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Simple Summary: Radiomics could increase the value of medical images for oncologic patients, allowing for the identification of novel imaging biomarkers and building prediction models. Unfortunately, despite the many promises and encouraging findings, the translation of radiomics into clinical practice appears as a distant goal. Indeed, challenges such as generalizability and reproducibility are slowing down the process and must be faced with a rigorous and robust radiomic methodology. In this review, we turn the spotlight to the methodological complexity of radiomics, providing an outline of dos and don'ts aimed at facilitating state-of-the-art research. Imaging plays a crucial role in the management of oncologic patients, from the initial diagnosis to staging and treatment response monitoring. Recently, it has been suggested that its importance could be further increased by accessing a new layer of previously hidden quantitative data at the pixel level. Using a multi-step process, radiomics extracts potential biomarkers from medical images that could power decision support tools. Despite the growing interest and rising number of research articles being published, radiomics is still far from fulfilling its promise of guiding oncologic imaging toward personalized medicine. This is, at least partly, due to the heterogeneous methodological quality in radiomic research, caused by the complexity of the analysis pipelines. In this review, we aim to disentangle this complexity with a stepwise approach. Specifically, we focus on challenges to face during image preprocessing and segmentation, how to handle imbalanced classes and avoid information leaks, as well as strategies for the proper validation of findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Modern, personalized therapy approaches are increasingly changing advanced cancer into a chronic disease. Compared to imaging, novel omics methodologies in molecular biology have already achieved an individual characterization of cancerous lesions. With quantitative imaging biomarkers, analyzed by radiomics or deep learning, an imaging-based assessment of tumoral biology can be brought into clinical practice. Combining these with other non-invasive methods, e.g., liquid profiling, could allow for more individual decision making regarding therapies and applications. Similar to the transformation towards personalized oncology treatment, emerging techniques for evaluating oncologic imaging are fostering a transition from traditional response assessment towards more comprehensive cancer characterization via imaging. This development can be seen as key to the achievement of truly personalized and optimized cancer diagnosis and treatment. This review gives a methodological introduction for clinicians interested in the potential of quantitative imaging biomarkers, treating of radiomics models, texture visualization, convolutional neural networks and automated segmentation, in particular. Based on an introduction to these methods, clinical evidence for the corresponding imaging biomarkers—(i) dignity and etiology assessment; (ii) tumoral heterogeneity; (iii) aggressiveness and response; and (iv) targeting for biopsy and therapy—is summarized. Further requirements for the clinical implementation of these imaging biomarkers and the synergistic potential of personalized molecular cancer diagnostics and liquid profiling are discussed. [ABSTRACT FROM AUTHOR]