Progress in computing power and advances in medical imaging over recent decades have culminated in new opportunities for artificial intelligence (AI), computer vision, and using radiomics to facilitate clinical decision-making. These opportunities are growing in medical specialties, such as radiology, pathology, and oncology. As medical imaging and pathology are becoming increasingly digitized, it is recently recognized that harnessing data from digital images can yield parameters that reflect the underlying biology and physiology of various malignancies. This greater understanding of the behaviour of cancer can potentially improve on therapeutic strategies. In addition, the use of AI is particularly appealing in oncology to facilitate the detection of malignancies, to predict the likelihood of tumor response to treatments, and to prognosticate the patients' risk of cancer-related mortality. AI will be critical for identifying candidate biomarkers from digital imaging and developing robust and reliable predictive models. These models will be used to personalize oncologic treatment strategies, and identify confounding variables that are related to the complex biology of tumors and diversity of patient-related factors (ie, mining ''big data''). This commentary describes the growing body of work focussed on AI for precision oncology. Advances in AI-driven
PURPOSE Neoadjuvant chemotherapy (NAC) is used to treat locally advanced breast cancer (LABC) and high-risk early breast cancer (BC). Pathological complete response (pCR) has prognostic value depending on BC subtype. Rates of pCR, however, can be variable. Predictive modeling is desirable to help identify patients early who may have suboptimal NAC response. Here, we test and compare the predictive performances of machine learning (ML) prediction models to a standard statistical model, using clinical and pathological data. METHODS Clinical and pathological variables were collected in 431 patients, including tumor size, patient demographics, histological characteristics, molecular status, and staging information. A standard multivariable logistic regression (MLR) was developed and compared with five ML models: k-nearest neighbor classifier, random forest (RF) classifier, naive Bayes algorithm, support vector machine, and multilayer perceptron model. Model performances were measured using a receiver operating characteristic (ROC) analysis and statistically compared. RESULTS MLR predictors of NAC response included: estrogen receptor (ER) status, human epidermal growth factor-2 (HER2) status, tumor size, and Nottingham grade. The strongest MLR predictors of pCR included HER2+ versus HER2− BC (odds ratio [OR], 0.13; 95% CI, 0.07 to 0.23; P < .001) and Nottingham grade G3 versus G1-2 (G1-2: OR, 0.36; 95% CI, 0.20 to 0.65; P < .001). The area under the curve (AUC) for the MLR was AUC = 0.64. Among the various ML models, an RF classifier performed best, with an AUC = 0.88, sensitivity of 70.7%, and specificity of 84.6%, and included the following variables: menopausal status, ER status, HER2 status, Nottingham grade, tumor size, nodal status, and presence of inflammatory BC. CONCLUSION Modeling performances varied between standard versus ML classification methods. RF ML classifiers demonstrated the best predictive performance among all models.
Complete pathological response (pCR) to neoadjuvant chemotherapy (NAC) is a prognostic factor for breast cancer (BC) patients and is correlated with improved survival. However, pCR rates are variable to standard NAC, depending on BC subtype. This study investigates quantitative digital histopathology coupled with machine learning (ML) to predict NAC response a priori. Clinicopathologic data and digitized slides of BC core needle biopsies were collected from 149 patients treated with NAC. The nuclei within the tumor regions were segmented on the histology images of biopsy samples using a weighted U-Net model. Five pathomic feature subsets were extracted from segmented digitized samples, including the morphological, intensity-based, texture, graph-based and wavelet features. Seven ML experiments were conducted with different feature sets to develop a prediction model of therapy response using a gradient boosting machine with decision trees. The models were trained and optimized using a five-fold cross validation on the training data and evaluated using an unseen independent test set. The prediction model developed with the best clinical features (tumor size, tumor grade, age, and ER, PR, HER2 status) demonstrated an area under the ROC curve (AUC) of 0.73. Various pathomic feature subsets resulted in models with AUCs in the range of 0.67 and 0.87, with the best results associated with the graph-based and wavelet features. The selected features among all subsets of the pathomic and clinicopathologic features included four wavelet and three graph-based features and no clinical features. The predictive model developed with these features outperformed the other models, with an AUC of 0.90, a sensitivity of 85% and a specificity of 82% on the independent test set. The results demonstrated the potential of quantitative digital histopathology features integrated with ML methods in predicting BC response to NAC. This study is a step forward towards precision oncology for BC patients to potentially guide future therapies.
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