Improve clinical feature-based bladder cancer survival prediction models through integration with gene expression profiles and machine learning techniques

3607 Background: Through mining The Cancer Genome Atlas (TCGA) data and a large set of transcriptomes of CRC in GEO, we constructed 15 metagenes reflecting the transcriptomic impact of major driver genes of CRC. Independent of any clinical information, we used metagenes as features to further develop an ML model, then tested it using gene expression (GE) data from C-07 and C-08. Methods: We carried out a prospectively designed and double-blind study to evaluate the clinical utility of the ML model in the adjuvant setting. Samples were classified as Sig+ or Sig-. Association of signatures with recurrence free interval were tested using log-rank test, and significance was set at P<0.05. Cox regression models were used to estimate hazard ratios in univariate and multivariate models and for significance testing in multivariate models. Clinical variables included in multivariate models were nodal status, age, sex, and T stage. Results: We tested the ML model for its ability to predict oxaliplatin benefit in all C-07 pts with available GE data (n=846). Sig+ pts received significant benefit from oxaliplatin (HR=0.68, 95% CI=0.48-0.95, p=0.025) but Sig- did not (Sig- HR=1.05, 95% CI=0.72-1.53, p=0.79), however, the int p value showed only a trend for significance (int p=0.091). Sig+ remained significant for oxaliplatin benefit in multivariate analysis (HR=0.67, 95% CI=0.48-0.95, p=0.024). When we combined all C-07 pts (C-07 FULV-trtd n=298, FLOX n=304) with C-08 FOLFOX-treated pts (n=226) the Sig+ was significantly associated with oxaliplatin benefit (HR=0.65, 95% CI=0.48-0.89, p=0.0065) with a significant int p=0.03. We also tested the signature for association with bev benefit in C-08 (n=438), using a different cut off. Sig+ showed only a trend for an association with bev benefit (HR=0.63, 95% CI=0.35-1.12, p=0.11). To increase the power to detect bev benefit, we also tested the signature for association with bev benefit in all C-08 patients and C-07 pts treated with FLOX. The Sig+ group received significant benefit from bev (HR=0.58, 95% CI=0.36-0.94, p=0.025) but the Sig- group did not (HR=1.02, 95% CI=0.64-1.63, p=0.94), however, the int p was not significant (p=0.101). The model also showed an association with prognosis within the FULV treatment arm in C-07 (HR=1.51, 95% CI=1.07-2.14, p=0.018) and the FOLFOX+bev arm in C-08 (HR=0.55, 95% CI=0.30-1.01, p=0.049). Conclusions: Although our study is not optimally powered, our analyses indicate that the ML model was predictive for oxaliplatin benefit in stage II and III CC and may be useful for detecting bev benefit. Importantly, the Sig- population is candidate for omitting oxaliplatin (de-escalation) in adjuvant setting but will require further validation. Support: PA DOH, U10CA-180868, -180822, -196067, Genentech, Sanofi; NSABP. Clinical trial information: 00096278, 00004931.

12074 Background: Skeletal-related events (SREs) are detrimental clinical events in bone metastasis from advanced cancer, defined by pathologic fracture, spinal cord compression, and inevitable surgical or radiational intervention to the bone. Given their negative impact on quality of life and prognosis and interpatient heterogeneity in the SRE risk, accurate identification of patients with high SRE risk is critical. Methods: The patient-level data from three randomized clinical trials that administered zoledronic acid (ZA) to patients with bone-metastatic breast cancer, castration-resistant prostate cancer (CRPC), and other types of cancer were analyzed. (N = 460, 452, and 315, respectively) Machine learning (ML) models to predict SREs within 18 months (breast cancer), 12 months (CRPC), and 9 months (other cancers) were developed based on more than 40 baseline clinical and laboratory data. Seven ML algorithms and five feature selection methods were utilized to develop multiple models. The ML model with the best performance was identified based on the F1 score and the area under the receiver operating characteristic curve (AUC-ROC) for each cancer type and interrogated for important features with Shapley additive explanations. Lastly, the ML models’ ability to stratify patients by the cumulative SRE risk was evaluated by calculating hazard ratio (HR) with Cox-proportional hazards models. Results: Among the multiple ML models developed with different algorithms and feature selection methods, the model developed utilizing the random forests algorithm and the Boruta method for selecting features demonstrated the best performance in all types of cancer (F1 0.70, 0.67, and 0.67, and AUC-ROC 0.72, 0.68, and 0.73 for breast cancer, CRPC, and other cancers, respectively). In the ML model for breast cancer, performance status (PS), history of SRE, serum alkaline phosphatase (ALP), history of anti-neoplastic surgery, radiation therapy, and pathologic fracture were included as important features. Serum ALP, albumin, sodium, Gleason scores, and geographic regions were shown to be relevant in the CRPC model. For other cancers, serum ALP, albumin, total protein, phosphorus, red blood cell count, white blood cell count, visceral metastases, and history of arthritis were incorporated in the ML model. The ML model prediction successfully stratified the patients for cumulative SRE risk in all three cohorts. (HR with 95% confidence interval: 2.43 [1.86 – 3.18], 1.92 [1.51 – 2.45], and 3.06 [2.29 – 4.09] for breast cancer, CRPC, and other types of cancer, respectively). Conclusions: ML models incorporating baseline clinical and laboratory data can identify patients with bone metastasis on ZA harboring a high SRE risk.

BackgroundBladder cancer (BLCA) is a common urogenital malignancy with significant heterogeneity, and gemcitabine serves as a key chemotherapeutic agent for BLCA. This study examined gemcitabine sensitivity-related long noncoding RNA (GSRlncRNA) in BLCA and constructed a prognostic signature.MethodsGene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The gemcitabine sensitivity of BLCA samples was quantitatively calculated. Using weighted gene coexpression network analysis (WGCNA), we analyzed the role of GSRlncRNA in BLCA. We developed a prognostic signature using machine learning algorithm integration, with the TCGA-BLCA cohort (n=405) serving as the training set and GSE31684 (n=93) serving as the validation cohort. Patients were stratified into low- and high-risk groups based on risk scores. Comparative analyses included prognosis, immune infiltration, mutational profiles, and pathway enrichment. Single-cell RNA sequencing (scRNA-seq) and in vitro experiments further validated the expression and functional roles of GSRlncRNA in BLCA.ResultsGSRlncRNAs were identified via WGCNA. The partial least squares regression for Cox (plsRcox) was selected as the optimal modeling approach. A prognostic signature comprising 37 GSRlncRNAs effectively stratified patients into distinct risk groups, which demonstrated significant differences in survival outcomes, pathway enrichment, immune infiltration, and mutational profiles. To enhance clinical utility, a nomogram and web-based calculator were developed. scRNA-seq clarified the critical roles of LINC00930 and EMX2OS in BLCA progression. Real-time quantitative polymerase chain reaction confirmed the differential expression of GSRlncRNA in BLCA compared to that in normal tissues. Functional assays demonstrated that LINC00930 and EMX2OS suppression impaired BLCA cell proliferation, migration, invasion, apoptosis, cell cycle, and gemcitabine sensitivity.ConclusionsWe identified critical prognostic associations between GSRlncRNAs and BLCA. Based on these findings, we constructed a GSRlncRNA-based predictive signature, which demonstrated considerable potential for risk stratification and personalized treatment decisions. Functional experiments further validated the involvement of GSRlncRNAs in BLCA progression.

Machine learning based survival prediction of DLBCL: Using multimodal data.

The premise for this study emanated from the need to understand SARS-CoV-2 infections at the molecular level and to develop predictive tools for managing COVID-19 severity. With the varied clinical outcomes observed among infected individuals, creating a reliable machine learning (ML) model for predicting the severity of COVID-19 became paramount. Despite the availability of large-scale genomic and clinical data, previous studies have not effectively utilized multi-modality data for disease severity prediction using data-driven approaches. Our primary goal is to predict COVID-19 severity using a machine-learning model trained on a combination of patients' gene expression, clinical features, and co-morbidity data. Employing various ML algorithms, including Logistic Regression (LR), XGBoost (XG), Naïve Bayes (NB), and Support Vector Machine (SVM), alongside feature selection methods, we sought to identify the best-performing model for disease severity prediction. The results highlighted XG as the superior classifier, with 95% accuracy and a 0.99 AUC (Area Under the Curve), for distinguishing severity groups. Additionally, the SHAP analysis revealed vital features contributing to prediction, including several genes such as COX14, LAMB2, DOLK, SDCBP2, RHBDL1, and IER3-AS1. Notably, two clinical features, the absolute neutrophil count and Viremia Categories, emerged as top contributors. Integrating multiple data modalities has significantly improved the accuracy of disease severity prediction compared to using any single modality. The identified features could serve as biomarkers for COVID-19 prognosis and patient care, allowing clinicians to optimize treatment strategies and refine clinical decision-making processes for enhanced patient outcomes.

Accurate prediction of in-hospital mortality for patients with severe community-acquired pneumonia (SCAP) complicated by respiratory failure admitted to the intensive care unit (ICU) remains a critical challenge. This study aimed to develop and validate a machine learning (ML) model to predict this risk and compare its performance with conventional scoring systems. In this retrospective study, data from 164 patients with SCAP and respiratory failure admitted to the ICU between January 2017 and January 2024 were analyzed. Patients were randomly divided into a training set (n = 114) and a validation (test) set (n = 50). Forty-five clinical features collected at admission were used as candidate predictors. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed for feature selection. Six ML models, including Gradient Boosting Decision Tree (GBDT), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Decision Tree(DT),Support Vector Machine (SVM), and Logistic Regression(LR), were constructed and evaluated.Use SHAP analysis to assess the contribution of each feature in a machine learning model. Construct a nomogram using the top six most influential features. The GBDT model demonstrated the best predictive performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI: 0.757-0.927) in the internal validation set, significantly outperforming the Acute Physiology and Chronic Health Evaluation II (APACHE-II, AUC = 0.70). Calibration curves demonstrated good agreement between predicted and observed mortality risks, particularly across the mid-probability range. Decision curve analysis indicated that the model provided a higher net benefit than "treat-all" and "treat-none" strategies across a broad range of threshold probabilities. SHapley Additive exPlanations (SHAP) analysis identified lactate, D-dimer, temperature, albumin, Prothrombin Time and Fraction of Inspired Oxygen as the six most influential predictors of in-hospital mortality. Based on these key predictors, we further developed a simplified nomogram to facilitate bedside risk estimation. The GBDT ML model, developed from routinely available clinical data, provides a highly accurate and clinically interpretable tool for predicting in-hospital mortality in SCAP patients with respiratory failure. It outperforms traditional severity scores and holds promise for assisting clinicians in risk stratification and early intervention.

Machine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. In a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. PubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. In total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. Statistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. PROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250.

Purpose: Unnecessary prostate biopsies for detecting prostate cancer (PCa) should be minimized. Therefore, this study developed a machine learning (ML) model to predict PCa in Korean men and evaluated its usability.Materials and Methods: We retrospectively analyzed clinical data from 928 patients who underwent prostate biopsies at Kangwon National University Hospital between May 2013 and May 2023. Of these, 377 (41.6%) were diagnosed with PCa, and 551 (59.4%) did not have cancer. For external validation, clinical data from 385 patients aged 48–89 years who underwent prostate biopsies from September 2005 to September 2023 at Wonju Severance Christian Hospital were also included. Twenty-two clinical features were used to develop an ML model to predict PCa. Features were selected based on their contributions to model performance, leading to the inclusion of 15 features. A meta-learner was constructed using logistic regression to predict the probability of PCa, and the classifier was trained and validated on randomly extracted training and test sets at an 8:2 ratio.Results: The prostate health index, prostate volume, age, nodule on digital rectal examination, and prostate-specific antigen were the top 5 features for predicting PCa. The area under the receiver operating characteristic curve (AUC) of the meta-learner logistic regression model was 0.89, and the accuracy, sensitivity, and specificity were 0.828, 0.711, and 0.909, respectively. Our model also showed excellent prediction performance for high-grade PCa, with a Gleason score of 7 or higher and an AUC of 0.903. Furthermore, we evaluated the performance of the model using external cohort clinical data and achieved an AUC of 0.863.Conclusions: Our ML model excelled in predicting PCa, specifically clinically significant PCa. Although extensive cross-validation in other clinical cohorts is needed, this ML model is a promising option for future diagnostics.

PD27-01 DEVELOPMENT OF A MACHINE LEARNING (ML) MODEL TO AUTOMATICALLY AND PRECISELY IDENTIFY KIDNEY STONES FROM URETEROSCOPY VIDEO RECORDINGS

CT-DERIVED BODY COMPOSITION AND MACHINE LEARNING FOR PROGNOSTIC IMPROVEMENT IN COLORECTAL CANCER

Interpretable vs. noninterpretable machine learning models for data-driven hydro-climatological process modeling

Aim: The majority of machine learning (ML) models in healthcare are built on retrospective data, much of which is collected without explicit patient consent for use in artificial intelligence (AI) and ML applications. The primary aim of this study was to evaluate whether clinicians and scientific researchers themselves consent to provide their own data for the training of ML models. Materials and Methods: This survey was conducted through an anonymous online survey, utilizing platforms such as Telegram, LinkedIn, and Viber. The target audience comprised specific international groups, primarily Russian, German, and English-speaking, of clinicians and scientific researchers. These participants ranged in their levels of expertise and experience, from beginners to veterans. The survey centered on a singular, pivotal question: “Do You Consent to the Use of Your Biological and Private Data for Training Machine Learning and AI Models?” Respondents had the option to choose from three responses: “Yes” and “No”. Results: The survey was conducted in January 2024. A total of 119 unique and verified individuals participated in the survey. The results revealed that only 50% of respondents (63 persons) expressed consent to provide their own data for the training of ML and AI models. Conclusion: In the development of ML and AI models, particularly open-source ones, it is crucial to ascertain whether participants are willing to provide their private data. While ML algorithms can transform the nature of data, it is important to remember that the primary owner of this data is the individual. Our findings show that in 50% of the cases, even participants from scientific research and clinical backgrounds – individuals typically accountable for ensuring data quality in AI and ML model development – do not consent to the use of their data in AI and ML settings. This highlights the need for more stringent consent processes and ethical considerations in the utilization of personal data in AI and ML research.

Accurate estimation of reference evapotranspiration (ETo) plays a vital role in irrigation and water resource planning. The Penman–Monteith method recommended by the Food and Agriculture Organization (FAO PM56) is widely used and considered a standard to calculate ETo. However, FAO PM56 cannot be used with limited meteorological variables, so it is compulsory to choose an alternative model for ETo estimation, which requires fewer variables. This study built ten machine learning (ML) models based on multi-function, neural network, and tree-based structure against the FAO PM56 method. For this purpose, time series temperature data on a monthly scale are only used to train ML models. The developed ML models were applied to estimate ETo at different test stations and the obtained results were compared with the FAO PM56 method to verify and validate their performance in ETo estimation for the selected stations. In addition, multiple statistical indicators, including root-mean-square error (RMSE), coefficient of determination (R2), mean absolute error (MAE), Nash–Sutcliffe efficiency (NSE), and correlation coefficient (r) were calculated to compare the performance of each ML model on ETo estimation. Among the applied ML models, the ETo tree boost (TB) ML model outperformed the other ML models in estimating ETo in diverse climatic conditions based on statistical indicators (R2, NSE, r, RMSE, and MAE). Moreover, the observed R2, NSE, and r were the highest for the TB ML model, while RMSE and MAE were found to be the lowest at the study sites compared to other applied ML models. Lastly, ETo point data yielded from the TB ML model was used in an interpolation process to create monthly and annual ETo maps. Based on the ETo maps, this study suggests mainly a focus on areas with high ETo values and proper irrigation scheduling of crops to ensure water sustainability.

This study focuses on using various machine learning (ML) models to evaluate the shear behaviors of ultra-high-performance concrete (UHPC) beams reinforced with glass fiber-reinforced polymer (GFRP) bars. The main objective of the study is to predict the shear strength of UHPC beams reinforced with GFRP bars using ML models. We use four different ML models: support vector machine (SVM), artificial neural network (ANN), random forest (R.F.), and extreme gradient boosting (XGBoost). The experimental database used in the study is acquired from various literature sources and comprises 54 test observations with 11 input features. These input features are likely parameters related to the composition, geometry, and properties of the UHPC beams and GFRP bars. To ensure the ML models' generalizability and scalability, random search methods are utilized to tune the hyperparameters of the algorithms. This tuning process helps improve the performance of the models when predicting the shear strength. The study uses the ACI318M-14 and Eurocode 2 standard building codes to predict the shear capacity behavior of GFRP bars-reinforced UHPC I-shaped beams. The ML models' predictions are compared to the results obtained from these building code standards. According to the findings, the XGBoost model demonstrates the highest predictive test performance among the investigated ML models. The study employs the SHAP (SHapley Additive exPlanations) analysis to assess the significance of each input parameter in the ML models' predictive capabilities. A Taylor diagram is used to statistically compare the accuracy of the ML models. This study concludes that ML models, particularly XGBoost, can effectively predict the shear capacity behavior of GFRP bars-reinforced UHPC I-shaped beams.

Machine learning-based water quality prediction using octennial in-situ Daphnia magna biological early warning system data