate comprising a TROP-2 antibody and an exatecan payload. Patients with recurrent or metastatic cervical cancer (r/m CC) who have progressed on platinum-based chemotherapy have limited treatment options and poor prognosis. This study reports the safety and efficacy of BAT8008 in a cohort of r/m CC patients from a phase 1 trial. Methods: This analysis is part of BAT-8008-001-CR, a multi-center, open-label phase 1 study with dose escalation and expansion cohorts. Patients with r/m CC who had failed prior systemic treatments were enrolled. BAT8008 was administered 2.4 mg/kg or 2.1mg/kg intravenously every two weeks (Q2W) 2.4 mg/kg. Results: As of Jan 5, 2026, 68 evaluable patients with r/m CC were enrolled (27 at 2.1 mg/kg, 41 at the 2.4 mg/kg). Patients were heavily pre-treated, with 55.9% having received ≥2 prior lines of therapy. 64.7% had prior anti-angiogenic therapy and 38.2% had prior immunotherapy. At the 2.4 mg/kg dose (n=44), the most common TRAEs (any grade/≥G3) were anemia (63.6%/15.9%), WBC decreased (68.2%/25.0%), stomatitis (54.5%/6.8%), and neutrophil count decreased (45.5%/20.5%). No treatment-related deaths occurred. For the RP2D cohort (n=41), the confirmed objective response rate (cORR) was 29.3% and disease control rate (DCR) was 78.0%. The median progression-free survival (mPFS) was 6.7 months (95% CI: 3.5-12.1) and median duration of response (mDoR) was 9.0 months (95% CI: 4.2-12.3). Efficacy was observed across subgroups and was independent of TROP-2 expression level. Conclusions: BAT8008 demonstrated promising and durable anti-tumor activity with a manageable safety profile in heavily pre-treated patients with r/m cervical cancer. These findings support the continued development of BAT8008 in this patient population. Clinical trial information: NCT05620017 . Efficacy Endpoint 2.1 mg/kg (n=27) 2.4 mg/kg (n=41) Overall (n=68) cORR, % (95% CI) 22.2 (10.6-40.8) 29.3 (17.6-44.5) 26.5 (17.4-38.0) DCR, % (95% CI) 81.5 (63.3-91.8) 78.0 (63.3-88.0) 79.4 (68.4-87.3) mPFS, months (95% CI) 5.3 (3.3-8.3) 6.7 (3.5-12.1) 6.5 (3.5-8.3) mDoR, months (95% CI) Not Reached 9.0 (4.2-12.3) 9.0 (5.3-12.3)

A pillar of safety: Standardizing oral chemotherapy protocols.

e23323 Background: Standardizing protocols for oral chemotherapy treatment and delivery is a critical quality improvement initiative to reduce variability and enhance reliability in oncologic care. Oral anticancer agents introduce complex workflows involving prescribing, education, monitoring, and adherence. Each of which is vulnerable to process gaps and errors. Inconsistent practices across providers can lead to delayed treatment, suboptimal monitoring, and preventable adverse events. A standardized approach enables the use of clear process measures, supports multidisciplinary coordination, and facilitates timely identification of deviations from best practice. Protocol-driven workflows improve patient education, documentation, and follow-up, allowing for consistent measurement of outcomes and continuous performance improvement. Here, we present our data on oral chemotherapy delivery after implementing a standardized protocol across the clinic amongst all providers to improve safety and efficiency. Methods: Oral chemotherapy was set up and ordered in the following manner, Step 1: Primary Oncologist obtained consent, wrote communication order, and chemotherapy orders. Step 2: A secure chart message was sent to the Oral Chemotherapy Pharmacy Pool with the starting time frame. Step 3: An appointment is scheduled with an advanced practitioner for chemotherapy teaching and pill pick up. The first four appointments for pill pickup dates will also be scheduled concurrently. Patients are scheduled for toxicity checks and follow-ups at the discretion of the primary Oncologist as stated in the communication order. Step 4: Physician orders are placed through administrative appointment slots on the Thursday of each week prior to the planned cycle. At each medication pick-up, patients complete an anonymous survey that assesses patient’s safety and understanding of their medication. The survey also identified information on any delays in treatment due to staffing, scheduling availability, delayed lab results, and/or logistic confusion. Data was collected over 4 months and evaluated for improvements in quality of care based on frequency of treatment delays not related to toxic side effects and patient satisfaction. Results: We found at least a 20% decrease in treatment delays due to missing lab results, chemotherapy orders, and appropriate scheduling of cycles. Patient satisfaction improved from an average score of 2.5 out of 5 to 3.5 out of 5. Conclusions: Implementing a standardized protocol for oral chemotherapy decreased treatment delays due to missing lab results, delay in chemotherapy orders, and appropriate scheduling of cycles. We also saw an increase in patient satisfaction in the pill-pick up process.

Clinicopathologic features and prognostic factors of breast cancer brain metastases patients based on molecular subtypes: A real-world retrospective analysis.

e13077 Background: The incidence of breast cancer brain metastases (BCBM) is increasing. Molecular subtypes of breast cancer are important evidences for the development of follow-up strategies and systemic therapy for patients with BCBM. The study aimed to analyze the clinicopathological characteristics and identify prognostic factors for BCBM based on molecular subtype. Methods: In order to conduct a more detailed study on the clinical characteristics of brain metastases about BC, we divided them into four molecular subtypes. The clinicopathological data from 295 patients were retrospectively evaluated. COX regression analysis was used to identify the independent risk factors affecting survival following brain metastases. Results: There were significant differences in histological grade ( P < 0.001) among the four different molecular subtypes. The pathological inconsistency rate was higher for hormone receptor (HR) postive / human epidermal growth factor receptor 2 (HER2) negative BCBM (30.0%). The molecular subtypes in BCBM patients showed the trend of HR+ transforming into HR- subtypes. When brain metastases occurred, there were statistical differences in extracranial organs metastases among different molecular subtypes of BCBM ( P = 0.017). HR+/HER2- BCBM was often accompanied by bone metastasis (66.7%), while TNBC brain metastases was often accompanied by lung metastasis (61.0%). More patients with HER2+ BC were diagnosed by imaging examination ( P = 0.042). The median disease-free survival (DFS) and brain metastases-free survival (BMFS) in all BCBM patients were 20 and 40 months (both P < 0.001). According to the ranking, BMFS was 65 months (HR+/HER2-), 44.5 months (HR+/HER2+), 31 months (HR-/HER2+), and 28 months (TNBC). The median time from recurrence to brain metastases was 12 months ( P = 0.216). The median SFBM in patients with different BC molecular subtypes was ranked as HR-/HER2+ (33 months), HR+/HER2+ (25 months), HR+/HER2- (13 months), and TNBC (7 months). Molecular subtype of BC, Karnofsky performance status (KPS) score, metastases of extracranial organs, leptomeningeal metastasis, location of brain metastases craniocerebral radiotherapy and systemic therapy were independent prognostic factors of survival following brain metastases (SFBM). Conclusions: The risk of brain metastasis among the four primary tumor subtypes is ranked as follows: HR-/HER2+ (25.4%), TNBC (25.1%), HR+/HER2+ (19.0%), and HR+/HER2+ (19.0%). During disease progression, two factors increase brain metastasis risk: pathological loss of HR expression or acquisition of HER2 expression, and the presence of extracranial organ metastases in different subtypes. Median BMFS and SFBM vary across breast cancer subtypes. Timely imaging screening facilitates early diagnosis of brain metastases, thereby improving patient outcomes.

Associations between mindfulness, psychological distress, and coping among hematopoietic stem cell transplant caregivers.

e18567 Background: Caregivers of allogeneic hematopoietic stem cell transplantation (HCT) patients experience significant distress due to the demands involved in caregiving (e.g., monitoring symptoms, managing medications, coordinating appointments). Therefore, identifying protective factors that promote coping for this population is essential. Mindfulness has been linked to reduced psychological distress and improved coping in the general population, yet its potential among HCT caregivers is not well characterized. This study examined baseline associations between mindfulness, psychological distress, and coping difficulty prior to transplant. Methods: As part of a randomized controlled trial, this study conducted a cross-sectional analysis of data from caregivers (N=279), who completed baseline measures of general trait mindfulness (FFMQ), attentional awareness (MAAS), perceived stress (PSS), depressive symptoms (CES-D), and anxiety (GAD-7). Coping was assessed through Likert items rating coping difficulty (from 0=not at all to 5=all the time) and current coping ability (from 0=none to 5=excellent). All measures were completed 1-2 weeks pre-transplant. Associations were examined using nonparametric Spearman’s rho correlations. Results: Caregivers ranged from 22-65 years old ( M =58, SD =13.5) and were mostly female (72%), White (92%), and non-Hispanic (90%); 84% had some college education or above. Higher FFMQ scores (i.e., greater trait mindfulness) were associated with lower perceived stress, r (277)=-.52, depressive symptoms, r (276)=-.60, and anxiety, r (277)=-.46. Higher MAAS scores (i.e., greater attentional awareness) were negatively correlated with perceived stress, r (277) = -.55, depressive symptoms, r (276)=-.59, and anxiety, r (277)=-.58. More coping difficulty was positively correlated with perceived stress, r (277)=.64, depressive symptoms, r (276)=.66, and anxiety, r (277)=.61. More coping difficulty was negatively correlated with total FFMQ, r (277)=-.46, and MAAS, r (277)=-.51, scores. Current coping ability was positively correlated with FFMQ, r (277)=.53 and MAAS, r (277)=.33. All reported correlations were significant at p <.001. Conclusions: Caregivers reporting higher trait mindfulness and attentional awareness experienced lower psychological distress and less coping difficulty. Based on these results, future research should examine whether mindfulness mediates the relationship between distress and coping, which was unable to be examined here since these data were cross sectional. Additionally, studies including more demographically diverse caregiver samples are needed to improve generalizability. Because mindfulness is a skill that can be cultivated through structured interventions, it may represent a modifiable target for improving caregiver distress and coping during the allogeneic HCT process. Clinical trial information: NCT05078229 .