The identification of biomarkers plays a crucial role in personalized medicine, both in the clinical and research settings. However, the contrast between predictive and prognostic biomarkers can be challenging due to the overlap between the two. A prognostic biomarker predicts the future outcome of cancer, regardless of treatment, and a predictive biomarker predicts the effectiveness of a therapeutic intervention. Misclassifying a prognostic biomarker as predictive (or vice versa) can have serious financial and personal consequences for patients. To address this issue, various statistical and machine learning approaches have been developed. The aim of this study is to present an in-depth analysis of recent advancements, trends, challenges, and future prospects in biomarker identification. A systematic search was conducted using PubMed to identify relevant studies published between 2017 and 2023. The selected studies were analyzed to better understand the concept of biomarker identification, evaluate machine learning methods, assess the level of research activity, and highlight the application of these methods in cancer research and treatment. Furthermore, existing obstacles and concerns are discussed to identify prospective research areas. We believe that this review will serve as a valuable resource for researchers, providing insights into the methods and approaches used in biomarker discovery and identifying future research opportunities.

Predicting early in treatment whether a tumor is likely to be responsive is a difficult yet important task to support clinical decision making. Studies have shown that multimodal biomarkers could provide complementary information and lead to more accurate treatment outcome prognosis than unimodal biomarkers. However, the prognosis accuracy could be affected by multimodal data heterogeneity and incompleteness. The small-sized and imbalance datasets also bring additional challenges for training a designed prognosis model. In this study, a modular framework employing multimodal biomarkers for cancer treatment outcome prediction was proposed. It includes four modules of synthetic data generation, deep feature extraction, multimodal feature fusion, and classification to address the challenges described above. The feasibility and advantages of the designed framework were demonstrated through an example study, in which the goal was to stratify oropharyngeal squamous cell carcinoma (OPSCC) patients with low and high risks of treatment failures by use of the positron emission tomography (PET) image data and microRNA (miRNA) biomarkers. The superior prognosis performance and the comparison with other methods demonstrated the efficiency of the proposed framework and its ability of enabling seamless integration, validation, and comparison of various algorithms in each module of the framework. The limitation and future work were discussed as well.

Objectives: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population. Methods: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and 420 CT scans from 414 cancer patients. In particular, the habitat imaging pipeline was developed to quantify the complex infection patterns by partitioning the whole lung regions into phenotypically different subregions. Subsequently, various machine learning models nested with feature selection were built for COVID-19 detection and severity prediction. Results: These models showed almost perfect performance in COVID-19 infection diagnosis and predicting its severity during cross validation. Our analysis revealed that models built separately on the cancer population performed significantly better than those built on the general population and locked to test on the cancer population. This may be because of the significant difference among the habitat features across the two different cohorts. Conclusions: Taken together, our habitat imaging analysis as a proof-of-concept study has highlighted the unique radiologic features of cancer patients and demonstrated effectiveness of CT-based machine learning model in informing COVID-19 management in the cancer population.

Purpose Imaging biomarkers (IBMs) are increasingly investigated as prognostic indicators. IBMs might be capable of assisting treatment selection by providing useful insights into tumor-specific factors in a non-invasive manner. Methods We investigated six three-dimensional shape-based IBMs: eccentricities between (I) intermediate–major axis (E_imaj), (II) intermediate–minor axis (E_imin), (III) major–minor axis (E_mj-mn) and volumetric index of (I) sphericity (VioS), (II) flattening (VioF), (III) elongating (VioE). Additionally, we investigated previously established two-dimensional shape IBMs: eccentricity (E), index of sphericity (IoS), and minor-to-major axis length (Mn_Mj). IBMs were compared in terms of their predictive performance for 5-year overall survival in two independent cohorts of patients with lung cancer. Cohort 1 received surgical excision, while cohort 2 received radiation therapy alone or chemo-radiation therapy. Univariate and multivariate survival analyses were performed. Correlations with clinical parameters were evaluated using analysis of variance. IBM reproducibility was assessed using concordance correlation coefficients (CCCs). Results E was associated with reduced survival in cohort 1 (hazard ratio [HR]: 0.664). E_imin and VioF were associated with reduced survival in cohort 2 (HR 1.477 and 1.701). VioS was associated with reduced survival in cohorts 1 and 2 (HR 1.758 and 1.472). Spherical tumors correlated with shorter survival durations than did irregular tumors (median survival difference: 1.21 and 0.35 years in cohorts 1 and 2, respectively). VioS was a significant predictor of survival in multivariate analyses of both cohorts. All IBMs showed good reproducibility (CCC ranged between 0.86–0.98). Conclusions In both investigated cohorts, VioS successfully linked shape morphology to patient survival.

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce a novel dual global fusion network to incorporate global and inter-patch features of cell distribution, which enables the sufficient fusion of different types and locations of cells. We further validate the proposed pipeline using The Cancer Genome Atlas lung adenocarcinoma dataset. Our model achieves a C-index of 0.675 (±0.05) in the five-fold cross-validation setting and surpasses comparable methods. Further, we extensively analyze embedded map features and survival probabilities. These experimental results manifest the potential of our proposed pipeline for applications using WSI in lung adenocarcinoma and other malignancies.