Breast MRI radiomics for the pretreatment prediction of response to neoadjuvant chemotherapy in node-positive breast cancer patients

Abstract. The purpose of this study was to evaluate breast MRI radiomics in predicting, prior to any treatment, the response to neoadjuvant chemotherapy (NAC) in patients with invasive lymph node (LN)-positive breast cancer for two tasks: (1) prediction of pathologic complete response and (2) prediction of post-NAC LN status. Our study included 158 patients, with 19 showing post-NAC complete pathologic response (pathologic TNM stage T0,N0,MX) and 139 showing incomplete response. Forty-two patients were post-NAC LN-negative, and 116 were post-NAC LN-positive. We further analyzed prediction of response by hormone receptor subtype of the primary cancer (77 hormone receptor-positive, 39 HER2-enriched, 38 triple negative, and 4 cancers with unknown receptor status). Only pre-NAC MRIs underwent computer analysis, initialized by an expert breast radiologist indicating index cancers and metastatic axillary sentinel LNs on DCE-MRI images. Forty-nine computer-extracted radiomics features were obtained, both for the primary cancers and for the metastatic sentinel LNs. Since the dataset contained MRIs acquired at 1.5 T and at 3.0 T, we eliminated features affected by magnet strength using the Mann–Whitney U-test with the null-hypothesis that 1.5 T and 3.0 T samples were selected from populations having the same distribution. Bootstrapping and ROC analysis were used to assess performance of individual features in the two classification tasks. Eighteen features appeared unaffected by magnet strength. Pre-NAC tumor features generally appeared uninformative in predicting response to therapy. In contrast, some pre-NAC LN features were able to predict response: two pre-NAC LN features were able to predict pathologic complete response (area under the ROC curve (AUC) up to 0.82 [0.70; 0.88]), and another two were able to predict post-NAC LN-status (AUC up to 0.72 [0.62; 0.77]), respectively. In the analysis by a hormone receptor subtype, several potentially useful features were identified for predicting response to therapy in the hormone receptor-positive and HER2-enriched cancers.

[1]  M. Giger,et al.  Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics. , 2004, Medical physics.

[2]  Maryellen L. Giger,et al.  Robustness of radiomic breast features of benign lesions and luminal A cancers across MR magnet strengths , 2018, Medical Imaging.

[3]  Maryellen L. Giger,et al.  Breast MRI radiomics for the pre-treatment prediction of response to neoadjuvant chemotherapy in node-positive breast cancer patients , 2019, Medical Imaging.

[4]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[5]  Ruijiang Li,et al.  Intratumoral Spatial Heterogeneity at Perfusion MR Imaging Predicts Recurrence-free Survival in Locally Advanced Breast Cancer Treated with Neoadjuvant Chemotherapy. , 2018, Radiology.

[6]  Yemi Kim,et al.  Predicting neo‐adjuvant chemotherapy response and progression‐free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F‐18 FDG PET/CT and diffusion‐weighted MR imaging , 2019, The breast journal.

[7]  Maryellen L. Giger,et al.  A Fuzzy C-Means (FCM)-Based Approach for Computerized Segmentation of Breast Lesions in Dynamic Contrast-Enhanced MR Images1 , 2006 .

[8]  Oliver Geier,et al.  Diffusion-weighted magnetic resonance imaging for pretreatment prediction and monitoring of treatment response of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy , 2010, Acta oncologica.

[9]  Steinar Lundgren,et al.  Predicting survival and early clinical response to primary chemotherapy for patients with locally advanced breast cancer using DCE‐MRI , 2009, Journal of magnetic resonance imaging : JMRI.

[10]  Li Lan,et al.  Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers. , 2010, Academic radiology.

[11]  Nola Hylton,et al.  Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  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.

[13]  Ruijiang Li,et al.  Intratumor partitioning and texture analysis of dynamic contrast‐enhanced (DCE)‐MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy , 2016, Journal of magnetic resonance imaging : JMRI.

[14]  Maciej A. Mazurowski,et al.  Multivariate machine learning models for prediction of pathologic response to neoadjuvant therapy in breast cancer using MRI features: a study using an independent validation set , 2018, Breast Cancer Research and Treatment.

[15]  M. Giger,et al.  A fuzzy c-means (FCM)-based approach for computerized segmentation of breast lesions in dynamic contrast-enhanced MR images. , 2006, Academic radiology.

[16]  Xiao-Ting Li,et al.  Predictive value of DCE-MRI for early evaluation of pathological complete response to neoadjuvant chemotherapy in resectable primary breast cancer: A single-center prospective study. , 2016, Breast.

[17]  Roger K C Ngan Management of hormone-receptor positive human epidermal receptor 2 negative advanced or metastatic breast cancers. , 2018, Annals of translational medicine.

[18]  M. Giger,et al.  Automatic identification and classification of characteristic kinetic curves of breast lesions on DCE-MRI. , 2006, Medical physics.

[19]  M L Giger,et al.  Computerized analysis of breast lesions in three dimensions using dynamic magnetic-resonance imaging. , 1998, Medical physics.

[20]  M. Giger,et al.  Volumetric texture analysis of breast lesions on contrast‐enhanced magnetic resonance images , 2007, Magnetic resonance in medicine.

[21]  M. Colleoni,et al.  Optimal management of luminal breast cancer: how much endocrine therapy is long enough? , 2018, Therapeutic advances in medical oncology.

[22]  Xiaobo Zhou,et al.  Preoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Using Mammography-Based Radiomics Method , 2019, Scientific Reports.

[23]  Ruijiang Li,et al.  Integrating Tumor and Nodal Imaging Characteristics at Baseline and Mid-Treatment Computed Tomography Scans to Predict Distant Metastasis in Oropharyngeal Cancer Treated With Concurrent Chemoradiotherapy. , 2019, International journal of radiation oncology, biology, physics.

[24]  T. Helbich,et al.  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 , 2019, Investigative radiology.

[25]  C. Metz Basic principles of ROC analysis. , 1978, Seminars in nuclear medicine.

[26]  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.

[27]  Ovidio Salvetti,et al.  Investigating the Role of Model-Based and Model-Free Imaging Biomarkers as Early Predictors of Neoadjuvant Breast Cancer Therapy Outcome , 2019, IEEE Journal of Biomedical and Health Informatics.

[28]  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.

[29]  Ying Li,et al.  Diffusion-weighted MR imaging in prediction of response to neoadjuvant chemotherapy in patients with breast cancer , 2017, Oncotarget.

[30]  Chuan Huang,et al.  Preoperative prediction of sentinel lymph node metastasis in breast cancer by radiomic signatures from dynamic contrast‐enhanced MRI , 2018, Journal of magnetic resonance imaging : JMRI.

[31]  Mitchell D Schnall,et al.  Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL. , 2016, Radiology.

[32]  Zaiyi Liu,et al.  Radiomics of Multiparametric MRI for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer: A Multicenter Study , 2019, Clinical Cancer Research.

[33]  Massimo Cristofanilli,et al.  Comparing the Performances of Magnetic Resonance Imaging Size vs Pharmacokinetic Parameters to Predict Response to Neoadjuvant Chemotherapy and Survival in Patients With Breast Cancer. , 2019, Current problems in diagnostic radiology.

[34]  Lubomir M. Hadjiiski,et al.  Classifier performance prediction for computer-aided diagnosis using a limited dataset. , 2008, Medical physics.