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Co-creating patient partnership within a national cancer trials network: Experience from Cancer Trials Ireland in partnership with the Irish Cancer Society.
11061 Background: Structured patient partnership is increasingly recognised in oncology research, yet less is known about how cancer trials groups and cancer charities can collaborate to sustain partnership system-wide. Cancer Trials Ireland (CTI) has established a patient partnership model through its Patient Consultants Committee, supported by the Irish Cancer Society (ICS), enabling integration of research infrastructure, charity support, and advocacy. Methods: The development and implementation of patient partnership at CTI from inception in 2016 was reviewed. The role of the ICS in enabling this model through funding, strategic alignment and public engagement was considered. Organisational learnings, barriers and facilitators to integration, research and strategic outputs, public outreach, clinical trial impacts, national and international collaborations, and engagement with early career investigators were synthesised from descriptive programme data and documented outputs. Results: By 2026, 33 patient partners were embedded across all adult Disease-Specific Subgroups, with patient and ICS representation in CTI governance. Key facilitators included a funded coordination role, enhanced partner recruitment, aligned public messaging, shared advocacy for clinical trial access and funding, and international research network engagement. Barriers to integration included challenges in patient diversity, competing commitments, and sustainable funding. Several were mitigated through partnership resourcing, advocacy and alignment of strategic priorities. Since 2023, patient partners have contributed to four investigator-initiated trial concepts and participated in Trial Management Groups. They contributed to grant applications, trainee research projects, and the development of a CTI climate change charter. Five patient-led, trainee-integrated research projects were delivered, resulting in international conference presentations and peer-reviewed publications. The CTI-ICS partnership supported sustainability and visibility through public engagement and policy activity, including contributions to the National Clinical Trials Oversight Group, engagement on GDPR barriers, election manifesto advocacy, and the Value of Cancer Trials campaign (co-launched with ICS and a patient partner). These findings demonstrate feasible integration of patient partners into a national cancer trials network at scale. Conclusions: A structured partnership between a national cancer trials organisation and a cancer charity can accelerate and sustain patient partnership beyond individual studies, embedding patient perspectives across trial selection, development, and dissemination. This experience complements cooperative group frameworks and offers a replicable approach for oncology research systems.
Understanding palliative care gaps in young adult ovarian cancer: A population-based study of 37,880 hospitalizations.
5557 Background: Palliative care (PalC) improves both quality of life and survival compared to usual care. Despite this, significant implementation gaps persist due to delayed or absent utilization. This study examines the determinants, trends, clinical profiles, and outcomes of PalC among young women hospitalized with ovarian cancer. Methods: We identified ovarian cancer patients among young adults aged 18-45 years using the National Inpatient Sample (NIS) from 2016-2022. We first estimated the prevalence of PalC utilization and then developed a multivariable logistic regression model to estimate the association of demographic, clinical, and hospital-level variables with PalC use. The in-hospital mortality burden associated with PalC receipt was also estimated. Results: We found 37,880 ovarian cancer young adults with 8.78% using PalC. Several variables were associated with PalC utilization. Clinical comorbidities demonstrated the strongest associations: metastatic cancer( aOR 4.123, 95% CI: 3.385-5.023, p<0.001), frailty (aOR 3.407, 95% CI: 2.803-4.142, p<0.001), and cachexia (aOR 3.817, 95% CI: 2.460-5.922, p<0.001). Depression was also significantly associated with PalC utilization (aOR 1.360, 95% CI: 1.056-1.751, p=0.017). Temporal trends revealed increasing PalC utilization in more recent years compared to 2016, with significantly higher odds in 2020 (aOR 1.412, 95% CI: 1.005-1.985, p=0.047) and 2021 (aOR 1.565, 95% CI: 1.122-2.184, p=0.008). Weekend admissions were associated with 38.2% higher odds of PalC receipt (aOR 1.382, 95% CI: 1.107-1.727, p=0.004), and each additional year of age increased odds by 1.5% (aOR 1.015, 95% CI: 1.001-1.029, p=0.034). Insurance status significantly influenced PalC receipt. Compared to Medicare beneficiaries, patients with private insurance had 36.6% lower odds of receiving PalC (aOR 0.634, 95% CI: 0.452-0.890, p=0.008), while self-pay patients had 51.1% lower odds (aOR 0.489, 95% CI: 0.293-0.816, p=0.006). Additionally, patients from the highest income quartile had 25.7% lower odds of PalC compared to those in the lowest income quartile (aOR 0.743, 95% CI: 0.555-0.996, p=0.047). Race, hospital location/teaching status, hospital region, and hospital bed size were not significantly associated with PalC receipt. The overall in-hospital mortality rate was 3.0%, with stark differences by PalC receipt: 21.5% among those receiving PalC versus 1.22% among those not receiving PalC (aOR 16.532, 95% CI: 11.205-24.389, p<0.001). Conclusions: Among hospitalized young adults with ovarian cancer, fewer than 1 in 10 received PalC. Services concentrated among patients with metastasis, frailty, and cachexia, suggesting late rather than early integration. Significant disparities by insurance and income highlight access barriers requiring intervention for equitable PalC integration into comprehensive cancer care.
Effects of prophylactic fibrin glue on post-gastric ESD bleeding in gastric neoplasm: A meta-analysis of randomized controlled trials.
e16148 Background: Post-procedural bleeding remains a significant complication following gastric endoscopic submucosal dissection (ESD), occurring in up to 15% of cases. Fibrin glue has been proposed as a protective barrier to mitigate this risk. We conducted a meta-analysis of randomized controlled trials (RCTs) to synthesize current evidence regarding the efficacy of fibrin glue in preventing post-ESD bleeding. Methods: A systematic review identified three RCTs (Kim 2025, Lee 2023, Kataoka 2019) comparing fibrin glue application versus standard care in patients undergoing gastric ESD. A total of 636 patients were included (318 fibrin glue; 318 standard care). The primary outcome was overall post-ESD bleeding within 4 weeks. Secondary outcomes included acute ( < 24 hours) and delayed ( > 24 hours) bleeding. Pooled risk ratios (RR) were calculated using random-effects models. Results: The analysis revealed no significant reduction in overall post-ESD bleeding with fibrin glue compared to control (9.7% vs. 10.7%; RR 0.91, 95% CI 0.57–1.44). Heterogeneity for the primary outcome was negligible (I 2 = 0.0%), indicating highly consistent findings across studies. Furthermore, no significant differences were observed in secondary outcomes, including acute bleeding (RR 0.72, 95% CI 0.15–3.44) or delayed bleeding (RR 1.11, 95% CI 0.52–2.36). While acute bleeding rates were numerically lower in the intervention group (3.9% vs. 5.5%), this did not reach statistical significance. Conclusions: Based on high-quality evidence from recent RCTs, prophylactic fibrin glue application does not significantly reduce bleeding rates following gastric ESD. The data suggest that routine use of fibrin glue is unwarranted in the general patient population. Future research should pivot toward identifying specific high-risk subgroups that may derive benefit, rather than unselected prophylaxis.
<i>CCND1</i> amplification and breast cancer–specific survival in estrogen receptor–positive, HER2-negative disease.
e12723 Background: Amplification of Cyclin D1 ( CCND1 ) is common in estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER⁺/HER2⁻) breast cancer and has been implicated in resistance to hormone therapy. However, the prognostic value of CCND1 amplification in clinically defined luminal breast cancer treated with hormone therapy remains unclear. This study evaluated the association between CCND1 amplification and breast cancer–specific survival (BCSS) in Luminal A and Luminal B breast cancer. Methods: For this retrospective cohort study, patients were identified from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. Analyses were restricted to ER⁺/HER2⁻ Luminal A and Luminal B tumors treated with hormone therapy, with or without chemotherapy. CCND1 amplification was defined as a GISTIC copy-number score ≥+2. The primary endpoint was BCSS, defined as time from diagnosis to breast cancer–specific death, with other deaths censored . BCSS was estimated using Kaplan–Meier methods and compared with log-rank tests. Multivariable Cox proportional hazards models adjusted for histologic grade, tumor size, and lymph-node status were constructed. Sensitivity analyses included restriction to patients treated with hormone therapy alone and those with ≥12 months of follow-up. Results: Among 751 eligible patients, CCND1 amplification was present in 22%. On Kaplan–Meier analysis, five- and ten-year BCSS were 79% and 62% in amplified tumors versus 90% and 78% in non-amplified tumors, respectively (log-rank P < 0.001). CCND1 amplification was associated with worse BCSS in the primary cohort (hazard ratio [HR] 1.64; 95% CI, 1.22–2.27; P = 0.002). This association persisted in patients treated with hormone therapy alone (HR 1.76; 95% CI, 1.27–2.44; P < 0.001) and in those with ≥12 months of follow-up (HR 1.66; 95% CI, 1.22–2.27; P = 0.001). Subtype-specific analyses suggested a stronger association in Luminal A tumors than in Luminal B tumors. Conclusions: CCND1 amplification is associated with reduced BCSS in ER⁺/HER2⁻ luminal breast cancer treated with hormone therapy. These findings support further evaluation of CCND1 copy-number status as a prognostic marker in luminal breast cancer.
Outcomes following surgery versus non-surgical management for gallbladder cancer patients presenting with jaundice: A systematic review and meta-analysis.
e16230 Background: Gallbladder cancer (GBC) presenting with obstructive jaundice typically indicates advanced disease and poor prognosis. There remains no consensus on whether surgical resection or non-surgical management offers superior outcomes. We conducted a systematic review and meta-analysis to compare survival, morbidity, mortality and quality of life in jaundiced GBC patients undergoing surgery versus non-surgical approaches. Methods: PubMed, Embase, Scopus, Google Scholar were searched for studies reporting outcomes in jaundiced GBC patients treated surgically or conservatively. Eligible studies included prospective or retrospective cohorts comparing overall survival, disease-free survival, perioperative mortality, and complications. Data were extracted by two reviewers, and pooled analyses were conducted using random-effects meta-analysis, calculating hazard ratios (HR) or risk ratios with 95% confidence intervals. Results: Six studies (five retrospective, one prospective) with 800 patients were included. Resectability in jaundiced GBC ranged from 27-62%. Surgical patients had significantly longer median survival (20 months) versus non-surgical patients (median 6 months). Pooled HR for mortality was 0.35 in favor of surgery. One-year survival with surgery was 40–70%, versus < 30% with non-surgical treatment. However, surgical morbidity exceeded 50% in some series, with perioperative mortality up to 7%. Notably, jaundice remained an adverse prognostic factor post-resection (HR 2.2). Conclusions: Surgery in selected jaundiced GBC patients confers a survival benefit over conservative management, though with high risks. Conservative treatment yields dismal outcomes. Given selection bias and lack of randomized trials, individualized decision-making and further research are warranted.
National trends for cervical cancer–related mortality rates from 1999-2020: A National Inpatient Sample–based analysis.
e17517 Background: Cervical cancer is a malignant epithelial tumor that forms in the cervix of the uterus, caused primarily by the persistent infection with sexually transmitted human papillomavirus (HPV). It is the fourth most common malignancy in women with nearly half a million women diagnosed with cervical cancer annually worldwide. We aim to analyze the trends for cervical cancer-related mortality in adult females in the United States stratified by age, race and ethnicity, and region. Methods: Using the CDC WONDER mortality database, we determined age-adjusted mortality rates (AAMRs) and crude death rates (CRs) per 100,000 females aged 25 and above from 1999 to 2020. Changes in CRs and AAMRs were determined through annual percentage changes (APCs) and average annual percentage changes (AAPCs) using Joinpoint regression. Results: From 1999-2020, cervical cancer caused a total of 99,994 deaths in adult females across the US. The overall AAMR declined from 4.90 in 1999 to 3.85 in 2020, demonstrating a significant decreasing trend (AAPC: -1.34, 95% Confidence Interval (CI), -1.47 to -1.19). Non-Hispanic (NH) Black or African American experienced the highest mortality (AAMR: 6.97), followed by Hispanic or Latino (4.61), NH American Indian or Alaska Native (AAMR: 4.55), NH White (3.61), and NH Asian or Pacific Islander (3.14). Despite the highest mortality burden, NH Blacks showed the highest decrease in mortality (AAPC: -2.76, 95% CI: -3.01 to -2.44), and NH Whites showed the lowest (AAPC: -0.89, 95% CI: -1.09 to -0.66). Regionally, the mortality burden was the highest in the South (AAMR: 4.63), followed by the Midwest (3.85), the West (3.7), and the Northeast (3.60). Among the census regions, the Northeast showed the highest decline in mortality (AAPC: -2.41, 95% CI: -2.66 to -1.97), while the Southeast showed the lowest (AAPC: -1.00, 95% CI: -1.26 to -0.7) despite having the highest burden. Non-metropolitan areas (AAMR: 4.72) had higher mortality than metropolitan areas (3.94) and experienced almost half the decline as in the metropolitan areas (AAPCs: -0.76 vs 1.37 respectively). Mississippi (6.21) and Arkansas (5.87) had the highest state AAMRs, while Utah (2.60) and Massachusetts (2.32) had the lowest. Conclusions: Our analysis shows a significant decline in cervical cancer-related mortality among adult females across the US, particularly in NH Black or African American women. However, NH Whites, the Southern region, and the non-metropolitan areas showed the least decline despite having the highest mortality burden. Targeted healthcare policies are needed to address these disparities.
Distinct immunologic vs progenitor landscapes in myeloid leukemia recurrence: Adaptive immune persistence in pediatrics vs niche exhaustion in adults.
10021 Background: Recurrent myeloid leukemia remains a therapeutic challenge with distinct clinical trajectories across age groups. While our parallel study identified a "universal adipogenic shift" in the marrow stroma common to all ages, the specific cellular drivers distinguishing pediatric from adult relapse remain undefined. We hypothesized that against this shared stromal background, the mechanism of recurrence diverges: the pediatric marrow mounts an adaptive immune response, whereas the aging adult marrow suffers from hematopoietic reservoir depletion. Methods: We analyzed the tumor microenvironment (TME) of 2,378 myeloid leukemia samples (2,007 primary, 371 recurrent) using xCell transcriptomic deconvolution. The cohort was stratified into Pediatric (< 18y, n = 2,071) and Adult ( ≥ 18y, n = 307) subgroups to control for ontogenic baselines. We compared differential expression rankings between primary and recurrent states using Mann-Whitney U tests with Bonferroni correction (Padj) to identify age-specific dominance in TME remodeling. Results: Comparative analysis revealed divergent TME landscapes between age groups. In pediatrics, recurrence was characterized by an "Immune-Adaptive" program; CD4+ Memory T-cells were the dominant signature (rank 4, p < 10⁻²⁷), alongside significant increases in Preadipocytes ( p < 10⁻⁴⁹) and pro-B cells. Conversely, adult recurrence exhibited "Niche Exhaustion," primarily losing hematopoietic progenitors (CMP/GMP, p <10⁻⁷) and mesenchymal stem cells (MSC, p < 10⁻⁹). While CD4+ Memory T-cells increased in adults, the signal was less prominent (rank 18, p < 10⁻⁵). Both groups shared significant vascular collapse (Pericyte loss, p < 10⁻⁷), identifying it as a universal hallmark of relapse. Conclusions: Myeloid leukemia recurrence is driven by age-distinct microenvironmental remodeling. Pediatric relapse is defined by immune adaptation and adipogenesis, while adult relapse is characterized by progenitor and niche exhaustion. Vascular collapse represents a universal therapeutic target. These findings suggest that immunotherapy and niche-directed treatments must be tailored to the patient’s age-specific TME landscape to improve outcomes. Top age-specific trends in recurrent vs. primary myeloid leukemias. Cohort Cell Type Direction Mean Diff (Rec - Pri) Padj Pediatric (<18y) Pericytes Primary- High -0.085 P < 0.05 Preadipocytes Recurrence- High +0.064 P < 0.05 MSC Primary- High -0.099 P < 0.05 CD4+ Memory T-cells Recurrence- High +0.849 P < 0.05 pro-B cells Recurrence- High +0.301 P < 0.05 Adult (≥18y) MSC Primary- High -0.165 P < 0.05 Pericytes Primary- High -0.078 P < 0.05 CMP Primary- High -0.526 P < 0.05 Smooth muscle Primary- High -0.094 P < 0.05 GMP Primary- High -0.765 P < 0.05 CD4+ Memory T-cells* Recurrence- High +1.184 P < 0.05 *Manually added row for comparison purposes.
A National Cancer Database analysis of hepatoid adenocarcinoma: Epidemiology, socioeconomic, and clinical factors.
e20767 Background: Hepatoid adenocarcinoma (HAC) is a rare extrahepatic neoplasm that displays histologic similarity to hepatocellular carcinoma features. This cancer most commonly occurs in the stomach, pancreas, or lungs. HAC is frequently detected at advanced stages and presents with poor prognoses, demonstrating the need for further epidemiological investigation and comprehension. Accordingly, the National Cancer Database (NCDB) was analyzed to characterize the demographic, clinical, and socioeconomic factors in patients diagnosed with hepatoid adenocarcinoma in the United States. Methods: Utilizing the 2004-2020 National Cancer Database (NCDB), a retrospective cohort study was conducted to identify patients with a histologically confirmed diagnosis of HAC (ICD-O-3 code 8576, N = 584). Descriptive statistics were applied to evaluate patient demographic, socioeconomic, and clinical factors, such as tumor characteristics and treatment options (sex, race, Hispanic status, year of diagnosis, and Charleson-Deyo score), whereas the incidence patterns and survival analysis were assessed using regression analysis and the Kaplan-Meier estimated methodology, respectively. Results: Between 2004 to 2020, the NCDB documented 584 patients with HAC, indicating the incidence rate fluctuated substantially with a non-linear trend (R² = 0.709). The majority of patients were male (60.8%), White (79.6%), and non-Hispanic (89.9%). The mean age at diagnosis is 65.2 (STD ER 0.51). The most common primary sites within the bronchus or lung included the upper lobe (25.3%), lower lobe (9.10%), and NOS (6.50%), with the secondary involvement of the liver (7.40%) and stomach (4.60%). Regarding diagnosis, nearly half of cases (46.9%) were identified as Stage IV, followed by Stage III (9.90%) and Stage II (6.20%). The majority of patients (64.6%) had a low comorbidity burden with a Charlson-Deyo Score of 0. Post-surgical mortality rates were 4.8% at 30 days following surgery, and 11.6% at 90 days following surgery. 35.6% of patients used radiation as their primary form of therapy. 53.3% of patients used chemotherapy, 0.50% used hormone therapy and 5.7% primarily used immunotherapy. The survival rates at 2, 5, and 10 years were 0.227%, 0.128%, and 0.108%, respectively. The mean survival was 30.9 months. Conclusions: This is the first NCDB analysis on hepatoid adenocarcinoma to the best of our knowledge, helping fill a gap in literature on national epidemiological trends. The majority of patients tend to be White males with a primary site of diagnosis being the lung, similar to descriptions in case studies. Most patients use chemotherapy as primary treatment. Further research is needed to understand the gender and racial factors in the diagnosis, treatment, and survival of patients with hepatoid adenocarcinoma.
Influence of a vertically integrated care system on mortality risks in insured patients by socio-economic status.
e13560 Background: Vertically integrated health care delivery systems may help reduce disparities in cancer outcomes due to socioeconomic status by providing coordinated, comprehensive care. Kaiser Permanente Southern California (KPSC), a large integrated healthcare organization serving more than 5 million patients in Southern California, offers an opportunity to assess whether diagnosis within this system is associated with lower mortality particularly for individuals from lower socioeconomic status (SES) groups. Methods: We analyzed 416,574 insured adult cancer patients diagnosed with invasive malignancies in Southern California between January 1, 2015 and December 31, 2021, from the California Cancer Registry, with follow-up through December 31, 2022 to assess all-cause mortality. Patients with in situ cancers were excluded. Patients were categorized by site of diagnosis: Kaiser Foundation Hospitals (KFH) vs. non-KFH hospitals. Mortality rates were calculated overall as deaths per 1000 person-years (d/1000PY) with 95% confidence intervals (95% CI) and by geocoded SES quintile. Cox proportional hazards models adjusted for age, sex, race/ethnicity, SES, county, insurance type, and stage at diagnosis to estimate the association between diagnosis at healthcare setting and overall mortality risk among KFH and non-KFH hospitals by SES quintile. Results: Overall mortality rates were lower among patients diagnosed in KFH hospitals compared with non-KFH hospitals 87.4 deaths per 1,000 person-years (d/1000PY) (95% CI: 86.3, 88.4) vs. 103.1 d/1000PY (95% CI: 102.4, 103.8). Mortality rates for KFH versus non KFH by SES quintiles were: highest 77.8 d/1000PY (95% CI: 75.4, 80.3) vs. 75.0 d/1000PY (95% CI: 73.8, 76.3), mid-high 82.6 d/1000PY (95% CI: 80.5. 84.6) vs. 92.4 d/1000PY (95% CI: 91.0, 93.7), mid 89.5 d/1000PY (95% CI: 87.4, 91.7) vs. 109.3 d/1000PY (95% CI:107.6, 110.9), mid-low 92.6 d/1000PY (CI: 93.3, 99,2) vs. 125.3 d/1000PY (CI: 123.4, 127.3), and lowest 96.2 d/1000PY (95% CI:93.3, 99.2) vs. 140.8 d/1000PY (95% CI:138.4, 143.2), respectively. Mortality risks were lower amongst KFH patients after multivariate adjustment (non-KFH, ref) HR = 0.83 (95% CI 0.82, 0,84). Stratified hazard ratios by SES quintiles: highest 0.97 (95% CI: 0.94, 1.0), mid-high 0.86 (95% CI: 0.84, 0.88), mid 0.82 (95% CI 0.79, 0.84), mid-low 0.78 (95% CI 0.76, 0.81), and lowest 0.72 (95% CI 0.69, 0.71). Conclusions: Diagnosis in a vertically integrated health system was associated with lower all-cause mortality rates, with the greatest benefit observed among patients in the lowest SES quintile (28% mortality reduction). These findings suggest that integrated healthcare systems can mitigate mortality risks amongst socioeconomically disadvantaged patients.
Second-line cetuximab monotherapy following PD-1 inhibitor treatments in patients with recurrent/metastatic head and neck carcinoma.
6055 Background: PD-1 inhibitors, alone or in combination with chemotherapy, are standard first-line therapy for recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). No established second-line standard exists for majority of patients who progress on immunotherapy. Cetuximab, the only approved targeted biologic agent in HNSCC, has historically shown modest activity as monotherapy, with a 13% response rate. We hypothesized that cetuximab administered after PD-1 inhibitors may demonstrate enhanced efficacy due to potentially synergistic, immunomodulatory effects. Methods: This non-randomized single-institution study included patients with R/M HNSCC who experienced disease progression or intolerance to PD-1 inhibitor therapy, with or without chemotherapy, and were subsequently treated with cetuximab monotherapy. Imaging was performed every 6 weeks, and response was assessed per RECIST v1.1. Outcomes included best overall response (BOR), progression-free survival (PFS), overall survival (OS), and toxicity. Survival outcomes were estimated using Kaplan–Meier methods. Results: Twenty-seven patients (8 female, 19 male) were included; 5 were HPV-positive. All HPV-positives had metastatic disease, while all HPV-negatives had recurrent disease. Two patients experienced anaphylaxis with the first cetuximab infusion, and two died from tumor-related complications prior to first restaging; all were included in outcome analyses. Nine patients (33.3%) achieved a partial response (PR), while 18 (66.7%) were non-responders, including 10 (37.0%) with stable disease (SD), 4 (14.8%) with progressive disease (PD), and 4 (14.8%) non-evaluable. Median follow-up was 32.4 mos, with 21 deaths observed. Median OS was 11.6 mos (95% CI, 8.0–21.0) in all patients, 15.5 mos (95% CI, 4.2–24.9) in responders and 11.4 mos (95% CI, 5.3–25.0) in non-responders, with 18.0 mos (95% CI, 4.4–32.0) in patients with SD. Median PFS was 4.4 mos overall, 5.3 mos (2.7 to 11.5) in responders, and 4.4 mos (2.6 to 6.2) in non-responders, with 5.9 mos (2.5 to 7.0) in patients with SD. Median OS was 32.0 mos (11.7 to NE) in HPV-positive patients and 10.8 mos (5.3 to 18.0) in HPV-negatives. Two patients experienced anaphylactic reaction with the initial cetuximab administration. All treated patients developed acneiform skin rash, with 17 (68%) experiencing grade 3, necessitating oral antibiotics. Conclusions: Cetuximab monotherapy following PD-1 inhibitor therapy demonstrated encouraging clinical activity in patients with R/M HNSCC, with improved outcomes compared with historical cetuximab monotherapy. These findings suggest that sequential targeting of immune-mediated pathways may provide clinical benefit after an immunotherapy failure. Larger prospective studies are warranted to validate these results and to better define response patterns in the immunotherapy setting. Clinical trial information: NCT04375384 .
Characterization and clinical impact of temozolomide-induced hepatotoxicity in <i>IDH</i> -wild type glioblastoma: A comprehensive analysis of injury patterns, CTCAE grade transitions, and survival outcomes.
e14075 Background: Temozolomide (TMZ) is the cornerstone of glioblastoma (GBM) treatment but is associated with potential hepatotoxicity. Real-world data regarding the spectrum of liver function test (LFT) abnormalities, specific injury patterns, and their impact on overall survival (OS) remain limited. We aimed to characterize longitudinal changes in LFTs during TMZ therapy, classify injury patterns, and evaluate survival outcomes in a cohort of IDH-wildtype GBM patients. Methods: This retrospective study included 107 patients with IDH-wildtype GBM treated with TMZ. Serum levels of ALT, AST, ALP, GGT, and bilirubin were assessed at baseline and at peak values during follow-up. Hepatotoxicity was graded according to CTCAE v5.0. Liver injury patterns among patients with Grade ≥2 abnormalities were categorized as hepatocellular, cholestatic, or mixed based on R-ratio and enzyme predominance. OS was estimated using the Kaplan–Meier method and compared using the log-rank test, stratified by LFT toxicity grades. Results: At baseline, 38 patients (36%) exhibited Grade 1 LFT abnormalities, with no Grade ≥2 cases. During TMZ therapy, 95% (102/107) developed at least Grade 1 toxicity, and grade escalation from baseline occurred in 63 patients (59%). Grade ≥2 and Grade ≥3 abnormalities were observed in 37 (34.6%) and 22 (20.6%) patients, respectively. While transaminase elevations were predominantly mild, higher-grade toxicities were more frequently characterized by ALP and GGT elevations. Among Grade ≥2 cases (n=37), the mixed injury pattern predominated (75.7%), followed by cholestatic (16.2%) and hepatocellular (8.1%) patterns. In the Grade ≥3 subgroup (n=22), 95.5% exhibited a mixed pattern. Grade ≥3 events occurred during concurrent chemoradiotherapy (54.5%), adjuvant TMZ (27.3%), or post-adjuvant phases (18.2%). Management of Grade ≥3 toxicity involved TMZ discontinuation (18.2%) or interruption (31.8%); LFTs resolved in 31.8% of these cases. Exploratory survival analysis revealed no significant difference in median OS between patients with or without Grade ≥2 toxicity (16.0 vs 16.0 months; p=0.824) or Grade ≥3 toxicity (17.7 vs 16.0 months; p=0.762). Conclusions: LFT abnormalities are highly prevalent during TMZ therapy for IDH-wildtype GBM, with approximately one-fifth of patients experiencing Grade ≥3 toxicity, predominantly exhibiting a mixed injury pattern. Importantly, higher-grade hepatotoxicity was not associated with compromised OS. These findings support vigilant monitoring and individualized management of LFT elevations without necessarily adversely affecting survival.
Inpatient palliative care utilization and outcomes among decedent patients with metastatic cancer in the U.S.
11119 Background: Palliative care (PC) is a key component of high quality cancer care, especially at the end of life. However, real world national data describing inpatient PC utilization remain limited. We evaluated patterns of PC use and associated outcomes among decedent patients with metastatic cancer in the U.S. Methods: We conducted a cross-sectional analysis of the 2021–2023 National Inpatient Sample of decedent patients with metastatic cancer. Palliative care, cancer type, and metastatic status were identified using ICD-10 codes. Patient characteristics included age, sex, race, comorbidity burden, insurance status, and household income. Hospital characteristics included location (urban vs rural) and ownership (public, private not-profit, and private invest-own). Outcomes included length of stay (LOS), inpatient procedures, and total costs. Factors associated with palliative care use and adjusted mean differences in outcomes were estimated. Results: An estimated 52,841 hospitalizations of decedent patients with metastatic cancer were identified, with 34,955 (66.2%) involving palliative care. PC utilization varied by cancer type (Table) and increased over time (aOR per year 1.15; 95% CI 1.12–1.18). PC use was independently associated with older age, female sex, private insurance, higher neighborhood income, and care at private not-for-profit hospitals (all p<0.001). PC was associated with fewer inpatient procedures (adjusted mean difference −1.38; 95% CI −1.45 to −1.31), shorter LOS (−1.25 days; 95% CI −1.45 to −1.06), and lower total costs (−$10,557; 95% CI −$11,421 to −$9,694). Reductions in procedures, LOS and costs were significant across most cancer types. (Table). Conclusions: Inpatient PC was associated with lower care intensity and costs across cancer types among decedent patients with metastatic cancer. Yet, about one third never received PC, highlighting a major end-of-life care gap and the need for earlier, more equitable integration to improve value based oncology care. Palliative care utilization and outcomes by major cancer type. Cancer Type PC use Adjusted Procedures difference Adjusted Cost difference ($) Adjusted LOS difference (days) Breast 2646 (66.7%) -1.47 (-1.70,-1.24) -12512 (-16301, -8722) -1.90 (-2.63,-1.17) Colorectal 2932 (65.8%) -1.75 (-1.49,-2.00) -12231 (-15261, -9201) -1.09 (-1.83,-0.35) Lung 8942 (67.9%) -1.14 (-1.28,-1.00) -6341 (-7894, -4968) -0.90 (-1.24,-0.56) Prostate 1897 (62.3%) -1.24 (-1.52,-0.97) -9736 (-12915, -6558) -0.88 (-1.82,0.05)* Pancreas 2574 (68.4%) -1.46 (-1.72,-1.21) -7396 (-9525, -5266) -0.39 (-0.94,0.17)* Kidney 936 (66.3%) -1.72 (-2.20,-1.23) -12353 (-17623, -7082) -1.93 (-3.11,-0.75) Liver 1362 (67.8%) -0.87 (-1.24,-0.51) -8896 (-13426, -4367) -1.27 (-0.33,-2.20) All p<0.001 unless noted with *.
Demographics and trends of acute myeloid leukemia among young adults in the United States and Puerto Rico, 1999-2021.
e18502 Background: We assessed racial and sex-related trends in deaths from Acute Myeloid Leukemia (AML) among US and Puerto Rico young adults (15–49 years) from 1999–2021. Methods: Cross-sectional analysis of CDC WONDER mortality data was performed. AML deaths were extracted, and age-adjusted mortality rates (AAMR) per 100,000 with annual percent changes (APC) were calculated using Joinpoint regression. Analyses were stratified by sex and race/ethnicity. Results: There were 20,295 AML deaths among young adults. Overall AAMR declined from 0.65/100,000 in 1999 to 0.47/100,000 in 2021 (28% reduction). Joinpoint analysis showed no change from 1999–2008 (APC –0.21%, p=0.65) but significant decline 2008–2021 (APC –2.38%, p<0.0001). By sex, males and females had similar 1999 AAMRs (0.65 vs. 0.66); by 2021 both were 0.47. Males showed a significant decrease 2008–2021 (APC –2.62%, p<0.0001), females declined steadily across the study period (APC –1.52%, p<0.0001). By race, Whites declined from 0.67 to 0.49 (APC –2.51%, p=0.0004, 2008–2021), Blacks from 0.67 to 0.48 (APC –1.31%, p=0.0008), and Asian/Pacific Islanders from 0.67 to 0.36 with significant decrease 2016–2021 (APC –9.82%, p=0.002). American Indian/Alaska Native rates were suppressed due to small counts. Conclusions: AML mortality among US/PR young adults significantly declined over two decades, likely due to improved chemotherapy, supportive care, risk-adapted therapy, and advances in bone marrow transplantation.
Study of the cytostatic effect of a new compound of the tropolon series on primary cultures of glioma cells.
e14056 Background: Brain tumors present a genuine challenge for medicine due to their anatomical features, high resistance to existing chemotherapeutic drugs, a strongly immunosuppressive environment, and the presence of the blood-brain barrier. The research and development of new anti-tumor drugs remains an important task. Tropolone derivatives represent a promising class of organic compounds that could serve as new pharmaceutical anti-tumor agents. There is currently a growing interest in tropolone alkaloids, as many of them possess a broad spectrum of pharmacological activity. The aim of the study was to investigate the cytotoxic effect of a new tropolone derivative 2-(1,1-dimethyl-1H-benzo[e]indoline-2-yl)-5,6,7-trichloro-1,3-tropolone (JO-122(2)) on primary glioma cell cultures in an in vitro experiment. Methods: The tumor material for primary cell cultures was obtained from a patient who was diagnosed with grade 4 glioblastoma on the background of anaplastic astrocytoma (Culture 1) and a patient with histologically verified grade 4 giant cell glioblastoma (Culture 2) who were treated at the Department of Neuro-Oncology of the National Medical Research Centre for Oncology of the Ministry of Health of the Russian Federation. Cell cultures were cultured on DMEM medium (Gibco, USA) with the addition of 10% FBS (Hyclone, USA). The cells were planted in a 96-well plate (Eppendorf, Germany) in the amount of 5,000 cells in 100 µl of medium per well and incubated for 24 hours at a temperature of 37 ° C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing JO-122(2) in a series of double dilutions. The maximum amount of JO-122(2) was 24 μmol. The MTT test was performed according to the standard procedure, the exposure time was 24, 48 and 72 hours. The optical density was determined at a wavelength of 540 nm using a tablet reader. The inhibition index (IC50) was defined as the percentage of surviving cells after exposure to JO-122(2) from the control. Results: The results of the in vitro cytotoxic effect study showed that the IC50 for Culture 1 after incubation with the addition of JO-122(2) for 24 hours was 5.3668 μmol, 48 hours - 3.9358 μmol, 72 hours - 1.5418 μmol. For Culture 2, the IC50 after incubation for 24 hours was 2.9146 μmol, 48 hours - 2.1581 μmol, 72 hours - 1.1187 μmol. Conclusions: Our results indicate that JO-122(2) has a pronounced cytotoxic effect on primary glioma cell cultures. It is noted that an increase in the duration of incubation contributes to a decrease in cell viability.
Early neutrophil incompetence following allogeneic stem cell transplant.
6565 Background: Neutrophils are key immune effector cells against fungal pathogens such as Candida albicans . After allogeneic stem cell transplant (allo-SCT), absolute neutrophil count (ANC) is used to measure myeloid engraftment and estimate infection risk, but post-transplant neutrophil function remains poorly understood. Our prior work showed impaired neutrophil function after both myeloablative (MAC) and reduced-intensity conditioning (RIC) regimens. Here, we assess broader neutrophil functions and hypothesize post-transplant neutrophil impairment persists for at least one month despite numeric recovery. Methods: Peripheral blood was collected from patients undergoing RIC or MAC allo-SCT and healthy donors at four time points: immediately post-engraftment (P1), and at one (P2), three (P3), and seven (P4) months. Neutrophil function was analyzed by multiparametric flow cytometry to assess phagocytosis, degranulation (CD66b), reactive oxygen species (ROS) production (dihydrorhodamine-123), and ectodomain shedding (CD62L) after incubation with fluorescent C. albicans . At P1, neutrophil deformability was quantified to generate a sepsis risk index: Band 1 (low risk, 0.1-4.9), Band 2 (intermediate risk, 5-6.2) and Band 3 (high risk, 6.3-10). Neutrophil antifungal activity was assessed in vitro using microscale platforms to quantify and image swarming (cumulative neutrophil response) during restriction of C. albicans growth over 12 hours. Results: Nineteen subjects were included. The most common underlying malignancy was acute myeloid leukemia (12/19, 63%). Conditioning regimens included fludarabine/melphalan (14/19, 74%), busulfan/fludarabine (4/19, 21%), or fludarabine/total body irradiation (1/19, 5%), with post-transplant cyclophosphamide and tacrolimus. The majority received grafts from matched unrelated donors (14/19, 74%). Median ANC (K/uL) was 3.59 at P1 (15/19 subjects, 79%), 4.55 at P2 (14/19, 74%), 4.03 at P3 (5/19, 26%) and 2.94 at P4 (7/19, 37%). Functional analyses revealed significant impairment in allo-SCT recipients compared with controls at P1, with trends of persistent impairment at P2, and evidence of recovery by P3-P4. At P1, eight recipients demonstrated altered neutrophil deformability, yielding a higher sepsis risk index [median (IQR) 5.93 (3.88–6.80)] versus controls [median (IQR) 0.95 (0.33–2.33)]. Swarming analysis revealed impaired collective behavior in fungal containment compared with controls. Conclusions: Despite normalization of ANC after allo-SCT, early post-engraftment neutrophils exhibit significant functional and biophysical impairments, indicating transient immune incompetence. This early window of vulnerability may persist for at least one month post-transplant. Ongoing follow-up and expanded analyses will further characterize the underlying mechanisms and define the trajectory of delayed functional neutrophil recovery.
Clinical outcomes with brexucabtagene autoleucel in refractory mantle cell lymphoma: A systematic review and single-arm meta-analysis with contextual comparison to lisocabtagene maraleucel.
e19010 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has improved outcomes for patients with refractory mantle cell lymphoma (MCL). Two CD19-directed CAR-T products, brexucabtagene autoleucel (brexu-cel) and lisocabtagene maraleucel (liso-cel), have demonstrated activity, but no direct comparative trials exist. We conducted a systematic review and single-arm meta-analysis to summarize brexu-cel outcomes and contextualize them with TRANSCEND liso-cel results. Methods: Clinical trials and observational studies of brexu-cel in adults with MCL were identified. Primary outcomes were complete response (CR), progression-free survival (PFS), and grade ≥3 cytokine release syndrome (CRS). Secondary outcomes included overall response rate (ORR), overall survival (OS), duration of response (DOR), and immune effector cell–associated neurotoxicity syndrome (ICANS). Brexu-cel outcomes were pooled using random-effects model; liso-cel outcomes were summarized descriptively. Results: Four brexu-cel studies (n=796) and TRANSCEND liso-cel (n=88) were analyzed. Median age ranged from 65 to 68.5 years. TP53 mutations and central nervous system involvement were more frequent in liso-cel–treated patients, while active CNS disease was excluded in ZUMA-2. For brexu-cel, pooled ORR was 90.2% (95% CI, 88.8–91.5) with CR 81.7% (95% CI, 80.1–83.4). Twelve-month DOR, PFS, and OS were 69.7%, 61.9%, and 76.3%, respectively. In TRANSCEND, liso-cel ORR was 86.5% with CR 74.3%; twelve-month DOR, PFS, and OS were 52.9%, 50.8%, and 61.8%. All-grade CRS occurred in 90.0% of brexu-cel–treated patients (grade ≥3, 9.1%) versus 61.0% (grade ≥3, 1.0%) with liso-cel. All-grade and grade ≥3 ICANS occurred in 61.1% and 29.4% with brexu-cel versus 31.0% and 8.0% with liso-cel. Conclusions: Brexu-cel demonstrated high pooled efficacy in refractory MCL. When contextualized with TRANSCEND, brexu-cel was associated with higher rates of CRS and ICANS compared with liso-cel. Interpretation is limited by cross-trial comparisons and limited real-world data for liso-cel. These findings inform CAR-T selection in refractory MCL in the absence of head-to-head trials. CD19 CAR-T outcomes in refractory MCL. Characteristics/outcomesValues shown as % (95% CI) Liso-cel (TRANSCEND, n=88) Brexu-cel (pooled, n=796)* Age, yTP53 mut, %CNS involvement, % 68.5238 65–6815–480–10 ORR, %CR, % 86.5 (78.1–94.9)74.3 (63.8–84.8) 90.2 (88.8–91.5)81.7 (80.1–83.4) DOR 12 mo, %PFS 12 mo, %OS 12 mo, % 52.9 (40.9–65.0)50.8 (39.6–62.0)61.8 (51.2–72.4) 69.7 (61.5–77.9)61.9 (58.3–65.5)76.3 (73.2–79.4) CRS any, %CRS ≥3, % 61.0 (50.5–71.5)1.0 (–5.8–7.8) 90.0 (88.6–91.3)9.1 (6.8–11.4) ICANS any, %ICANS ≥3, % 31.0 (21.3–40.7)8.0 (2.3–13.7) 61.1 (57.7–64.6)29.4 (26.0–32.9) *ZUMA-2 (n=68); Ahmed (n=476); O’Reilly (n=83); Wang (n=169).
Temporal trends in cardiovascular mortality among ovarian cancer patients in the United States: A 22-year analysis of United States mortality data by age, race, and geographic region, 1999-2020.
e17584 Background: Cardiovascular disease (CVD) represents a significant competing cause of death among ovarian cancer survivors, with survivors showing increased risk of heart failure compared to the general population. Temporal trends in CVD mortality remain poorly characterized but are critical for survivorship planning and risk stratification. We analyzed 22-year U.S. mortality data to evaluate trends by race, geographic region, age, and CVD subtype. Methods: We analyzed CDC WONDER database mortality data from 1999 to 2020 for ovarian cancer patients (ICD-10 code C56) with cardiovascular causes of death (ICD-10 codes I00-I99). Age-adjusted mortality rates (AAMR) per 100,000 populations were calculated using the US standard population. We used Joinpoint Regression Program to identify trends by race/ethnicity, US Census region, cardiovascular disease subtype, and ten-year age groups, with annual percent change (APC) calculated for each variable. American Indian/Alaska Native excluded from racial analyses due to insufficient data. Results: We identified 77,499 cardiovascular deaths with comorbid ovarian cancer. The AAMR decreased from 3.44 (95% CI [3.33–3.56]) in 1999 to 2.59 (95% CI [2.51–2.68]) in 2020, representing a 24.7% reduction. The three most common CVD causes were other forms of heart disease (64.6%), hypertensive disease (25.4%), and ischemic heart disease (16.9%). Joinpoint analysis revealed significant decreases for most CVD subtypes: ischemic heart disease (APC -5.13, 2003-2020, p<0.05), other forms of heart disease (APC -2.89, 1999-2018, p<0.05), and cerebrovascular disease (APC -4.06, 1999-2016, p<0.05), except hypertensive diseases which increased after 2018 (APC +10.03, p<0.05). Mortality was concentrated in older age groups (75-84 years: 9.58 to 6.69 per 100,000; 85+ years: 13.84 to 9.49). Black or African American patients showed steady decline (APC -2.39, p<0.05) with AAMR decreasing from 2.45 (95% CI [2.20–2.70]) to 1.60 (95% CI [1.45–1.75]), while White patients had accelerated decline post-2006 (APC -3.16, p<0.05). The Northeast had highest initial AAMR at 2.64 (95% CI [2.47–2.80]) with most rapid decline during 2007-2012 (APC -6.35, p<0.05). Racial and geographic disparities narrowed considerably. Conclusions: Cardiovascular mortality among ovarian cancer patients declined significantly over 22 years with substantial narrowing of disparities. However, recent dramatic increases in hypertensive disease mortality warrant enhanced blood pressure management in survivorship care programs. Integrating cardiovascular risk mitigation into ovarian cancer follow-up may further improve outcomes.
Same day/next day cancer care program: An early access program for patients with aggressive malignancies.
11095 Background: Rapid referral of patients with suspected malignant disease to an oncology specialist is associated with improved earlier-stage diagnosis and survival benefits. The advantage of such rapid care transition can be especially pronounced in aggressive malignancies, where early interventions are critical in reducing mortality. Patients with already established cancer diagnosis may also benefit from such programs. Same Day/Next Day Cancer Care (SDND) is a Jefferson Health enterprise designated referral system allowing patients with newly diagnosed cancers to be seen by an advanced practice clinicians via telemedicine within 48 hours at the Sidney Kimmel Comprehensive Cancer Center (SKCC). Methods: Adult patients with an established diagnosis of aggressive types of malignancies were referred through SDND to SKCCC in the Greater Philadelphia Area if they had concerning symptoms related to disease. The following malignancies were selected: acute leukemias, T-cell lymphomas, diffused large B-cell lymphomas, Burkitt lymphomas, melanomas, glioblastoma multiforme, pancreatic adenocarcinoma, esophageal or gastric carcinoma, small cell lung carcinoma, biliary tract malignancy, anaplastic thyroid cancer. Socio-demographics, time to appointment with an oncologist and treatment were analyzed. Results: Between July 2024 and December 2025, 209 patients with aggressive malignancies, of which 49% were female with a median age of 67 years, were referred to oncology specialists. Only 19% were new patients, while 81% had already established care. Medical providers made 78.3% of referrals, while other 21.7% were self-referred. Average SDND schedule lag days was 1.04 days. About 85% of patients had medical oncologist consultation appointments, of which 68.8% completed the planned visit. Thirty-four patients (16%) were referred for infusion therapy, of which 64.7% successfully initiated infusion therapy within 50 days. Similarly, 76 patients (36%) had scheduled a surgical specialty consultation, of which 77.9% completed the appointment. Importantly, 53.7% of the patients underwent surgery within 30 days of the SDND referral. Conclusions: SDND is a centralized access program aimed at reducing time to first appointments for newly diagnosed cancer patients. It led to accelerated assessment by oncology providers with high adherence to the management plan. It can ensure faster diagnostic workups and symptom management related to aggressive malignancies by advanced care clinicians, with the potential to improve survival rates, patient satisfaction, reduce treatment–related anxiety and cancer-related morbidity. Further research is needed to determine if this early clinical evaluation by advanced practice providers via telemedicine may reduce complications warranting high-cost care, such as emergency department visits or hospitalizations in high-risk cancer population.
<i>HER2</i> mutations in advanced NSCLC: Prevalence, mutational context, and clinical outcomes from an Australian clinico-genomic database.
e20673 Background: ERBB2 mutations ( HER2 mut) are an emerging target in non-squamous non-small cell lung cancer (ns-NSCLC), with second-line response rates >50% to tyrosine kinase inhibitors or antibody–drug conjugates (HER2tx). Their novelty necessitates large-scale studies to better define the clinico-molecular context. Methods: 1,257 ns-NSCLC patients in Australia underwent comprehensive genomic profiling (TSO-500, FoundationOne CDx, or Avenio). HER2 mut were curated for oncogenicity and co-mutation patterns. Logistic regression was conducted for raw prevalence values, accounting for sex, smoking status and ethnicity. Overall survival (OS) was assessed via Kaplan-Meier curves relative to 3:1 propensity-matched wild-type cases (matched by age, sex, histology). Results: HER2 mut prevalence was 6.2% (78/1,257), excluding 22 additional (1.8%) amplification-only cases. Never-smokers had a 4.43 odds ratio for HER2 mut after adjusting for ethnicity and sex (p < .001). Sixty (77%) mapped to the kinase domain, with 54 (69%) in exon 20. Mutations were mutually exclusive for KRAS, BRAF, and EGFR (p < .001). HER2 mut were less frequently TMB-high or PD-L1 high (p = .007) and were depleted for KEAP1/STK11 , enriched for ARID1A, and showed over-representation of 9p21/ MTAP loss (22% vs 9%; p < .001). OS was shorter in HER2 mut vs wild-type patients (median 20.1 vs 28.7 mo; p = .01), while amplification-only tumours had an OS of 16.4 mo. HER2tx exposure in HER2 mut cases showed a trend for improved OS vs HER2tx-naïve patients (median 22.9 vs 19.3 mo; p = .176). Conclusions: HER2 mut was relatively common in non-smokers. While typically not TMB-H, an enrichment of other features provides opportunity for immunotherapy combination and potentially MTAP inhibition. HER2 mut had a poor prognosis relative to wild-type, with a trend to improved outcomes in those HER2tx exposed.
Evaluating performance of an AI-based recurrence score in early breast cancer patients treated with chemoendocrine therapy: A secondary analysis of the UNIRAD trial.
550 Background: Patients with node-positive HR+/HER2- early breast cancer are at high risk for relapse within 5 years of diagnosis, suggesting the potential need for treatment escalation. However, it is unclear which patients may experience worse recurrence-free outcomes and thus benefit from additional therapy. Ataraxis Breast (ATX) is an artificial intelligence (AI) test that integrates clinicopathologic variables with features extracted from whole-slide H&E images to estimate recurrence risk. Here, we perform a secondary analysis of the control arm of the UNIRAD trial, evaluating the ability of ATX to identify patients treated with standard-of-care therapy who may be candidates for treatment escalation. Methods: Clinical information and scanned H&E slides were sourced for 365 patients enrolled in the UNIRAD trial who were randomized to the control arm (standard-of-care therapy). ATX scores were generated using a locked model with pre-specified thresholds. No patients from UNIRAD were used in the training of ATX. Recurrence-free interval (RFI) was used as the primary endpoint. Kaplan-Meier estimators were used to predict the probability of meeting the RFI endpoint. To quantify relative differences in the hazard of experiencing an event contributing to the RFI endpoint associated with ATX scores, Cox proportional hazards models were fitted, from which hazard ratios (HRs) were estimated. The discriminative performance of ATX was evaluated using C-index. Results: Of the 365 patients randomized to the control arm of the UNIRAD trial with H&E slides available, 163 (45%) were classified as ATX low risk, and 202 (55%) as ATX high risk. Patients classified as ATX high risk had lower Kaplan-Meier-estimated probability of meeting the RFI endpoint (77%, 95% CI = 70-83%) than patients classified as ATX low risk (93%, 95% CI = 88-97%). Consistent with these findings, when modeled as a continuous variable, higher ATX scores were associated with a significantly higher hazard of an RFI-contributing event (HR = 1.57, 95% CI = 1.29-1.99, p-value < 0.001) and demonstrated strong discriminatory performance (C-index = 0.66, 95% CI = 0.59-0.72). This association remained significant after controlling for receipt of neoadjuvant therapy, tumor, and nodal stage (HR = 1.53, 95% CI = 1.05-2.23, p = 0.027). Conclusions: In the clinically homogenous UNIRAD trial cohort of patients with node-positive HR+/HER2- early breast cancer, ATX high risk patients treated with standard-of-care therapy had a significantly increased hazard of an RFI-contributing event. These findings suggest that AI-based risk stratification identifies biologically high risk patients who may derive benefit from adjuvant treatment escalation. Clinical trial information: NCT01805271 .