Continuous Variables Research Articles

Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Machine learning-based radiomics analysis in predicting RAS mutational status using magnetic resonance imaging.

To assess the efficacy of radiomics features, obtained by magnetic resonance imaging (MRI) with hepatospecific contrast agent, in pre-surgical setting, to predict RAS mutational status in liver metastases. Patients with MRI in pre-surgical setting were enrolled in a retrospective study. Manual segmentation was made by means 3D Slicer image computing, and 851 radiomics features were extracted as median values using the PyRadiomics Python package. The features were extracted considering the agreement with the Imaging Biomarker Standardization Initiative (IBSI). Balancing was performed through synthesis of samples for the underrepresented classes using the self-adaptive synthetic oversampling (SASYNO) approach. Inter- and intraclass correlation coefficients (ICC) were calculated to assess the between-observer and within-observer reproducibility of all radiomics characteristics. For continuous variables, nonparametric Wilcoxon-Mann-Whitney test was utilized. Benjamini and Hochberg's false discovery rate (FDR) adjustment for multiple testing was used. Receiver operating characteristics (ROC) analysis with the calculation of area under the ROC curve (AUC), sensitivity (SENS), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) were assessed for each parameter. Linear and non-logistic regression model (LRM and NLRM) and different machine learning-based classifiers including decision tree (DT), k-nearest neighbor (KNN) and support vector machine (SVM) were considered. Moreover, features selection were performed before and after a normalized procedure using two different methods (3-sigma and z-score). McNemar test was used to assess differences statistically significant between dichotomic tables. All statistical procedures were done using MATLAB R2021b Statistics and Machine Toolbox (MathWorks, Natick, MA, USA). Seven normalized radiomics features, extracted from arterial phase, 11 normalized radiomics features, from portal phase, 12 normalized radiomics features from hepatobiliary phase and 12 normalized features from T2-W SPACE sequence were robust predictors of RAS mutational status. The multivariate analysis increased significantly the accuracy in RAS prediction when a LRM was used, combining 12 robust normalized features extracted by VIBE hepatobiliary phase reaching an accuracy of 99%, a sensitivity 97%, a specificity of 100%, a PPV of 100% and a NPV of 98%. No statistically significant increase was obtained, considering the tested classifiers DT, KNN and SVM, both without normalization and with normalization methods. Normalized approach in MRI radiomics analysis allows to predict RAS mutational status.

Analysis of echocardiographic features and postnatal management of fetal pulmonary valve stenosis

Objective: To investigate the echocardiographic features, consistency of diagnosis between fetal and postnatal periods and postnatal clinical outcomes of fetal pulmonary valve stenosis (PS) with different degrees. Methods: This study was a retrospective cohort study comprising 108 cases of fetal PS diagnosed during the fetal period and followed up postnatally at Xinhua Hospital, Shanghai Jiaotong University School of Medicine from November 2012 to February 2023. Echocardiographic characteristics, including morphological and hemodynamic features were collected for all fetuses who were then were followed up to at least 6 months after birth. One-way analysis of variance and Kruskal-Wallis test were used to compare the differences in the echocardiographic features among fetuses with different degrees of PS. Subsequently, McNemar test was used to assess the consistency of diagnosis between the fetal and postnatal periods. Furthermore, Logistic regression analysis was applied to explore the risk factors for neonatal intervention in fetuses with moderate PS and the receiver operating characteristic (ROC) curve was utilized to ascertain the optimal cut-off value for continuous variables. Results: The age of the mothers of the 108 fetuses at the initial assessment was (30.8±4.0) years, and the gestational age was 26.5 (24.6, 30.0) weeks. The fetuses were categorized into mild (17 cases), moderate (49 cases), and severe groups (42 cases) based on the initial echocardiographic features. Mild PS was characterized by valve thickening and hyperechogenicity combined with systolic flow acceleration or dilation of main pulmonary artery. Moderate PS exhibited both restricted valve motion and a colorful blood flow pattern at the valve orifice. The peak flow velocities of fetuses with moderate and critical PS were notably higher than those in the mild group ((2.66±0.86) and (2.77±1.30) vs. (1.43±0.59)m/s, F=14.52, P<0.001). In critical PS, all cases showed retrograde ductal flow, with a significantly higher proportion of a small right ventricle compared to the mild and moderate PS (42.9% (18/42) vs. 0 and 2.0% (1/49), χ2=31.73, P<0.001). The proportion of severe tricuspid regurgitation was also higher (35.7% (15/42) vs. 0 and 10.2% (5/49), χ2=36.94, P<0.001). Compared to mild and severe PS, the consistency of diagnosis between fetal and postnatal periods in moderate PS was lower (40.8% (20/49) vs.13/17 and 80.3% (35/42), χ2=12.45, P=0.006). The systolic flow velocity was identified as an independent risk factor for neonatal intervention in fetuses with moderate PS (OR=7.21, 95%CI2.11-24.62). A flow velocity of ≥2.18 m/s in second trimester and ≥3.15 m/s in third trimester indicated the necessity of neonatal intervention for fetal moderate PS. Among the 108 fetuses, 68 underwent surgical intervention and all survived. Additionally, 39 fetuses were regularly followed up. A sole non-surgical fatality occurred, leading to a 6-month survival rate of 99.1% (107/108). Conclusions: Various degrees of fetal PS demonstrate distinctive morphological and hemodynamic alterations in echocardiography. The disparity in severity between the postnatal and fetal stages requires ongoing monitoring for fetal PS. The prognosis for fetal PS is generally favorable.

Role of tumor mutational burden (TMB) and microsatellite instability (MSI) in patients (pts) with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitor (ICI).

654 Background: MSI and TMB correlate with ICI efficacy. We assessed the association between TMB and MSI with outcomes in pts with aUC treated with anti-PD1/L1 in a ‘real-world’ cohort. We hypothesize that pts with high TMB and MSI-high (H) have better outcomes with ICI. Methods: In this retrospective study we included pts from 13 sites treated with ICI for aUC. We calculated overall response rate (ORR), median overall and progression-free survival (mOS, mPFS) using KM method from ICI start. TMB and MSI were assessed by NGS. TMB was analyzed as dichotomous (≥10 vs &lt;10 mut/Mb) and continuous variable. The analysis was stratified by therapy line (1L/upfront, 2+L). Multivariable models were adjusted by Khaki factors for 1L/upfront and Bellmunt factors for 2+L. We separately analyzed pts on maintenance avelumab (mAV). MSI is reported with descriptive statistics only. Results: 342 pts were treated with ICI 1L/upfront or 2+L (69% pure UC, median age at ICI start 69, 77% men, 90% White, 16% upper tract primary, 12% liver metastases [mets], 78% ECOG PS 0-1). Median f/u from ICI start was 34 months (mo). ORR was 36% (95%CI 26-46%) in pts with TMB≥10 vs 30% (95%CI 23-36%) with TMB&lt;10 (OR=1.4 [95%CI 0.8-2.5] p=0.3). ORR was 75% (6/8) in pts with MSI-H and 30% (60/200) with MSI stable (MSI-S). mPFS was similar between TMB≥10 and &lt;10 groups (6 vs 4 mo; HR=0.88 [95%CI 0.61-1.26] p=0.48) and between MSI-H and MSI-S (5 mo). mOS was numerically longer (not significant) in pts with TMB≥10 vs TMB&lt;10: 25 vs 21 mo; (HR=0.7 [95%CI 0.50-1.09] p=0.12) and with MSI-H and MSI-S (NR and 20 mo). A significant association was found between TMB (continuous variable) and OS (HR=0.97 [95%CI 0.95-0.99] p=0.01). TMB analyses by therapy line are shown in Table. In the 1L/upfront setting (N=144), ORR 71% (5/7) vs 33% (45/135), mPFS 5 and 4 mo, mOS NR and 22 mo for MSI-H and MSI-S, respectively. Pts on mAV (n=77) were 77% men, 92% White, 16% upper primary, 13% liver mets, 84% ECOG PS 0-1 with median f/u 15 mo from avelumab start; mOS was NR for MSI-H and 24 mo for MSI-S; mPFS was 4 mo for both groups. Of 3 pts on mAV with MSI-H: 1 CR, 2 SD; of 58 pts with MSI-S: 4CR, 4PR, 24 SD, 21 PD, 5 unknown. Conclusions: MSI-H had numerically higher ORR and higher TMB was associated with longer OS with ICI, but further validation is needed. Limitations: retrospective design, small sample size for MSI-H cases, lack of randomization and central scan review, selection/confounding. [Table: see text]

Abstract TP103: Association Between Neighborhood-Level Disadvantage and Patient-Reported Mental Health Outcomes in Intracerebral Hemorrhage Survivors

Introduction: The influence of social determinants of health (SDH) is well-documented across a range of medical conditions and health outcomes. Less clear is the impact of SDH on patient-reported outcomes, particularly mental health outcomes, in intracerebral hemorrhage (ICH). This study examines the association between the Area Deprivation Index (ADI), a measure of neighborhood-level disadvantage, and self-reported health outcomes in ICH survivors. Methods: This investigation is nested within the REDUCE clinical trial, an ongoing, randomized trial comparing standard-of-care to spironolactone-containing hypertension regimens in ICH survivors. Participants complete the PROMIS Global Health survey at baseline. Global Mental Health (GMH) and Global Physical Health (GPH) scores are standardized to t-scores (GMH 21.2-67.6; GPH 16.2-67.7) around a reference population mean (50 ± 10). ADI uses elements of income, education, employment, and housing quality to assign a composite score (1-100), with a higher score signifying greater disadvantage. Patients were grouped into tertiles based on ADI. GMH and GPH scores were analyzed against the reference mean via a one-sample t-test and across tertiles with a one-way ANOVA. Bivariable linear regression examined ADI as a continuous variable. Multivariable models adjusted for sex, age, race, ethnicity, ICH to baseline interval, and baseline mRS. Results: Fifty patients were included in the analysis. Those in the third, most disadvantaged, tertile had significantly lower GMH scores (39.5 ± 8.17) than the reference population (p&lt;0.001), the first tertile (54.10 ± 10.20, p&lt;0.001), and the second tertile (50.4 ± 8.90, p=0.003). In multivariable analysis, these differences remained significant (T3 vs. T1, B= -18.31, p&lt;0.001; T3 vs. T2, B= -14.67, p&lt;0.001). Further, ADI as a continuous variable was significantly associated with GMH scores in bivariable (B= -0.22, p&lt;0.001) and multivariable analysis (B= -0.23, p=0.005). No significant relationship was found between ADI and GPH. Conclusions: Higher ADI is associated with worse patient-reported mental health outcomes after ICH. Neighborhood disadvantage, and its constituting factors, should be considered in reporting post-ICH patient care and outcomes.

FDA pooled analysis of overall survival according to depth of response as a continuous variable in frontline advanced immuno-oncology renal cell carcinoma trials.

418 Background: Retrospective analyses of individual studies of immune-oncology-containing combinations (IOC) for advanced renal cell carcinoma (aRCC) suggest that depth of response (DepOR; % reduction from baseline in sum of target lesion diameters) is associated with overall survival (OS). However, these analyses are limited by use of DepOR categories with a small number of patients and guarantee-time bias. We therefore sought to investigate the relationship of week 12 DepOR as a continuous variable with OS, hypothesizing not only complete but also deep partial responses might portend favorable longer-term survival. Methods: We pooled data from patients with treatment (tx)-naïve aRCC enrolled in randomized IO-based frontline aRCC trials submitted to FDA that included a Week 12 imaging assessment. We developed 36-month (mo) overall survival (OS) prediction models based on Week 12 DepOR per Independent Review Committee using Cox proportional hazards with natural spline in the IO-TKI combination (IOC) and sunitinib (SUN) groups. To avoid guarantee-time bias, OS was defined from date of an individual patient’s 12-week imaging, among the subset of patients who were alive and in follow-up at the Week 12 scan. Results: Four trials met inclusion criteria (KEYNOTE-426, JAVELIN Renal 100, CheckMate 9ER, CheckMate 214); in total there were 1364 patients in the IOC group and 1267 patients in the SUN group. Eligibility criteria, baseline patient characteristics, and endpoints were similar both between the trials and between tx groups. Deepest response occurred at median 31 weeks (interquartile range [IQR], 18-55) in the IOC group and 29 weeks (IQR range, 17-48) in the SUN group. At Week 12, 34.7% of patients had DepOR of at least 30%; median DepOR was 27.6% (interquartile range [IQR] 8.7 to 43.4%) in the IOC and 13.7% (IQR 2.5 to 26.3%) in the SUN group. DepOR and 36-month OS were correlated throughout the entire range of DepOR in both tx groups; at each DepOR, the IOC group had slightly higher 36-mo OS over SUN. We saw similar results modeling 24-month OS compared to 36-month OS. Conclusions: This pooled exploratory analysis suggests that deeper response is associated with better 36-month OS in patients treated with IOC or SUN and slightly higher probability of 36-month OS for any given DepOR for IOC vs. SUN. We saw no plateau in OS as DepOR approached complete response. However, caution should be used when interpreting DepOR at the tails due to sparse data. Further work characterizing the relationship between DepOR and OS at the trial level may advance understanding of the utility of DepOR as an early endpoint in signal-seeking trials and to facilitate efficient drug development. Additionally, identifying patients with favorable long-term prognosis based on DepOR provides hypotheses for new trial designs.

Abstract WP258: Younger Patients Have a Higher Likelihood of Recurrent Vessel Small Subcortical Infarct: A Post-Hoc Analysis of the SPS3 Trial

Introduction: Recurrent ischemic stroke due to intracranial large artery disease occurs in up to 20% of patients and is associated with uncontrolled cardiovascular risk factors. However less is known of recurrent vessel small subcortical infarcts (rvSSI), which may be related to branch atherosclerotic disease. The aim of this study was to describe the clinical risk factors associated with rvSSI. Methods: We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled participants between 2003 and 2007. All participants were ≥ 30 years old and had a SSI index event within the preceding 6 months of randomization, confirmed by MRI with a maximal diameter on diffusion weighted imaging (DWI) of ≤ 20 mm, and were without competing stroke mechanism (e.g. ipsilateral carotid stenosis ≥ 50%). Participants were followed over a mean duration of 4 years post-enrollment during which stroke recurrence was noted and characterized. rvSSI was defined as recurrent SSI within the same vascular distribution as an index enrolling infarct confirmed by brain MRI. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Adjusted logistic regression models were formed to calculate odds ratio. Statistical significance was ≤ 0.05. Results: Of the 3020 participants enrolled in SPS3, 1245 participants met inclusion criteria with 15 having a rvSSI (mean time post-enrollment: 427 days). Participants with rvSSI were younger (54.5 ± 10.2 years vs 61.2 ± 10.6 years, p = 0.008) and had enrollment diagnoses of obesity [BMI ≥ 30 kg/m2; 80% (12/15) vs 49% (598/1230), p = 0.016] and hyperlipidemia [87% (13/15) vs 58% (713/1230), p = 0.025]. Sex, former/current tobacco use, and known diagnoses of hypertension and diabetes mellitus did not differ. For every advancing decade of life, the likelihood of developing a rvSSI was 0.46 (95%CI 0.26 - 0.82, p = 0.008). Conclusions: Participants of the SPS3 trial who were younger in age had rvSSI more frequently with the likelihood decreasing by roughly half with advancing decade of life.

Abstract WP226: Perioperative Stroke and Cardiac Anomalies Associated With Posterior Cerebral Artery Stenosis in Children With Moyamoya

Introduction: Moyamoya is a progressive steno-occlusive arteriopathy of the intracranial circulation affecting the anterior circulation and less often the posterior circulation. Risk factors and severity of disease progression in children with moyamoya and posterior cerebral artery (PCA) stenosis have not been well described in the literature. Previous research has shown an association between PCA stenosis and increased risk of post-operative stroke. We wanted to further explore this relationship in children with moyamoya and delineate the associated risk factors. Methods: Children with moyamoya who underwent surgical revascularization at our institution between December 2015 and December 2022 were reviewed for presence of PCA stenosis. Clinical and radiographic features were compared between children with moyamoya with and without PCA involvement. Categorical variables were compared using Fisher's exact test and continuous variables using Wilcoxon rank-sum. Associations between perioperative stroke and PCA stenosis were analyzes using a multivariate logistic regression. Results: In our cohort of 160 children with moyamoya, 45 (28%) had PCA stenosis; 26 of these 45 (57%) had PCA stenosis at time of diagnosis. Of the 19 children who did not have PCA stenosis at time of diagnosis but developed it during follow up, the median time to development of PCA stenosis was 1.0 years. Children with moyamoya and PCA stenosis had significant more cardiac anomalies than those without (p=0.02). Other associated disorders were found in 13 (28%) including trisomy 21 (6, 13%), cranial radiation (2,4%) and NF1 (3,7%). Interestingly, we found no significant difference in age, sex or prevalence of bilateral disease between the groups. Children with moyamoya and PCA stenosis had a 3.5 higher odds of having a stroke within 2 weeks of surgery (p=0.049). Conclusion: Children with moyamoya and PCA stenosis had a 3 fold higher odds of perioperative stroke compared to those without PCA stenosis. Genetic evaluations may be warranted given association of PCA stenosis and cardiac anomalies.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

Distal humeral osteotomy for cubitus varus in children compared to adolescents

BackgroundWhile pediatric cubitus varus has often been considered merely a cosmetic deformity, long-standing cubitus varus can lead to symptomatic pain and elbow instability in adults and may present as early as adolescence. The purpose of this study was to compare patient and radiographic characteristics, surgical factors, and symptom resolution after distal humeral osteotomy for cubitus varus in pediatric versus adolescent patients. MethodsThis is a retrospective single-institution review of 17 patients (12 patients <10.0 years (group Peds); 5 patients >10.0 years (group Adol)) were treated for cubitus varus with distal humeral osteotomy from 2003 to 2019. Peds had a median age of 6.3 years (range, 2.7-7.8 years) at the time of osteotomy, and Adol had a median age of 14.1 years (range, 13.5-16.7 years). A Fisher’s exact test was used to compare categorical variables between Peds and Adol, and continuous variables were compared using Mann-Whitney or Student’s t-test depending on normality results using the Shapiro-Wilk test. Statistical significance was set at P<.05. ResultsPreoperative pain was present in 17% (2/12) of Pediatric patients (Peds) but 100% (5/5) of Adolescent patients (Adols). Mechanical symptoms were present in 17% (2/12) of Peds and 80% (4/5) in Adol. Radiographic correction and final range of motion did not significantly differ between the 2 groups. The mean tourniquet time was 83 minutes in Peds and 117 minutes in Adol. Pin fixation was used in 100% (12/12) of Peds; 80% (4/5) of Adol had plates. At the final follow-up, all Peds had resolution of symptoms, but 60% (3/5) Adol had continued pain and mechanical symptoms. ConclusionsAlthough both pediatric and adolescent patients have similar radiographic correction and range of motion after distal humeral osteotomy to correct cubitus varus, the surgery may be more technically difficult in adolescent patients, with longer tourniquet times and the use of plate instead of pin fixation. Adolescents should be counseled that, like adults, their symptoms may not completely resolve after correction of radiographic and clinical deformity. The authors recommend that cubitus varus be corrected in childhood prior to the development of symptoms in adolescence. Key Concepts1)Cubitus varus following pediatric distal humerus fracture may present with pain and mechanical symptoms as early as adolescence.2)Although pediatric and adolescent patients may have similar radiographic correction and range of motion after distal humeral osteotomy, the surgery is technically more difficult in adolescent patients.3)Adolescents should be counseled that pre-operative symptoms may not completely resolve after correction of radiographic and clinical limb deformity.4)It is the authors’ opinion that cubitus varus should be surgically corrected before a child reaches adolescence, when it is technically less demanding and before mechanical symptoms and pain develop. Level of EvidenceLevel III – Retrospective Cohort Study

Abstract B034: Characterization of MHC-I-mediated immune evasion in triple-negative breast cancer using human transcriptomic datasets and immunocompetent mouse models

Abstract In Triple-Negative Breast Cancer (TNBC) patients, adaptive immune system activity in the tumor microenvironment is associated with improved prognosis. However, tumors can evolve to evade immune detection, likely leading to worse patient outcomes. Multi-omic data of paired primary and metastatic breast tumors demonstrate that TNBC metastases frequently lose expression of genes involved in major histocompatibility complex class I (MHC-I) antigen presentation, a key pathway for adaptive immune activation (PMID: 36585450). Therefore, understanding and addressing MHC-I-mediated immune evasion may have profound clinical benefits for TNBC patients. We hypothesize that breast tumor MHC-I loss results in a unique immune-evasive phenotype, which we are characterizing using human clinical datasets and immunocompetent mouse models of breast cancer. First, using large transcriptomic datasets (i.e., SCAN-B and TCGA), we are characterizing molecular and clinical features of MHC-I-low human breast tumors using expression of the MHC-I gene human leukocyte antigen A (HLA-A) as a continuous variable. We found HLA-A expression varies significantly between PAM50 molecular and clinical subtypes of breast cancer and has differing impacts on patient survival based on clinical subtype. In TNBCs, low HLA-A expression is associated with worse outcomes, while in HR+/HER2- tumors, low HLA-A predicts improved outcomes. We also identified genes highly correlated with HLA-A regardless of molecular subtype. This list was functionally rich, related to antigen processing machinery, adaptive immune-mediated cytotoxicity, and T cell exhaustion features. To complement human genomic data, we are empirically testing the role of MHC-I in syngeneic mouse mammary tumor models by individually knocking out murine MHC-I genes–H2-K, H2-D, and B2m–through CRISPR/Cas9-mediated genome editing. We have generated and validated knockouts (KOs) of H2-K and B2m, as well as empty vector control clones from the “immune-hot” and immune checkpoint inhibitor (ICI) responsive mammary tumor cell lines KPB25L-UV and T11-APOBEC. RNA sequencing of KPB25L-UV H2-K and B2m KO versus wildtype cell lines in vitro identified lists of differentially expressed genes, many of which are related to proteolytic and peptide antigen processing. Next, these CRISPR-modified cell lines were injected into the mammary fat pad of syngeneic immunocompetent mice, and the resulting tumors were harvested for RNA sequencing. Differentially expressed genes in KPB25L-UV H2-K KO versus wildtype tumors were related to increased MHC Class II antigen presentation and dendritic cell activity. Preliminary data suggests that mice bearing KPB25L-UV H2-K KO tumors have shortened survival compared to H2-K wildtype tumors. Experiments are ongoing to further characterize the growth dynamics, metastatic potential, single-cell transcriptomic profiles, and ICI sensitivities of these KO tumors in vivo. Our long-term goal is to identify therapeutic means to overcome this common immune-evasive phenotype to improve TNBC patient outcomes. Citation Format: Constandina E O'Connell, Brooke M Felsheim, Aranzazu Fernandez-Martinez, Kevin R Mott, Charles M Perou. Characterization of MHC-I-mediated immune evasion in triple-negative breast cancer using human transcriptomic datasets and immunocompetent mouse models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B034.

Abstract WP124: Dual Energy Head CT Immediately Following Mechanical Thrombectomy Rarely Leads to Changes in Clinical Management

Introduction: No guidelines exist regarding imaging after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Dual Energy Head CT (DECT) can differentiate between contrast staining and intracranial hemorrhage (ICH). We obtained routine DECT for AIS patients immediately following MT. We aimed to understand the impact of DECT on clinical management. Methods: We conducted a single-center retrospective study of AIS patients who underwent MT and immediate post-procedure DECT between March 2021 and February 2023. Patients were grouped by whether or not DECT results changed management, compared to our standard post-thrombectomy protocol and as documented in clinical notes. Continuous variables were compared using Wilcoxon Rank-Sum tests, and categorical variables were compared using Chi-square tests. Results: Of 173 patients who met inclusion criteria, 13 (7.5%) had documented changes in management following DECT. Management changes included delayed anti-thrombotic administration, lowered systolic blood pressure goals, and serial imaging. There were no statistically significant differences in age, gender, initial NIHSS, ischemic core size pre-MT, or treated vessel between patients with and without a change in management. Patients with management changes were more likely to have had procedural complications, contrast staining, any ICH, and symptomatic ICH (Table). While 34 patients had ICH on DECT, this only led to a documented change in management for 11 (32.4%) patients. Conclusion: Routine DECT immediately after MT rarely changed clinical management. Immediate DECT may be reserved for patients with intraprocedural complications or those with clinical suspicion of ICH.

Differences in reproductive health discussions in an urban Hispanic population with SLE: lessons from the field

ObjectiveManagement of reproductive health-related issues is crucial for patients with SLE, given this is a disease that primarily affects women of childbearing age. Little is known as to how the...

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging

BackgroundInaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. MethodsFrom 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. ResultsOf the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. ConclusionsThe presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Effect of Lateral Surgery Compared with Posterior Surgery on Lumbar Degenerative Disease: A Meta-Analysis of 41 Cohort Studies

PurposeThe purpose of this study was to compare the efficacy of the lateral approach and posterior approach in the treatment of lumbar degenerative diseases. MethodsThrough a systematic search of relevant articles published on or before July 20, 2023, in the Embase, PubMed and Cochrane libraries, the two authors independently extracted data and used the Newcastle‒Ottawa scale (NOS) to evaluate the quality of the included studies. Using Stata16 software, the continuous variables were presented as the standard mean deviation (SMD), and the bipartite variables were analyzed using the pooled odds ratio (ORs) with 95% confidence interval (CIs). ResultsA total of 13,892 articles were screened, and 10,908 studies were identified after deleting duplicates, of which 41 met the criteria and were included in the meta-analysis. The meta-analysis showed that the lateral approach was superior to the posterior approach in reducing blood loss, operation time and hospital stay. At the same time, compared with the posterior approach, the lateral approach has more advantages in the long-term JOA score and ODI score, adjusting mid-term and long-term LL and short-term and long-term DH. ConclusionLateral and posterior surgery have similar clinical effects in the treatment of lumbar degenerative diseases and can significantly reduce pain and improve postoperative SL. At the same time, the lateral approach has more advantages in improving long-term quality of life, reducing the long-term disability index, adjusting mid-term and long-term LL and short-term and long-term DH.

Abstract 152: Endovascular Therapy versus Medical Management for Acute Ischemic Stroke With Large Infarct: A Time-Benefit Relationship Analysis

Objective: Recent randomized trials demonstrated the benefit of endovascular thrombectomy for acute ischemic stroke with large infarct. We aimed to characterize the effect of time to treatment on the benefit of endovascular therapy compared to medical management among patients with acute large ischemic stroke. Methods: Analysis the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial (ANGEL-ASPECT), which was a multicenter, randomized trial at 46 comprehensive stroke centers in China from August 2020 to October 2022. Onset to arterial puncture time (OPT) associated with outcomes of endovascular therapy were analyzed as a category and continuous variable. The primary outcome was favorable outcome (modified Rankin scale 0-3) at 90 days. Secondary outcomes included degree of disability (modified Rankin scale range), symptomatic intracranial hemorrhage, any intracranial hemorrhage, and mortality. Results: Among 455 eligible patients, the median age was 68 years, and median Alberta Stroke Program Early Computed Tomography Score was 3 (interquartile range 3-4). Compared with medical management alone, endovascular therapy plus medical management was associated with higher rates of favorable outcome with OPT within 6 hours (44.4% vs 29.9%, adjusted odds ratio[aOR] 2.78 [95% confidence interval [CI] 1.22-6.32]), 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI, 0.88-4.77]). The benefit in favorable outcome became nonsignificant after OPT of 13 hours and 22 minutes. In three OPT intervals, the odds of better disability outcome with endovascular therapy plus medical management than medical management alone were observed; the rates of symptomatic intracranial hemorrhage and mortality were similar, though the rates of any intracranial hemorrhage increased. Conclusion: In patients with large cerebral infarction, endovascular therapy plus medical management was efficacious in improving functional outcomes with acceptable safety in a broad time window of 0 to 24 hours, but greater benefit was observed with earlier treatment. A pooled analysis with larger sample size is needed.

Abstract 124: Pre-Stroke Aspirin Use Does Not Impact Small Subcortical Stroke Size: A Secondary Analysis of the SPS3 Trial

Introduction: The use of pre-stroke aspirin is associated with smaller stroke size in first-time stroke related to large vessel occlusion. However, it is unknown whether pre-stroke aspirin use impacts stroke size for an acute small subcortical infarct (SSI). We hypothesized that pre-stroke aspirin use would be associated with a smaller sized SSI. Methods: We performed a secondary analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled between 2003 and 2007. We included participants ≥ 55 years old with brain-MRI confirmed SSI being ≤ 20 mm in maximal diameter on diffusion weighted imaging. Stroke size was determined retrospectively by the study team on the index event brain MRI. Pre-stroke medications were recorded at the time of enrollment. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Binary logistic regression models were fitted for likelihood ratios. Results: Of the 3020 participants enrolled in SPS3, a total of 2183 met inclusion criteria: 663 with pre-stroke aspirin monotherapy and 1520 without pre-stroke antithrombotic use, Table 1. Those with aspirin use were older with a higher incidence of diagnoses of hypertension, hyperlipidemia, and diabetes mellitus, though otherwise sex, and tobacco use did not differ. The mean maximal stroke width, trended towards, but was not statistically impacted by pre-stroke aspirin use [pre-stroke aspirin: 11.8 (4.1) mm vs 11.4 (4.1) mm, p =0.065]. After adjustment for significant variables, pre-stroke aspirin use did not impact the odds of a larger infarct size (OR 0.779, 95%CI 0.615-1.04, p =0.092). Conclusion: Despite those with pre-stroke aspirin use having more vascular risk factors, its use did not impact stroke size amongst those with an acute SSI enrolled in the SPS3 trial.

Abstract 53: Patients With Tandem Lesions Undergoing Thrombectomy Have Increased In-Hospital Stroke Recurrence Risk

Introduction: Mechanical Thrombectomy improves outcomes in patients with acute ischemic stroke due to large vessel occlusion. Nearly 15% of patients have a tandem extracranial and intracranial occlusion. There is limited data on in-hospital outcomes in patients with acute tandem lesions undergoing thrombectomy. Methods: We included patients hospitalized with acute ischemic stroke and large vessel occlusion undergoing thrombectomy at our comprehensive stroke center over a 7-year period. Data on demographics and baseline risk factors, occlusion site, and acute treatment was pulled from the stroke registry. Records were reviewed for the study outcome which was recurrent ischemic stroke during the in-hospital period, defined as new or worsening neurological symptoms due to new infarct or extension of the infarct. All outcomes were confirmed by a second neurologist. Patients were followed for 90-days and received a 90-day call to determine their modified rankin scale. We defined good functional outcome as 90-day mRS 0-2. We used fisher’s exact test and t-tests to compare categorical and continuous variables and built binary logistic regression model to compare 90-day mRS across the two groups (tandem vs. non-tandem lesions), adjusting for age and NIHSS scale. Results: We identified a total of 1347 patients (mean age 72 years, 51% women) who underwent thrombectomy and 226 (16.7%) had tandem lesions and 108/226 (47.8%) underwent acute stenting. Patients with tandem lesions were more likely to be men (60.6% vs. 46.6%,), have hyperlipidemia (60.9% vs. 52.1%), coronary artery disease (25.3% vs. 19.0%), smokers (35.9% vs. 20.5%) and less likely to have atrial fibrillation (20.0% vs. 46.2%) and history of congestive heart failure (8.0% vs. 16.8%), all p&lt;0.05. Patients tandem occlusions were more likely to have in-hospital recurrent ischemic stroke (8.0% vs. 4.1%, p = 0.012). Acute stenting was not associated with improved functional outcome at 90-days (aOR 0.86, 95% CI 0.41-1.82, p = 0.703). Conclusion: In this large cohort of thrombectomy patients, patients with tandem lesions had increased in-hospital recurrent stroke and acute stenting in this sub-group was not associated with improved functional outcome at 90-days.

Abstract 153: First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke is Modified by Procedure Time: Proposal of a New Measure for Thrombectomy Procedures

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs &gt;30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and &gt; 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT &gt;30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (&gt;30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Abstract WP172: A Novel Score to Predict Early Time From Symptom Onset to Hospital Arrival in Patients With Intracerebral Hemorrhage

Introduction: Up to 40% of ICH patients have unknown onset time, leading to uncertainty regarding the use of hyperacute ICH treatments and their exclusion from acute ICH treatment trials. We aimed to develop a prediction score that can reliably identify ICH patients presenting within 3 hours of symptom onset. Methods: Spontaneous ICH patients participating in the iDEF trial with available prerequisite data were analyzed. A stepwise multivariable logistic regression model was used to determine predictors of early presentation (symptom onset-to-baseline CT scan time ≤3 hours) with a p-value &lt; 0.15. To develop the prediction score, we allocated scores proportional to the standardized odds ratio (OR) of each binary variable. Continuous variables were dichotomized using the lowest threshold above which there was no additional gain in the positive predictive value (PPV) for early presentation. Results: Of 291 iDEF participants, 132 (45%) presented early. Baseline NIHSS (OR 1.05 per 1-score increase; 95% CI, 0.99-1.11), Glasgow Coma Scale (1.18 per 1-score increase; 1.01-1.39), ICH volume (1.17 per 10-ml increase; 0.98-1.39), absolute perihematomal edema volume (0.81 per 10-ml increase; 0.66-1.00), irregular hematoma shape (2.24; 1.12-4.48), blend sign (0.45; 0.21-0.97), white blood cell count (0.89 per 10 3 cell/ml increase; 0.82-0.96), and blood glucose levels (0.91 per mmol/l increase; 0.82-0.99) were associated with early presentation (c-statistic=0.71). The PPV for an early ICH presentation score (Figure) of &gt;7 was 69%. Conclusion: This novel early ICH presentation score using readily available clinical, neuroimaging, and laboratory data has good performance for identification of ICH patients presenting within 3 hours of symptom onset. If validated in external datasets, the early ICH presentation score can be used to improve recruitment feasibility in acute ICH trials and support clinical decision-making in ICH patients with an unknown symptom onset time.