Phase II Trial of Gemcitabine and nab-Paclitaxel for Recurrent Osteosarcoma with Serial Monitoring Using Liquid Biopsy: A Report from the National Pediatric Cancer Foundation.

BACKGROUND: The combination of gemcitabine and docetaxel is often used to treat patients with recurrent osteosarcoma. Nab-paclitaxel has preclinical activity against osteosarcoma and is potentially less myelosuppressive than docetaxel. We conducted a prospective multi-institutional phase II trial combining gemcitabine and nab-paclitaxel for patients 12-30 years with recurrent osteosarcoma and measurable disease. METHODS: A Simon's two-stage design was used to test a 4-month progression-free survival (PFS-4) of 10% vs. 35%. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 weekly x 3 in 4-week cycles. Immunohistochemical analysis of archival tissue and serial assessment of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) using ultralow passage whole-genome sequencing were performed to identify potential biomarkers of response. RESULTS: Eighteen patients received 56 total cycles (median 2, range 1 - 12). Two patients (11%) experienced confirmed partial response, and 6 (33%) received > 2 cycles. The PFS-4 was 28% (95% CI 13-59%). Six patients required dose reductions and three patients were removed due to toxicities. All 18 patients had detectable CTCs, and 10 had ctDNA identified. All 8 patients with MYC amplification at study-entry experienced disease progression. CONCLUSIONS: Gemcitabine and nab-paclitaxel demonstrated similar clinical activity and toxicity compared to previous retrospective reports utilizing gemcitabine and docetaxel in patients with recurrent osteosarcoma. Serial analysis of CTC and ctDNA was feasible in this prospective multi-institution study and provides preliminary data on the use of these assays in patients with relapsed disease.

GDF15 and LCN2 for early detection and prognosis of pancreatic cancer.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain. METHODS: Circulating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated. FINDINGS: Our results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity. INTERPRETATION: Our findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.

Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

BACKGROUND: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. OBJECTIVES: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. METHODS: Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro-B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. RESULTS: At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro-B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). CONCLUSIONS: Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).

Glucagon-like peptide-1 receptor agonists significantly affect the quality of bowel preparation for colonoscopy.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) affect gastrointestinal motility, slowing gastric emptying and colonic transit. GLP-1RAs have an impact on gastric residue before endoscopy, but only limited data are available regarding its effect on the adequacy of colonic preparation. We investigated the association between GLP-1RA use and inadequate bowel preparation (IBP) for colonoscopy. METHODS: We performed a multicenter retrospective study with GLP-1RA cases matched with controls (using propensity scores for age, sex, diabetes mellitus [DM], obesity, and co-morbidities). Data on demographics, medication use, procedural indications, and colonoscopy findings were collected. IBP ("poor preparation" on Aronchik scale or Boston Bowel preparation scale <5) was the primary outcome. RESULTS: 4876 patients treated with GLP-1RAs were included in the analysis and compared with 4876 controls selected from 333 648 patients without GLP-1RA use. Among the GLP-1RA patients, 10% (n = 487) had IBP compared with 197 (4%) of the control group (P<0.001). Subgroup analysis showed a higher rate of IBP among diabetic patients treated with GLP-1RA (284/2364 [12%]) than among diabetic patients without GLP-1RA treatment (118/2364 [5%]; P<0.001). Additionally, 203/2512 nondiabetic patients treated with GLP-1RAs had IBP (8%) compared with 79 of the nondiabetic non-GLP-1RA group (3%; P<0.001). On multivariate analysis, diabetes and GLP-1RA use were both found to be independent risk factors for IBP (odds ratio [OR] 1.4 and OR 2.7, respectively; both P<0.001). CONCLUSION: Our findings highlight the necessity for special attention and tailored recommendations for both diabetic and nondiabetic patients treated with GLP-1RAs in terms of colonic preparation prior to colonoscopy.

Predicting response to intravesical BCG in high-risk non-muscle invasive bladder cancer using an artificial intelligence-powered pathology assay: development and validation in an international 12 center cohort.

PURPOSE: There are few markers to identify those likely to recur or progress after treatment with intravesical BCG. We developed and validated artificial intelligence-based histologic assays that extract interpretable features from transurethral resection of bladder tumor digitized pathology images to predict risk of recurrence, progression, development of BCG unresponsive disease, and cystectomy. MATERIALS AND METHODS: Pre-BCG resection-derived whole-slide images and clinical data were obtained for high-risk non-muscle invasive bladder cancer cases treated with BCG from 12 centers and were analyzed through a segmentation and feature extraction pipeline. Features associated with clinical outcomes were defined and tested on independent development and validation cohorts. Cases were classified into high or low risk for recurrence, progression, BCG unresponsive disease, and cystectomy. RESULTS: 944 cases (development:303, validation:641, median follow-up:36 months) representative of the intended use population were included (high-grade Ta:34.1%, high-grade T1:54.8%; carcinoma-in-situ only:11.1%, any carcinoma-in-situ:31.4%). In the validation cohort, "High recurrence risk" cases had inferior high-grade recurrence-free survival versus "Low recurrence risk" cases (HR 2.08, p<0.0001). "High progression risk" patients had poorer progression-free survival (HR 3.87, p<0.001) and higher risk of cystectomy (HR 3.35, p<0.001) than "Low progression risk". Cases harboring the BCG unresponsive disease signature had a shorter time to development of BCG unresponsive disease than cases without the signature (HR 2.31, p<0.0001). AI assays provided predictive information beyond clinicopathologic factors. CONCLUSIONS: We developed and validated AI-based histologic assays that identify high-risk non-muscle invasive bladder cancer cases at higher risk of recurrence, progression, BCG unresponsive disease, and cystectomy, potentially aiding clinical decision-making.

Human papillomavirus-associated nasopharyngeal carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region. DATA SOURCES: EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022. REVIEW METHODS: We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features. RESULTS: Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC. CONCLUSION: This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.

Supportive care 2030 movement: towards unifying ambitions for global excellence in supportive cancer care-an international Delphi study.

Background: Supportive care to ensure optimal quality of life is an essential component of cancer care and symptom control across the lifespan. Ongoing advances in cancer treatment, increasing toxicity from many novel treatment regimes, and variations in access to care and cancer outcomes across the globe and resource settings present significant challenges for supportive care delivery. To date, no overarching framework has been developed to guide supportive care development worldwide. As an initial step of the Multinational Association of Supportive Care in Cancer (MASCC) Supportive Care 2030 Movement, we developed a targeted, unifying set of ambition statements to envision the future of supportive cancer care. Methods: From September 2022 until June 2023, we used a modified Delphi methodology to develop and attain consensus about ambition statements related to supportive cancer care. Leaders of MASCC Study Groups were invited to participate in an Expert Panel for the first two Delphi rounds (and a preliminary round to suggest potential ambition statements). Patient Advocates then examined and provided input regarding the ambition statements. Findings: Twenty-seven Expert Panelists and 11 Patient Advocates participated. Consensus was attained on 13 ambition statements, with two sub-statements. The ambition statements addressed global standards for guideline development and implementation, coordinated and individualized care, dedicated supportive oncology services, self-management, needs for screening and actions, patient education, behavioral support, financial impact minimization, comprehensive survivorship care, and timely palliative care, reflecting collaboration, coordination and team-based approach across all levels. Interpretation: This study is the first to develop shared ambitions for the future of supportive cancer care on a global level. These ambition statements can facilitate a coordinated, resource-stratified, and person-centered approach and inform research, education, clinical services, and policy efforts. Funding: This project received funding support from Prof Raymond Chan's NHMRC Investigator Grant (APP1194051).

Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.

The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted in various preclinical investigations, yet the mechanism of action in humans remains unknown. To decipher the combinatory mode of action of TLR8 agonism and PD-1 blockade, we employed a unique, open-label, phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC) patients. Matched pre- and post-treatment tumor biopsies from the same lesion were obtained. We used single-cell RNA sequencing and custom multiplex staining to leverage the unique advantage of same-lesion longitudinal sampling. Patients receiving dual TLR8 agonism and anti-PD-1 blockade exhibited marked upregulation of innate immune effector genes and cytokines, highlighted by increased CLEC9A+ dendritic cell and CLEC7A/SYK expression. This was revealed via comparison with a previous cohort from an anti-PD-1 blockade monotherapy single-cell RNA sequencing study. Furthermore, in dual therapy patients, post-treatment mature dendritic cells increased in adjacency to CD8+ T-cells. Increased tumoral cytotoxic T-lymphocyte densities and expanded CXCL13+CD8+ T-cell populations were observed in responders, with increased tertiary lymphoid structures (TLSs) across all three patients. This study provides key insights into the mode of action of TLR8 agonism and anti-PD-1 blockade immune targeting in HNSCC patients.

Probabilistic inference of epigenetic age acceleration from cellular dynamics.

The emergence of epigenetic predictors was a pivotal moment in geroscience, propelling the measurement and concept of biological aging into a quantitative era; however, while current epigenetic clocks show strong predictive power, they are data-driven in nature and are not based on the underlying biological mechanisms driving methylation dynamics. We show that predictions of these clocks are susceptible to several confounding non-age-related phenomena that make interpretation of these estimates and associations difficult. To address these limitations, we developed a probabilistic model describing methylation transitions at the cellular level. Our approach reveals two measurable components, acceleration and bias, which directly reflect perturbations of the underlying cellular dynamics. Acceleration is the proportional increase in the speed of methylation transitions across CpG sites, whereas bias corresponds to global changes in methylation levels. Using data from 15,900 participants from the Generation Scotland study, we develop a robust inference framework and show that these are two distinct processes confounding current epigenetic predictors. Our results show improved associations of acceleration and bias with physiological traits known to impact healthy aging, such as smoking and alcohol consumption, respectively. Furthermore, a genome-wide association study of epigenetic age acceleration identified seven genomic loci.

Classifiers of anterior cruciate ligament status in female and male adolescents using return-to-activity criteria.

PURPOSE: A lack of standardization exists for functional tasks in return-to-activity (RTA) guidelines for adolescents with anterior cruciate ligament injury (ACLi). Identifying the variables that discern ACLi status among adolescents is a first step in the creation of such guidelines following surgical reconstruction. This study investigated the use of classification models to discern ACLi status of adolescents with and without injury using spatiotemporal variables from functional tasks typically used in RTA guidelines for adults. METHODS: Sixty-four adolescents with ACLi and 70 uninjured adolescents completed single-limb hops, lunges, squats, countermovement jumps and drop-vertical jumps. Jumping distances, heights, and depths were collected. Decision trees (DTs) were used to classify ACLi status and were evaluated using the F-measure (F1), kappa statistic (ĸ) and area under the precision-recall curve (PRC). Independent t tests and effect sizes were calculated for each important classifier of the DT models. RESULTS: A five-variable model classified ACLi status with an accuracy of 67.5% (F1 = 0.6842; ĸ = 0.350; PRC = 0.491) with sex as a classifier. Significant differences were found in three of the four spatiotemporal variables (p ≤ 0.002). Separate models then classified ACLi status in males and females with an accuracy of 53.3% (F1 = 0.5882; ĸ = 0.0541; PRC = 0.476) and 76.9% (F1 = 0.7692; ĸ = 0.541; PRC = 0.528), respectively, with significant differences for all variables (p ≤ 0.013). CONCLUSIONS: Among the DT models, females were better able to classify ACLi status compared to males, highlighting the importance of sex-specific rehabilitation guidelines for adolescents. LEVEL OF EVIDENCE: Level III.

Human Papillomavirus-Associated Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Objective: Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region. Data Sources: EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022. Review Methods: We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features. Results: Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC. Conclusion: This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.

Professional identity formation for all physicians on the surgery clerkship.

No abstract is necessary for an invited commentary.

Equipoise Lost? Trial Conduct Challenges in an Era of Breakthrough Therapies.

FDA Oncology Center's @Falleh_Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO_ASCO.

Comparative Assessment of Otolaryngology Knowledge Among Large Language Models.

OBJECTIVE: The purpose of this study was to evaluate the performance of advanced large language models from OpenAI (GPT-3.5 and GPT-4), Google (PaLM2 and MedPaLM), and an open source model from Meta (Llama3:70b) in answering clinical test multiple choice questions in the field of otolaryngology-head and neck surgery. METHODS: A dataset of 4566 otolaryngology questions was used; each model was provided a standardized prompt followed by a question. One hundred questions that were answered incorrectly by all models were further interrogated to gain insight into the causes of incorrect answers. RESULTS: GPT4 was the most accurate, correctly answering 3520 of 4566 questions (77.1%). MedPaLM correctly answered 3223 of 4566 (70.6%) questions, while llama3:70b, GPT3.5, and PaLM2 were correct on 3052 of 4566 (66.8%), 2672 of 4566 (58.5%), and 2583 of 4566 (56.5%) questions. Three hundred and sixty-nine questions were answered incorrectly by all models. Prompts to provide reasoning improved accuracy in all models: GPT4 changed from incorrect to correct answer 31% of the time, while GPT3.5, Llama3, PaLM2, and MedPaLM corrected their responses 25%, 18%, 19%, and 17% of the time, respectively. CONCLUSION: Large language models vary in their understanding of otolaryngology-specific clinical knowledge. OpenAI's GPT4 has a strong understanding of core concepts as well as detailed information in the field of otolaryngology. Its baseline understanding in this field makes it well-suited to serve in roles related to head and neck surgery education provided that the appropriate precautions are taken and potential limitations are understood. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Development of a monoclonal antibody to study MARCH6, an E3 ligase that regulates proteins that control lipid homeostasis.

MARCH6, also designated as TEB4 or RNF176, is an E3 ligase that is embedded in membranes of the endoplasmic reticulum (ER) where it ubiquitinates many substrate proteins to consign them to proteasome-mediated degradation. In recent years, MARCH6 has been identified as a key regulator of several metabolic pathways, including cholesterol and lipid droplet homeostasis, protein quality control, ferroptosis, and tumorigenesis. Despite its importance, there are currently no specific antibodies to detect and monitor MARCH6 levels in cultured cells and animals. Here, we address this deficiency by generating a monoclonal antibody that specifically detects MARCH6 in cultured cells of insect, mouse, hamster, and human origin, as well as in mouse tissues, with minimal cross-reactivity against other proteins. We then used this antibody to assess two properties of MARCH6. First, analysis of mouse tissues with this antibody revealed that the liver contained the highest levels of MARCH6. Second, analysis of five different cell lines with this antibody showed that endogenous levels of MARCH6 are unchanged as the cellular content of cholesterol is varied. This reagent promises to be a useful tool in interrogating additional signaling roles of MARCH6.

Immune Cell Densities Predict Response to Immune Checkpoint-Blockade in Head and Neck Cancer.

Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The current approach for predicting the likelihood of response to ICB is a single proportional biomarker (PD-L1) expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with ICB response than PD-L1. However, their exact composition, size, and spatial biology in HNSCC remain understudied. A detailed understanding of TLS is required for future use as a clinically applicable predictive biomarker. Methods: Pre-ICB tumor tissue sections were obtained from 9 responders (complete response, partial response, or stable disease) and 11 non-responders (progressive disease) classified via RECISTv1.1. A custom multi-immunofluorescence (mIF) staining assay was designed, optimized, and applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblasts (α Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). Spatial metrics were compared among groups. Serial tissue sections were scored for TLS in both H&E and mIF slides. A machine learning model was employed to measure the effect of these metrics on achieving a response to ICB (SD, PR, or CR). Results: A higher density of B lymphocytes (CD20+) was found in responders compared to non-responders to ICB (p=0.022). A positive correlation was observed between mIF and pathologist identification of TLS (R 2 = 0.66, p-value= <0.0001). TLS trended toward being more prevalent in responders to ICB (p=0.0906). The presence of TLS within 100 µm of the tumor was associated with improved overall (p=0.04) and progression-free survival (p=0.03). A multivariate machine learning model identified TLS density as a leading predictor of response to ICB with 80% accuracy. Conclusion: Immune cell densities and TLS spatial location within the tumor microenvironment play a critical role in the immune response to HNSCC and may potentially outperform CPS as a predictor of ICB response.

Analysis of Surgeon and Program Characteristics Associated with Success on American Board of Surgery Exam Outcomes.

BACKGROUND: Existing research exploring predictors of success on American Board of Surgery (ABS) exams focused on either resident or residency program characteristics, but limited studies focus on both. This study examines relationships between both resident and program characteristics and ABS Qualifying (QE) and Certifying Exam (CE) outcomes. STUDY DESIGN: Multilevel logistic regression was used to analyze the relationship between resident and program characteristics and ABS QE and CE 1st attempt pass and eventual certification. Resident characteristics were gender, IMG status, and prior performance, measured by 1st attempt USMLE Step 2 CK and Step 3 scaled scores. Program characteristics were size, %female, %International Medical Graduate (IMG), and program type. The sample included surgeons with QE and CE data from 2007-2019 and matched USMLE scores. RESULTS: Controlling for other variables, prior medical performance positively related to all ABS exam outcomes. The relationships between USMLE scores and success on ABS exams varied but were generally strong. Other resident characteristics that predicted ABS exam outcomes were gender and IMG (QE 1st attempt pass). The only program characteristic that significantly predicted ABS outcomes was %IMG (QE and CE 1st attempt pass). Despite statistical significance, gender, IMG, and %IMG translated to small differences in predicted probabilities of ABS exam success. CONCLUSION: This study highlights resident and program characteristics that predict success on ABS exams. USMLE scores consistently and strongly related to ABS exam success, providing evidence that USMLE scores relate to future high-stakes consequences like board certification. After controlling for prior performance, gender, IMG, and program %IMG significantly related to ABS exam success, but effects were small.