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Background: Radiomics represents an emerging field of precision‐medicine. Its application in head and neck is still at the beginning. Methods: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010–2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic‐software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical‐radiomic models) and compared using C‐index. Results: In almost all clinical‐radiomic models radiomic‐score maintained statistical significance. In all cases C‐index was higher in clinical‐radiomic models than in clinical ones. ADC provided the best fit to the models (C‐index 0.98, 0.86, 0.84 in loco‐regional recurrence, cause‐specific mortality, overall survival, respectively). Conclusion: MRI‐based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The aim of this study is to test whether radiomic and blood-derived biomarkers are good candidates for refining the prognostic stratification in OPSCC. The results show that the integration of clinical, immunological, and computed tomography-derived features generally yields an improvement, regardless of the HPV status, in the prognostic stratification of OPSCC patients who are candidates for curative-intent radiotherapy. Specifically, we documented a significant role of the Lymphocyte-to-Monocyte Ratio (LMR) in this population, which has been scarcely investigated in OPSCC, as well as the detrimental effects of lymphopenia and anemia. Results are promising, and model performances compare favorably with available radiomic scores in the same setting. Further investigations on our findings are warranted to validate the results and include a more in-depth study of the prognostic role of the LMR in OPSCC. Future analyses of this dataset are planned to provide a more complete overview of the tumor-immune system interplay. Aims: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Methods: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. Results: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52–66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5–7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80–0.84] for OS and 0.77 [CI: 0.75–0.79] for LRPFS. Conclusions: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients. [ABSTRACT FROM AUTHOR]

Featured Application: This study provides quantitative data about the loss of informative content of MRI radiomic features when calculated on small volumes. Besides providing useful information for the design of MRI radiomic studies in the pelvic region, it proposes a methodology that might be replicated for other imaging modalities and clinical scenarios upon the development of suitable phantoms. Radiomics is emerging as a promising tool to extract quantitative biomarkers—called radiomic features—from medical images, potentially contributing to the improvement in diagnosis and treatment of oncological patients. However, technical limitations might impair the reliability of radiomic features and their ability to quantify clinically relevant tissue properties. Among these, sampling the image signal in a too-small region can reduce the ability to discriminate tissues with different properties. However, a volume threshold guaranteeing a reliable analysis, which might vary according to the imaging modality and clinical scenario, has not been assessed yet. In this study, an MRI phantom specifically developed for radiomic investigation of gynecological malignancies was used to explore how the ability of radiomic features to discriminate different image textures varies with the volume of the analyzed region. The phantom, embedding inserts with different textures, was scanned on two 1.5T and one 3T scanners, each using the T2-weighted sequence of the clinical protocol implemented for gynecological studies. Within each of the three inserts, six cylindrical regions were drawn with volumes ranging from 0.8 cm3 to 29.8 cm3, and 944 radiomic features were extracted from both original images and from images processed with different filters. For each scanner, the ability of each feature to discriminate the different textures was quantified. Despite differences observed among the scanner models, the overall percentage of discriminative features across scanners was >70%, with the smallest volume having the lowest percentage of discriminative features for all scanners. Stratification by feature class, still aggregating data for original and filtered images, showed statistical significance for the association between the percentage of discriminative features with VOI sizes for features classes GLCM, GLDM, and GLSZM on the first 1.5T scanner and for first-order and GLSZM classes on the second 1.5T scanner. Poorer results in terms of features' discriminative ability were found for the 3T scanner. Focusing on original images only, the analysis of discriminative features stratified by feature class showed that the first-order and GLCM were robust to VOI size variations (>85% discriminative features for all sizes), while for the 1.5T scanners, the GLSZM and NGTDM feature classes showed a percentage of discriminative features >80% only for volumes no smaller than 3.3 cm3, and equal or larger than 7.4 cm3 for the GLRLM. As for the 3T scanner, only the GLSZM showed a percentage of discriminative features >80% for all volume sizes above 3.3 cm3. Analogous considerations were obtained for each filter, providing useful indications for feature selection in this clinical case. Similar studies should be replicated with suitably adapted phantoms to derive useful data for other clinical scenarios and imaging modalities. [ABSTRACT FROM AUTHOR]

• Phantoms are a useful tool to study feature repeatability and reproducibility. • The proposed phantom contains heterogeneous inserts to mimic lung tumour texture. • A commercial phantom with homogeneous inserts is not suitable to mimic tumours. • Feature repeatability is texture dependent. • Most features are repeatable, especially from firstorder and glcm categories. Phantoms mimicking human tissue heterogeneity and intensity are required to establish radiomic features robustness in Computed Tomography (CT) images. We developed inserts with two different techniques for the radiomic study of Non-Small Cell Lung Cancer (NSCLC) lesions. We developed two insert prototypes: two 3D-printed made of glycol-modified polyethylene terephthalate (PET-G), and nine with sodium polyacrylate plus iodinated contrast medium. The inserts were put in a handcraft phantom (HeLLePhant). We also analysed four materials of a commercial homogeneous phantom (Catphan® 424) and collected 29 NSCLC patients for comparison. All the CT acquisitions were performed with the same clinical protocol and scanner at 120kVp. The HeLLePhant phantom was scanned ten times in fixed condition at 120kVp and 100kVp for repeatability investigation. We extracted 153 radiomic features using Pyradiomics. To compare the features between phantoms and patients, we computed how many phantom features fell in the range between 10th and 90th percentile of the corresponding patient values. We deemed repeatable the features with a coefficient of variation (CV) less than or equal to 0.10. The best similarity with the patients was obtained with the polyacrylate inserts (55.6–90.2%), the worst with Catphan (15.7–19.0%). For the PET-G inserts 35.3% and 36.6% of the features match the patient range. We found high repeatability for all the inserts of the HeLLePhant phantom (74.3–100% at 120kVp, 75.7–97.9% at 100kVp), and observed a texture dependency in repeatability. Our study shows a promising way to construct heterogeneous inserts mimicking a target tissue for radiomic studies. [ABSTRACT FROM AUTHOR]

Radiomics is an emerging translational field of medicine based on the extraction of highdimensional data from radiological images, with the purpose to reach reliable models to be applied into clinical practice for the purposes of diagnosis, prognosis and evaluation of disease response to treatment. We aim to provide the basic information on radiomics to radiologists and clinicians who are focused on breast cancer care, encouraging cooperation with scientists to mine data for a better application in clinical practice. We investigate the workflow and clinical application of radiomics in breast cancer care, as well as the outlook and challenges based on recent studies. Currently, radiomics has the potential ability to distinguish between benign and malignant breast lesions, to predict breast cancer's molecular subtypes, the response to neoadjuvant chemotherapy and the lymph node metastases. Even though radiomics has been used in tumor diagnosis and prognosis, it is still in the research phase and some challenges need to be faced to obtain a clinical translation. In this review, we discuss the current limitations and promises of radiomics for improvement in further research. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the repeatability and reproducibility of radiomic features extracted from MR images and provide a workflow to identify robust features. Methods: T2‐weighted images of a pelvic phantom were acquired on three scanners of two manufacturers and two magnetic field strengths. The repeatability and reproducibility of features were assessed by the intraclass correlation coefficient and the concordance correlation coefficient, respectively, and by the within‐subject coefficient of variation, considering repeated acquisitions with and without phantom repositioning, and with different scanner and acquisition parameters. The features showing intraclass correlation coefficient or concordance correlation coefficient >0.9 were selected, and their dependence on shape information (Spearman's ρ > 0.8) analyzed. They were classified for their ability to distinguish textures, after shuffling voxel intensities of images. Results: From 944 two‐dimensional features, 79.9% to 96.4% showed excellent repeatability in fixed position across all scanners. A much lower range (11.2% to 85.4%) was obtained after phantom repositioning. Three‐dimensional extraction did not improve repeatability performance. Excellent reproducibility between scanners was observed in 4.6% to 15.6% of the features, at fixed imaging parameters. In addition, 82.4% to 94.9% of the features showed excellent agreement when extracted from images acquired with echo times 5 ms apart, but decreased with increasing echo‐time intervals, and 90.7% of the features exhibited excellent reproducibility for changes in pulse repetition time. Of nonshape features, 2.0% was identified as providing only shape information. Conclusion: We showed that radiomic features are affected by MRI protocols and propose a general workflow to identify repeatable, reproducible, and informative radiomic features to ensure robustness of clinical studies. [ABSTRACT FROM AUTHOR]

Background: Digital breast tomosynthesis (DBT) systems employ a sophisticated set of acquisition parameters to generate an image set, and the DBT acquisition angle is considered to be one of the most important parameters. The aim of this study was to use texture analysis to assess how the DBT acquisition angle might influence DBT images of breast parenchyma. Methods: Thirty-four patients were selected from a clinical study conducted at IRST Institute. Each patient underwent a dual DBT scan performed with Fujifilm Amulet Innovality (Fujifilm Corp, Tokyo, Japan) in standard (ST, angular range = 15°) and high-resolution (HR, angular range = 40°) modalities. Texture analysis was applied on the paired dataset using histogram-based features and gray level co-occurrence matrix (GLCM) features. Wilcoxon-signed rank and Pearson-rank tests were used to assess the statistical differences and correlations between extracted features. Results: The DBT acquisition angle did not affect histogram-based features, whereas there was a significant difference in five GLCM features (p < 0.05) between DBT images generated with 15° and 40° acquisition angles. Correlation analysis showed that two GLCM features were not correlated at a p < 0.05 significance level. Conclusions: DBT acquisition angle affects the textures extracted from DBT images and this dependence should be considered when establishing baselines for classifiers of malignant tissue. Furthermore, texture analysis could be proposed as a quantitative method for comparing and scoring the contrast of DBT images. [ABSTRACT FROM AUTHOR]

• Normalizing images with respect to healthy prostate tissue is optimal. • Histogram-based normalization should be used otherwise. • Over 87% of radiomic features drastically change after normalization. • Improper normalization is worse than no normalization. The variance in intensities of MRI scans is a fundamental impediment for quantitative MRI analysis. Intensity values are not only highly dependent on acquisition parameters, but also on the subject and body region being scanned. This warrants the need for image normalization techniques to ensure that intensity values are consistent within tissues across different subjects and visits. Many intensity normalization methods have been developed and proven successful for the analysis of brain pathologies, but evaluation of these methods for images of the prostate region is lagging. In this paper, we compare four different normalization methods on 49 T2-w scans of prostate cancer patients: 1) the well-established histogram normalization, 2) the generalized scale normalization, 3) an extension of generalized scale normalization called generalized ball-scale normalization, and 4) a custom normalization based on healthy prostate tissue intensities. The methods are compared qualitatively and quantitatively in terms of behaviors of intensity distributions as well as impact on radiomic features. Our findings suggest that normalization based on prior knowledge of the healthy prostate tissue intensities may be the most effective way of acquiring the desired properties of normalized images. In addition, the histogram normalization method outperform the generalized scale and generalized ball-scale methods which have proven superior for other body regions. [ABSTRACT FROM AUTHOR]

• The instructions to build the first MR radiomic phantom mimicking pelvis are given. • The phantom reproduces the relaxation times of muscle and tumour tissue. • It includes inserts that simulate the texture of representative pelvic tumours. • It can be used to study the radiomic features stability in different MR settings. • It is useful to optimise the radiomic workflow in MR. To develop a phantom for methodological radiomic investigation on Magnetic Resonance (MR) images of female patients affected by pelvic cancer. A pelvis-shaped container was filled with a MnCl 2 solution reproducing the relaxation times (T 1 , T 2) of muscle surrounding pelvic malignancies. Inserts simulating multi-textured lesions were embedded in the phantom. The relaxation times of muscle and tumour were measured on an MR scanner on healthy volunteers and patients; T 1 and T 2 of MnCl 2 solutions were evaluated with a relaxometer to find the concentrations providing a match to in vivo relaxation times. Radiomic features were extracted from the phantom inserts and the patients' lesions. Their repeatability was assessed by multiple measurements. Muscle T 1 and T 2 were 1128 (806–1378) and 51 (40–65) ms, respectively. The phantom reproduced in vivo values within 13% (T 1) and 12% (T 2). T 1 and T 2 of tumour tissue were 1637 (1396–2121) and 94 (79–101) ms, respectively. The phantom insert best mimicking the tumour agreed within 7% (T 1) and 24% (T 2) with in vivo values. Out of 1034 features, 75% (95%) had interclass correlation coefficient greater than 0.9 on T 1 (T 2)-weighted images, reducing to 33% (25%) if the phantom was repositioned. The most repeatable features on phantom showed values in agreement with the features extracted from patients' lesions. We developed an MR phantom with inserts mimicking both relaxation times and texture of pelvic tumours. As exemplified with repeatability assessment, such phantom is useful to investigate features robustness and optimise the radiomic workflow on pelvic MR images. [ABSTRACT FROM AUTHOR]

Simple Summary: Nowadays, the only widely recognized method for evaluating the efficacy of neoadjuvant chemotherapy is the assessment of the pathological response through surgery. However, delivering chemotherapy to not-responders could expose them to unnecessary drug toxicity with delayed access to other potentially effective therapies. Radiomics could be useful in the early detection of resistance to chemotherapy, which is crucial for switching treatment strategy. We determined whether tumor radiomic features extracted from a highly homogeneous database of breast MRI can improve the prediction of response to chemotherapy in patients with breast cancer, in addiction to biological characteristics, potentially avoiding unnecessary treatment. Objectives: We aimed to determine whether radiomic features extracted from a highly homogeneous database of breast MRI could non-invasively predict pathological complete responses (pCR) to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: One hundred patients with breast cancer receiving NACT in a single center (01/2017–06/2019) and undergoing breast MRI were retrospectively evaluated. For each patient, radiomic features were extracted within the biopsy-proven tumor on T1-weighted (T1-w) contrast-enhanced MRI performed before NACT. The pCR to NACT was determined based on the final surgical specimen. The association of clinical/biological and radiomic features with response to NACT was evaluated by univariate and multivariable analysis by using random forest and logistic regression. The performances of all models were assessed using the areas under the receiver operating characteristic curves (AUC) with 95% confidence intervals (CI). Results: Eighty-three patients (mean (SD) age, 47.26 (8.6) years) were included. Patients with HER2+, basal-like molecular subtypes and Ki67 ≥ 20% presented a pCR to NACT more frequently; the clinical/biological model's AUC (95% CI) was 0.81 (0.71–0.90). Using 136 representative radiomics features selected through cluster analysis from the 1037 extracted features, a radiomic score was calculated to predict the response to NACT, with AUC (95% CI): 0.64 (0.51–0.75). After combining the clinical/biological and radiomics models, the AUC (95% CI) was 0.83 (0.73–0.92). Conclusions: MRI-based radiomic features slightly improved the pre-treatment prediction of pCR to NACT, in addiction to biological characteristics. If confirmed on larger cohorts, it could be helpful to identify such patients, to avoid unnecessary treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiomics aims to extract high-dimensional features from clinical images and associate them to clinical outcomes. These associations may be further investigated with machine learning models; however, guidelines on the most suitable method to support clinical decisions are still missing. To improve the reliability and the accuracy of radiomic features in the prediction of a binary variable in a lung cancer setting, we compared several machine learning classifiers and feature selection methods on simulated data. These account for important characteristics that may vary in real clinical datasets: sample size, outcome balancing and association strength between radiomic features and outcome variables. We were able to suggest the most suitable classifiers for each studied case and to evaluate the impact of method choices. Our work highlights the importance of these choices in radiomic analyses and provides guidelines on how to select the best models for the data at hand. Radiomics uses high-dimensional sets of imaging features to predict biological characteristics of tumors and clinical outcomes. The choice of the algorithm used to analyze radiomic features and perform predictions has a high impact on the results, thus the identification of adequate machine learning methods for radiomic applications is crucial. In this study we aim to identify suitable approaches of analysis for radiomic-based binary predictions, according to sample size, outcome balancing and the features–outcome association strength. Simulated data were obtained reproducing the correlation structure among 168 radiomic features extracted from Computed Tomography images of 270 Non-Small-Cell Lung Cancer (NSCLC) patients and the associated to lymph node status. Performances of six classifiers combined with six feature selection (FS) methods were assessed on the simulated data using AUC (Area Under the Receiver Operating Characteristics Curves), sensitivity, and specificity. For all the FS methods and regardless of the association strength, the tree-based classifiers Random Forest and Extreme Gradient Boosting obtained good performances (AUC ≥ 0.73), showing the best trade-off between sensitivity and specificity. On small samples, performances were generally lower than in large–medium samples and with larger variations. FS methods generally did not improve performances. Thus, in radiomic studies, we suggest evaluating the choice of FS and classifiers, considering specific sample size, balancing, and association strength. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using different platforms for radiomic extraction affects models' performance. • Variables' relevance is inconsistent among platforms. • MRI features are correlated to radiosurgery response in brain metastases from NSCLC. • Higher number of radiomic features does not necessarily imply better performance. Radiomics enables the mining of quantitative features from medical images. The influence of the radiomic feature extraction software on the final performance of models is still a poorly understood topic. This study aimed to investigate the ability of radiomic features extracted by two different radiomic platforms to predict clinical outcomes in patients treated with radiosurgery for brain metastases from non-small cell lung cancer. We developed models integrating pre-treatment magnetic resonance imaging (MRI)-derived radiomic features and clinical data. Pre-radiotherapy gadolinium enhanced axial T1-weighted MRI scans were used. MRI images were re-sampled, intensity-shifted, and histogram-matched before radiomic extraction by means of two different platforms (PyRadiomics and SOPHiA Radiomics). We adopted LASSO Cox regression models for multivariable analyses by creating radiomic, clinical, and combined models using three survival clinical endpoints (local control, distant progression, and overall survival). The statistical analysis was repeated 50 times with different random seeds and the median concordance index was used as performance metric of the models. We analysed 276 metastases from 148 patients. The use of the two platforms resulted in differences in both the quality and the number of extractable features. That led to mismatches in terms of end-to-end performance, statistical significance of radiomic scores, and clinical covariates found significant in combined models. This study shed new light on how extracting radiomic features from the same images using two different platforms could yield several discrepancies. That may lead to acute consequences on drawing conclusions, comparing results across the literature, and translating radiomics into clinical practice. [ABSTRACT FROM AUTHOR]