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Background: The role of artificial intelligence and radiomics in prediction model development in cancer has been increasing every passing day. Cervical cancer is the 4th most common cancer in women worldwide, contributing to 6.5% of all cancer types. The treatment outcome of cervical cancer patients varies and individualized prediction of disease outcome is of paramount importance. Purpose: The purpose of this study is to develop and validate the digital signature for 5-year overall survival prediction in cervical cancer using robust CT radiomic and clinical features. Materials and Methods: Pretreatment clinical features and CT radiomic features of 68 patients, who were treated with chemoradiation therapy in our hospital, were used in this study. Radiomic features were extracted using an in-house developed python script and pyradiomic package. Clinical features were selected by the recursive feature elimination technique. Whereas radiomic feature selection was performed using a multi-step process i.e., step-1: only robust radiomic features were selected based on our previous study, step-2: a hierarchical clustering was performed to eliminate feature redundancy, and step-3: recursive feature elimination was performed to select the best features for prediction model development. Four machine algorithms i.e., Logistic regression (LR), Random Forest (RF), Support vector classifier (SVC), and Gradient boosting classifier (GBC), were used to develop 24 models (six models using each algorithm) using clinical, radiomic and combined features. Models were compared based on the prediction score in the internal validation. Results: The average prediction accuracy was found to be 0.65 (95% CI: 0.60– 0.70), 0.72 (95% CI: 0.63–0.81), and 0.77 (95% CI: 0.72–0.82) for clinical, radiomic, and combined models developed using four prediction algorithms respectively. The average prediction accuracy was found to be 0.69 (95% CI: 0.62–0.76), 0.79 (95% CI: 0.72–0.86), 0.71 (95% CI: 0.62–0.80), and 0.72 (95% CI: 0.66–0.78) for LR, RF, SVC and GBC models developed on three datasets respectively. Conclusion: Our study shows the promising predictive performance of a robust radiomic signature to predict 5-year overall survival in cervical cancer patients. [ABSTRACT FROM AUTHOR]

Background: Computerized radiological image analysis (radiomics) enables the investigation of image-derived phenotypes by extracting large numbers of quantitative features. We hypothesized that radiomics features may contain prognostic information that enhances conventional body composition analysis. We aimed to investigate whether body composition-associated radiomics features hold additional value over conventional body composition analysis and clinical patient characteristics used to predict survival of pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Computed tomography images of 304 patients undergoing elective pancreatic cancer resection were analysed. 2D radiomics features were extracted from skeletal muscle and subcutaneous and visceral adipose tissue (SAT and VAT) compartments from a single slice at the third lumbar vertebra. The study population was randomly split (80:20) into training and holdout subsets. Feature ranking with Least Absolute Shrinkage Selection Operator (LASSO) followed by multivariable stepwise Cox regression in 1000 bootstrapped resamples of the training data was performed and tested on the holdout data. The fitted regression predictors were used as "scores" for a clinical (C-Score), body composition (B-Score), and radiomics (R-Score) model. To stratify patients into the highest 25% and lowest 25% risk of mortality compared to the middle 50%, the Harrell Concordance Index was used. Results: Based on LASSOand stepwise cox regression for overall survival, ASA ≥3 and age were the most important clinical variables and constituted the C-score, and VAT-index (VATI) was the most important body composition variable and constituted the B-score. Three radiomics features (SATI_original_shape2D_Perimeter, VATI_original_glszm_SmallAreaEmphasis, and VATI_original_firstorder_Maximum) emerged as the most frequent set of features and yielded an R-Score. Of the mean concordance indices of C-, B-, and R-scores, R-score performed best (0.61, 95% CI 0.56--0.65, p<0.001), followed by the C-score (0.59, 95% CI 0.55-0.63, p<0.001) and B-score (0.55, 95% CI 0.50--0.60, p=0.03). Kaplan-Meier projection revealed that C-, B, and R-scores showed a clear split in the survival curves in the training set, although none remained significant in the holdout set. Conclusion: It is feasible to implement a data-driven radiomics approach to body composition imaging. Radiomics features provided improved predictive performance compared to conventional body composition variables for the prediction of overall survival of PDAC patients undergoing primary resection. [ABSTRACT FROM AUTHOR]

With the continuous development of human life and society, the medical field is constantly improving. However, modern medicine still faces many limitations, including challenging and previously unsolvable problems. In these cases, artificial intelligence (AI) can provide solutions. The research and application of generative adversarial networks (GAN) are a clear example. While most researchers focus on image augmentation, there are few one-dimensional data augmentation examples. The radiomics feature extracted from RT and CT images is one-dimensional data. As far as we know, we are the first to apply the WGAN-GP algorithm to generate radiomics data in the medical field. In this paper, we input a portion of the original real data samples into the model. The model learns the distribution of the input data samples and generates synthetic data samples with similar distribution to the original real data, which can solve the problem of obtaining annotated medical data samples. We have conducted experiments on the public dataset Heart Disease Cleveland and the private dataset. Compared with the traditional method of Synthetic Minority Oversampling Technique (SMOTE) and common GAN for data augmentation, our method has significantly improved the AUC and SEN values under different data proportions. At the same time, our method has also shown varying levels of improvement in ACC and SPE values. This demonstrates that our method is effective and feasible. [ABSTRACT FROM AUTHOR]

Background: Cancer prognosis before and after treatment is key for patient management and decision making. Handcrafted imaging biomarkers—radiomics—have shown potential in predicting prognosis. Purpose: However, given the recent progress in deep learning, it is timely and relevant to pose the question: could deep learning based 3D imaging features be used as imaging biomarkers and outperform radiomics? Methods: Effectiveness, reproducibility in test/retest, across modalities, and correlation of deep features with clinical features such as tumor volume and TNM staging were tested in this study. Radiomics was introduced as the reference image biomarker. For deep feature extraction, we transformed the CT scans into videos, and we adopted the pre‐trained Inflated 3D ConvNet (I3D) video classification network as the architecture. We used four datasets—LUNG 1 (n = 422), LUNG 4 (n = 106), OPC (n = 605), and H&N 1 (n = 89)—with 1270 samples from different centers and cancer types—lung and head and neck cancer—to test deep features' predictiveness and two additional datasets to assess the reproducibility of deep features. Results: Support Vector Machine–Recursive Feature Elimination (SVM–RFE) selected top 100 deep features achieved a concordance index (CI) of 0.67 in survival prediction in LUNG 1, 0.87 in LUNG 4, 0.76 in OPC, and 0.87 in H&N 1, while SVM‐RFE selected top 100 radiomics achieved CIs of 0.64, 0.77, 0.73, and 0.74, respectively, all statistically significant differences (p < 0.01, Wilcoxon's test). Most selected deep features are not correlated with tumor volume and TNM staging. However, full radiomics features show higher reproducibility than full deep features in a test/retest setting (0.89 vs. 0.62, concordance correlation coefficient). Conclusion: The results show that deep features can outperform radiomics while providing different views for tumor prognosis compared to tumor volume and TNM staging. However, deep features suffer from lower reproducibility than radiomic features and lack the interpretability of the latter. [ABSTRACT FROM AUTHOR]

Background: As a means to extract biomarkers from medical imaging, radiomics has attracted increased attention from researchers. However, reproducibility and performance of radiomics in low‐dose CT scans are still poor, mostly due to noise. Deep learning generative models can be used to denoise these images and in turn improve radiomics' reproducibility and performance. However, most generative models are trained on paired data, which can be difficult or impossible to collect. Purpose: In this article, we investigate the possibility of denoising low‐dose CTs using cycle generative adversarial networks (GANs) to improve radiomics reproducibility and performance based on unpaired datasets. Methods and materials: Two cycle GANs were trained: (1) from paired data, by simulating low‐dose CTs (i.e., introducing noise) from high‐dose CTs and (2) from unpaired real low dose CTs. To accelerate convergence, during GAN training, a slice‐paired training strategy was introduced. The trained GANs were applied to three scenarios: (1) improving radiomics reproducibility in simulated low‐dose CT images and (2) same‐day repeat low dose CTs (RIDER dataset), and (3) improving radiomics performance in survival prediction. Cycle GAN results were compared with a conditional GAN (CGAN) and an encoder–decoder network (EDN) trained on simulated paired data. Results: The cycle GAN trained on simulated data improved concordance correlation coefficients (CCC) of radiomic features from 0.87 (95%CI, [0.833,0.901]) to 0.93 (95%CI, [0.916,0.949]) on simulated noise CT and from 0.89 (95%CI, [0.881,0.914]) to 0.92 (95%CI, [0.908,0.937]) on the RIDER dataset, as well improving the area under the receiver operating characteristic curve (AUC) of survival prediction from 0.52 (95%CI, [0.511,0.538]) to 0.59 (95%CI, [0.578,0.602]). The cycle GAN trained on real data increased the CCCs of features in RIDER to 0.95 (95%CI, [0.933,0.961]) and the AUC of survival prediction to 0.58 (95%CI, [0.576,0.596]). Conclusion: The results show that cycle GANs trained on both simulated and real data can improve radiomics' reproducibility and performance in low‐dose CT and achieve similar results compared to CGANs and EDNs. [ABSTRACT FROM AUTHOR]

• Generative models can improve radiomics performance in different tasks when radiomics extracted from low dose CTs. • Simulation paired low-high dose CTs trained generative models can be used to denoise low dose CT without re-training. • Generative models can improve AUC by 0.05 of radiomics in survival predication and lung cancer diagnosis. • Denoising using generative models seems to be a necessary pre-processing step for radiomic features from low dose CTs. Radiomics is an active area of research focusing on high throughput feature extraction from medical images with a wide array of applications in clinical practice, such as clinical decision support in oncology. However, noise in low dose computed tomography (CT) scans can impair the accurate extraction of radiomic features. In this article, we investigate the possibility of using deep learning generative models to improve the performance of radiomics from low dose CTs. We used two datasets of low dose CT scans – NSCLC Radiogenomics and LIDC-IDRI – as test datasets for two tasks – pre-treatment survival prediction and lung cancer diagnosis. We used encoder-decoder networks and conditional generative adversarial networks (CGANs) trained in a previous study as generative models to transform low dose CT images into full dose CT images. Radiomic features extracted from the original and improved CT scans were used to build two classifiers – a support vector machine (SVM) and a deep attention based multiple instance learning model – for survival prediction and lung cancer diagnosis respectively. Finally, we compared the performance of the models derived from the original and improved CT scans. Denoising with the encoder-decoder network and the CGAN improved the area under the curve (AUC) of survival prediction from 0.52 to 0.57 (p-value < 0.01). On the other hand, the encoder-decoder network and the CGAN improved the AUC of lung cancer diagnosis from 0.84 to 0.88 and 0.89 respectively (p-value < 0.01). Finally, there are no statistically significant improvements in AUC using encoder-decoder networks and CGAN (p-value = 0.34) when networks trained at 75 and 100 epochs. Generative models can improve the performance of low dose CT-based radiomics in different tasks. Hence, denoising using generative models seems to be a necessary pre-processing step for calculating radiomic features from low dose CTs. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of lung cancer is a key intervention for the treatment of lung cancer in which computer‐aided diagnosis (CAD) can play a crucial role. Most published CAD methods perform lung cancer diagnosis by classifying each lung nodule in isolation. However, this does not reflect clinical practice, where clinicians diagnose a patient based on a set of images of nodules, instead of looking at one nodule at a time. Besides, the low interpretability of the output provided by these methods presents an important barrier for their adoption. Method: In this article, we treat lung cancer diagnosis as a multiple instance learning (MIL) problem, which better reflects the diagnosis process in the clinical setting and provides higher interpretability of the output. We selected radiomics as the source of input features and deep attention‐based MIL as the classification algorithm. The attention mechanism provides higher interpretability by estimating the importance of each instance in the set for the final diagnosis. To improve the model's performance in a small imbalanced dataset, we propose a new bag simulation method for MIL. Results and conclusion: The results show that our method can achieve a mean accuracy of 0.807 with a standard error of the mean (SEM) of 0.069, a recall of 0.870 (SEM 0.061), a positive predictive value of 0.928 (SEM 0.078), a negative predictive value of 0.591$0.591$ (SEM 0.155), and an area under the curve (AUC) of 0.842 (SEM 0.074), outperforming other MIL methods. Additional experiments show that the proposed oversampling strategy significantly improves the model's performance. In addition, experiments show that our method provides a good indication of the importance of each nodule in determining the diagnosis, which combined with the well‐defined radiomic features, to make the results more interpretable and acceptable for doctors and patients. [ABSTRACT FROM AUTHOR]

Radiomics is an active area of research in medical image analysis, however poor reproducibility of radiomics has hampered its application in clinical practice. This issue is especially prominent when radiomic features are calculated from noisy images, such as low dose computed tomography (CT) scans. In this article, we investigate the possibility of improving the reproducibility of radiomic features calculated on noisy CTs by using generative models for denoising. Our work concerns two types of generative models—encoder–decoder network (EDN) and conditional generative adversarial network (CGAN). We then compared their performance against a more traditional 'non-local means' denoising algorithm. We added noise to sinograms of full dose CTs to mimic low dose CTs with two levels of noise: low-noise CT and high-noise CT. Models were trained on high-noise CTs and used to denoise low-noise CTs without re-training. We tested the performance of our model in real data, using a dataset of same-day repeated low dose CTs in order to assess the reproducibility of radiomic features in denoised images. EDN and the CGAN achieved similar improvements on the concordance correlation coefficients (CCC) of radiomic features for low-noise images from 0.87 [95%CI, (0.833, 0.901)] to 0.92 [95%CI, (0.909, 0.935)] and for high-noise images from 0.68 [95%CI, (0.617, 0.745)] to 0.92 [95%CI, (0.909, 0.936)], respectively. The EDN and the CGAN improved the test-retest reliability of radiomic features (mean CCC increased from 0.89 [95%CI, (0.881, 0.914)] to 0.94 [95%CI, (0.927, 0.951)]) based on real low dose CTs. These results show that denoising using EDN and CGANs could be used to improve the reproducibility of radiomic features calculated from noisy CTs. Moreover, images at different noise levels can be denoised to improve the reproducibility using the above models without need for re-training, provided the noise intensity is not excessively greater that of the high-noise CTs. To the authors' knowledge, this is the first effort to improve the reproducibility of radiomic features calculated on low dose CT scans by applying generative models. [ABSTRACT FROM AUTHOR]

Purpose: One of the most frequently cited radiomics investigations showed that features automatically extracted from routine clinical images could be used in prognostic modeling. These images have been made publicly accessible via The Cancer Imaging Archive (TCIA). There have been numerous requests for additional explanatory metadata on the following datasets — RIDER, Interobserver, Lung1, and Head–Neck1. To support repeatability, reproducibility, generalizability, and transparency in radiomics research, we publish the subjects' clinical data, extracted radiomics features, and digital imaging and communications in medicine (DICOM) headers of these four datasets with descriptive metadata, in order to be more compliant with findable, accessible, interoperable, and reusable (FAIR) data management principles. Acquisition and validation methods: Overall survival time intervals were updated using a national citizens registry after internal ethics board approval. Spatial offsets of the primary gross tumor volume (GTV) regions of interest (ROIs) associated with the Lung1 CT series were improved on the TCIA. GTV radiomics features were extracted using the open‐source Ontology‐Guided Radiomics Analysis Workflow (O‐RAW). We reshaped the output of O‐RAW to map features and extraction settings to the latest version of Radiomics Ontology, so as to be consistent with the Image Biomarker Standardization Initiative (IBSI). Digital imaging and communications in medicine metadata was extracted using a research version of Semantic DICOM (SOHARD, GmbH, Fuerth; Germany). Subjects' clinical data were described with metadata using the Radiation Oncology Ontology. All of the above were published in Resource Descriptor Format (RDF), that is, triples. Example SPARQL queries are shared with the reader to use on the online triples archive, which are intended to illustrate how to exploit this data submission. Data format: The accumulated RDF data are publicly accessible through a SPARQL endpoint where the triples are archived. The endpoint is remotely queried through a graph database web application at http://sparql.cancerdata.org. SPARQL queries are intrinsically federated, such that we can efficiently cross‐reference clinical, DICOM, and radiomics data within a single query, while being agnostic to the original data format and coding system. The federated queries work in the same way even if the RDF data were partitioned across multiple servers and dispersed physical locations. Potential applications: The public availability of these data resources is intended to support radiomics features replication, repeatability, and reproducibility studies by the academic community. The example SPARQL queries may be freely used and modified by readers depending on their research question. Data interoperability and reusability are supported by referencing existing public ontologies. The RDF data are readily findable and accessible through the aforementioned link. Scripts used to create the RDF are made available at a code repository linked to this submission: https://gitlab.com/UM‐CDS/FAIR‐compliant_clinical_radiomics_and_DICOM_metadata. [ABSTRACT FROM AUTHOR]

• We investigated the presence of volume-confounding effects in radiomics features. • Our results show that many radiomics features are volume-confounded. • We offered the radiomics community a workflow for introducing safeguards in signature developments. Highlighting the risk of biases in radiomics-based models will help improve their quality and increase usage as decision support systems in the clinic. In this study we use machine learning-based methods to identify the presence of volume-confounding effects in radiomics features. Methods 841 radiomics features were extracted from two retrospective publicly available datasets of lung and head neck cancers using open source software. Unsupervised hierarchical clustering and principal component analysis (PCA) identified relations between radiomics and clinical outcomes (overall survival). Bootstrapping techniques with logistic regression verified features' prognostic power and robustness. Results Over 80% of the features had large pairwise correlations. Nearly 30% of the features presented strong correlations with tumor volume. Using volume-independent features for clustering and PCA did not allow risk stratification of patients. Clinical predictors outperformed radiomics features in bootstrapping and logistic regression. Conclusions The adoption of safeguards in radiomics is imperative to improve the quality of radiomics studies. We proposed machine learning (ML) – based methods for robust radiomics signatures development. [ABSTRACT FROM AUTHOR]

Purpose: Radiomics is the process to automate tumor feature extraction from medical images. This has shown potential for quantifying the tumor phenotype and predicting treatment response. The three major challenges of radiomics research and clinical adoption are: (a) lack of standardized methodology for radiomics analyses, (b) lack of a universal lexicon to denote features that are semantically equivalent, and (c) lists of feature values alone do not sufficiently capture the details of feature extraction that might nonetheless strongly affect feature values (e.g. image normalization or interpolation parameters). These barriers hamper multicenter validation studies applying subtly different imaging protocols, preprocessing steps and radiomics software. We propose an open‐source ontology‐guided radiomics analysis workflow (O‐RAW) to address the above challenges in the following manner: (a) distributing a free and open‐source software package for radiomics analysis, (b) deploying a standard lexicon to uniquely describe features in common usage and (c) provide methods to publish radiomic features as a semantically interoperable data graph object complying to FAIR (findable accessible interoperable reusable) data principles. Methods: O‐RAW was developed in Python, and has three major modules using open‐source component libraries (PyRadiomics Extension and PyRadiomics). First, PyRadiomics Extension takes standard DICOM‐RT (Radiotherapy) input objects (i.e. a DICOM series and an RTSTRUCT file) and parses them as arrays of voxel intensities and a binary mask corresponding to a volume of interest (VOI). Next, these arrays are passed into PyRadiomics, which performs the feature extraction procedure and returns a Python dictionary object. Lastly, PyRadiomics Extension parses this dictionary as a W3C‐compliant Semantic Web "triple store" (i.e., list of subject‐predicate‐object statements) with relevant semantic meta‐labels drawn from the radiation oncology ontology and radiomics ontology. The output can be published on an SPARQL endpoint, and can be remotely examined via SPARQL queries or to a comma separated file for further analysis. Results: We showed that O‐RAW executed efficiently on four datasets with different modalities, RIDER (CT), MMD (CT), CROSS (PET) and THUNDER (MR). The test was performed on an HP laptop running Windows 7 operating system and 8GB RAM on which we noted execution time including DICOM images and associated RTSTRUCT matching, binary mask conversion of a single VOI, batch‐processing of feature extraction (105 basic features in PyRadiomics), and the conversion to an resource description framework (RDF) object. The results were (RIDER) 407.3, (MMD) 123.5, (CROSS) 513.2 and (THUNDER) 128.9 s for a single VOI. In addition, we demonstrated a use case, taking images from a public repository and publishing the radiomics results as FAIR data in this study on www.radiomics.org. Finally, we provided a practical instance to show how a user could query radiomic features and track the calculation details based on the RDF graph object created by O‐RAW via a simple SPARQL query. Conclusions: We implemented O‐RAW for FAIR radiomics analysis, and successfully published radiomic features from DICOM‐RT objects as semantic web triples. Its practicability and flexibility can greatly increase the development of radiomics research and ease transfer to clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiomics is referred to as quantitative image biomarker analysis. Due to the uncertainty in image acquisition, processing, and segmentation (delineation) protocols, the radiomic biomarkers lack reproducibility. In this manuscript, we show how this protocol-induced uncertainty can drastically reduce prognostic model performance and propose some insights on how to use it for developing better prognostic models. Problem. Image biomarker analysis, also known as radiomics, is a tool for tissue characterization and treatment prognosis that relies on routinely acquired clinical images and delineations. Due to the uncertainty in image acquisition, processing, and segmentation (delineation) protocols, radiomics often lack reproducibility. Radiomics harmonization techniques have been proposed as a solution to reduce these sources of uncertainty and/or their influence on the prognostic model performance. A relevant question is how to estimate the protocol-induced uncertainty of a specific image biomarker, what the effect is on the model performance, and how to optimize the model given the uncertainty. Methods. Two non-small cell lung cancer (NSCLC) cohorts, composed of 421 and 240 patients, respectively, were used for training and testing. Per patient, a Monte Carlo algorithm was used to generate three hundred synthetic contours with a surface dice tolerance measure of less than 1.18 mm with respect to the original GTV. These contours were subsequently used to derive 104 radiomic features, which were ranked on their relative sensitivity to contour perturbation, expressed in the parameter η. The top four (low η) and the bottom four (high η) features were selected for two models based on the Cox proportional hazards model. To investigate the influence of segmentation uncertainty on the prognostic model, we trained and tested the setup in 5000 augmented realizations (using a Monte Carlo sampling method); the log-rank test was used to assess the stratification performance and stability of segmentation uncertainty. Results. Although both low and high η setup showed significant testing set log-rank p-values (p = 0.01) in the original GTV delineations (without segmentation uncertainty introduced), in the model with high uncertainty, to effect ratio, only around 30% of the augmented realizations resulted in model performance with p < 0.05 in the test set. In contrast, the low η setup performed with a log-rank p < 0.05 in 90% of the augmented realizations. Moreover, the high η setup classification was uncertain in its predictions for 50% of the subjects in the testing set (for 80% agreement rate), whereas the low η setup was uncertain only in 10% of the cases. Discussion. Estimating image biomarker model performance based only on the original GTV segmentation, without considering segmentation, uncertainty may be deceiving. The model might result in a significant stratification performance, but can be unstable for delineation variations, which are inherent to manual segmentation. Simulating segmentation uncertainty using the method described allows for more stable image biomarker estimation, selection, and model development. The segmentation uncertainty estimation method described here is universal and can be extended to estimate other protocol uncertainties (such as image acquisition and pre-processing). [ABSTRACT FROM AUTHOR]

Simple Summary: The management of locally advanced (stages II–III) non-small cell lung cancer patients is very challenging because of poor survival rates and patient/tumor heterogeneity. In this review, we identify the critical points that can be addressed by artificial intelligence (AI) algorithms to improve care of these patients and to present a roadmap for AI applications that will support better treatments. Locally advanced non-small cell lung cancer patients represent around one third of newly diagnosed lung cancer patients. There remains a large unmet need to find treatment strategies that can improve the survival of these patients while minimizing therapeutical side effects. Increasing the availability of patients' data (imaging, electronic health records, patients' reported outcomes, and genomics) will enable the application of AI algorithms to improve therapy selections. In this review, we discuss how artificial intelligence (AI) can be integral to improving clinical decision support systems. To realize this, a roadmap for AI must be defined. We define six milestones involving a broad spectrum of stakeholders, from physicians to patients, that we feel are necessary for an optimal transition of AI into the clinic. [ABSTRACT FROM AUTHOR]

Immunotherapy-induced pneumonitis (IIP) is a serious side-effect which requires accurate diagnosis and management with high-dose corticosteroids. The differential diagnosis between IIP and other types of pneumonitis (OTP) remains challenging due to similar radiological patterns. This study was aimed to develop a prediction model to differentiate IIP from OTP in patients with stage IV non-small cell lung cancer (NSCLC) who developed pneumonitis during immunotherapy. Consecutive patients with metastatic NSCLC treated with immunotherapy in six centres in the Netherlands and Belgium from 2017 to 2020 were reviewed and cause-specific pneumonitis events were identified. Seven regions of interest (segmented lungs and spheroidal/cubical regions surrounding the inflammation) were examined to extract the most predictive radiomic features from the chest computed tomography images obtained at pneumonitis manifestation. Models were internally tested regarding discrimination, calibration and decisional benefit. To evaluate the clinical application of the models, predicted labels were compared with the separate clinical and radiological judgements. A total of 556 patients were reviewed; 31 patients (5.6%) developed IIP and 41 patients developed OTP (7.4%). The line of immunotherapy was the only predictive factor in the clinical model (2nd versus 1st odds ratio = 0.08, 95% confidence interval:0.01–0.77). The best radiomic model was achieved using a 75-mm spheroidal region of interest which showed an optimism-corrected area under the receiver operating characteristic curve of 0.83 (95% confidence interval:0.77–0.95) with negative and positive predictive values of 80% and 79%, respectively. Good calibration and net benefits were achieved for the radiomic model across the entire range of probabilities. A correct diagnosis was provided by the radiomic model in 10 out of 12 cases with non-conclusive radiological judgements. Radiomic biomarkers applied to computed tomography imaging may support clinicians making the differential diagnosis of pneumonitis in patients with NSCLC receiving immunotherapy, especially when the radiologic assessment is non-conclusive. • There is no gold-standard to make the differential diagnosis of pneumonitis. • The best radiomic model was developed using the 75-mm spheroidal region of interest. • The proposed radiomic model had area under the receiver operating characteristic curve = 0.83 with good calibration and net benefits. • The radiomic model diagnosed 83% of cases with non-conclusive radiological judgement. [ABSTRACT FROM AUTHOR]

Radiation pneumonitis (RP) is one of the common side effects of radiation therapy in the thoracic region. Radiomics and dosiomics quantify information implicit within medical images and radiation therapy dose distributions. In this study we demonstrate the prognostic potential of radiomics, dosiomics, and clinical features for RP prediction. Radiomics, dosiomics, dose-volume histogram (DVH) metrics, and clinical parameters were obtained on 314 retrospectively collected and 35 prospectively enrolled patients diagnosed with lung cancer between 2013 to 2019. A radiomics risk score (R score) and dosiomics risk score (D score), as well as a DVH-score, were calculated based on logistic regression after feature selection. Six models were built using different combinations of R score, D score, DVH score, and clinical parameters to evaluate their added prognostic power. Overoptimism was evaluated by bootstrap resampling from the training set, and the prospectively collected cohort was used as the external test set. Model calibration and decision-curve characteristics of the best-performing models were evaluated. For ease of further evaluation, nomograms were constructed for selected models. A model built by integrating all of the R score, D score, and clinical parameters had the best discriminative ability with areas under the curve of 0.793 (95% confidence interval [CI], 0.735-0.851), 0.774 (95% CI, 0.762-0.786), and 0.855 (95% CI, 0.719-0.990) in the training, bootstrapping, and external test sets, respectively. The calibration curve image showed good agreement between the predicted and actual values, with a slope of 1.21 and intercept of –0.04. The decision curve image showed a positive net benefit for the final model based on the nomogram. Radiomic and dosiomic features have the potential to assist with the prediction of RP, and the combination of radiomics, dosiomics, and clinical parameters led to the best prognostic model in the present study. [ABSTRACT FROM AUTHOR]

• A CT-derived radiomics model can predict OS in patients with a glioblastoma. • Discrimination based on the combined clinical and radiomics model was comparable to previous MRI-based models. • Qualitatively high-level datasets will support further model development. Glioblastoma (GBM) is the most common malignant primary brain tumour which has, despite extensive treatment, a median overall survival of 15 months. Radiomics is the high-throughput extraction of large amounts of image features from radiographic images, which allows capturing the tumour phenotype in 3D and in a non-invasive way. In this study we assess the prognostic value of CT radiomics for overall survival in patients with a GBM. Clinical data and pre-treatment CT images were obtained from 218 patients diagnosed with a GBM via biopsy who underwent radiotherapy +/− temozolomide between 2004 and 2015 treated at three independent institutes (n = 93, 62 and 63). A clinical prognostic score (CPS), a simple radiomics model consisting of volume based score (VPS), a complex radiomics prognostic score (RPS) and a combined clinical and radiomics (C + R)PS model were developed. The population was divided into three risk groups for each prognostic score and respective Kaplan–Meier curves were generated. Patient characteristics were broadly comparable. Clinically significant differences were observed with regards to radiation dose, tumour volume and performance status between datasets. Image acquisition parameters differed between institutes. The cross-validated c-indices were moderately discriminative and for the CPS ranged from 0.63 to 0.65; the VPS c-indices ranged between 0.52 and 0.61; the RPS c-indices ranged from 0.57 to 0.64 and the combined clinical and radiomics model resulted in c-indices of 0.59–0.71. In this study clinical and CT radiomics features were used to predict OS in GBM. Discrimination between low-, middle- and high-risk patients based on the combined clinical and radiomics model was comparable to previous MRI-based models. [ABSTRACT FROM AUTHOR]

• Radiomics is quantitative image analysis that can predict immunotherapy response. • We found seven relevant studies, most of them focusing on non-small cell lung cancer. • Most reviewed studies had methodological shortcomings that limit their relevance. • Main issues were deficiencies in feature selection and lack of external validation. • Prospective studies that test the clinical utility of these models are needed. Systemic therapy agents targeting immune checkpoint inhibitors have been approved for use since 2011. This type of therapy aims to trigger a patient's immune response to attack tumor cells, rather than acting against the tumor directly. Radiomics is an automated method of medical image analysis that is now being actively investigated for predictive markers of treatment response in immunotherapy. To conduct an early systematic review determining the current status of radiomic features as potential predictive markers of immunotherapy response. Provide a detailed critical appraisal of methodological quality of models, as this informs the degree of confidence about current reports of model performance. In addition, to offer some recommendations for future studies that could establish robust evidence for radiomic features as immunotherapy response markers. A PubMed citation search was conducted for publications up to and including April 2020, followed by full-text screening. A total of seven articles meeting the eligibility criteria were examined in detail for study characteristics, model information and methodological quality. The review was conducted in the Cochrane style but has not been prospectively registered. Results are reported following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines. A total of seven studies were examined in detail, comprising non-small cell lung cancer, metastatic melanoma and a diverse assortment of solid tumors. Methodological robustness of reviewed studies varied greatly. Principal shortcomings were lack of prospective registration, and deficiencies in feature selection and dimensionality reduction, model calibration, clinical utility and external validation. A few studies with overall moderate to good methodological quality were identified. These results suggest that current state-of-the-art performance of radiomics in regards to discrimination (area under the curve or concordance index) is in the vicinity of 0.7, but the very small number of studies to date prevents any conclusive remarks to be made. We recommended future improvements in regards to prospective study registration, clinical utility, methodological procedure and data sharing. Radiomics has a potentially significant role for predicting immunotherapy response. Additional multi-institutional studies with robust methodological underpinning and repeated external validations are required to establish the (added) value of radiomics within the pantheon of clinical tools for decision-making in immunotherapy. [ABSTRACT FROM AUTHOR]

• This study examined the stability of radiomic features in ADC maps of cervix cancer patients. • Interobserver variability in contouring and image pre-processing (normalization/quantization) affected feature reproducibility. • Urine-based normalization with fixed-bin width quantization approach was the most reproducible. The aims of this study are to evaluate the stability of radiomic features from Apparent Diffusion Coefficient (ADC) maps of cervical cancer with respect to: (1) reproducibility in inter-observer delineation, and (2) image pre-processing (normalization/quantization) prior to feature extraction. Two observers manually delineated the tumor on ADC maps derived from pre-treatment diffusion-weighted Magnetic Resonance imaging of 81 patients with FIGO stage IB-IVA cervical cancer. First-order, shape, and texture features were extracted from the original and filtered images considering 5 different normalizations (four taken from the available literature, and one based on urine ADC) and two different quantization techniques (fixed-bin widths from 0.05 to 25, and fixed-bin count). Stability of radiomic features was assessed using intraclass correlation coefficient (ICC): poor (ICC < 0.75); good (0.75 ≤ ICC ≤ 0.89), and excellent (ICC ≥ 0.90). Dependencies of the features with tumor volume were assessed using Spearman's correlation coefficient (ρ). The approach using urine-normalized values together with a smaller bin width (0.05) was the most reproducible (428/552, 78% features with ICC ≥ 0.75); the fixed-bin count approach was the least (215/552, 39% with ICC ≥ 0.75). Without normalization, using a fixed bin width of 25, 348/552 (63%) of features had an ICC ≥ 0.75. Overall, 26% (range 25–30%) of the features were volume-dependent (ρ ≥ 0.6). None of the volume-independent shape features were found to be reproducible. Applying normalization prior to features extraction increases the reproducibility of ADC-based radiomics features. When normalization is applied, a fixed-bin width approach with smaller widths is suggested. [ABSTRACT FROM AUTHOR]

Following the personalized medicine paradigm, there is a growing interest in medical agents capable of predicting the effect of therapies on patients, by exploiting the amount of data that is now available for each patient. In disciplines like oncology, where images and scans are available, the exploitation of medical images can provide an additional source of potentially useful information. The study and analysis of features extracted by medical images, exploited for predictive purposes, is termed radiomics. A number of tools are available for supporting some of the steps of the radiomics process, but there is a lack of approaches which are able to deal with all the steps of the process. In this paper, we introduce a medical agent-based decision support system capable of handling the whole radiomics process. The proposed system is tested on two independent data sets of patients treated for rectal cancer. Experimental results indicate that the system is able to generate highly performant centre-specific predictive model, and show the issues related to differences in data sets collected by different centres, and how such issues can affect the performance of the generated predictive models. [ABSTRACT FROM AUTHOR]

Highlights • PET image features have shown additional prognostic value in oesophageal cancer. • Harmonisation of PET images to standardise slice thickness is possible. • The prognostic model did not enable discrimination between the external risk groups. • A second model suggested transferable prognostic ability between cohorts. Abstract Aim Enhanced prognostic models are required to improve risk stratification of patients with oesophageal cancer so treatment decisions can be optimised. The primary aim was to externally validate a published prognostic model incorporating PET image features. Transferability of the model was compared using only clinical variables. Methods This was a Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis (TRIPOD) type 3 study. The model was validated against patients treated with neoadjuvant chemoradiotherapy according to the Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS) trial regimen using pre- and post-harmonised image features. The Kaplan–Meier method with log-rank significance tests assessed risk strata discrimination. A Cox proportional hazards model assessed model calibration. Primary outcome was overall survival (OS). Results Between 2010 and 2015, 449 patients were included in the development (n = 302), internal validation (n = 101) and external validation (n = 46) cohorts. No statistically significant difference in OS between patient quartiles was demonstrated in prognostic models incorporating PET image features (X 2 = 1.42, df = 3, p = 0.70) or exclusively clinical variables (age, disease stage and treatment; X 2 = 1.19, df = 3, p = 0.75). The calibration slope β of both models was not significantly different from unity (p = 0.29 and 0.29, respectively). Risk groups defined using only clinical variables suggested differences in OS, although these were not statistically significant (X 2 = 0.71, df = 2, p = 0.70). Conclusion The prognostic model did not enable significant discrimination between the validation risk groups, but a second model with exclusively clinical variables suggested some transferable prognostic ability. PET harmonisation did not significantly change the results of model validation. [ABSTRACT FROM AUTHOR]

Highlights • Presented Safeguards ensure productive progress of the radiomic field. • Radiomic models and features should be tested to determine added prognostic and predictive accuracy compared to accepted clinical factors. • Radiomic features are susceptible to underlying dependencies and multi-collinearity within models. • Open-source software should be used in radiomic developments to increase development accountability and facilitate inter-institutional research. Abstract Purpose Refinement of radiomic results and methodologies is required to ensure progression of the field. In this work, we establish a set of safeguards designed to improve and support current radiomic methodologies through detailed analysis of a radiomic signature. Methods A radiomic model (MW2018) was fitted and externally validated using features extracted from previously reported lung and head and neck (H&N) cancer datasets using gross-tumour-volume contours, as well as from images with randomly permuted voxel index values; i.e. images without meaningful texture. To determine MW2018's added benefit, the prognostic accuracy of tumour volume alone was calculated as a baseline. Results MW2018 had an external validation concordance index (c-index) of 0.64. However, a similar performance was achieved using features extracted from images with randomized signal intensities (c-index = 0.64 and 0.60 for H&N and lung, respectively). Tumour volume had a c-index = 0.64 and correlated strongly with three of the four model features. It was determined that the signature was a surrogate for tumour volume and that intensity and texture values were not pertinent for prognostication. Conclusion Our experiments reveal vulnerabilities in radiomic signature development processes and suggest safeguards that can be used to refine methodologies, and ensure productive radiomic development using objective and independent features. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common cancers in women with an incidence of around 6.5 % of all the cancer in women worldwide. Early detection and adequate treatment according to staging improve the patient's life expectancy. Outcome prediction models might aid treatment decisions, but a systematic review on prediction models for cervical cancer patients is not available. We performed a systematic review for prediction models in cervical cancer following PRISMA guidelines. Key features that were used for model training and validation, the endpoints were extracted from the article and data were analyzed. Selected articles were grouped based on prediction endpoints i.e. Group1: Overall survival, Group2: progression-free survival; Group3: recurrence or distant metastasis; Group4: treatment response; Group5: toxicity or quality of life. We developed a scoring system to evaluate the manuscript. As per our criteria, studies were divided into four groups based on scores obtained in our scoring system, the Most significant study (Score > 60 %); Significant study (60 % > Score > 50 %); Moderately Significant study (50 % > Score > 40 %); least significant study (score < 40 %). A meta-analysis was performed for all the groups separately. The first line of search selected 1358 articles and finally 39 articles were selected as eligible for inclusion in the review. As per our assessment criteria, 16, 13 and 10 studies were found to be the most significant, significant and moderately significant respectively. The intra-group pooled correlation coefficient for Group1, Group2, Group3, Group4, and Group5 were 0.76 [0.72, 0.79], 0.80 [0.73, 0.86], 0.87 [0.83, 0.90], 0.85 [0.77, 0.90], 0.88 [0.85, 0.90] respectively. All the models were found to be good (prediction accuracy [c-index/AUC/R2] >0.7) in endpoint prediction. Prediction models of cervical cancer toxicity, local or distant recurrence and survival prediction show promising results with reasonable prediction accuracy [c-index/AUC/R2 > 0.7]. These models should also be validated on external data and evaluated in prospective clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: “Radiomics” refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput from medical images obtained with computed tomography, positron emission tomography or magnetic resonance imaging. Importantly, these data are designed to be extracted from standard-of-care images, leading to a very large potential subject pool. Radiomics data are in a mineable form that can be used to build descriptive and predictive models relating image features to phenotypes or gene–protein signatures. The core hypothesis of radiomics is that these models, which can include biological or medical data, can provide valuable diagnostic, prognostic or predictive information. The radiomics enterprise can be divided into distinct processes, each with its own challenges that need to be overcome: (a) image acquisition and reconstruction, (b) image segmentation and rendering, (c) feature extraction and feature qualification and (d) databases and data sharing for eventual (e) ad hoc informatics analyses. Each of these individual processes poses unique challenges. For example, optimum protocols for image acquisition and reconstruction have to be identified and harmonized. Also, segmentations have to be robust and involve minimal operator input. Features have to be generated that robustly reflect the complexity of the individual volumes, but cannot be overly complex or redundant. Furthermore, informatics databases that allow incorporation of image features and image annotations, along with medical and genetic data, have to be generated. Finally, the statistical approaches to analyze these data have to be optimized, as radiomics is not a mature field of study. Each of these processes will be discussed in turn, as well as some of their unique challenges and proposed approaches to solve them. The focus of this article will be on images of non-small-cell lung cancer. [Copyright &y& Elsevier]

Purpose: To externally validate the previously published pre-treatment prediction models for lymph nodes failure after definitive radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients.Materials and Methods: This external validation cohort consisted of 143 node positive HNSCC patients treated between July 2007 and June 2016 by curative radiotherapy with or without either cisplatin or cetuximab. Imaging and pathology reports during follow-up were analyzed to indicate persisting or recurring nodes. The previously established clinical, radiomic and combined models were validated on this cohort by assessing the concordance index (c-index) and model calibration.Results: Overall 113 patients with 374 pLNs were suitable for final analysis. There were 20 (5.3%) nodal failures from 15 patients after a median follow-up of 36.1 months. Baseline characteristics and radiomic features were comparable to the training cohort. Both the radiomic model (Least-axis-length of lymph node (LALLN) and correlation of gray level co-occurrence matrix (Corre-GLCM)) and the combined model (T stage, gender, WHO performance score, LALLN and Corre-GLCM) showed good agreement between predicted and observed nodal control probabilities. The radiomic (c-index: 0.71; 95% confidence interval (CI): 0.59-0.84) and combined (c-index: 0.71; 95% CI: 0.59-0.82) models performed better than the clinical model (c-index: 0.57; 95% CI: 0.47-0.68) on this cohort, with a significant difference between the combined and clinical models (z-score test: p = 0.005).Conclusion: The combined model including clinical and radiomic features was externally validated and proved useful to predict nodal failures and could be helpful to guide treatment choices before and after curative radiation treatment for node positive HNSCC patients. [ABSTRACT FROM AUTHOR]