Diagnostic value of radiomics and machine learning with dynamic contrast-enhanced magnetic resonance imaging for patients with atypical ductal hyperplasia in predicting malignant upgrade.

PURPOSE: To investigate whether radiomics features extracted from magnetic resonance imaging (MRI) of patients with biopsy-proven atypical ductal hyperplasia (ADH) coupled with machine learning can differentiate high-risk lesions that will upgrade to malignancy at surgery from those that will not, and to determine if qualitatively and semi-quantitatively assessed imaging features, clinical factors, and image-guided biopsy technical factors are associated with upgrade rate. METHODS: This retrospective study included 127 patients with 139 breast lesions yielding ADH at biopsy who were assessed with multiparametric MRI prior to biopsy. Two radiologists assessed all lesions independently and with a third reader in consensus according to the BI-RADS lexicon. Univariate analysis and multivariate modeling were performed to identify significant radiomic features to be included in a machine learning model to discriminate between lesions that upgraded to malignancy on surgery from those that did not. RESULTS: Of 139 lesions, 28 were upgraded to malignancy at surgery, while 111 were not upgraded. Diagnostic accuracy was 53.6%, specificity 79.2%, and sensitivity 15.3% for the model developed from pre-contrast features, and 60.7%, 86%, and 22.8% for the model developed from delta radiomics datasets. No significant associations were found between any radiologist-assessed lesion parameters and upgrade status. There was a significant correlation between the number of specimens sampled during biopsy and upgrade status (p = 0.003). CONCLUSION: Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.

MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.

BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20). FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test). INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients. FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.

MRI background parenchymal enhancement, fibroglandular tissue, and mammographic breast density in patients with invasive lobular breast cancer on adjuvant endocrine hormonal treatment: associations with survival.

BACKGROUND: To investigate if baseline and/or changes in contralateral background parenchymal enhancement (BPE) and fibroglandular tissue (FGT) measured on magnetic resonance imaging (MRI) and mammographic breast density (MD) can be used as imaging biomarkers for overall and recurrence-free survival in patients with invasive lobular carcinomas (ILCs) undergoing adjuvant endocrine treatment. METHODS: Women who fulfilled the following inclusion criteria were included in this retrospective HIPAA-compliant IRB-approved study: unilateral ILC, pre-treatment breast MRI and/or mammography from 2000 to 2010, adjuvant endocrine treatment, follow-up MRI, and/or mammography 1-2 years after treatment onset. BPE, FGT, and mammographic MD of the contralateral breast were independently graded by four dedicated breast radiologists according to BI-RADS. Associations between the baseline levels and change in levels of BPE, FGT, and MD with overall survival and recurrence-free survival were assessed using Kaplan-Meier survival curves and Cox regression analysis. RESULTS: Two hundred ninety-eight patients (average age = 54.1 years, range = 31-79) fulfilled the inclusion criteria. The average follow-up duration was 11.8 years (range = 2-19). Baseline and change in levels of BPE, FGT, and MD were not significantly associated with recurrence-free or overall survival. Recurrence-free and overall survival were affected by histological subtype (p < 0.0001), number of metastatic axillary lymph nodes (p < 0.0001), age (p = 0.01), and adjuvant endocrine treatment duration (p < 0.001). CONCLUSIONS: Qualitative evaluation of BPE, FGT, and mammographic MD changes cannot predict which patients are more likely to benefit from adjuvant endocrine treatment.

Improved characterization of sub-centimeter enhancing breast masses on MRI with radiomics and machine learning in BRCA mutation carriers.

OBJECTIVES: To investigate whether radiomics features extracted from MRI of BRCA-positive patients with sub-centimeter breast masses can be coupled with machine learning to differentiate benign from malignant lesions using model-free parameter maps. METHODS: In this retrospective study, BRCA-positive patients who had an MRI from November 2013 to February 2019 that led to a biopsy (BI-RADS 4) or imaging follow-up (BI-RADS 3) for sub-centimeter lesions were included. Two radiologists assessed all lesions independently and in consensus according to BI-RADS. Radiomics features were calculated using open-source CERR software. Univariate analysis and multivariate modeling were performed to identify significant radiomics features and clinical factors to be included in a machine learning model to differentiate malignant from benign lesions. RESULTS: Ninety-six BRCA mutation carriers (mean age at biopsy = 45.5 ± 13.5 years) were included. Consensus BI-RADS classification assessment achieved a diagnostic accuracy of 53.4%, sensitivity of 75% (30/40), specificity of 42.1% (32/76), PPV of 40.5% (30/74), and NPV of 76.2% (32/42). The machine learning model combining five parameters (age, lesion location, GLCM-based correlation from the pre-contrast phase, first-order coefficient of variation from the 1st post-contrast phase, and SZM-based gray level variance from the 1st post-contrast phase) achieved a diagnostic accuracy of 81.5%, sensitivity of 63.2% (24/38), specificity of 91.4% (64/70), PPV of 80.0% (24/30), and NPV of 82.1% (64/78). CONCLUSIONS: Radiomics analysis coupled with machine learning improves the diagnostic accuracy of MRI in characterizing sub-centimeter breast masses as benign or malignant compared with qualitative morphological assessment with BI-RADS classification alone in BRCA mutation carriers. KEY POINTS: • Radiomics and machine learning can help differentiate benign from malignant breast masses even if the masses are small and morphological features are benign. • Radiomics and machine learning analysis showed improved diagnostic accuracy, specificity, PPV, and NPV compared with qualitative morphological assessment alone.

Combining molecular and imaging metrics in cancer: radiogenomics.

BACKGROUND: Radiogenomics is the extension of radiomics through the combination of genetic and radiomic data. Because genetic testing remains expensive, invasive, and time-consuming, and thus unavailable for all patients, radiogenomics may play an important role in providing accurate imaging surrogates which are correlated with genetic expression, thereby serving as a substitute for genetic testing. MAIN BODY: In this article, we define the meaning of radiogenomics and the difference between radiomics and radiogenomics. We provide an up-to-date review of the radiomics and radiogenomics literature in oncology, focusing on breast, brain, gynecological, liver, kidney, prostate and lung malignancies. We also discuss the current challenges to radiogenomics analysis. CONCLUSION: Radiomics and radiogenomics are promising to increase precision in diagnosis, assessment of prognosis, and prediction of treatment response, providing valuable information for patient care throughout the course of the disease, given that this information is easily obtainable with imaging. Larger prospective studies and standardization will be needed to define relevant imaging biomarkers before they can be implemented into the clinical workflow.

Insights into Hypoxia: Non-invasive Assessment through Imaging Modalities and Its Application in Breast Cancer.

Oxygen is crucial to maintain the homeostasis in aerobic cells. Hypoxia is a condition in which cells are deprived of the oxygen supply necessary for their optimum performance. Whereas oxygen deprivation may occur in normal physiological processes, hypoxia is frequently associated with pathological conditions. It has been identified as a stressor in the tumor microenvironment, acting as a key mediator of cancer development. Numerous pathways are activated in hypoxic cells that affect cell signaling and gene regulation to promote the survival of these cells by stimulating angiogenesis, switching cellular metabolism, slowing their growth rate, and preventing apoptosis. The induction of dysregulated metabolism in cancer cells by hypoxia results in aggressive tumor phenotypes that are characterized by rapid progression, treatment resistance, and poor prognosis. A non-invasive assessment of hypoxia-induced metabolic and architectural changes in tumors is advisable to fully improve breast cancer (BC) patient management, by potentially reducing the need for invasive biopsy procedures and evaluating tumor response to treatment. This review provides a comprehensive overview of the molecular changes in breast tumors secondary to hypoxia and the non-invasive imaging alternatives to evaluate oxygen deprivation, with an emphasis on their application in BC and the advantages and limitations of the currently available techniques.