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Clinical implementation of an online family cascade genetic testing platform: The Preventive Risk Outreach and Cascade Testing (PROACT) initiative.
10609 Background: Cascade genetic testing of relatives in families with hereditary cancer susceptibility is an essential strategy to reduce the burden of cancer through targeted risk reduction. However, current testing rates for eligible relatives are low. A promising strategy is to directly engage relatives of affected patients through an online referral service that delivers genetic risk education and the option for home genetic testing to relatives. In the recent GIFT randomized clinical trial, we evaluated an online cascade testing platform for relatives of cancer patients identified through SEER registries. Here, we asked whether a clinical genetic counseling encounter could extend the reach of this approach. Methods: We implemented a pilot project at the Stanford Clinical Cancer Genetics Program that deployed an online hereditary cancer education and germline testing platform for first- and second-degree relatives of patients with a pathogenic or likely pathogenic variant (PV/LPV) in a cancer susceptibility gene. Eligible patients had a germline PV/LPV identified within the past year, spoke English, and had at least one adult first- or second-degree relative in the United States or Canada who had not, to the patient’s knowledge, been tested for the PV/LPV. The virtual family referral service was offered to all eligible patients seen over a six-month period. Primary endpoints were the proportions of eligible relatives in the family who 1) were invited by the enrolled patient through the platform; and 2) ordered testing through the platform (processed by Color Health Inc). Here we report preliminary results from the initial project period; we will report results from the six-month project at time of presentation. Results: Between October 14, 2025 and January 20, 2026, 58 patients with germline PV/LPVs were offered the online tool and 23 patients (40%) enrolled. For these 23 patients, genetic counselors presumptively identified 191 relatives eligible for testing (70 first-degree and 121 second-degree). Patients invited 113 relatives (59%) of whom 57 (50%) accessed the tool and 50 confirmed their eligibility (no prior testing). Among confirmed eligible relatives who accessed the tool, 33 (66%) ordered testing, representing 17% (33/191) of all presumptively eligible relatives. Conclusions: Preliminary results from this clinic-based initiative to deliver cascade genetic testing through an online platform show promise. The findings suggest that an online platform can amplify the clinical genetics encounter and increase cascade testing of relatives in families with hereditary cancer susceptibility. Digital approaches to cascade testing may be particularly impactful for reaching relatives with limited access to care, where traditional cascade testing pathways are challenging. A multi-site clinical trial is planned through the PROACT Initiative.
Effect of immune checkpoint inhibitor infusion timing on overall survival in non–small cell lung cancer: A real-world retrospective study.
e20595 Background: Circadian regulation of immune function has been proposed as a modifier of immune checkpoint inhibitor (ICI) efficacy, with retrospective studies suggesting improved outcomes with earlier infusion timing. Whether these findings translate to routine oncology practice, where ICIs are administered across multiple lines, frequently combined with chemotherapy, and subject to treatment interruptions, remains uncertain. We evaluated the association between ICI infusion timing and overall survival (OS) in a real-world cohort of patients with non-small cell lung cancer (NSCLC). Methods: A retrospective cohort study included adults with NSCLC who received at least one line of ICI therapy at a community oncology center between January 2018 and December 2024. Infusion timing was defined at the patient level as morning-only ( < 1300 hours), evening-only (≥1300 hours), or mixed timing, reflecting receipt of infusions exclusively in different time-of-day categories across treatment lines. OS was measured from diagnosis to death or last follow-up. Kaplan-Meier and Cox proportional hazards models were used. Multivariable analyses adjusted for stage, ECOG performance status, body mass index, and premature ICI discontinuation. Line of therapy was excluded due to collinearity with mixed-timing classification and risk of immortal time bias. Results: A total of 127 patients were included (morning-only n = 77; mixed timing n = 36; evening-only n = 14). Staging data were available for 99.2%, and 94 deaths occurred. Median OS was 495 days for morning-only, 850 days for mixed timing, and 388 days for evening-only patients. Kaplan-Meier analysis showed no statistically significant OS differences across groups. In sensitivity analysis excluding patients with mixed infusion timing, morning-only and evening-only groups demonstrated overlapping survival curves, with no evidence of a time-of-day–specific survival advantage. In univariate analysis, mixed timing was associated with a borderline reduction in mortality compared with morning-only infusions (HR 0.63, 95% CI 0.39-1.00), while evening-only timing was not (HR 1.63, 95% CI 0.85-3.16). In multivariate analysis restricted to stage III-IV disease, infusion timing was not independently associated with OS. ECOG performance status, premature ICI discontinuation and advanced staging were the strongest predictors of mortality. Conclusions: In this real-world NSCLC cohort, ICI infusion timing was not independently associated with overall survival after adjustment for patient fitness and treatment continuity. These findings suggest that in pragmatic settings, clinical factors may outweigh subtle chronotherapy effects reported in more selected populations.
A Morphology‐Driven Cascade Delivery of Antigens for Potent T Cell Immunity
ABSTRACT Subunit vaccines are hampered by their inability to elicit robust cellular immunity and cross‐protection. The spatiotemporal fate of vaccine components within the body is key to overcoming this hurdle. Here, we report a cascade “Lymph nodes–Antigen presenting cells–Endoplasmic reticulum (LAE)” delivery strategy enabled by engineering the surface topography of nanoparticles. We designed mesoporous silica nanoparticles with smooth, short‐spiked, and long‐spiked (SNL) morphologies. Among them, SNL showed superior antigen peptide delivery and APC activation. Mechanistically, SNL enhanced Piezo1‐mediated calcium influx through mechanical stimulation, promoting dendritic cell activation and increasing antigen trafficking to the endoplasmic reticulum (ER), a key site for cross‐presentation. Capitalizing on this ER‐targeting capability, we co‐loaded the STING agonist 2′3′‐cGAMP with antigen peptides into SNL, yielding synergistic immune activation. This combination induced potent CD8 + T cell responses, delayed tumor progression in lymphoma and cervical cancer models, and conferred cross‐protective immunity in a SARS‐CoV‐2 vaccination model. Our study establishes nanoparticle morphology as an important design parameter for orchestrating the precise intracellular delivery of vaccine components, offering a generalizable platform for next‐generation vaccines.
Incidence, spectrum, and clinical outcomes of immune-related adverse events in 227 consecutive patients treated with immune checkpoint inhibitors: An Indian real-world cohort.
e23392 Background: Real-world safety data on immune checkpoint inhibitors (ICIs) from low- and middle-income countries remain limited. We evaluated the incidence, spectrum, severity, and clinical outcomes of immune-related adverse events (irAEs) in routine oncology practice in India. Methods: This single-centre observational study included 227 consecutive patients treated with PD-1, PD-L1, or CTLA-4 inhibitors between May 2024 and November 2025. irAEs were graded using CTCAE v5.0. Categorical variables were summarized as frequencies and percentages. irAEs were managed per established immunotherapy toxicity guidelines. Results: Among 227 patients, 60 (26.4%) developed ≥1 irAE, accounting for 68 total events; 8 patients experienced multiple events. Grade ≥3 irAEs occurred in 12 events (17.6%). Six Grade ≥3 events led to permanent discontinuation, affecting 4 patients (1.8%). One treatment-related death (0.4%) occurred due to myocarditis. Conclusions: In this real-world cohort, irAEs were predominantly endocrine and dermatologic and were generally manageable. Severe events were uncommon, with low rates of permanent discontinuation and mortality. Organ-system distribution and severity of immune-related adverse events (N=68 events). Organ system Events n (%) ≥ Grade 3 (n) Endocrine 36 (52.9%) 3 Dermatological 18 (26.5%) 3 Hepatic 4 (5.9%) 2 Lung 5 (7.4%) 2 Neurological 1 (1.5%) 1 Cardiac 1 (1.5%) 1 Others 3 (4.4%) 0 *Includes colitis (n=1), uveitis (n=1), and transfusion reaction (n=1).
National trends in sudden cardiac death among patients with hematologic malignancies in the United States: CDC analysis, 1999–2023.
e18622 Background: Sudden cardiac death (SCD) is a significant cause of mortality and this risk could be more pronounced in patients with hematological malignancies because of the effects of cardiotoxic therapies, systemic inflammation and comorbidity in cardiovascular disease. As survival from hematologic cancers has improved, understanding long-term population trends in SCD-related mortality has become increasingly relevant to survivorship care and cardio-oncology risk stratification. However, national long-term trends in SCD-associated mortality within this population remain poorly characterized. Methods: Death certificate data from the CDC WONDER database for adults aged ≥65 years from 1999 to 2023 were analyzed. Sudden cardiac death was defined using multiple cause of death ICD-10 codes I46.0, I46.1, and I46.9, while hematologic malignancies were identified as the underlying cause of death using ICD-10 codes C81–C96. Age-adjusted and age-specific mortality rates per 100,000 persons were calculated. Temporal trends were assessed using annual percent change (APC) and average annual percent change (AAPC) via Joinpoint regression. Results: From 1999 to 2023, 95,677 adults aged ≥65 years died from sudden cardiac death associated with hematological malignancies in the United States. The overall age-adjusted mortality rate (AAMR) was 11.69 in 1999, declining to 6.76 in 2023, with a significant downward trend over the study period (AAPC: −1.98%; 95% CI [−2.13 to −1.83]; p < 0.000001), and no joinpoints identified. AAMRs were consistently higher in men (12.00) than women (7.08), although both sexes experienced significant declines over time (males AAPC: −1.80%; 95% CI [−1.99 to −1.61]; p < 0.000001; females AAPC: −2.42%; 95% CI [−2.57 to −2.28]; p < 0.000001). Across race and ethnicity, Hispanic or Latino individuals exhibited the highest AAMR (11.86), followed by non-Hispanic Black (10.56), non-Hispanic Asian or Pacific Islander (9.50), and non-Hispanic White populations (8.97). All racial and ethnic groups demonstrated significant long-term declines, with the steepest reductions observed among Asian or Pacific Islander (AAPC: −2.71%; 95% CI [−3.17 to −2.25]; p < 0.000001). Regionally, the Northeast had the highest mortality burden (AAMR: 15.11) and the Midwest had the lowest AAMR (4.19). Conclusions: Targeted interventions are needed to address sudden cardiac death–related mortality among patients with hematologic malignancies in the United States. Efforts should focus on sustained surveillance, improved cardiovascular risk stratification, and survivorship-oriented cardio-oncology care, alongside targeted screening and prevention strategies.
Late infectious complications after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphomas (LCBL): Real-world predictors and outcomes.
7022 Background: CD19-directed CAR-T therapy is a curative option for patients (pts) with relapsed/refractory (R/R) LBCL. Infectious complications are a major source of morbidity and non-relapse mortality (NRM). While early infections are attributed to lymphodepleting chemotherapy and management of immune-related toxicities, real-world data defining predictors of late infections after CAR-T remain limited. Methods: We performed a single-center retrospective study of adult pts with R/R LBCL, including transformed indolent lymphomas, treated with anti-CD19 CAR-T. Infectious events were defined by compatible clinical features supported by laboratory, microbiologic, or radiographic evidence. Early infections were defined as ≤30 days post-infusion and late infections as >30 days. Logistic regression assessed associations with late infection risk. Multivariable models included a priori selected clinically relevant covariates. Stepwise logistic regression was performed as a sensitivity analysis. Results: Ninety-five pts were included (median age 65 years; median follow-up 32 months). Most pts received axi-cel (88%); 10% received liso-cel and 2% tisa-cel. Salvage and/or bridging therapy prior to CAR-T was administered in 59% of pts. Early infections occurred in 16% of pts, while 63% experienced late infectious complications. Among patients with late infections, 53% were in remission post CAR-T; 43% had both viral and bacterial infections over time, 33% viral only, 22% bacterial only, and 2% fungal overall. Hypogammaglobulinemia (IgG <400 mg/dL at day +30 and/or +90) occurred in 48%, and grade 4 neutropenia between days +30 and +90 in 31%. Five-year NRM was 12%, with infections contributing to 80% of deaths. On univariate analysis, hypogammaglobulinemia was associated with higher infection risk (OR 2.38, 95% CI 1.00–5.85; p=0.053). After adjustment for prespecified covariates, the association was attenuated but directionally consistent (p=0.082) and remained the only variable retained on stepwise regression. Conclusions: Infectious complications are common following anti-CD19 CAR-T therapy for R/R LBCL and occur predominantly beyond 30 days post-infusion. Hypogammaglobulinemia showed a consistent association with infection risk across multiple modeling strategies. Ongoing prospective studies will clarify the role of immunoglobulin replacement in mitigating late infectious complications in CAR-T recipients.
Prognostic and therapeutic implications of HRR gene mutations in non-cutaneous melanoma: Association with anti-PD-1 efficacy.
9537 Background: Homologous recombination deficiency (HRD) describes a tumor cell state characterized by impaired DNA double-strand break repair via the homologous recombination repair (HRR) pathway. Deficiencies in this pathway may serve as predictive biomarkers. However, the relevance of HRR gene mutations remains inadequately characterized in non-cutaneous melanoma. In this study, we aimed to delineate the mutational landscape of HRR genes in this population and evaluate their predictive implications for clinical management. Methods: We conducted a retrospective analysis of 932 patients with non-cutaneous melanoma treated at Beijing Cancer Hospital from January 2008 to January 2026. Tumor genomic profiling was performed using targeted next-generation sequencing with either an 81- (n=852) or a 425-gene (n=80) panel. Associations between HRR mutation status and survival outcomes were assessed using Kaplan-Meier survival estimates and Cox proportional hazards regression models. Results: HRR mutations were identified in 92 patients (9.9%), with the most frequent alterations occurring in ATM (3.5%), ARID1A (3.4%), BRCA2 (2.7%), and BRCA1 (1.8%). Within this HRR-mutated cohort, the primary subtypes were mucosal (44.6%) and acral (29.3%) melanoma. And the disease stages were distributed as follows: stage I, 31 patients (33.7%); stage II, 15 (16.3%); stage III, 22 (23.9%) and stage IV, 24 (25.0%). After a median follow-up of 63.7 months, the median overall survival (OS) was 57.5 months (95% CI: 43.4–71.7), with 1-, 2-, 3-, and 5-year OS rates of 92.1%, 84.9%, 74.7%, and 56.8%, respectively. Multivariate analysis confirmed age ≥65 years as an independent predictor of poorer overall survival (HR 2.7, 95% CI 1.3–5.4, P = 0.005), whereas ATM mutation emerged as a significant protective factor associated with a 68% reduction in mortality risk (HR 0.32, 95% CI 0.1–0.7, P = 0.007). Among 59 HRR-mutated patients who received first-line systemic therapy, 41 were treated with anti-PD-1-based regimens and 18 with non-PD-1-based regimens. In the 54 evaluable patients, median progression-free survival (PFS) was 9.0 months (95% CI: 3.8–14.2) and median OS was 55.0 months (95% CI: 39.0–71.0). The objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 61.1%. The DCR was 77.8% (21/27) in the mucosal subgroup versus 37.5% (6/16) in the acral subgroup with a statistically significant difference (P = 0.028). In a subgroup analysis, although not statistically significant, anti-PD-1-treated patients trended toward a longer median PFS compared with those not receiving anti-PD-1 therapy (15.0 vs. 6.0 months, P = 0.249). Conclusions: HRR mutations define a distinct molecular subset in non-cutaneous melanoma. ATM mutation serves as an important prognostic biomarker, and patients with HRR-mutated melanoma may derive survival benefit from anti-PD-1 immunotherapy.
Comparing sequencing methods to detect chimeric sites for ex vivo cell and gene therapy and developing ISAL: A bioinformatics tool to monitor clonal dynamics of chimeric sites.
e15204 Background: Ex vivo cell and gene therapies such as autologous CAR-T cells recently have emerged as core modality for targeted gene delivery. Distinctly, allogeneic stem cell-mediated gene therapy provides an advantage of scalable production through long-term expansion; among stem cells, mesenchymal stem cells (MSC) offer additional value as versatile cellular vehicles for their innate homing properties to cancer and injured sites via chemokine signals. Using integrating vectors such as retroviral vectors to introduce stable ex vivo transgene expression raises a concern for insertional mutagenesis. In this study, we have developed ISAL (Integration Site Analysis of LTR), bioinformatics workflow designed to monitor clonal dynamics of chimeric sites, compared performance of sequencing methods in various contexts, and evaluated the long-term clonal diversity and genomic safety of allogeneic MSC transduced with a bacterial suicide gene, cytosine deaminase (CD). Methods: MSC/CD (MSC transduced for CD gene expression) were analyzed at various time points throughout long-term culture. ISAL was used to compare the performance of sequencing methods—whole genome sequencing (WGS), restriction-enzyme mediated amplification, and LTR-specific amplification—to detect integration sites with varying heterogeneity. After identifying the optimal sequencing method, we tracked clonal dynamics and annotated integration sites to assess potential tumorigenicity associated with long-term expansion. Results: LTR-specific amplification was selected for its top performance and in conjunction with ISAL, achieved accuracy of 99% and detection limit of 1% clonal purity, outperforming WGS and restriction-enzyme mediated amplification in heterogeneous contexts. While clonal diversity decreased over long-term culture, genomic profile of insertion sites remained consistent. No emergence of prominent integration sites near tumorigenic regions was observed, suggesting that genomic stability was maintained throughout the long-term expansion. Conclusions: ISAL is an efficient tool for monitoring genomic stability in cell and gene therapy. Our findings suggest that observed clonal reduction may reflect the innate heterogeneity of stem cells and varying stemness potential rather than the emergence of dominant, potentially malignant clones. This bioinformatic profiling underscores the genomic stability of cell and gene therapy including ex vivo CAR-T cells and engineered allogeneic MSC and facilitates their clinical application for gene therapy.
Sonesitatug vedotin (Sone-Ve) monotherapy in patients (pts) with claudin 18.2–positive (CLDN18.2+) advanced or metastatic gastric or gastroesophageal junction (GEJ) cancers: Data from CLARITY-PanTumor01.
4023 Background: Sone-Ve (AZD0901), an antibody-drug conjugate comprising an anti-CLDN18.2 antibody and monomethyl auristatin E, showed promising antitumor activity and a manageable safety profile in pts with advanced or metastatic gastric/GEJ cancers in the first-in-human study conducted in China. Methods: CLARITY-PanTumor01 is an ongoing, global, phase 2 study (NCT06219941) evaluating Sone-Ve in gastric/GEJ cancers, PDAC, and BTC outside of China. Here we report data for pts with CLDN18.2+ advanced or metastatic gastric/GEJ cancers and ≤2 lines of prior systemic therapy (substudy 1) receiving Sone-Ve 2.2 mg/kg IV Q3W (pts randomized to 1.8 mg/kg are not reported). Primary endpoints were safety and objective response rate (ORR; 30 pts were selected to estimate ORR; lack of efficacy is concluded if ≤6 confirmed responses). Secondary endpoints included duration of response (DoR) and progression-free survival (PFS). Molecular responses (MRs) based on circulating tumor DNA (ctDNA) were evaluated. Results: As of Oct 31, 2025, 67 pts received Sone-Ve 2.2 mg/kg, including 30, 31, and 6 pts from the randomized (RC), paired biopsy (PBC), and Japanese safety (JSC) cohorts, respectively. All pts had adverse events (AEs; grade ≥3 in 34.3% overall, 36.7% of the RC, and 35.5% of the PBC). The most common grade ≥3 AEs were neutrophil count decreased (7.5%), anemia (7.5%), vomiting (6.0%), and nausea (6.0%). Dose reductions were most commonly due to gastrointestinal (GI) AEs and occurred in 40.3% of pts overall, 56.7% of the RC, and 19.4% of the PBC (adoption of a 4-drug antiemetic regimen improved GI tolerability in the PBC). The ORR was 28.4% (95% CI: 18.0–40.7). Median DoR has not yet been reached. Additional data are in the Table. Among evaluable pts, 58.6% (17/29) had sufficient baseline ctDNA levels to enable MR analysis; of these, 10 (58.8%) had at least a partial MR (>50% ctDNA reduction) within 2 cycles of Sone-Ve initiation. Conclusions: Sone-Ve 2.2 mg/kg demonstrated clinically meaningful efficacy and a manageable safety profile consistent with the first-in-human study. ctDNA MRs were observed in over half the evaluable pts. Clinical trial information: NCT06219941 . RC(n=30) PBC (n=31) Total*(n=67) ORR, % (95% CI) † 26.7 (12.3–45.9) 29.0 (14.2–48.0) 28.4 (18.0–40.7) Best overall response, n (%) † Complete response Partial response Stable disease Progressive disease Not evaluable 2 (6.7)6 (20.0)14 (46.7)7 (23.3)1 (3.3) 1 (3.2)8 (25.8)18 (58.1)4 (12.9)0 3 (4.5)16 (23.9)35 (52.2)12 (17.9)1 (1.5) 6-month response rate, % (95% CI) 87.5 (38.7–98.1) NC (NC–NC) 71.9 (39.2–89.1) PFS † Events, n/N (%) Median, months (95% CI) 6-month, % (95% CI) 22/31 (71.0)4.2 (2.9–8.6)44.8 (26.5–61.6) 19/31 (61.3)3.1 (2.8–5.5)30.3 (13.3–49.3) 47/68 (69.1)4.2 (3.0–7.0)39.9 (27.7–51.9) NC, not calculable. *Includes the JSC. † Investigator-assessed per RECIST v1.1.
Implementing ASCO’s PGA at an NCI-designated comprehensive cancer center.
e13764 Background: Randomized controlled trials demonstrate that geriatric assessments (GA) improve outcomes for older adults with cancer. ASCO recommends GA for patients aged ≥65 years prior to initiating therapy and endorses the Practical Geriatric Assessment (PGA) as a guideline concordant tool. However, cited barriers to implementation of GA include workflow burden, time constraints, and staffing limitations. Our objective was to implement an EHR-integrated PGA questionnaire embedded within routine oncology clinic visit intake at an NCI-designated Comprehensive Cancer Center and evaluate PGA completion and documentation. Methods: We integrated the questionnaire components of the PGA, consisting of 19 questions that address 7 health domains, into an EHR delivery platform and administered the questionnaire on a tablet during new-patient check-in. A programmed structured documentation template enables scored results to populate in the clinical encounter note with an embedded EHR-linked order set to facilitate concordant supportive care referrals. Eligible patients are aged ≥65 years seen for a new patient oncology visit. A rule-based algorithm identified new-patient encounters, triggering automatic assignment of the PGA at visit creation. Pre-specified implementation outcomes included PGA initiation and completion at check-in, provider documentation uptake via the structured documentation template, and referrals generated through the PGA-linked order set. The implementation pilot period is 11/19/2025-6/1/2026. Results were analyzed using descriptive statistics. Results: During the first two months of implementation, 236 new oncology patient visits were eligible for the PGA. The EHR-based algorithm successfully assigned the electronic PGA to 224 of 236 eligible visits (94.9%). Of these, 131 patients (58.5%) signed into a tablet at check-in, (surrogate marker for tablet receipt). Among patients who received a tablet, 113 of 131 (86.3%) answered PGA questions. Mean completion time was 9.35 minutes (SD 5.39). On average, 15.8 of the 19 questions were answered. PGA results were incorporated into provider documentation for 18 encounters (8.0%), representing six unique providers. Two referrals were placed via the PGA-linked order set. Conclusions: Early results suggest this EHR native approach offers a scalable framework for implementing guideline recommended GA. Additional stakeholder education is planned during this pilot to increase tablet receipt during check-in and physician review and use of data to support geriatric assessment guided management plans. Updated results will be presented at the annual meeting.
Survival outcomes according to ramucirumab (RAM)-related hypertension (HTN) in patients (pts) with advanced HER2-negative gastric (G) or gastro-esophageal junction (GEJ) cancer: An exploratory analysis of the phase III ARMANI trial.
4051 Background: Retrospective studies suggest an association between treatment-related HTN and improved outcomes with anti-angiogenic agents, with most evidence derived from colorectal cancer pts treated with bevacizumab. Data on the prognostic significance of RAM-induced HTN are limited. We therefore explored the association between treatment-related HTN and survival outcomes in the ARMANI trial. Methods: ARMANI was a phase III trial enrolling pts with advanced HER2-negative G/GEJ cancer who had disease control after a 3-month first-line fluoropyrimidine and oxaliplatin (FOX) induction chemotherapy. Pts were randomized to switch maintenance with paclitaxel plus RAM (PTX-RAM) or the continuation of FOX. The objectives of this exploratory analysis were to evaluate the association between grade (G)≥2 HTN and survival outcomes across treatment arms (using the FOX arm as reference [ref]) and within the PTX–RAM arm. To mitigate time-related bias, Cox proportional hazards models were fitted with HTN modeled as a time-dependent covariate, considering pts ‘non-HTN’ until G≥2 HTN onset and ‘HTN’ thereafter. Because HTN is a post-randomization event, survival analyses in the PTX-RAM arm by HTN status were adjusted for baseline characteristics using inverse probability weighting based on propensity scores derived from a logistic regression model. Results: Among 276 pts (141 in PTX-RAM and 135 in FOX arm), G≥2 HTN occurred in 20 cases (7.2%), all observed in the PTX-RAM arm (20/141, 14.2%). The incidence of G≥2 HTN was similar between males and females (15.8% versus 10.9%) and between pts aged < 70 and ≥70 years (14.4% versus 13.5%). Median time to G≥2 HTN-onset was 3 months. In the between-arm comparison, the PTX–RAM arm showed improved progression-free survival (PFS) versus FOX regardless of HTN development (p = 0.192). In contrast, the overall survival (OS) benefit was greater in the HTN group (p = 0.071). These findings are detailed in the Table below. In analyses restricted to the PTX–RAM arm, G≥2 HTN onset was associated with improved OS (HR 0.43; 95% CI, 0.22-0.83; p = 0.033), whereas no significant difference was observed for PFS (HR 0.88; 95% CI, 0.50-1.57; p = 0.735). Conclusions: The development of G≥2 HTN was associated with a significant OS benefit in pts treated with PTX–RAM in the ARMANI trial. These findings support further research to identify biomarkers predictive of HTN onset to refine pts selection for switch maintenance strategies. Clinical trial information: NCT02934464 . Median PFS (months) (95% CI) HR (95% CI) Median OS (months) (95% CI) HR (95% CI) FOX 3.5 (2.8−4.2) ref 10.5 (8.5−13.5) ref PTX-RAM (non-HTN) 6.5 (5.8−7.7) 0.44 (0.32−0.60) 12.2 (10.6−14.4) 0.65 (0.49−0.87) PTX-RAM (HTN) 9.0 (4.2−16.9) 0.61 (0.38−0.99) 24.6 (13.3−64.4) 0.39 (0.22−0.69)
Restrictive trial eligibility criteria as a barrier to clinical trial enrollment among veterans with aerodigestive cancers.
e13524 Background: Clinical trials are critical to advancing cancer care, yet enrollment remains low, with only 7.1% of adults with cancer enrolling in treatment trials nationally. We sought to characterize reasons for non-enrollment among patients screened for clinical trial participation at two VA Medical Centers, where Veterans often present with higher comorbidity burden that may disproportionately affect trial eligibility. Methods: We conducted a retrospective chart review of 76 consecutive Veterans screened for eligibility in oncology clinical trials for lung and esophageal cancers between 2021 and 2025 at the Ann Arbor and Cleveland VA Medical Centers. Demographic, disease-related, and trial-related factors were abstracted. Reasons for non-enrollment were categorized into predefined domains and descriptive statistics were used to summarize findings. Patients with multiple reasons for non-enrollment were categorized by the primary limiting factor. Results: Of 76 patients screened, 70 were ultimately not enrolled in a clinical trial, corresponding to a screen failure rate of 92.1%. Trial ineligibility at the time of screening accounted for 77% of non-enrollment cases (54/70). Among trial ineligible patients, the most frequent barrier was mismatch between disease characteristics and restrictive trial inclusion criteria (n = 34), followed by prior therapy that precluded eligibility (n = 20), and medical comorbidity (n = 3). Patient-related factors accounted for 13 cases of non-enrollment, most commonly preference for standard-of-care treatment and patient hesitation. Overall, non-enrollment was driven predominantly by trial-related eligibility constraints rather than patient refusal. Multiple concurrent barriers to enrollment were common; however, restrictive trial inclusion criteria were most often identified as the primary limiting factor. Conclusions: We highlight a critical misalignment between contemporary clinical trial eligibility criteria and the clinical realities of Veterans with aerodigestive cancers. Earlier trial referral and the availability of more pragmatic trial designs are essential to improve trial access and equity for Veteran populations. Clinical trial screening and enrollment outcomes. Category Number of Patients % of Total Patients Screened Total Patients Screened 76 100% Enrolled on any clinical trial 6 7.9% Not Enrolled 70 92.1% Mismatch between Disease Characteristics and Inclusion Criteria 34 44.7% Prior Therapy precluded inclusion 20 26.3% Medical Comorbidity 3 3.9% Patient Preference for SOC 13 17.1%
Risk and survival outcomes of Hispanic patients with germ cell tumors at a multihospital academic center.
e17007 Background: Testicular germ cell tumors (TGCTs) are the leading solid-organ malignancy of adolescent/young adult males. National data has noted a rising incidence in all racial/ethnic groups, most rapidly in Hispanics who also have worse prognosis and advanced disease at diagnosis. We sought to explore differences between Hispanic white (HW) and non-Hispanic white (NHW) patients with TGCTs. Methods: We identified patients with pathologically confirmed TGCT treated from 2015 to 2022 at two major referral centers in southern California with a large HW population. Demographic, clinical, treatment, and outcome data was collected, including race/ethnicity, age, location of initial presentation to care, insurance type, TNMS stage, histology, location of metastases, and IGCCCG risk score. Differences between HW and NHW patients were evaluated using Kruskal-Wallis rank sum for numeric variables and Chi-square tests for categorical variables. Cox proportional hazards model was utilized for univariate analyses of OS, PFS, and RFS, which were censored at last follow-up or event of interest. Results: Among 124 NHW and 176 HW patients, 5-year OS was 94.1%, PFS was 75.4%, and RFS was 73.2%. HW patients were younger at diagnosis (29 vs 31 years, P = 0.026), more likely to initially present to acute services (68% vs 42%, P <0.001) and have public insurance (77% vs 21%, P <0.001). No difference in risk prevalence was found in HW patients with seminoma; however, HW patients with nonseminoma had higher prevalence of intermediate/poor risk disease (40% vs 22%, P = 0.014), had higher prevalence of non-retroperitoneal lymph node metastases (21% vs 7%, P = 0.012), and were more likely to require chemotherapy initiation before orchiectomy (16% vs 3%, P = 0.032). Stage III disease was associated with worse OS (HR = 4.96, 95%CI 1.03-23.9, P = 0.046) and PFS (HR = 2.76, 95%CI 1.48-5.14, P = 0.001). Poor risk disease was associated with worse OS (HR = 30.1, 95%CI 6.37-142, P < 0.001), RFS (HR = 3.29, 95%CI 1.72-6.32, P < 0.001), and PFS (HR = 6.29, 95%CI 3.61 -10.9, P < 0.001). HW ethnicity was not associated with worse survival in stage III or poor risk cohorts. Conclusions: In a multihospital cohort with significant HW representation, HW patients with nonseminoma had more prevalent advanced stage and poor risk disease. Poor risk and stage III disease was found to be associated with worse survival and prognostic outcomes, independent of ethnicity. Hispanic N=176 Non-Hispanic White (N=124) Total (N=300) P-value Presented to Clinic (vs Acute) 30 (17.0%) 42 (33.9%) 72 (24.0%) <0.001 Private (vs Public) Insurance 36 (20.5%) 89 (71.8%) 125 (41.7%) <0.001 Good Risk 128 (72.7%) 96 (77.4%) 224 (74.7%) 0.197 Intermediate Risk 27 (15.3%) 13 (7.4%) 40 (13.3%) Poor Risk 21 (11.9%) 12 (9.7%) 33 (11.0%) Nonseminoma 105 (59.7%) 73 (58.9%) 178 (59.3%) 0.834 Seminoma 67 (38.1%) 49 (39.5%) 116 (38.7%) Teratoma 64 (36.4%) 38 (30.6%) 102 (34.0%) 0.238
Anti-tumor activity of Man 9 x PS targeting immunotherapies in diffuse intrinsic pontine glioma (DIPG) and pancreatic cancers.
2530 Background: Aberrant cell-surface glycans and lipids are attractive immunotherapy targets due to their stable tumor expression. High-mannose glycan mannose-9 (Man9), and phosphatidylserine (PS) are co-expressed across multiple malignancies and contribute to immune suppression. We developed Man9×PS-targeting effector immunotherapy platforms for the treatment of solid tumors, with a focus on pancreatic cancer and diffuse intrinsic pontine glioma (DIPG). Methods: The Man9×PS×CD3 trispecific T cell engager (TCE), VTRU200, was expressed and purified from CHO cells. The Man9×PS CAR T cell, VCAR300, was generated from murine splenic T cells transduced with a Man9×PS CAR-encoding viral vector. In vitro tumor cytotoxicity of VTRU200 was assessed using human T cells co-cultured with cell lines (PANC-1, AsPC-1) or patient-derived primary cultures (DIPG-008, DIPG-011) and compared with bispecific Man9×CD3 or PS×CD3 controls. Tumor selectivity and potential off-target binding were evaluated by immunohistochemistry (IHC) on pancreatic and breast tumors with matched normal tissues, and by immunofluorescence (IF) across a panel of 33 normal human tissues. In vivo dose escalation of VCAR300 was evaluated by bioluminescence imaging in a Panc02 murine orthotopic pancreatic tumor model. Cancer stem cell binding was verified by co-staining with anti-CD133 antibody. Previously, VTRU200 was evaluated in syngeneic, xenograft, and patient-derived xenograft (PDX) acute myeloid leukemia (AML) models, and VCAR300 persistence was tested in a pilot orthotopic pancreatic cancer model. Results: VTRU200 demonstrated potent, target-dependent cytotoxicity with 0.1-5 nM EC50 values across multiple solid tumor cell lines in the presence of human T cells. Cytotoxicity required engagement of both Man9 and PS, with additive effects relative to bispecific controls. IHC demonstrated strong staining in pancreatic and breast tumors with absence of staining in corresponding paired normal tissues, while there was no detectable reactivity across normal human tissue panels by IF. Consistent with prior AML studies showing robust anti-leukemic activity, VCAR300 exhibited high anti-tumor activity in vitro with an effector:target ratio at 50% maximum killing (ET50) of less than 1, and in a murine orthotopic pancreatic cancer model (25-fold reduction in tumor size after 2 weeks of treatment with 2x10 6 CAR T/mouse) with an excellent safety profile. Anti-tumor activity was associated with tumor stem cell targeting and release of inflammatory cytokines. Conclusions: Man9 x PS dual targeting is a promising strategy for treating solid tumors. VTRU200 and VCAR300 are potential therapeutic candidates with potent anti-tumor activity across multiple tumor types and impressive safety. Following a successful pre-IND interaction with the FDA, first-in-human studies are planned to initiate in 2027.
Projected trends in ischemic heart disease mortality among patients with multiple myeloma in the United States: A forecast analysis through 2035.
e19544 Background: With progress in the treatment of multiple myeloma (MM), survival has improved significantly, and long-term mortality is being transferred to causes other than malignancy. Ischemic heart disease (IHD) has become a major cause of death in MM patients, influenced by aging, common cardiovascular risk factors, treatment outcomes. While earlier population-based studies had shown decreasing IHD mortality in the early 2020s, recent results suggest that these trends have attenuated with remaining sex, race, age, geographic disparities. The trend of mortality from IHD in MM remains unclear. We are attempting to predict national and subgroup-specific trends in IHD mortality among MM patients in the United States up to 2035. Methods: Using CDC WONDER multiple-cause-of-death data from 1999–2023, previously estimated age-adjusted mortality rates (AAMRs) and Joinpoint-derived annual percent changes were used to construct log-linear forecast models. Projections were generated for 2024–2035 overall and stratified by sex, race/ethnicity, age group, and U.S. region. Forecasts incorporated observed post-2018 trend attenuation to account for emerging plateau or reversal patterns. Outcomes are reported as projected AAMRs per million population. Results: Under base-case projections, overall IHD-related mortality among MM patients is expected to stabilize rather than continue declining, with AAMRs plateauing between 4.8–5.2 per million by 2035. Male patients are projected to maintain substantially higher mortality than females, with the sex gap narrowing minimally over time. Black patients are forecasted to experience the highest absolute IHD mortality burden through 2035, with projected AAMRs remaining nearly 1.6–1.8× higher than those of White patients. The ≥85-year age group is expected to account for an increasing proportion of IHD-related deaths, driven by improved MM survivorship. Regionally, the Northeast is projected to continue demonstrating the highest mortality rates, with limited convergence across U.S. regions. Conclusions: Using this national forecasting analysis, we predict IHD–attributed deaths will plateau in patients with MM through 2035 instead of continuing to decrease. Disparate outcomes by sex, race, age, and geography will likely endure, but with greater mortality among male ,Black patients, and an increasing burden in older age group. These data highlight the importance of incorporating CVD risk screening and targeted prevention strategies into long-term survivorship care in patients with MM, particularly high-risk groups. Observed and projected AAMR of IHD among patients with MM. Population Group Observed AAMR 2023 Projected AAMR 2030 Projected AAMR 2035 Overall 4.9 5.0 5.1 Male 8.3 8.5 8.7 Female 2.5 2.6 2.6 Black 9.1 9.4 9.6 White 5.3 5.4 5.5 Hispanic 4.1 4.0 4.0 Age ≥85 years 22.8 24.5 26.1 Northeast 6.4 6.6 6.8
Implementing a clinical research coordinator–led care delivery model (CRC model) in an early-phase oncology program: A pilot to streamline workflow, improve collaboration, and enhance patient-centered trial conduct.
1585 Background: Early-phase oncology trials involve medically complex patients with narrow enrollment windows. Traditionally, CRC roles focused on data management and scheduling, with limited integration into visit-based workflows, creating gaps in protocol execution and prescreening. This pilot embedded CRCs into patient-facing workflows to improve visit preparedness, protocol reliability, and enrollment readiness in biomarker-driven Phase I trials. Methods: CRCs were embedded alongside investigators and research nurses during patient visits to support coordination of protocol requirements. This included standardized patient schedule education; CRC-led week-ahead planning; proactive symptom monitoring with escalation pathways; multidisciplinary supportive care coordination; and prescreening/enrollment support for biomarker-driven trials, including tissue tracking and coordination of enrollment-sensitive testing timelines. A pre- and post-evaluation was conducted. Active patients during matched 8-month pre- and post-implementation periods were identified through a CRC-maintained prescreening tracker and electronic health record review. Protocol deviations were categorized by primary attribution. Visit preparedness, timeliness of symptom escalation, supportive care coordination, and prescreening workflow adoption were assessed. Statistical significance was evaluated using the Wilcoxon signed-rank test. Results: Scheduling protocol deviations decreased from 42 pre- to 20 post-implementation (52% reduction), driven by fewer missed or delayed assessments and communication gaps. CRC-led week-ahead reviews improved visit preparedness, with assessment-related deviations decreasing from 37 to 4 over matched 8-month periods (~89% reduction). CRC presence centralized protocol and logistical oversight, supporting timely trial readiness in Phase I. CRC-led prescreening improved visibility into tissue availability, biomarker testing status, and cohort eligibility. Mean time to tissue submission decreased from 9 business days pre-implementation (range, 2–25; n = 20) to 2.2 business days post-implementation (range, 1–4; n = 20; p = 3.54 × 10⁻⁵). Across three tissue-dependent interventional trials, identification of patients meeting protocol-specified eligibility criteria increased from 39 to 59 over matched 8-month periods (51.3% increase). Conclusions: Adopting a CRC model improved operational reliability and prescreening efficiency, enabling faster tissue submission, quicker identification of biomarker-eligible patients, and top of scope team function. Programs facing trial complexity or staffing constraints may benefit from CRCs in visit support and prescreening roles to improve efficiency and trial access.
Palliative care utilization and disparities among adults with advanced cancer hospitalized for sepsis: A National Inpatient Sample analysis (2018–2021).
e23194 Background: Sepsis is associated with high inpatient mortality, particularly among patients with advanced cancer. Although disparities in palliative care utilization are well described in oncology, palliative care delivery has been studied primarily in outpatient or elective settings. Less is known about inpatient palliative care use during acute septic hospitalizations in this population. We evaluated sociodemographic and regional disparities in inpatient palliative care utilization and associated outcomes among adults with advanced cancer hospitalized for sepsis. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2018–2021), including adults with advanced cancer hospitalized primarily for sepsis. Inpatient palliative care utilization was identified using ICD-10 diagnosis codes. Outcomes included aggressive life-sustaining treatments, in-hospital mortality, length of stay (LOS), total hospital charges, and discharge disposition. Multivariable regression models examined adjusted associations between palliative care use, patient sociodemographic factors, and hospital characteristics, accounting for the complex survey design. Results: Inpatient palliative care utilization varied by race, insurance status, hospital region, and hospital characteristics. Black patients had higher odds of receiving palliative care and lower in-hospital mortality compared with White patients, while zip-code income quartile was not associated with palliative care use. Palliative care was associated with lower odds of aggressive treatment, shorter LOS, and differences in hospital charges. Patients receiving palliative care had higher in-hospital mortality, consistent with preferential use among patients with greater illness severity. Non-White patients experienced longer hospital stays and higher charges independent of palliative care use, with substantial regional variation. Conclusions: In this national cohort of adults with advanced cancer hospitalized for sepsis, inpatient palliative care utilization was more strongly associated with hospital and regional characteristics than with neighborhood income. Higher palliative care use and lower in-hospital mortality among Black patients contrasts with prior oncology studies, suggesting palliative care delivery during acute critical illness may differ from outpatient care. These findings support more consistent integration of inpatient palliative care among adults with advanced cancer hospitalized for sepsis. Multivariable adjusted association of inpatient palliative care with outcomes. Outcome Estimate 95% CI Aggressive treatment OR 0.66 (0.64–0.69) <0.001 In-hospital mortality OR 4.23 (4.06–4.41) <0.001 Home discharge OR 0.41 (0.39–0.42) <0.001 LOS −6.2% (−7.4 to −5.0) <0.001 Total charges 2.0% (0.5–3.5) 0.011
A self-administered e-health dietary quality (DQ) assessment in patients (pts) at increased hereditary risk of cancer (CA): Feasibility and preliminary findings.
e22544 Background: Pts at increased hereditary CA risk frequently express interest in “eating healthier”. Many providers have limited nutrition training and lack user-friendly tools to gauge DQ. Computerized DQ assessment can simplify reporting of eating habits with visual cues and provides immediate feedback, allowing comparison of results to national standards (USDA Healthy Eating Index/HEI). Here, we examine feasibility and preliminary efficacy of eHealth DQ assessment in pts seen by a CA risk assessment service for genetic counseling, testing, and high-risk follow-up. Methods: Pts undergoing cancer risk assessment are invited to complete a 20-min eHealth DQ assessment (VioScreen) with repeat assessment at 3-mo (FU). Sampling is purposeful using select risk criteria (e.g., any PV+, prostate CA risk). VioScreen offers detailed DQ feedback, an HEI score (adult optimal > 80), and a dietary inflammatory index (DII) score. Pts can opt for a registered dietician (RD) consult to review DQ feedback. Demographic/survey measures are collected at baseline/FU. Goal accrual is 210 pts. Primary outcome is feasibility defined by completion of: informed consent >25% by interested pts; baseline VioScreen >75%; all study parts >50% after baseline VioScreen, and favorable acceptability (mean < 3 on 5-pt Likert). Descriptive statistics and chi-square tests are used in data reporting. Results: To date, 171 pts have expressed interest, and 73.1% (125/171) have provided informed consent. Of these, 81.6% (102/125) completed baseline VioScreen, and 55.9% (57/102) completed the study with acceptability means of 1.56-2.42. Those w/complete data (n = 57) have mean age 52.1 yrs, 84% F sex, 88% White race, 86% college degree and 65% income > $100K. > 50% have a PV in a CA risk gene, 66% are overweight/obese, and 32% are current/past smokers. 33% (19/57) consulted with an RD, and 40% reported weight loss (baseline to FU). Mean HEI (n = 57) was 71.2 baseline and 71.8 FU and was significantly lower for overweight/obese pts at both timepoints (p = 0.009 and p = 0.031, respectively). Men had larger gains in HEI (+4.9, p = 0.071), while carriers of non-BRCA1/2 mutations had significantly improved DII scores at FU (p = 0.009). Pts who met w/RD had greater numeric gains in HEI (+2.2) and DII (-0.7) (p = NS) but reported VioScreen results more difficult to understand (p = 0.017) and had less confidence in their DQ at baseline (p = 0.022) and their ability to achieve the VioScreen recommendations (p = 0.060). At FU, pts who met w/RD reported higher motivation to take vitamins/supplements (p = 0.012), while those who lost weight were more confident in their ability to be healthy (p = 0.023) and to control their health (p = 0.016). Conclusions: eHealth DQ assessment is feasible in high-risk patients. Preliminary results identify prevalent modifiable CA risk factors including suboptimal DQ and excess body weight.
Targeting PI3K-β to develop novel combinational therapies for melanoma.
2620 Background: Melanoma is the deadliest skin cancer, and more than 100,000 people in the United States were diagnosed in 2024. While the 5-year survival rate is 99% for localized disease, it is just 10-25% in metastasis. Treatment for metastatic melanoma often involves powerful immunotherapies (e.g. checkpoint inhibitors). However, approximately 55% of patients have innate resistance and 25% of responders develop resistance within two years. Immunotherapy resistance is due to continued checkpoint protein expression and antagonization of T-cell activation – processes controlled by the phosphatidyl inositol 3-kinase (PI3K) system. Of the four PI3K kinases (α, β, δ and γ), recent work from the Sheng lab suggests that PI3Kβ has the largest role in the growth of BRAF V600E /PTEN null (PI3K inhibitor) melanoma and is a prime drug target. There is an 18-residue motif found only in PI3Kβ that has close interactions with p85 - a key regulatory protein responsible for kinase activation. The Sheng lab harnessed this motif and developed a novel peptide (CPP-β18) that selectively blocks PI3Kβ with high affinity and decreases viability in cells that hyper-express PI3Kβ. Given the vital role of PI3K in immunosuppression, further investigation into CPP-β18’s sensitizing effects on checkpoint inhibitors is urgently needed to lead to new therapies. Methods: PI3K inhibition in BRAF V600E /PTEN null YUMM1.7 and BRAF V600E /PTEN WT YUMM5.2 murine cell lines was validated by exposing cells to various commercial PI3K inhibitors and CPP-β18. Cell viability was measured via MTS colorimetric response. Advanced live-cell imaging techniques were employed to assess apoptosis when melanoma cells were treated with these selective inhibitors. Both cell lines were fluorescently labeled to differentiate cells from cytotoxic T-cells in future co-culture work. Results: MTS colorimetric assays reveal decreased YUMM1.7 cell viability with various PI3Kβ inhibitors (IC 50 values = 6-10 µM) in comparison to increased YUMM5.2 cell viability (IC 50 values = 21-30 µM). PI3Kδ and PI3Kγ inhibition had negligible effect on cell survival. YUMM1.7 cell death (>70%) was also demonstrated when treated with the novel CPP-β18 peptide inhibitor. Live cell imaging studies confirm feasibility to investigate interactions between drug therapy and melanoma cells and to appreciate early and late stages of apoptosis on a cellular level. Both cell lines are successfully fluorescently labeled to undergo further drug challenge experiments. Conclusions: Our data strongly supports CPP-β18 as a potential drug therapy to augment checkpoint inhibitor efficacy and mitigate the development of resistance. Cell line validation demonstrates increased PI3K activity with deleted PTEN and decreased viability when challenged with PI3Kβ inhibitors. Selectively blocking PI3Kβ via CPP-β18 may augment checkpoint inhibitors and mitigate resistance, giving patients improved treatment options.
The impact of the COVID-19 pandemic on breast cancer stage at time of diagnosis at a major health system in New Jersey.
11142 Background: The COVID-19 pandemic led to strict social distancing protocols in all aspects of daily life creating barriers to healthcare access. This resulted in a decrease in cancer screening, including mammography, which in turn led to higher stage of breast cancer at the time of diagnosis. This is reflected in the current literature 1 . We completed a study at our institution to evaluate the impact of the COVID-19 pandemic on breast cancer screening and stage at diagnosis. Methods: We performed a retrospective chart review of patients aged 18 and older in a large New Jersey health system. IRB approval was obtained. Clinical and pathologic stage at time of breast cancer diagnosis as well as number of screening mammograms ordered and completed in the pre-COVID era (January 1, 2016 – December 31, 2019) and post-COVID era (January 1, 2020 – December 31, 2023) were evaluated. Chi-square hypothesis testing was used for data analysis. Of the 5613 patients identified, 4279 patients had clinical staging data documented. Results: Between 2016-2019, 80.1% of ordered screening mammograms were completed in our health system. As expected, the percentage of completed screening mammograms decreased to 63.7% during the peak of the COVID-19 pandemic from 2020-2021. However, this percentage further decreased to 61.8% between 2022-2023; p-value < 0.001 (Table 1). We also noted an increase in stage 0 and 1 breast cancers and a decline in stage 2-4 breast cancers during these time periods; p-value < 0.001. Conclusions: Our study demonstrates an expected decline in screening mammogram rates during the peak of the COVID-19 pandemic (2020-2021). This can be explained by the uncertainties around health care and social distancing recommendations. Despite participation in a national cancer screening campaign led by the American Cancer Society from May to December 2021, the completion rates of screening mammograms unfortunately continued to decline in the post-COVID years. Contrary to what has been reported, this study found that patients were diagnosed at an earlier stage in the post-COVID era. Our study demonstrates that completion rates of screening mammogram dropped during the COVID-19 pandemic and have not improved in the post-COVID times. We hypothesize that with longer-term studies an increase in late-stage breast cancers may be identified due to missed screening mammograms. 1. Pintican, Roxana et al. “COVID-19 pandemic resulted in more metastatic breast cancer cases at diagnosis.” Scientific reports 15,1 29296. 11 Aug. 2025, doi:10.1038/s41598-025-14582-z. Number and percentage of mammography orders completed and canceled by year. Orders Completed Orders Canceled Total 2016 – 2019 157,50780.1% 39,05419.9% 196,561100% 2020 – 2021 99,57163.7% 56,76636.3% 156,337100% 2022 – 2023 129,72261.8% 80,33038.2% 210,052100% Total 386,80068.7% 176,15031.3% 562,950100%