Recent technological developments have led to an increase in the size and types of data in the medical field derived from multiple platforms such as proteomic, genomic, imaging, and clinical data. Many machine learning models have been developed to support precision/personalized medicine initiatives such as computer-aided detection, diagnosis, prognosis, and treatment planning by using large-scale medical data. Bias and class imbalance represent two of the most pressing challenges for machine learning-based problems, particularly in medical (e.g., oncologic) data sets, due to the limitations in patient numbers, cost, privacy, and security of data sharing, and the complexity of generated data. Depending on the data set and the research question, the methods applied to address class imbalance problems can provide more effective, successful, and meaningful results. This review discusses the essential strategies for addressing and mitigating the class imbalance problems for different medical data types in the oncologic domain.

Determining the aggressiveness of gliomas, termed grading, is a critical step toward treatment optimization to increase the survival rate and decrease treatment toxicity for patients. Streamlined grading using molecular information has the potential to facilitate decision making in the clinic and aid in treatment planning. In recent years, molecular markers have increasingly gained importance in the classification of tumors. In this study, we propose a novel hierarchical voting-based methodology for improving the performance results of the feature selection stage and machine learning models for glioma grading with clinical and molecular predictors. To identify the best scheme for the given soft-voting-based ensemble learning model selections, we utilized publicly available TCGA and CGGA datasets and employed four dimensionality reduction methods to carry out a voting-based ensemble feature selection and five supervised models, with a total of sixteen combination sets. We also compared our proposed feature selection method with the LASSO feature selection method in isolation. The computational results indicate that the proposed method achieves 87.606% and 79.668% accuracy rates on TCGA and CGGA datasets, respectively, outperforming the LASSO feature selection method.

Glioma grading plays a pivotal role in guiding treatment decisions, predicting patient outcomes, facilitating clinical trial participation and research, and tailoring treatment strategies. Current glioma grading in the clinic is based on tissue acquired at the time of resection, with tumor aggressiveness assessed from tumor morphology and molecular features. The increased emphasis on molecular characteristics as a guide for management and prognosis estimation underscores is driven by the need for accurate and standardized grading systems that integrate molecular and clinical information in the grading process and carry the expectation of the exposure of molecular markers that go beyond prognosis to increase understanding of tumor biology as a means of identifying druggable targets. In this study, we introduce a novel application (GradWise) that combines rank-based weighted hybrid filter (i.e., mRMR) and embedded (i.e., LASSO) feature selection methods to enhance the performance of feature selection and machine learning models for glioma grading using both clinical and molecular predictors. We utilized publicly available TCGA from the UCI ML Repository and CGGA datasets to identify the most effective scheme that allows for the selection of the minimum number of features with their names. Two popular feature selection methods with a rank-based weighting procedure were employed to conduct comprehensive experiments with the five supervised models. The computational results demonstrate that our proposed method achieves an accuracy rate of 87.007% with 13 features and an accuracy rate of 80.412% with five features on the TCGA and CGGA datasets, respectively. We also obtained four shared biomarkers for the glioma grading that emerged in both datasets and can be employed with transferable value to other datasets and data-based outcome analyses. These findings are a significant step toward highlighting the effectiveness of our approach by offering pioneering results with novel markers with prospects for understanding and targeting the biologic mechanisms of glioma progression to improve patient outcomes.

Glioblastomas (GBM) are rapidly growing, aggressive, nearly uniformly fatal, and the most common primary type of brain cancer. They exhibit significant heterogeneity and resistance to treatment, limiting the ability to analyze dynamic biological behavior that drives response and resistance, which are central to advancing outcomes in glioblastoma. Analysis of the proteome aimed at signal change over time provides a potential opportunity for non-invasive classification and examination of the response to treatment by identifying protein biomarkers associated with interventions. However, data acquired using large proteomic panels must be more intuitively interpretable, requiring computational analysis to identify trends. Machine learning is increasingly employed, however, it requires feature selection which has a critical and considerable effect on machine learning problems when applied to large-scale data to reduce the number of parameters, improve generalization, and find essential predictors. In this study, using 7k proteomic data generated from the analysis of serum obtained from 82 patients with GBM pre- and post-completion of concurrent chemoirradiation (CRT), we aimed to select the most discriminative proteomic features that define proteomic alteration that is the result of administering CRT. Thus, we present a novel rank-based feature weighting method (RadWise) to identify relevant proteomic parameters using two popular feature selection methods, least absolute shrinkage and selection operator (LASSO) and the minimum redundancy maximum relevance (mRMR). The computational results show that the proposed method yields outstanding results with very few selected proteomic features, with higher accuracy rate performance than methods that do not employ a feature selection process. While the computational method identified several proteomic signals identical to the clinical intuitive (heuristic approach), several heuristically identified proteomic signals were not selected while other novel proteomic biomarkers not selected with the heuristic approach that carry biological prognostic relevance in GBM only emerged with the novel method. The computational results show that the proposed method yields promising results, reducing 7k proteomic data to 7 selected proteomic features with a performance value of 93.921%, comparing favorably with techniques that do not employ feature selection.

Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor, defined by nearly uniform rapid progression despite the current standard of care involving maximal surgical resection followed by radiation therapy (RT) and temozolomide (TMZ) or concurrent chemoirradiation (CRT), with an overall survival (OS) of less than 30% at 2 years. The diagnosis of tumor progression in the clinic is based on clinical assessment and the interpretation of MRI of the brain using Response Assessment in Neuro-Oncology (RANO) criteria, which suffers from several limitations including a paucity of precise measures of progression. Given that imaging is the primary modality that generates the most quantitative data capable of capturing change over time in the standard of care for GBM, this renders it pivotal in optimizing and advancing response criteria, particularly given the lack of biomarkers in this space. In this study, we employed artificial intelligence (AI)-derived MRI volumetric parameters using the segmentation mask output of the nnU-Net to arrive at four classes (background, edema, non-contrast enhancing tumor (NET), and contrast-enhancing tumor (CET)) to determine if dynamic changes in AI volumes detected throughout therapy can be linked to PFS and clinical features. We identified associations between MR imaging AI-generated volumes and PFS independently of tumor location, MGMT methylation status, and the extent of resection while validating that CET and edema are the most linked to PFS with patient subpopulations separated by district rates of change throughout the disease. The current study provides valuable insights for risk stratification, future RT treatment planning, and treatment monitoring in neuro-oncology.