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Simple Summary: In radiotherapy treatment, organs at risk and target volumes are contoured by the clinicians to prepare a dosimetry plan. In retrospective data, these structures are not often standardised to universal names across the patients plans, which is required to enable data mining and analysis. In this paper, a new method was proposed and evaluated to automatically standardise radiotherapy structures names using machine learning algorithms. The proposed approach was deployed over a dataset with 1613 patients collected from Liverpool & Macarthur Cancer Therapy Centres, New South Wales, Australia. It was concluded that machine learning techniques can standardise the dosimetry plan structures, taking into consideration the integration of multiple modalities representing each structure during the training process. In progressing the use of big data in health systems, standardised nomenclature is required to enable data pooling and analyses. In many radiotherapy planning systems and their data archives, target volumes (TV) and organ-at-risk (OAR) structure nomenclature has not been standardised. Machine learning (ML) has been utilised to standardise volumes nomenclature in retrospective datasets. However, only subsets of the structures have been targeted. Within this paper, we proposed a new approach for standardising all the structures nomenclature by using multi-modal artificial neural networks. A cohort consisting of 1613 breast cancer patients treated with radiotherapy was identified from Liverpool & Macarthur Cancer Therapy Centres, NSW, Australia. Four types of volume characteristics were generated to represent each target and OAR volume: textual features, geometric features, dosimetry features, and imaging data. Five datasets were created from the original cohort, the first four represented different subsets of volumes and the last one represented the whole list of volumes. For each dataset, 15 sets of combinations of features were generated to investigate the effect of using different characteristics on the standardisation performance. The best model reported 99.416% classification accuracy over the hold-out sample when used to standardise all the nomenclatures in a breast cancer radiotherapy plan into 21 classes. Our results showed that ML based automation methods can be used for standardising naming conventions in a radiotherapy plan taking into consideration the inclusion of multiple modalities to better represent each volume. [ABSTRACT FROM AUTHOR]

Simple Summary: The High Throughput Truthing project aims to develop a dataset of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer specimens fit for a regulatory purpose. After completion of the pilot study, the analysis demonstrated inconsistencies and gaps in the provided training to pathologists. Select regions of interest (ROIs) were reviewed by an expert panel, who provided annotations and commentary on the challenges of the sTILs assessment. We used these annotations to develop a training document and reference standard for new training materials. These materials will train crowd-sourced pathologists to help create an algorithm validation dataset and contribute to sTILs evaluations in clinical practice. The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models. [ABSTRACT FROM AUTHOR]

Simple Summary: New technologies, particularly artificial intelligence (AI) and machine learning, enable the utilization of extensive data for personalized medicine. Future challenge involve acquiring limited biological data and extracting information for predictive models. This perspective focuses on triple-negative breast cancer (TNBC), a disease lacking specific treatment, where ongoing investigations explore therapies like immunotherapy. Drawing from the successful use of immunotherapy in melanoma, this perspective explores the identified strengths and weaknesses to inform more successful strategies. In this context, AI and predictive tools are invaluable. Advancements in melanoma immunotherapy serve as a foundation for developing effective immunotherapies for TNBC. Common principles, including immune system activation, checkpoint inhibitors, and personalized treatment, offer prospects for improving the outcomes in aggressive breast cancer cases, presenting new hope for challenging-to-treat patients, avoiding overtreatment, and reducing costs. Thanks to new technologies using artificial intelligence (AI) and machine learning, it is possible to use large amounts of data to try to extract information that can be used for personalized medicine. The great challenge of the future is, on the one hand, to acquire masses of biological data that nowadays are still limited and, on the other hand, to develop innovative strategies to extract information that can then be used for the development of predictive models. From this perspective, we discuss these aspects in the context of triple-negative breast cancer, a tumor where a specific treatment is still lacking and new therapies, such as immunotherapy, are under investigation. Since immunotherapy is already in use for other tumors such as melanoma, we discuss the strengths and weaknesses identified in the use of immunotherapy with melanoma to try to find more successful strategies. It is precisely in this context that AI and predictive tools can be extremely valuable. Therefore, the discoveries and advancements in immunotherapy for melanoma provide a foundation for developing effective immunotherapies for triple-negative breast cancer. Shared principles, such as immune system activation, checkpoint inhibitors, and personalized treatment, can be applied to TNBC to improve patient outcomes and offer new hope for those with aggressive, hard-to-treat breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer affects millions of women worldwide. We aim to provide radiologists with automatic support for mammography review. We propose deploying deep learning models with Multiple Instance Learning algorithms for breast cancer diagnosis (cancer versus non-cancer classification) based on digital mammography images, taking advantage of data annotated at an image level without indicating where the lesion is. We employed algorithms to analyse original, high-resolution images with minimal reduction in size. We used graphical suggestions of attentional maps to verify the correctness of the algorithm and to indicate the areas of the images where cancer lesions are. Finally, we performed comparative and validation studies on external datasets differing in the number of images, pixel intensity levels, and subtypes of existing lesions, showing high accuracy and potential for generalisability of the algorithms. Breast cancer is the most frequent female cancer, with a considerable disease burden and high mortality. Early diagnosis with screening mammography might be facilitated by automated systems supported by deep learning artificial intelligence. We propose a model based on a weakly supervised Clustering-constrained Attention Multiple Instance Learning (CLAM) classifier able to train under data scarcity effectively. We used a private dataset with 1174 non-cancer and 794 cancer images labelled at the image level with pathological ground truth confirmation. We used feature extractors (ResNet-18, ResNet-34, ResNet-50 and EfficientNet-B0) pre-trained on ImageNet. The best results were achieved with multimodal-view classification using both CC and MLO images simultaneously, resized by half, with a patch size of 224 px and an overlap of 0.25. It resulted in AUC-ROC = 0.896 ± 0.017, F1-score 81.8 ± 3.2, accuracy 81.6 ± 3.2, precision 82.4 ± 3.3, and recall 81.6 ± 3.2. Evaluation with the Chinese Mammography Database, with 5-fold cross-validation, patient-wise breakdowns, and transfer learning, resulted in AUC-ROC 0.848 ± 0.015, F1-score 78.6 ± 2.0, accuracy 78.4 ± 1.9, precision 78.8 ± 2.0, and recall 78.4 ± 1.9. The CLAM algorithm's attentional maps indicate the features most relevant to the algorithm in the images. Our approach was more effective than in many other studies, allowing for some explainability and identifying erroneous predictions based on the wrong premises. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of breast lesions through mammographic images is currently challenging, especially in dense breasts. Contrast-enhanced mammography has been shown to overcome the limitations of standard mammography but it greatly depends on the interpretative skills of the physician. The aim of this study was to evaluate the potentialities of statistical and artificial intelligence algorithms as a tool for helping the radiologists in the interpretation of images. The most remarkable results were achieved in discriminating benign from malignant lesions and in the identification of the presence of the hormone receptor. A tool to support the physician's decision-making process may be designed starting from simple logistic regression and tree-based algorithms. This type of tool may help the radiologist in assessing the investigated breast and in choosing the appropriate follow-up without resorting to histology. Purpose: To evaluate radiomics features in order to: differentiate malignant versus benign lesions; predict low versus moderate and high grading; identify positive or negative hormone receptors; and discriminate positive versus negative human epidermal growth factor receptor 2 related to breast cancer. Methods: A total of 182 patients with known breast lesions and that underwent Contrast-Enhanced Mammography were enrolled in this retrospective study. The reference standard was pathology (118 malignant lesions and 64 benign lesions). A total of 837 textural metrics were extracted by manually segmenting the region of interest from both craniocaudally (CC) and mediolateral oblique (MLO) views. Non-parametric Wilcoxon–Mann–Whitney test, receiver operating characteristic, logistic regression and tree-based machine learning algorithms were used. The Adaptive Synthetic Sampling balancing approach was used and a feature selection process was implemented. Results: In univariate analysis, the classification of malignant versus benign lesions achieved the best performance when considering the original_gldm_DependenceNonUniformity feature extracted on CC view (accuracy of 88.98%). An accuracy of 83.65% was reached in the classification of grading, whereas a slightly lower value of accuracy (81.65%) was found in the classification of the presence of the hormone receptor; the features extracted were the original_glrlm_RunEntropy and the original_gldm_DependenceNonUniformity, respectively. The results of multivariate analysis achieved the best performances when using two or more features as predictors for classifying malignant versus benign lesions from CC view images (max test accuracy of 95.83% with a non-regularized logistic regression). Considering the features extracted from MLO view images, the best test accuracy (91.67%) was obtained when predicting the grading using a classification-tree algorithm. Combinations of only two features, extracted from both CC and MLO views, always showed test accuracy values greater than or equal to 90.00%, with the only exception being the prediction of the human epidermal growth factor receptor 2, where the best performance (test accuracy of 89.29%) was obtained with the random forest algorithm. Conclusions: The results confirm that the identification of malignant breast lesions and the differentiation of histological outcomes and some molecular subtypes of tumors (mainly positive hormone receptor tumors) can be obtained with satisfactory accuracy through both univariate and multivariate analysis of textural features extracted from Contrast-Enhanced Mammography images. [ABSTRACT FROM AUTHOR]