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Simple Summary: There is still an overdiagnosis of indolent prostate cancer (iPCa) lesions using the Prostate Imaging-Reporting and Data System (PI-RADS), and radiomics has emerged as a promising tool to improve the diagnosis of clinically significant prostate cancer (csPCa) lesions. However, the current state and applicability of radiomics remains a challenge. This systematic review aims at evaluating the evidence of handcrafted and deep radiomics in differentiating lesions at risk of having csPCa from those with iPCa and benign pathology. The review highlighted a good performance of radiomics but without significant differences with radiologist assessment (PI-RADS), as well as several methodological limitations in the reported studies, which might induce bias. Future studies should improve methodological aspects to ensure the clinical applicability of radiomics, especially the need for clinical prospective studies and the comparison with PI-RADS. Early detection of clinically significant prostate cancer (csPCa) has substantially improved with the latest PI-RADS versions. However, there is still an overdiagnosis of indolent lesions (iPCa), and radiomics has emerged as a potential solution. The aim of this systematic review is to evaluate the role of handcrafted and deep radiomics in differentiating lesions with csPCa from those with iPCa and benign lesions on prostate MRI assessed with PI-RADS v2 and/or 2.1. The literature search was conducted in PubMed, Cochrane, and Web of Science databases to select relevant studies. Quality assessment was carried out with Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), Radiomic Quality Score (RQS), and Checklist for Artificial Intelligence in Medical Imaging (CLAIM) tools. A total of 14 studies were deemed as relevant from 411 publications. The results highlighted a good performance of handcrafted and deep radiomics methods for csPCa detection, but without significant differences compared to radiologists (PI-RADS) in the few studies in which it was assessed. Moreover, heterogeneity and restrictions were found in the studies and quality analysis, which might induce bias. Future studies should tackle these problems to encourage clinical applicability. Prospective studies and comparison with radiologists (PI-RADS) are needed to better understand its potential. [ABSTRACT FROM AUTHOR]

Simple Summary: A Machine Learning-based radiomics approach applied to hybrid 18F-FDG PET/MRI might predict axillary lymph node involvement in breast cancer based on the analysis of primary cancer lesions. Indeed, the depiction of tumor heterogeneity through the extraction of radiomics features for both morphological and functional images can be representative of tumor aggressiveness and propensity to invasion. In light of the new personalized treatment options, such as neoadjuvant systemic treatments or the possibility of omitting sentinel lymph node biopsy in patients with a clinically negative axilla, such an approach could result in a better preoperative stratification and also make hybrid 18F-FDG PET/MRI a comprehensive tool for both local and node (N) staging in breast cancer. In this prospective study, 117 female patients (mean age = 53 years) with 127 histologically proven breast cancer lesions (lymph node (LN) positive = 85, LN negative = 42) underwent simultaneous 18F-FDG PET/MRI of the breast. Quantitative parameters were calculated from dynamic contrast-enhanced (DCE) imaging (tumor Mean Transit Time, Volume Distribution, Plasma Flow), diffusion-weighted imaging (DWI) (tumor ADCmean), and PET (tumor SUVmax, mean and minimum, SUVmean of ipsilateral breast parenchyma). Manual whole-lesion segmentation was also performed on DCE, T2-weighted, DWI, and PET images, and radiomic features were extracted. The dataset was divided into a training (70%) and a test set (30%). Multi-step feature selection was performed, and a support vector machine classifier was trained and tested for predicting axillary LN status. 13 radiomic features from DCE, DWI, T2-weighted, and PET images were selected for model building. The classifier obtained an accuracy of 79.8 (AUC = 0.798) in the training set and 78.6% (AUC = 0.839), with sensitivity and specificity of 67.9% and 100%, respectively, in the test set. A machine learning-based radiomics model comprising 18F-FDG PET/MRI radiomic features extracted from the primary breast cancer lesions allows high accuracy in non-invasive identification of axillary LN metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: The preoperative definition of the Oncotype DX recurrence score would be critical to identify breast cancer patients who could benefit from chemotherapy before surgery. In this work, we built a machine learning model applied to DCE-MRI images of a publicly available dataset to predict the Oncotype DX score in patients with breast cancer. As a result, the model achieved an accuracy of 60% in the training set and 63% (AUC = 0.66) in the test set. Our findings support the feasibility of radiomics and machine learning for the prediction of prognostic data in breast cancer, encouraging further, preferably multicenter, investigations to further improve the performance of the model and assess its generalizability. Aim: To non-invasively predict Oncotype DX recurrence scores (ODXRS) in patients with ER+ HER2- invasive breast cancer (IBC) using dynamic contrast-enhanced (DCE) MRI-derived radiomics features extracted from primary tumor lesions and a ML algorithm. Materials and Methods: Pre-operative DCE-MRI of patients with IBC, no history of neoadjuvant therapy prior to MRI, and for which the ODXRS was available, were retrospectively selected from a public dataset. ODXRS was obtained on histological tumor samples and considered as positive if greater than 16 and 26 in patients aged under and over 50 years, respectively. Tumor lesions were manually annotated by three independent operators on DCE-MRI images through 3D ROIs positioning. Radiomic features were therefore extracted and selected using multistep feature selection process. A logistic regression ML classifier was then employed for the prediction of ODXRS. Results: 248 patients were included, of which 87 with positive ODXRS. 166 (66%) patients were grouped in the training set, while 82 (33%) in the test set. A total of 1288 features was extracted. Of these, 1244 were excluded as 771, 82 and 391 were excluded as not stable (n = 771), not variant (n = 82), and highly intercorrelated (n = 391), respectively. After the use of recursive feature elimination with logistic regression estimator and polynomial transformation, 92 features were finally selected. In the training set, the logistic regression classifier obtained an overall mean accuracy of 60%. In the test set, the accuracy of the ML classifier was 63%, with a sensitivity of 80%, specificity of 43%, and AUC of 66%. Conclusions: Radiomics and ML applied to pre-operative DCE-MRI in patients with IBC showed promises for the non-invasive prediction of ODXRS, aiding in selecting patients who will benefit from NAC. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to evaluate precision cancer therapies, it would be advantageous to measure at the same time their action on tumor growth and on the biological target of the therapy. New non-invasive hybrid imaging techniques allow access to multiple quantitative parameters. Here, we trained machine learning classifiers of features extracted from longitudinal in vivo co-registered metabolic, vascular and anatomical images in a mouse model of paraganglioma. We show that machine learning identifies ensembles of tumor states that correspond to stages of tumor evolution with or without anti-angiogenic treatment. These classifiers define individual trajectories of tumor progression and response to treatment, supporting the use of machine learning analysis of multiparametric imaging for the identification of response to anti-angiogenic treatment in this rodent model. The standard assessment of response to cancer treatments is based on gross tumor characteristics, such as tumor size or glycolysis, which provide very indirect information about the effect of precision treatments on the pharmacological targets of tumors. Several advanced imaging modalities allow for the visualization of targeted tumor hallmarks. Descriptors extracted from these images can help establishing new classifications of precision treatment response. We propose a machine learning (ML) framework to analyze metabolic–anatomical–vascular imaging features from positron emission tomography, ultrafast Doppler, and computed tomography in a mouse model of paraganglioma undergoing anti-angiogenic treatment with sunitinib. Imaging features from the follow-up of sunitinib-treated (n = 8, imaged once-per-week/6-weeks) and sham-treated (n = 8, imaged once-per-week/3-weeks) mice groups were dimensionally reduced and analyzed with hierarchical clustering Analysis (HCA). The classes extracted from HCA were used with 10 ML classifiers to find a generalized tumor stage prediction model, which was validated with an independent dataset of sunitinib-treated mice. HCA provided three stages of treatment response that were validated using the best-performing ML classifier. The Gaussian naive Bayes classifier showed the best performance, with a training accuracy of 98.7 and an average area under curve of 100. Our results show that metabolic–anatomical–vascular markers allow defining treatment response trajectories that reflect the efficacy of an anti-angiogenic drug on the tumor target hallmark. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-induced hypothyroidism (RIHT) commonly develops in cancer survivors that receive radiation therapy for cancers in the head and neck region. The state-of-art normal tissue complication probability (NTCP) models perform satisfactorily; however, they do not use the whole spectrum of information that can be obtained from imaging techniques. The radiomic approach offers the ability to efficiently mine features, which are imperceptible to the human eye, but may provide crucial data about the patient's condition. We gathered CT images and clinical data from 98 patients undergoing radiotherapy for head and neck cancers, 27 of whom later developed RIHT. For them, we created machine-learning models to predict RIHT using automatically extracted radiomic features and appropriate clinical and dosimetric parameters. We also validated the well-established external state-of-art NTCP models on our datasets and observed that our radiomic-based models performed very similarly to them. This shows that automated tools may perform as well as the current standard but can be theoretically applied faster and be implemented into existing imaging software used when planning radiotherapy. State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models (p > 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade gliomas (LGG) with the 1p/19q co-deletion mutation have been proven to have a better survival prognosis and response to treatment than individuals without the mutation. Identifying this mutation has a vital role in managing LGG patients; however, the current diagnostic gold standard, including the brain-tissue biopsy or the surgical resection of the tumor, remains highly invasive and time-consuming. We proposed a model based on the eXtreme Gradient Boosting (XGBoost) classifier to detect 1p/19q co-deletion mutation using non-invasive medical images. The performance of our model achieved 87% and 82.8% accuracy on the training and external test set, respectively. Significantly, the prediction was based on only seven optimal wavelet radiomics features extracted from brain Magnetic Resonance (MR) images. We believe that this model can address clinicians in the rapid diagnosis of clinical 1p/19q co-deletion mutation, thereby improving the treatment prognosis of LGG patients. The prognosis and treatment plans for patients diagnosed with low-grade gliomas (LGGs) may significantly be improved if there is evidence of chromosome 1p/19q co-deletion mutation. Many studies proved that the codeletion status of 1p/19q enhances the sensitivity of the tumor to different types of therapeutics. However, the current clinical gold standard of detecting this chromosomal mutation remains invasive and poses implicit risks to patients. Radiomics features derived from medical images have been used as a new approach for non-invasive diagnosis and clinical decisions. This study proposed an eXtreme Gradient Boosting (XGBoost)-based model to predict the 1p/19q codeletion status in a binary classification task. We trained our model on the public database extracted from The Cancer Imaging Archive (TCIA), including 159 LGG patients with 1p/19q co-deletion mutation status. The XGBoost was the baseline algorithm, and we combined the SHapley Additive exPlanations (SHAP) analysis to select the seven most optimal radiomics features to build the final predictive model. Our final model achieved an accuracy of 87% and 82.8% on the training set and external test set, respectively. With seven wavelet radiomics features, our XGBoost-based model can identify the 1p/19q codeletion status in LGG-diagnosed patients for better management and address the drawbacks of invasive gold-standard tests in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Approximately 50% of patients with metastatic NSCLC harbor BMs. Within the past decade, Gamma Knife radiosurgery (GKRS) has become one of the first-line treatments for BMs. Ability to predict treatment response after GKRS can therefore guide treatment strategy. This study aimed to determine whether pre-radiosurgical neuroimaging radiomics can predict survival and local tumor control after GKRS. Based on the collected magnetic resonance images and clinical characteristics of the 237 NSCLC BM patients with BMs (for survival prediction) and 256 NSCLC patients with 976 BMs (for prediction of local tumor control), we concluded that the identified radiomic features could provide valuable additional information to enhance the prediction of BM responses after GKRS. The proposed approach provided physicians with an intuitive way to predict the patient outcome based on pre-radiosurgical magnetic resonance images. The diagnosis of brain metastasis (BM) is commonly observed in non-small cell lung cancer (NSCLC) with poor outcomes. Accordingly, developing an approach to early predict BM response to Gamma Knife radiosurgery (GKRS) may benefit the patient treatment and monitoring. A total of 237 NSCLC patients with BMs (for survival prediction) and 256 patients with 976 BMs (for prediction of local tumor control) treated with GKRS were retrospectively analyzed. All the survival data were recorded without censoring, and the status of local tumor control was determined by comparing the last MRI follow-up in patients' lives with the pre-GKRS MRI. Overall 1763 radiomic features were extracted from pre-radiosurgical magnetic resonance images. Three prediction models were constructed, using (1) clinical data, (2) radiomic features, and (3) clinical and radiomic features. Support vector machines with a 30% hold-out validation approach were constructed. For treatment outcome predictions, the models derived from both the clinical and radiomics data achieved the best results. For local tumor control, the combined model achieved an area under the curve (AUC) of 0.95, an accuracy of 90%, a sensitivity of 91%, and a specificity of 89%. For patient survival, the combined model achieved an AUC of 0.81, an accuracy of 77%, a sensitivity of 78%, and a specificity of 80%. The pre-radiosurgical radiomics data enhanced the performance of local tumor control and survival prediction models in NSCLC patients with BMs treated with GRKS. An outcome prediction model based on radiomics combined with clinical features may guide therapy in these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiogenomics enables prediction of the status and prognosis of patients using non-invasively obtained imaging data. Current machine learning (ML) methods used in radiogenomics require huge datasets, which involve the handling of large heterogeneous datasets from multiple cohorts/hospitals. In this study, two different glioma datasets were used to test various ML and image pre-processing methods to confirm whether the models trained on one dataset are universally applicable to other datasets. Our result suggested that the ML method that yielded the highest accuracy in a single dataset was likely to be overfitted. We demonstrated that implementation of standardization and dimension reduction procedures prior to classification, enabled the development of ML methods that are less affected by the multiple cohort difference. We advocate using caution in interpreting the results of radiogenomic studies of the training and testing datasets that are small or mixed, with a view to implementing practical ML methods in radiogenomics. Radiogenomics use non-invasively obtained imaging data, such as magnetic resonance imaging (MRI), to predict critical biomarkers of patients. Developing an accurate machine learning (ML) technique for MRI requires data from hundreds of patients, which cannot be gathered from any single local hospital. Hence, a model universally applicable to multiple cohorts/hospitals is required. We applied various ML and image pre-processing procedures on a glioma dataset from The Cancer Image Archive (TCIA, n = 159). The models that showed a high level of accuracy in predicting glioblastoma or WHO Grade II and III glioma using the TCIA dataset, were then tested for the data from the National Cancer Center Hospital, Japan (NCC, n = 166) whether they could maintain similar levels of high accuracy. Results: we confirmed that our ML procedure achieved a level of accuracy (AUROC = 0.904) comparable to that shown previously by the deep-learning methods using TCIA. However, when we directly applied the model to the NCC dataset, its AUROC dropped to 0.383. Introduction of standardization and dimension reduction procedures before classification without re-training improved the prediction accuracy obtained using NCC (0.804) without a loss in prediction accuracy for the TCIA dataset. Furthermore, we confirmed the same tendency in a model for IDH1/2 mutation prediction with standardization and application of dimension reduction that was also applicable to multiple hospitals. Our results demonstrated that overfitting may occur when an ML method providing the highest accuracy in a small training dataset is used for different heterogeneous data sets, and suggested a promising process for developing an ML method applicable to multiple cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-invasive imaging modalities are commonly used in clinical practice. Recently, the application of machine learning (ML) techniques has provided a new scope for more detailed imaging analysis in esophageal cancer (EC) patients. Our review aims to explore the recent advances and future perspective of the ML technique in the disease management of EC patients. ML-based investigations can be used for diagnosis, treatment response evaluation, prognostication, and investigation of biological heterogeneity. The key results from the literature have demonstrated the potential of ML techniques, such as radiomic techniques and deep learning networks, to improve the decision-making process for EC patients in clinical practice. Recommendations have been made to improve study design and future applicability. Esophageal cancer (EC) is of public health significance as one of the leading causes of cancer death worldwide. Accurate staging, treatment planning and prognostication in EC patients are of vital importance. Recent advances in machine learning (ML) techniques demonstrate their potential to provide novel quantitative imaging markers in medical imaging. Radiomics approaches that could quantify medical images into high-dimensional data have been shown to improve the imaging-based classification system in characterizing the heterogeneity of primary tumors and lymph nodes in EC patients. In this review, we aim to provide a comprehensive summary of the evidence of the most recent developments in ML application in imaging pertinent to EC patient care. According to the published results, ML models evaluating treatment response and lymph node metastasis achieve reliable predictions, ranging from acceptable to outstanding in their validation groups. Patients stratified by ML models in different risk groups have a significant or borderline significant difference in survival outcomes. Prospective large multi-center studies are suggested to improve the generalizability of ML techniques with standardized imaging protocols and harmonization between different centers. [ABSTRACT FROM AUTHOR]

Simple Summary: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a high incidence rate in females. The COVID-19 epidemic posed an increased risk of treatment delay causing increased DTC morbidity and mortality rate of DTC. Several imaging techniques, including ultrasound (US), magnetic resonance imaging (MRI), and computer tomography (CT), have been applied in the early screening and diagnosis of DTC. However, these traditional methods have limited sensitivity and specificity due to dependence on the experience and skill of the radiologists. Radiomics is an emerging technique that allows the quantitative extraction of high-throughput features from single or multiple medical images, which cannot be observed directly with the naked eye, and then applies to machine learning approaches to construct classification or prediction models. This method makes it possible to evaluate tumor status and to differentiate malignant from benign tumors or nodules in a more objective manner. To date, the classification and prediction value of radiomics in DTC patients have been inconsistent. Herein, we summarize the available literature on the classification and prediction performance of radiomics-based DTC in various imaging techniques. More specifically, we reviewed the recent literature to discuss the capacity of radiomics to predict lymph node (LN) metastasis, distant metastasis, tumor extrathyroidal extension, disease-free survival, and B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation and differentiate malignant from benign nodules. This review discusses the application and limitations of the radiomics process, and explores its ability to improve clinical decision-making with the hope of emphasizing its utility for DTC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft-tissue sarcomas constitute a rare cancer type, with approximately 40% of patients experiencing disease recurrence. There is a need for a better identification of patients with especially aggressive tumors. Previous research demonstrated that the qualitative assessment of imaging data by radiologists ("semantic features") and the algorithm-based analysis of imaging data (termed "radiomics") may help to achieve a more thorough identification of patients at high risk for cancer-specific mortality. In this work, we compared the performance of predictions of patients' survival based on semantic features extracted by radiologists with a "radiomic" approach. While some semantic features were helpful to identify high-risk patients, the radiomic approach achieved an overall improved ability to identify patients at high risk. For the radiomic prediction, only one MRI sequence was sufficient and an MRI sequence without the need for contrast agent achieved good predictive performance. Background: In patients with soft-tissue sarcomas of the extremities, the treatment decision is currently regularly based on tumor grading and size. The imaging-based analysis may pose an alternative way to stratify patients' risk. In this work, we compared the value of MRI-based radiomics with expert-derived semantic imaging features for the prediction of overall survival (OS). Methods: Fat-saturated T2-weighted sequences (T2FS) and contrast-enhanced T1-weighted fat-saturated (T1FSGd) sequences were collected from two independent retrospective cohorts (training: 108 patients; testing: 71 patients). After preprocessing, 105 radiomic features were extracted. Semantic imaging features were determined by three independent radiologists. Three machine learning techniques (elastic net regression (ENR), least absolute shrinkage and selection operator, and random survival forest) were compared to predict OS. Results: ENR models achieved the best predictive performance. Histologies and clinical staging differed significantly between both cohorts. The semantic prognostic model achieved a predictive performance with a C-index of 0.58 within the test set. This was worse compared to a clinical staging system (C-index: 0.61) and the radiomic models (C-indices: T1FSGd: 0.64, T2FS: 0.63). Both radiomic models achieved significant patient stratification. Conclusions: T2FS and T1FSGd-based radiomic models outperformed semantic imaging features for prognostic assessment. [ABSTRACT FROM AUTHOR]