Survival analysis in breast cancer: evaluating ensemble learning techniques for prediction.

Breast cancer is most commonly faced with form of cancer amongst women worldwide. In spite of the fact that the breast cancer research and awareness have gained considerable momentum, there is still no one treatment due to disease heterogeneity. Survival data may be of specific interest in breast cancer studies to understand its dynamic and complex trajectories. This study copes with the most important covariates affecting the disease progression. The study utilizes the German Breast Cancer Study Group 2 (GBSG2) and the Molecular Taxonomy of Breast Cancer International Consortium dataset (METABRIC) datasets. In both datasets, interests lie in relapse of the disease and the time when the relapse happens. The three models, namely the Cox proportional hazards (PH) model, random survival forest (RSF) and conditional inference forest (Cforest) were employed to analyse the breast cancer datasets. The goal of this study is to apply these methods in prediction of breast cancer progression and compare their performances based on two different estimation methods: the bootstrap estimation and the bootstrap .632 estimation. The model performance was evaluated in concordance index (C-index) and prediction error curves (pec) for discrimination. The Cox PH model has a lower C-index and bigger prediction error compared to the RSF and the Cforest approach for both datasets. The analysis results of GBSG2 and METABRIC datasets reveal that the RSF and the Cforest algorithms provide non-parametric alternatives to Cox PH model for estimation of the survival probability of breast cancer patients.

Evaluating prognostic biomarkers for survival outcomes subject to informative censoring.

Prognostic biomarkers for survival outcomes are widely used in clinical research and practice. Such biomarkers are often evaluated using a C-index as well as quantities based on time-dependent receiver operating characteristic curves. Existing methods for their evaluation generally assume that censoring is uninformative in the sense that the censoring time is independent of the failure time with or without conditioning on the biomarker under evaluation. With focus on the C-index and the area under a particular receiver operating characteristic curve, we describe and compare three estimation methods that account for informative censoring based on observed baseline covariates. Two of them are straightforward extensions of existing plug-in and inverse probability weighting methods for uninformative censoring. By appealing to semiparametric theory, we also develop a doubly robust, locally efficient method that is more robust than the plug-in and inverse probability weighting methods and typically more efficient than the inverse probability weighting method. The methods are evaluated and compared in a simulation study, and applied to real data from studies of breast cancer and heart failure.

Comparison between single-muscle evaluation and cross-sectional area muscle evaluation for predicting the prognosis in patients with oral squamous cell carcinoma: a retrospective cohort study.

Introduction: The most effective method of assessing sarcopenia has yet to be determined, whether by single muscle or by whole muscle segmentation. The purpose of this study was to compare the prognostic value of these two methods using computed tomography (CT) images in patients with oral squamous cell carcinoma (OSCC). Materials and methods: Sex- and age-adjusted Cox proportional hazards models were employed for each parameter of sarcopenia related to overall survival, disease-free survival, and disease-specific survival. Harrell's concordance index was calculated for each model to assess discriminatory power. Results: In this study including 165 patients, a significant correlation was found between the CT-based assessment of individual muscles and their cross-sectional area. Single muscle assessments showed slightly higher discriminatory power in survival outcomes compared to whole muscle assessments, but the difference was not statistically significant, as indicated by overlapping confidence intervals for the C-index between assessments. To further validate our measurements, we classified patients into two groups based on intramuscular adipose tissue content (P-IMAC) of the spinous process muscle. Analysis showed that the higher the P-IMAC value, the poorer the survival outcome. Conclusion: Our findings indicate a slight advantage of single-muscle over whole-muscle assessment in prognostic evaluation, but the difference between the two methods is not conclusive. Both assessment methods provide valuable prognostic information for patients with OSCC, and further studies involving larger, independent cohorts are needed to clarify the potential advantage of one method over the other in the prognostic assessment of sarcopenia in OSCC.

Cost-effective prognostic evaluation of breast cancer: using a STAR nomogram model based on routine blood tests.

Background: Breast cancer (BC) is the most common and prominent deadly disease among women. Predicting BC survival mainly relies on TNM staging, molecular profiling and imaging, hampered by subjectivity and expenses. This study aimed to establish an economical and reliable model using the most common preoperative routine blood tests (RT) data for survival and surveillance strategy management. Methods: We examined 2863 BC patients, dividing them into training and validation cohorts (7:3). We collected demographic features, pathomics characteristics and preoperative 24-item RT data. BC risk factors were identified through Cox regression, and a predictive nomogram was established. Its performance was assessed using C-index, area under curves (AUC), calibration curve and decision curve analysis. Kaplan-Meier curves stratified patients into different risk groups. We further compared the STAR model (utilizing HE and RT methodologies) with alternative nomograms grounded in molecular profiling (employing second-generation short-read sequencing methodologies) and imaging (utilizing PET-CT methodologies). Results: The STAR nomogram, incorporating subtype, TNM stage, age and preoperative RT data (LYM, LYM%, EOSO%, RDW-SD, P-LCR), achieved a C-index of 0.828 in the training cohort and impressive AUCs (0.847, 0.823 and 0.780) for 3-, 5- and 7-year OS rates, outperforming other nomograms. The validation cohort showed similar impressive results. The nomogram calculates a patient's total score by assigning values to each risk factor, higher scores indicating a poor prognosis. STAR promises potential cost savings by enabling less intensive surveillance in around 90% of BC patients. Compared to nomograms based on molecular profiling and imaging, STAR presents a more cost-effective, with potential savings of approximately $700-800 per breast cancer patient. Conclusion: Combining appropriate RT parameters, STAR nomogram could help in the detection of patient anemia, coagulation function, inflammation and immune status. Practical implementation of the STAR nomogram in a clinical setting is feasible, and its potential clinical impact lies in its ability to provide an early, economical and reliable tool for survival prediction and surveillance strategy management. However, our model still has limitations and requires external data validation. In subsequent studies, we plan to mitigate the potential impact on model robustness by further updating and adjusting the data and model.

Development and validation of a promising 5-gene prognostic model for pediatric acute myeloid leukemia.

Risk classification in pediatric acute myeloid leukemia (P-AML) is crucial for personalizing treatments. Thus, we aimed to establish a risk-stratification tool for P-AML patients and eventually guide individual treatment. A total of 256 P-AML patients with accredited mRNA-seq data from the TARGET database were divided into training and internal validation datasets. A gene-expression-based prognostic score was constructed for overall survival (OS), by using univariate Cox analysis, LASSO regression analysis, Kaplan-Meier (K-M) survival, and multivariate Cox analysis. A P-AML-5G prognostic score bioinformatically derived from expression levels of 5 genes (ZNF775, RNFT1, CRNDE, COL23A1, and TTC38), clustered P-AML patients in training dataset into high-risk group (above optimal cut-off) with shorter OS, and low-risk group (below optimal cut-off) with longer OS (p < 0.0001). Meanwhile, similar results were obtained in internal validation dataset (p = 0.005), combination dataset (p < 0.001), two treatment sub-groups (p < 0.05), intermediate-risk group defined with the Children's Oncology Group (COG) (p < 0.05) and an external Japanese P-AML dataset (p = 0.005). The model was further validated in the COG study AAML1031(p = 0.001), and based on transcriptomic analysis of 943 pediatric patients and 70 normal bone marrow samples from this dataset, two genes in the model demonstrated significant differential expression between the groups [all log2(foldchange) > 3, p < 0.001]. Independent of other prognostic factors, the P-AML-5G groups presented the highest concordance-index values in training dataset, chemo-therapy only treatment subgroups of the training and internal validation datasets, and whole genome-sequencing subgroup of the combined dataset, outperforming two Children's Oncology Group (COG) risk stratification systems, 2022 European LeukemiaNet (ELN) risk classification tool and two leukemic stem cell expression-based models. The 5-gene prognostic model generated by a single assay can further refine the current COG risk stratification system that relies on numerous tests and may have the potential for the risk judgment and identification of the high-risk pediatric AML patients receiving chemo-therapy only treatment.

Diagnostic value of radiomics in predicting Ki-67 and cytokeratin 19 expression in hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Radiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC. Methods: Original studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression. Results: We identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86-0.92) in the training set, and 0.87 (95% CI: 0.82-0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81-0.90) in the training set, and 0.79 (95% CI: 0.73-0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I 2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased. Conclusion: Radiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953.