Risk Group Of Patients Research Articles

Editor's Choice – Development of a Risk Prediction Nomogram for Carotid Re-Stenosis in the One Year RECAST Registry

The long term benefit of carotid angioplasty and stenting (CAS) can be reduced by recurrent stroke related to in stent re-stenosis (ISR). An individualised predictive tool is needed to identify ISR events. A nomogram for individual risk assessment of ISR ≥ 70% after CAS is proposed. A national observational, prospective, multicentre registry was conducted between January 2015 and December 2020. Cohorts of patients with symptomatic or asymptomatic severe carotid stenosis who underwent CAS with a follow up of at least one year after CAS were included. Duplex ultrasound was used to assess in stent re-stenosis. Pre-operative factors were compared between the non-ISR and ISR groups. Kaplan-Meier and Cox regression were used for variable selection. The nomogram was formulated and validated by concordance indices and calibration curves. An in stent re-stenosis risk table was generated for risk stratification. A total of 354 patients were included in the analysis. The ISR rate of ≥ 70% was 7.6% (n= 27). Peripheral arterial disease (hazard ratio [HR] 3.18, 95% confidence interval [CI] 1.23 - 8.24, p= .017), anterior communicating artery absence (HR 3.38, 95% CI 1.27 - 8.94, p= .016), diabetes mellitus (HR 3.34, 95% CI 1.21 - 9.26, p= .020), female sex (HR 2.99, 95% CI 1.04 - 8.60, p= .041), and pre-procedure pathological ultrasound vasoreactivity (HR 3.87, 95% CI 1.43 -10.50, p= .008), as independent risk factors for ISR of ≥70%, were included in the nomogram. The concordance index at 12 and 24 months was 0.83. In low risk groups, ISR of ≥ 70% occurred in 4.8% of patients during follow up compared with 56.2% of patients in the high risk groups (p < .001). The nomogram and risk evaluation score have good predictive ability for ISR. They can be used as practical clinical tools for individualised risk assessment.

#2257 Kidney outcomes in ANCA-associated vasculitis—application of Berden's Classification and ANCA Renal Risk Score in a single centre cohort

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis is the most common cause of rapidly progressive glomerulonephritis and is a life-threatening condition. The course of the disease is variable and disease prognostication remains challenging. Histological and clinical scores have been developed to predict kidney outcomes, to tailor treatment. The aim of this study is to apply Berden´s histopathological classification (BHC) and ANCA renal risk score (ARRS), proposed by Brix and co-workers, in a cohort of patients with ANCA-associated vasculitis and to analyse their performance in renal outcomes prediction. Method In this retrospective observational study, we included patients with biopsy proven ANCA-associated vasculitis, diagnosed at our centre between March 2011 and March 2023. We consulted the clinical records and the kidney biopsy reports. Biopsies were categorized according to both scores. Follow up time was up to 48 months since the date of diagnosis. In BHC patients were divided into 4 groups (focal, crescentic, sclerotic and mixed) according to normal glomeruli, cellular crescents and globally sclerosed glomeruli proportion. When applying the ARRS, patients were divided into 3 groups: low, medium or high risk. This is a histopathological and biochemical score that combines normal glomeruli and tubular atrophy and interstitial fibrosis (IFTA) percentages with estimated glomerular filtration rate (eGFR) at time of diagnosis. Factors related to renal survival were evaluated by Spearman Rank Correlation, Binary Logistic Regression analysis and Kaplan-Meier curves were used for assessing time between diagnosis and end stage kidney disease (ESKD). Results Our study included 31 patients, 54.8% were male, median age at diagnosis was 62 (IQR, 53-69) years, with a median eGFR of 8.3 (IQR, 6.2-13.3) mL/min/1.73 m2 and a median urine albumin to creatinine ratio (uACR) of 1.5 (IQR, 0.88-2.2) g/g. 19 patients (61.3%) were positive for myeloperoxidase and 5 (16.1%) were proteinase 3 positive. Median follow up time was 36 (IQR, 9-48) months. 10 patients (32%) developed ESKD and 9 patients (29%) died. Regarding BHC, 4 patients (13%) presented a focal class, 18 (58%) crescentic, 7 (23%) mixed and 2 (6%) sclerotic. Progression to ESKD occurred in 7 patients with crescentic class (38.9%), 2 patients with mixed (28.6%) and 1 patient with sclerotic (50%). None of the patients with focal class developed ESKD. There were no significant differences in kidney survival curves by BHC class (Log Rank p = 0.47) (Fig. 1a). In ARRS, 1 patient (3%) was in the low-risk group, 19 patients (61%) in the medium risk and 11 patients (35%) in the high risk. Characteristics of the population by ARRS score group and detailed score discrimination are specified in Table 1. Progression to ESKD, occurred in 5 patients of medium risk group (26.3%) and also in 5 patients in the high-risk group which represented 45.5% of this group. Kidney survival curves by ARRS score group had no statistic difference (Log Rank p = 0.46) (Fig. 1b). ESKD was positively associated with serum creatinine (sCr) at admission (p = 0.02), highest sCr (p = 0.001) and leukocyturia (p = 0.05). By multivariate analysis adjusted to gender, age, sCr at admission, leukocyturia and BHC or ARRS, the only factor associated with ESKD was sCr at admission (OR 1.45, CI 1.03-2.06, p = 0.05). Conclusion In our cohort of patients, sCr at patient hospital admission was the best predictor for progression to ESKD. By ARRS, just one patient had low risk, and as expected, kidney survival was higher in the medium risk group (68.5%) than in the high-risk group (53%), although not reaching statistical significance. BHC also had no association with kidney outcomes, although kidney survival was 100% in focal class and sclerotic class had the lowest survival (50%), yet crescentic class revealed a worse kidney survival (57.1%) than mixed class (71.4%). The small number of patients, overall and in each group, and the short follow up period can be pointed as limitations of this study.

A prognostic binary classifier comprised of five critical mRNAs stratified pancreatic cancer patients following resection

BackgroundPancreatic cancer is characterized by an extremely poor prognosis, even following potentially curative resection. Classical prognostic markers such as histopathological or clinical parameters have limited predictive power. The present study aimed to establish a prognostic model combining mRNA expression data with histopathological and clinical data to better predict survival and stratify pancreatic cancer patients following resection. We pioneered three models in one study and systematically evaluated the clinical benefits of all three models. MethodsTo identify differentially expressed genes in pancreatic cancer, mRNA data from normal (GTEx database) and pancreatic cancer (TCGA database) tissues were used. Survival analysis was carried out to identify prognosis-relevant genes from the identified differentially expressed genes and LASSO regression was used to filter out hub genes. The risk score of several hub genes was calculated according to gene expression and coefficients. Validation was carried out using an independent set of GEO microarray data. Multivariate COX regression was used for identifying independent clinical and pathological risk factors related to patient's survival in the TCGA database and a prognostic model combining mRNA expression data with histopathological and clinical data was established. Another prognostic model using clinicopathological factors from the SEER database was conceived based on multivariate COX regression. NRI (net reclassification improvement) and IDI (integrated discrimination index) were used to compare the predictive capabilities of the different models. ResultsWe identified 1589 differentially expressed genes (DEGs) through the comparison of normal and pancreatic cancer tissues, of whom 317 were associated with prognosis(p < 0.05). LASSO regression identified five hub genes, MYEOV, ANXA2P2, MET, CEP55, and KRT7, that were used for the five-mRNA-classifier prognostic model. The classifier could stratify patients into a short and long survival group: 5-year overall survival in the training set (TCGA, 6 % vs 52 %, p < 0.001), test set (TCGA, 18 % vs 55 %,p < 0.01) and external validation set (GEO, 0 % vs 25 %, p < 0.05). Sensitivity analysis showed that the mRNA model (model 1) was better than the clinicopathological no-mRNA model (model 2) in predicting 5-year survival in the TCGA database (AUC: 0.877 vs 0.718, z = 3.165, p < 0.01) and better than the multi-factor prognostic model (model 3) from the SEER database (AUC: 0.754, z = 2.637, p < 0.01). On predictive performance, model 1 improved model 2 (NRI = 0.084, z = 1.288, p = 0.198; IDI = 0.055, z = 1.041,p = 0.298) and model 3 (NRI = 0.167,z = 1.961,p = 0.05; IDI = 0.086, z = 1.427, p = 0.154). ConclusionThe five-mRNA-classifier is a reliable and feasible instrument to predict the prognosis of pancreatic cancer patients following resection. It might help in patiens counseling and assist clinicians in providing individualized treatment for patients in different risk groups.

Identifying and Validating an Angiogenesis-related Signature for the Prognosis of Head and Neck Squamous Cell Carcinoma.

The present study aimed todevelop a prognostic model for HNSCC treatment on the basis of angiogenesis-related signatures. Head and Neck Squamous Cell Carcinoma (HNSCC) is the most frequent malignancy with poor prognostic outcomes in the head and neck. Angiogenesis plays a critical role in tumorigenesis and is expected to be an effective therapeutic target. The RNA-seq dataset TCGA-HNSCC and the hallmark gene set were used for angiogenesis-related RiskScore model construction. The RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA), and the hallmark gene set was used to measure the angiogenesis score using the GSVA R package. Then, the optimal cutoff point for prognostic classification was calculated by the survminer package, and Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify angiogenesis gene modules . Multi/univariable and Lasso Cox analyses were performed to develop the RiskScore model, and the classifier efficiency was evaluated by the Receiver Operating Characteristic curve (ROC). Furthermore, a nomogram was designed for survival probability prediction, and the immune infiltration and immunotherapy differences among different risk patients were assessed. After calculating the angiogenesis score, we found that this indicator and patients' prognosis were closely correlated, especially when patients with a high angiogenesis score had a poor prognosis. Then, WGCNA identified a blue gene module positively correlated with angiogenesis. Multivariate and Lasso Cox analysis further identified 9 risk model genes for developing a RiskScore, which was used to divide low- and high- -risk groups of patients. Those with a high risk tended to show poor prognosis, immune infiltration, and higher immune escape. Finally, a nomogram was developed to optimize the risk model, and it exhibited excellent short- and long-term survival prediction performance. We constructed a reliable RiskScore model for the prognostic prediction of HNSCC patients, contributing to precise therapeutic intervention of the cancer.

Early outcome in patients with STEMI undergoing primary PCI and high Zwolle risk score discharged within 72 hours

Abstract Funding Acknowledgements None. Introduction Zwolle risk score has been used to guide decision for early discharge in patients with ST- elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). There is limited evidence on the outcome of patients with high score discharged within 72 hours from primary PCI. Our study aim is to evaluate the outcomes via 1 - month follow up in patients with STEMI undergoing primary PCI, with different Zwolle risk who were discharged within 72 hours from the hospital. Purpose To evaluate 1-month outcome of STEMI patients treated with primary PCI discharged within 72 hours according to Zwolle risk score. Methods We studied 187 consecutive STEMI patients from April 2022 to December 2022, presented in hospital within 12 hours of initial of chest pain, treated with primary PCI and discharged within 72 hours from hospital admission based on physician’s clinical judgement and patient’s preference. Patients were divided in two groups according to Zwolle risk score – low risk (≤3) and high risk (&amp;gt;3). The composite of major adverse events (MACE) consisting of: death, non-fatal re-infarction, stroke and repeat intervention at 1-month follow up was the primary endpoint. Follow up rate was 100%. Results There were 131 patients in the low risk and 56 in high risk groups. Males were 90% versus 80.3% in the low vs high risk group; in addition, mean age was 58.64 ± 10.6 vs 67.8± 6.24 years, respectively; mean ischemic time was 4.78± 3.03 vs 6.9 ± 3.6 hours, respectively; anterior localization was present in 32.8% vs 46.4% of the patients, respectively; 3-vessel coronary artery disease was present in 29.0% vs 46.4% of the patients, respectively; final TIMI 3 flow was present in all vs 96.4% of the patients, respectively. MACE occurred in 7 patients (3.8%) in the low risk group versus 3 patients (5.3%) in the high risk group (P = 0.63). Conclusions In our study population at higher Zwolle risk score was not associated with a worse early outcome among STEMI patients discharged within 72 hours.

Abstract PO5-15-11: A Novel Biosignature to Predict Radiation Therapy Response in Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Surgery

Abstract Introduction: Radiation therapy (RT) is a standard component of treatment for most patients with early-stage, hormone receptor-positive, invasive breast cancer (BC) following breast-conserving surgery (BCS). RT recommendations are primarily based on clinicopathologic (CP) factors, such as tumor size, nodal status, and histological grade. While these factors provide prognostic information, their ability to accurately identify patients at a higher risk of ipsilateral breast recurrence (IBR) or those who will significantly benefit from RT is unclear. Therefore, incorporation of additional predictive markers beyond CP factors is warranted and there remains a need to refine the selection criteria for patients who will derive the greatest benefit from RT. In this study, we aimed to explore the role of immune and metabolic signaling axes as potential predictive markers for RT response in hormone receptor-positive breast cancer patients. Methods: A cohort of 939 women from Sweden were diagnosed with BC between 1987 and 2004. A subset of 471 patients was diagnosed with T1-T2N0M0 BC and underwent BCS with negative margins. Patients were treated with BCS plus/minus RT (median dose 50Gy) based upon physician preference. Biomarkers were assayed in formalin-fixed paraffin-embedded tissue micro arrays using multiplex immunofluorescence and multi-spectral imaging in a CLIA lab (Laguna Hills, CA). Immune and metabolic axes were defined employing biomarkers and used to classify patients into three risk groups: 1) Low Risk (lower baseline risk and no RT benefit), 2) Elevated Risk (higher baseline risk and significant RT benefit), and 3) Residual Risk (higher baseline risk and suboptimal RT benefit). Risk groups were analyzed for IBR rate using Kaplan-Meier and Cox proportional hazards analyses. Risk group prognosis and RT prediction was assessed for RT-risk group interaction in multivariable analysis, adjusting for CP factors. Results: Among the patients with complete biomarker data, 261 were hormone receptor-positive, and had a median follow-up of 140 months. Median age was 62 years (28-88 years), and median tumor size was 1.1 cm (0.1-4 cm). Some patients (21%) received endocrine therapy (ET), and most (76%) received RT, with 79% of patients who received ET also receiving RT. In the overall population, RT following BCS was associated with a reduction in HR for recurrence (HR=0.3, 95%CI [0.1, 0.5], p&amp;lt; 0.001). Patients classified as Low Risk (41%) did not have a significant benefit from RT (HR=0.9, 95%CI [0.1, 8.3], p=0.95) in multivariable analysis adjusted for CP factors. For patients who were classified as Elevated Risk (31%), multivariable analysis showed a higher IBR rate without RT (HR=5.7, 95%CI [1.3, 25.1], p&amp;lt; 0.021) relative to the Low Risk group who had a significant benefit from RT (HR=0.1, 95%CI [0.02, 0.2], p&amp;lt; 0.001). Patients classified into the Residual Risk group (28%) had no significant reduction from RT (HR=0.7, 95%CI [0.2, 2.0], p=0.61). However, in multivariable analysis adjusted for CP factors, patients treated with RT in the Residual Risk group had higher IBR rates (HR=3.7, 95%CI [1.6, 8.7], p=0.0026) compared to RT-treated patients in other risk groups. The biosignature was predictive for RT benefit in multivariable analysis adjusted for CP factors (p-interaction &amp;lt; 0.001). Conclusions:The biosignature used in this study demonstrated the potential to identify patients who may derive limited benefit from RT, allowing for tailored therapeutic approaches. These findings underscore the importance of individualized treatment decisions based on risk stratification. Further clinical validation and refinement of risk stratification strategies are warranted to optimize outcomes in hormone receptor-positive, BC patients undergoing BCS. Citation Format: Troy Bremer, Karuna Mittal, Chirag Shah, Frank Vicini, Steven Shivers, Charlotta Wadsten. A Novel Biosignature to Predict Radiation Therapy Response in Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-11.

Abstract PO4-16-11: De-escalation of anthracyclines during adjuvant therapy based on Oncotype RS: A single institution experience in Mexico City

Abstract Introduction: In Mexico, hormone positive HER2 negative breast cancer is the most frequent subtype, accounting for 76.6% of cases. For patients undergoing local control management through surgery; adjuvant chemotherapy is usually followed depending on different risk factors. In order to avoid overtreatment, different genomic firms have been approved aiding in a more objective decision. One of these genomic firms is the Oncotype Recurrence score. The TAILORx and RxPONDER trials have provided guidance in determining which patients are candidates for chemotherapy depending on their menopausal status. However, it has not yet been determined whether patients requiring chemotherapy can receive an anthracycline-free regimen. In the Plan B clinical trial, a non-inferiority analysis was conducted on early-stage breast cancer patients who received anthracycline-based or non-anthracycline-based chemotherapy, with the non-anthracycline regimen being non-inferior, including patients with a RS &amp;gt; 25. We intend to reevaluate these findings in our Mexican population. Methods: We evaluated 217 patients with early stage hormone sensitive HER2 negative breast cancer who had an Oncotype Recurrence score (RS) result. This retrospective cohort study took place by analyzing electronic records from January 2011 to December 2017 with patients treated at the National Cancer Institute in Mexico City. We included patients 18 years of age or older, any sex with an Oncotype RS ≥ 16 in premenopausal patients or ≥ 26 in postmenopausal patients who received adjuvant chemotherapy with or without anthracyclines. Our primary endpoint was iDFS comparing TC vs AC-T. Overall survival was set as a secondary endpoint. Results: Of the 217 patients with an Oncotype recurrence score, only 46 patients received adjuvant chemotherapy of which 71.7% were premenopausal with a median age of 45 years. Stage II was the most common stage with 91.3% of the population, as well as ductal carcinoma with 82.6%. All patients had positive lymph nodes, 54.3% at least 1 lymph node. Most patients received AC-T adjuvant chemotherapy (60.9%), and only 39.1% received TC. Of the 46 patients analyzed, only 19.6% (9) had a recurrence upon follow-up (Table 1). Median time of follow up was 87.5 months. Difference in Disease free survival could not be established between patients receiving AC-T with 105 months (CI 95% 94.36-117.43 months) vs TC with 94.09 months (CI 95% 83.85-104.34 months, &amp;lt; p.918) (Figure 1). Overall survival did not have a statistical difference between both chemotherapy regimens, p&amp;lt; 0.649 (Figure 2A), when comparing Oncotype RS, overall survival was better in those with Oncotype OS &amp;lt; 26, p&amp;lt; 0.023 (Figure 2B). Discusion As described previously in the Plan B trial, TC was non inferior to the conventional adjuvant regimen of AC-T in Hormone positive HER2 negative early-stage breast cancer. Our results tend to show similar results when compared to the Plan B. An important aspect to our study was that 71.7% of our patients were premenopausal, where in the Plan B trial only 35% were premenopausal, considered a higher risk group of patients. Although a statical difference couldn´t be established due to our small sample size, in DFS or OS when comparing the chemotherapy regimen. Premenopausal patients with an Oncotype RS &amp;lt; 26 could receive an anthracycline free regimen, without impact in their overall survival. Larger prospective studies are necessary to assure this conclusion. Figure 1 DFS (TC vs AC-T) Figure 2 A and B Overall Survival Table 1 (Baseline characteristics) Citation Format: Carlos Arturo González Núñez, Paula Cabrera-Galeana, Juan Enrique Bargalló Rocha, Rafael Vazquez-Romo, Sergio Aguilar-Villanueva, Alexandra Garcilazo, Areli Velazquez-Martinez, Andrea Maliachi, Ruben Rodriguez, Esmeralda Romero-Bañuelos. De-escalation of anthracyclines during adjuvant therapy based on Oncotype RS: A single institution experience in Mexico City [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-11.

Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.

Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

NET-related gene signature for predicting AML prognosis

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan–Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs—CFTR, ENO1, PARVB, DDIT4, MPO, LDLR—were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

Tailoring remote patient management in cardiovascular risk management for healthcare professionals using panel management: a qualitative study

BackgroundWhile remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among different patient subgroups. Panel management, which involves proactive care for specific patient risk groups, could offer a promising approach to tailor RPM to these groups. This study aims to (i) assess the perception of healthcare professionals and other stakeholders regarding the adoption and (ii) identify the barriers and facilitators for successfully implementing such a panel management approach.MethodsIn total, nineteen semi-structured interviews and two focus groups were conducted in the Netherlands. Three authors reviewed the audited transcripts. The Consolidated Framework for Implementation Strategies (CFIR) domains were used for the thematic analysis.ResultsA total of 24 participants (GPs, nurses, health insurers, project managers, and IT consultants) participated. Overall, a panel management approach to RPM in primary care was considered valuable by various stakeholders. Implementation barriers encompassed concerns about missing necessary risk factors for patient stratification, additional clinical and technical tasks for nurses, and reimbursement agreements. Facilitators included tailoring consultation frequency and early detection of at-risk patients, an implementation manager accountable for supervising project procedures and establishing agreements on assessing implementation metrics, and ambassador roles.ConclusionPanel management could enhance proactive care and accurately identify which patients could benefit most from RPM to mitigate CVD risk. For successful implementation, we recommend having clear agreements on technical support, financial infrastructure and the criteria for measuring evaluation outcomes.

Ischemia-Guided Coronary Revascularization Following Lower-Extremity Revascularization Improves 5-Year Survival of Patients With Chronic Limb-Threatening Ischemia.

To determine whether diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with targeted coronary revascularization of ischemia-producing coronary lesions following lower-extremity revascularization can reduce adverse cardiac events and improve long-term survival of patients with chronic limb-threatening ischemia (CLTI). Prospective cohort study of CLTI patients with no cardiac history or symptoms undergoing elective lower-extremity revascularization. Patients with pre-operative coronary computed tomography angiography (CTA) and FFRCT evaluation with selective post-operative coronary revascularization (FFRCT group) were compared with patients with standard pre-operative evaluation and no post-operative coronary revascularization (control group). Lesion-specific coronary ischemia was defined as FFRCT≤0.80 distal to a coronary stenosis with FFRCT≤0.75 indicating severe ischemia. Endpoints included all-cause death, cardiac death, myocardial infarction (MI) and major adverse cardiovascular (CV) events (MACE=CV death, MI, stroke, or unplanned coronary revascularization) during 5 year follow-up. In the FFRCT group (n=111), FFRCT analysis revealed asymptomatic (silent) coronary ischemia (FFRCT≤0.80) in 69% of patients, with severe ischemia (FFRCT≤0.75) in 58%, left main ischemia in 8%, and multivessel ischemia in 40% of patients. The status of coronary ischemia in the control group (n=120) was unknown. Following lower-extremity revascularization, 42% of patients in FFRCT had elective coronary revascularization with no elective revascularization in controls. Both groups received guideline-directed medical therapy. During 5 year follow-up, compared with control, the FFRCT group had fewer all-cause deaths (24% vs 47%, hazard ratio [HR]=0.43 [95% confidence interval [CI]=0.27-0.69], p<0.001), fewer cardiac deaths (5% vs 26%, HR=0.18 [95% CI=0.07-0.45], p<0.001), fewer MIs (7% vs 28%, HR=0.21 [95% CI=0.10-0.47], p<0.001), and fewer MACE events (14% vs 39%, HR=0.28 [95% CI=0.15-0.51], p<0.001). Ischemia-guided coronary revascularization of CLTI patients with asymptomatic (silent) coronary ischemia following lower-extremity revascularization resulted in more than 2-fold reduction in all-cause death, cardiac death, MI, and MACE with improved 5 year survival compared with patients with standard cardiac evaluation and care (76% vs 53%, p<0.001). Silent coronary ischemia in patients with chronic limb-threatening ischemia (CLTI) is common even in the absence of cardiac history or symptoms. FFRCT is a convenient tool to diagnose silent coronary ischemia perioperatively. Our data suggest that post-surgery elective FFRCT-guided coronary revascularization reduces adverse cardiac events and improves long-term survival in this very-high risk patient group. Randomized study is warranted to finally test this concept.

Machine Learning-Based Prediction of Pathological Responses and Prognosis After Neoadjuvant Chemotherapy for Non–Small-Cell Lung Cancer: A Retrospective Study

BackgroundNeoadjuvant chemotherapy has variable efficacy in patients with non–small-cell lung cancer (NSCLC), yet reliable noninvasive predictive markers are lacking. This study aimed to develop a radiomics model predicting pathological complete response and postneoadjuvant chemotherapy survival in NSCLC. Materials and MethodsRetrospective data collection involved 130 patients with NSCLC who underwent neoadjuvant chemotherapy and surgery. Patients were randomly divided into training and independent testing sets. Nine radiomics features from prechemotherapy computed tomography (CT) images were extracted from intratumoral and peritumoral regions. An auto-encoder model was constructed, and its performance was evaluated. X-tile software classified patients into high and low-risk groups based on their predicted probabilities. survival of patients in different risk groups and the role of postoperative adjuvant chemotherapy were examined. ResultsThe model demonstrated area under the receiver operating characteristic (ROC) curve of 0.874 (training set) and 0.876 (testing set). The larger the area under curve (AUC), the better the model performance. Calibration curve and decision curve analysis indicated excellent model calibration (Hosmer–Lemeshow test, P = .763, the higher the P-value, the better the model fit) and potential clinical applicability. Survival analysis revealed significant differences in overall survival (P = .011) and disease-free survival (P = .017) between different risk groups. Adjuvant chemotherapy significantly improved survival in the low-risk group (P = .041) but not high-risk group (P = 0.56). ConclusionThis study represents the first successful prediction of pathological complete response achievement after neoadjuvant chemotherapy for NSCLC, as well as the patients’ survival, utilizing intratumoral and peritumoral radiomics features.

Effect of Different Induction Immunosuppression on the Incidence of Infectious Complications after Kidney Transplantation-Single Center Study.

Background/Objectives: Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of infections. In order to decrease either infectious complications or acute rejection, it is necessary to identify risk groups of patients profiting from personalized induction immunosuppressive treatment. The aim of our analysis was to find whether there were higher incidences of infectious complications after kidney transplantation (KT) in groups with different induction immunosuppressive treatment and also to find independent risk factors for recurrent infections. Materials: We retrospectively evaluated all patients with induction treatment with basiliximab after kidney transplantation from 2014 to 2019 at our center relative to age- and sex-matched controls of patients with thymoglobulin induction immunosuppression. Results: Our study consisted of two groups: basiliximab (39) and thymoglobulin (39). In the thymoglobulin group we observed an increased incidence of recurrent infection in every observed interval; however, acute rejection was seen more often in the basiliximab group. A history of respiratory diseases and thrombocytopenia were identified as independent risk factors for recurrent bacterial infections from the first to sixth month after KT. Decreased eGFR from the first month, infections caused by multi-drug-resistant bacteria, and severe infections (reflected by the need for hospitalization) were identified as independent risk factors for recurrent bacterial infections from the first to the twelfth month after KT. Conclusions: We found that in the group of patients with thymoglobulin induction immunosuppressive treatment, infectious complications occurred significantly more often during the entire monitored period with decreased incidence of acute humoral and cellular rejection occurred more often.

A Nomogram Model Based on the Inflammation-Immunity-Nutrition Score (IINS) and Classic Clinical Indicators for Predicting Prognosis in Extranodal Natural Killer/T-Cell Lymphoma.

Systemic inflammation, immunity, and nutritional status are closely related to patients' outcomes in several kinds of cancers. This study aimed to establish a new nomogram based on inflammation-immunity-nutrition score (IINS) to predict the prognosis of extranodal natural killer/T-cell lymphoma (ENKTL) patients. The clinical data of 435 patients with ENTKL were retrospectively reviewed and randomly assigned to training cohort (n=305) and validation cohort (n=131) at a ratio of 7:3. Cox regression analysis was employed to identify independent prognostic factors and develop a nomogram in the training cohort. Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were employed to assess the performance of the nomogram and compare it with traditional prognostic systems (PINK, IPI, KPI). Internal validation was performed using 1000 bootstrap resamples in the validation cohort. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) of patients in different risk groups. In the training cohort, in addition to several classic parameters, IINS was identified as an independent prognostic factor significantly associated with the OS of patients. The nomogram established based on the independent prognostic indicators showed superior survival prediction efficacy, with C-index of 0.733 in the training cohort and 0.759 in the validation cohort compared to the PINK (0.636 and 0.737), IPI (0.81 and 0.707), and KPI (0.693 and 0.639) systems. Furthermore, compared with PINK, IPI, and IPI systems, the nomogram showed relatively superior calibration curves and more powerful prognostic discrimination ability in predicting the OS of patients. DCA curves revealed some advantages in terms of clinical applicability of the nomogram compared to the PINK, IPI, and IPI systems. Compared with traditional prognostic systems, the nomogram showed promising prospects for risk stratification in ENKTL patient prognosis, providing new insights into the personalized treatment.

Machine learning to identify a composite indicator to predict cardiac death in ischemic heart disease

BackgroundMachine learning (ML) employs algorithms that learn from data, building models with the potential to predict events by aggregating a large number of variables and assessing their complex interactions. The aim of this study is to assess ML potential in identifying patients with ischemic heart disease (IHD) at high risk of cardiac death (CD). Methods3987 (mean age 68 ± 11) hospitalized IHD patients were enrolled. We implemented and compared various ML models and their combination into ensembles. Model output constitutes a new ML indicator to be employed for stratification. Primary variable importance was assessed with ablation tests. ResultsAn ensemble classifier combining three ML models achieved the best performance to predict CD (AUROC of 0.830, F1-macro of 0.726). ML indicator use through Cox survival analysis outperformed the 18 variables individually, producing a better stratification compared to standard multivariate analysis (improvement of ∼20%). Patients in the low risk group defined through ML indicator had a significantly higher survival (88.8% versus 29.1%). The main variables identified were Dyslipidemia, LVEF, Previous CABG, Diabetes, Previous Myocardial Infarction, Smoke, Documented resting or exertional ischemia, with an AUROC of 0.791 and an F1-score of 0.674, lower than that of 18 variables. Both code and clinical data are freely available with this article. ConclusionML may allow a faster, low-cost and reliable evaluation of IHD patient prognosis by inclusion of more predictors and identification of those more significant, improving outcome prediction towards the development of precision medicine in this clinical field.

Abstract 471: Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy

Abstract Introduction: Liquid biopsies offer a novel approach to diagnose, predict cancer outcomes, and monitor treatment response by analyzing tumor-derived substances. Circulating cell-free microRNAs (miRNAs) show clinical promise as biomarkers within prostate cancer (PCa) and have been implicated with PCa prognosis and outcomes. However, their potential for monitoring and assessing radiotherapy (RT) treatment response remains understudied. Understanding miRNA expression changes during RT is crucial, as they impact RT efficacy by directly affecting genes and proteins within RT-response pathways. Aim: This study aimed to profile the expression of three oncogenes, miR-17-5p, miR-20b-5p, and miR-106a-5p and to determine their association with PCa risk groups in patients receiving proton therapy (PT). Patients and Methods: Plasma was obtained from the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank. Plasma was collected from men diagnosed with localized PCa without metastatic disease at three time points: prior to PT (PRE-PT), at 4 weeks following the start of PT (4WKSPD1), and at 8 weeks following the start of PT (8WKSPD1). The pilot study consisted of 38 patients, with 23 categorized as low-risk and 15 categorized as high-risk for PCa. MiRNA expression levels were evaluated using reverse transcription-polymerase chain reaction and quantified using the Livak method. Results: The study revealed a downregulation of miR-17-5p in response to PT, with median gene expression levels decreasing from 0.73 at PRE-PT to 0.587 at 8WKSPD1. Low-risk PCa patients also showed distinct miRNA expression changes with all three miRNAs (miR-17-5p, miR-20b-5p, and miR-106a-5p) downregulated from 0.953, 1.037, and 1.010 at PRE-PT to 0.398, 0.216, and 0.298 at 8WKSPD1, respectively. Statistical analysis using a Kruskal-Wallis test followed by a Dunn's post-hoc test identified significant differences (p=0.035) specifically between PRE-PT and 8WKSPD1 for miR-17-5p. Conclusion: The study revealed that PT led to a time-dependent reduction in miRNA levels, indicating a higher responsiveness in low-risk compared to high-risk PCa patients. This differential response highlights miR-17-5p, miR-20b-5p, and miR-106a-5p as potential PT response biomarkers, with clinical implications for personalizing PCa treatment. These results underscore the necessity for further validation of these miRNAs to maximize their clinical utility. Citation Format: Johnny Velasquez, Curtis Bryant, Nancy Mendenhall, Luisel Ricks-Santi. Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 471.

Abstract 2239: Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data

Abstract Background: More than 60,000 U.S. adults are diagnosed with non-muscle invasive bladder cancer (NMIBC) each year. These patients are recommended to undergo surveillance via repeated cystoscopies. However, the ideal frequency of post-diagnostic cystoscopy surveillance remains unknown, and efforts are underway to de-escalate surveillance given uncertainty regarding its effect on mortality. We therefore aimed to compare the effectiveness of different post-diagnostic cystoscopy surveillance strategies on bladder cancer specific mortality. Methods: We used observational data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage to emulate a target trial, i.e., a hypothetical, pragmatic randomized trial that would answer our causal question. Eligible individuals were aged 66 years or older, diagnosed with NMIBC (Ta, Tis, or T1) classified as urothelial carcinoma between January 1, 2000 and December 31, 2017, and had completed their first post-diagnostic cystoscopy. We compared 10-year risks of bladder cancer specific mortality under cystoscopy surveillance every 3, 6, and 12 months separately among individuals at low, intermediate, and high risk. We estimated mortality risks using inverse probability weighted pooled logistic regression. Results: Among 58,004 eligible individuals, the median age at diagnosis was 77 years (interquartile range: 72, 82) and 75.6% were male. Over the 10 year follow-up period, 4,977 bladder cancer deaths occurred. Among individuals at high risk, the estimated 10-year bladder cancer mortality risks were 24.5% under the 3 month strategy, 26.6% under the 6 month strategy, and 27.3% under the 12 month strategy. Compared with cystoscopy every 3 months, the risk differences were 2.1% (95% confidence interval [CI]: -0.3, 3.8) for cystoscopy every 6 months, and 2.8% (95% CI: 1.0, 4.4) for cystoscopy every 12 months. For patients in the intermediate risk group, 10-year bladder cancer mortality risks were 14.4% under the 3 month strategy, 15.1% under the 6 month strategy, and 15.9% under the 12 month strategy. The risk differences were 0.7% (95% CI: -0.6, 2.0) for 6 vs. 3 months and 1.6% (95% CI: 0.3, 2.7) for 12 vs. 3 months. Among individuals at low risk, these mortality risks were 8.3% under the 3 month strategy, 9.2% under the 6 month strategy, and 9.6% under the 12 month strategy. Risk differences were 1.1% (95% CI: -0.1, 2.5) for 6 vs. 3 months and 1.5% (95% CI: 0.2, 3.0) for 12 vs. 3 months. Conclusions: We estimated that more frequent cystoscopy may result in clinically meaningful reductions in bladder cancer mortality among high risk patients. Among low and intermediate risk patients, more frequent cystoscopy may result in modest absolute risk reductions. Decision-makers should also consider the clinical and financial burden and risk of complications associated with more frequent surveillance. Citation Format: Emma E. McGee, Xabier García de Albéniz, A. Heather Eliassen, Kendrick Yim, Barbra A. Dickerman, Mark A. Preston, Miguel Hernán. Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2239.

Social Risk Groups in Patients With Diabetes With Differing Eye Care Utilization and Vision Outcomes.

To evaluate whether latent class analysis on social determinants of health (SDoH) data can identify social risk groups that differ by adverse SDoH and vision outcomes in patients with diabetes. This was a prospective cohort study of adults ≥18years with diabetes who completed a SDoH survey. Latent class analysis was used to cluster patients into social risk groups. The association of social risk group and severity of diabetic retinopathy, history of lapses in diabetic retinopathy care, and visual acuity was evaluated. A total of 1006 participants were included. The three social risk groups differed by sociodemographic characteristics. The average age was 65, 60, and 54 in Groups 1, 2, and 3 respectively. Most (51%) patients in group 1 were non-Hispanic White, 66% in group 2 were non-Hispanic Black, and 80% in group 3 were Hispanic. Group 1 had the lowest burden of adverse SDoH per person (average 3.6), group 2 had 8.2, and group 3 had 10.5. In general, group 1 lacked diabetic retinopathy knowledge, group 2 had financial insecurity and difficulties with transportation, and group 3 had financial insecurity and did not have health insurance. Social risk group was associated with a history of lapses in diabetic retinopathy care, and presenting with worse vision. We identified distinct social risk groups among patients seeking care for diabetic retinopathy that differed by social needs, eye care utilization, and vision. Identifying these groups and their specific needs can help guide interventions to effectively address adverse SDoH and improve eye care utilization and vision outcomes among patients with diabetes.

The Current Situation and Thinking of Medical Services, Medical Quality, and Medical Safety in China

Medical service quality and patient safety are pivotal to hospital management. Recent years have witnessed the evolution of China’s medical quality management and control system, resulting in improvements in medical services and patient safety. Based on the 2021 National Report on the Services, Quality and Safety in Medical Care System, the authors analyzed the current situation of the health care quality and safety of China’s medical services using annual hospital quality survey data and routine administrative and quality control data. The key indicators primarily focused on medical services, medical quality and safety, clinical specialty services, and regional medical services. The authors’ findings indicate a steady improvement in the supply of medical resources and systematic advances in service coverage and efficiency. Decreases were observed in both mortality rates among low–risk group patients (defined by using diagnosis-related group classifications) and rates of unplanned readmission. The authors also identified improvements in the quality of treatments for major diseases and surgical procedures. Although the technical capability of clinical specialties was largely consistent, a marginal decrease was noted in secondary hospitals. A trend toward in-province but out-of-city care has been seen in the patient populations. For patients seeking out-of-province care, the average cost per hospitalization was higher compared with their in-province counterparts. Longer hospital stays and higher mortality rates were observed for patients treated in province, but these indicators declined over time. This study suggests promising advancements in China’s health care system; it also highlights areas requiring further attention and improvement, including regional health care provision and clinical specialty services in secondary hospitals. This research underscores the need for ongoing monitoring and evaluation to ensure optimized medical resource allocation, enhanced quality management, and specific goals of quality improvement.

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients.

The tumor immune environment and immune-related genes are instrumental in the development, progression, and prognosis of bladder cancer (BLCA). This study sought to pinpoint key immune-related genes influencing BLCA prognosis and decipher their mechanisms of action. We analyzed differentially expressed genes (DEGs) between high- and low- tumor mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on immune-related gene pairs (IRGPs) and analyzed DEGs between high- and low-risk groups. A total of 22 shared DEGs were identified across differential TMB and IRGPs-derived risk groups in BLCA patients. Through univariate Cox and multivariate Cox analyses, we highlighted five genes - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 - significantly correlated with BLCA patient prognosis. Notably, the FLRT2 gene emerged as an independent prognostic factor for BLCA, impacting patient prognosis via modulation of macrophage infiltration in immune microenvironment. Further investigation spotlighted methylation sites - cg25120290, cg02305242, and cg01832662 - as key regulators of FLRT2 expression. These findings identified pivotal prognostic genes in BLCA and illuminated the intricate mechanisms dictating patient prognosis. This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.