Impact of Machine Learning With Multiparametric Magnetic Resonance Imaging of the Breast for Early Prediction of Response to Neoadjuvant Chemotherapy and Survival Outcomes in Breast Cancer Patients

PurposeThe aim of this study was to assess the potential of machine learning with multiparametric magnetic resonance imaging (mpMRI) for the early prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and of survival outcomes in breast cancer patients. Materials and MethodsThis institutional review board–approved prospective study included 38 women (median age, 46.5 years; range, 25–70 years) with breast cancer who were scheduled for NAC and underwent mpMRI of the breast at 3 T with dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and T2-weighted imaging before and after 2 cycles of NAC. For each lesion, 23 features were extracted: qualitative T2-weighted and DCE-MRI features according to BI-RADS (Breast Imaging Reporting and Data System), quantitative pharmacokinetic DCE features (mean plasma flow, volume distribution, mean transit time), and DWI apparent diffusion coefficient (ADC) values. To apply machine learning to mpMRI, 8 classifiers including linear support vector machine, linear discriminant analysis, logistic regression, random forests, stochastic gradient descent, decision tree, adaptive boosting, and extreme gradient boosting (XGBoost) were used to rank the features. Histopathologic residual cancer burden (RCB) class (with RCB 0 being a pCR), recurrence-free survival (RFS), and disease-specific survival (DSS) were used as the standards of reference. Classification accuracy with area under the receiving operating characteristic curve (AUC) was assessed using all the extracted qualitative and quantitative features for pCR as defined by RCB class, RFS, and DSS using recursive feature elimination. To overcome overfitting, 4-fold cross-validation was used. ResultsMachine learning with mpMRI achieved stable performance as shown by mean classification accuracies for the prediction of RCB class (AUC, 0.86) and DSS (AUC, 0.92) based on XGBoost and the prediction of RFS (AUC, 0.83) with logistic regression. The XGBoost classifier achieved the most stable performance with high accuracies compared with other classifiers. The most relevant features for the prediction of RCB class were as follows: changes in lesion size, complete pattern of shrinkage, and mean transit time on DCE-MRI; minimum ADC on DWI; and peritumoral edema on T2-weighted imaging. The most relevant features for prediction of RFS were as follows: volume distribution, mean plasma flow, and mean transit time; DCE-MRI lesion size; minimum, maximum, and mean ADC with DWI. The most relevant features for prediction of DSS were as follows: lesion size, volume distribution, and mean plasma flow on DCE-MRI, and maximum ADC with DWI. ConclusionsMachine learning with mpMRI of the breast enables early prediction of pCR to NAC as well as survival outcomes in breast cancer patients with high accuracy and thus may provide valuable predictive information to guide treatment decisions.

[1]  Samuel J. Magny,et al.  Breast Imaging Reporting and Data System , 2020, Definitions.

[2]  E. Winer,et al.  De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  Karen Drukker,et al.  Most-enhancing tumor volume by MRI radiomics predicts recurrence-free survival “early on” in neoadjuvant treatment of breast cancer , 2018, Cancer Imaging.

[4]  Hiroyuki Abe,et al.  Use of clinical MRI maximum intensity projections for improved breast lesion classification with deep convolutional neural networks , 2018, Journal of medical imaging.

[5]  Natalia Antropova,et al.  A deep feature fusion methodology for breast cancer diagnosis demonstrated on three imaging modality datasets , 2017, Medical physics.

[6]  Lihua Li,et al.  Radiomic analysis of DCE-MRI for prediction of response to neoadjuvant chemotherapy in breast cancer patients. , 2017, European journal of radiology.

[7]  A. Madabhushi,et al.  Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI , 2017, Breast Cancer Research.

[8]  Alioune Ngom,et al.  Predicting Outcomes of Hormone and Chemotherapy in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) Study by Biochemically-inspired Machine Learning , 2017, F1000Research.

[9]  Wolfgang Bogner,et al.  Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer , 2016, European Radiology.

[10]  D. Collins,et al.  Multi-parametric MRI in the early prediction of response to neo-adjuvant chemotherapy in breast cancer: Value of non-modelled parameters. , 2016, European journal of radiology.

[11]  A. Beigzadeh,et al.  Machine learning models in breast cancer survival prediction. , 2016, Technology and health care : official journal of the European Society for Engineering and Medicine.

[12]  Alioune Ngom,et al.  Predicting Outcomes of Hormone and Chemotherapy in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) Study by Biochemically-inspired Machine Learning. , 2016, F1000Research.

[13]  Wei Qian,et al.  Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy. , 2015, Medical physics.

[14]  Ruey-Feng Chang,et al.  Evaluation of the treatment response to neoadjuvant chemotherapy in locally advanced breast cancer using combined magnetic resonance vascular maps and apparent diffusion coefficient , 2015, Journal of magnetic resonance imaging : JMRI.

[15]  Shangang Liu,et al.  Diffusion‐weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy , 2015, Journal of magnetic resonance imaging : JMRI.

[16]  Thomas E Yankeelov,et al.  Multiparametric Magnetic Resonance Imaging for Predicting Pathological Response After the First Cycle of Neoadjuvant Chemotherapy in Breast Cancer , 2015, Investigative radiology.

[17]  C. Geyer,et al.  Pathological Complete Response in Neoadjuvant Treatment of Breast Cancer , 2015, Annals of Surgical Oncology.

[18]  Dimitrios I. Fotiadis,et al.  Machine learning applications in cancer prognosis and prediction , 2014, Computational and structural biotechnology journal.

[19]  E. Rutgers,et al.  Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  John Kornak,et al.  Optimized breast MRI functional tumor volume as a biomarker of recurrence‐free survival following neoadjuvant chemotherapy , 2014, Journal of magnetic resonance imaging : JMRI.

[21]  Gideon Blumenthal,et al.  Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis , 2014, The Lancet.

[22]  Jung Hee Shin,et al.  Role of diffusion-weighted imaging as an adjunct to contrast-enhanced breast MRI in evaluating residual breast cancer following neoadjuvant chemotherapy. , 2014, European journal of radiology.

[23]  Thomas E Yankeelov,et al.  Early assessment of breast cancer response to neoadjuvant chemotherapy by semi-quantitative analysis of high-temporal resolution DCE-MRI: preliminary results. , 2013, Magnetic resonance imaging.

[24]  Xia Li,et al.  Research and applications: Machine learning for predicting the response of breast cancer to neoadjuvant chemotherapy , 2013, J. Am. Medical Informatics Assoc..

[25]  L. Esserman,et al.  Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. , 2012, Radiology.

[26]  Sunil Badve,et al.  Molecular profiling assays in breast cancer: are we ready for prime time? , 2012, Oncology.

[27]  Thomas E Yankeelov,et al.  Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning. , 2011, AMIA ... Annual Symposium proceedings. AMIA Symposium.

[28]  Giancarlo Mauri,et al.  A comparison of machine learning techniques for survival prediction in breast cancer , 2011, BioData Mining.

[29]  Thomas E. Yankeelov,et al.  Current and Future Trends in Magnetic Resonance Imaging Assessments of the Response of Breast Tumors to Neoadjuvant Chemotherapy , 2010, Journal of oncology.

[30]  S. Gautam,et al.  Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. , 2010, Radiology.

[31]  Wolfgang Bogner,et al.  A Combined High Temporal and High Spatial Resolution 3 Tesla MR Imaging Protocol for the Assessment of Breast Lesions: Initial Results , 2009, Investigative radiology.

[32]  Andreas Makris,et al.  Early Changes in Functional Dynamic Magnetic Resonance Imaging Predict for Pathologic Response to Neoadjuvant Chemotherapy in Primary Breast Cancer , 2008, Clinical Cancer Research.

[33]  Christos Hatzis,et al.  Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Hon J. Yu,et al.  MRI measurements of tumor size and pharmacokinetic parameters as early predictors of response in breast cancer patients undergoing neoadjuvant anthracycline chemotherapy , 2007, Journal of magnetic resonance imaging : JMRI.

[35]  Martin O. Leach,et al.  The UK MARIBS Breast Screening Study: Evaluation of radiological features for breast tumour classification in clinical screening with machine learning methods , 2005, Artif. Intell. Medicine.

[36]  Dursun Delen,et al.  Predicting breast cancer survivability: a comparison of three data mining methods , 2005, Artif. Intell. Medicine.

[37]  Robert M. Nishikawa,et al.  A study on several Machine-learning methods for classification of Malignant and benign clustered microcalcifications , 2005, IEEE Transactions on Medical Imaging.

[38]  Osman Ratib,et al.  OsiriX: An Open-Source Software for Navigating in Multidimensional DICOM Images , 2004, Journal of Digital Imaging.

[39]  Edward H. Shortliffe,et al.  The Computer Meets Medicine and Biology: Emergence of a Discipline , 2001 .