Multi-input deep learning architecture for predicting breast tumor response to chemotherapy using quantitative MR images

Neoadjuvant chemotherapy (NAC) aims to minimize the tumor size before surgery. Predicting response to NAC could reduce toxicity and delays to effective intervention. Computational analysis of dynamic contrast-enhanced magnetic resonance images (DCE-MRI) through deep convolution neural network (CNN) has shown a significant performance to distinguish responders and no responder’s patients. This study intends to present a new deep learning (DL) model predicting the breast cancer response to NAC based on multiple MRI inputs. A cohort of 723 axial slices extracted from 42 breast cancer patients who underwent NAC therapy was used to train and validate the developed DL model. This dataset was provided by our collaborator institute of radiology in Brussels. Fourteen external cases were used to validate the best obtained model to predict pCR based on pre- and post-chemotherapy DCE-MRI. The model performance was assessed by area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and feature map visualization. The developed multi-inputs deep learning architecture was able to predict the pCR to NAC treatment in the validation dataset with an AUC of 0.91 using combined pre- and post-NAC images. The visual results showed that the most important extracted features from non-pCR tumors are in the peripheral region. The proposed method was more productive than the previous ones. Even with a limited training dataset size, the proposed and developed CNN model using DCE-MR images acquired before and after the first chemotherapy was able to classify pCR and non-pCR patients with substantial accuracy. This model could be used hereafter in clinical analysis after its evaluation based on more extra data.

[1]  Sidi Ahmed Mahmoudi,et al.  Cloud-based platform for computer vision applications , 2017, ICSDE.

[2]  D. Chaplin Overview of the immune response. , 2003, The Journal of allergy and clinical immunology.

[3]  W. Kerwin,et al.  Contrast‐enhanced MRI of carotid atherosclerosis: Dependence on contrast agent , 2009, Journal of magnetic resonance imaging : JMRI.

[4]  Min-Ying Su,et al.  Monitoring the Size and Response of Locally Advanced Breast Cancers to Neoadjuvant Chemotherapy (Weekly Paclitaxel and Epirubicin) with Serial Enhanced MRI , 2003, Breast Cancer Research and Treatment.

[5]  Thierry Metens,et al.  Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy , 2016, European Radiology.

[6]  A. Rieber,et al.  Breast MRI for monitoring response of primary breast cancer to neo-adjuvant chemotherapy , 2002, European Radiology.

[7]  S E Harms,et al.  Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging , 1996, Cancer.

[8]  Mohammed Benjelloun,et al.  Deep Learning approach predicting breast tumor response to neoadjuvant treatment using DCE-MRI volumes acquired before and after chemotherapy , 2019, Medical Imaging.

[9]  Abhishek Das,et al.  Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization , 2016, 2017 IEEE International Conference on Computer Vision (ICCV).

[10]  M. Benjelloun,et al.  Early prediction of neoadjuvant treatment outcome in locally advanced breast cancer using parametric response mapping and radial heterogeneity from breast MRI , 2019, Journal of magnetic resonance imaging : JMRI.

[11]  N. Nachar The Mann ‐ Whitney U: A Test for Assessing Whether Two Independent Samples Come from the Same Distribution , 2007 .

[12]  W. Tran,et al.  Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features , 2018, PloS one.

[13]  Alexios Koutsoukas,et al.  Deep-learning: investigating deep neural networks hyper-parameters and comparison of performance to shallow methods for modeling bioactivity data , 2017, Journal of Cheminformatics.

[14]  Brian B. Avants,et al.  N4ITK: Improved N3 Bias Correction , 2010, IEEE Transactions on Medical Imaging.

[15]  Mohammed Benjelloun,et al.  A PRM approach for early prediction of breast cancer response to chemotherapy based on registered MR images , 2018, International Journal of Computer Assisted Radiology and Surgery.

[16]  Jennifer I. Hare,et al.  Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: How do permeability and perfusion vary between human tumours? , 2018, Magnetic resonance imaging.

[17]  Sibel Kul,et al.  Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in the characterization of breast tumors. , 2011, AJR. American journal of roentgenology.

[18]  Christopher Kermorvant,et al.  Dropout Improves Recurrent Neural Networks for Handwriting Recognition , 2013, 2014 14th International Conference on Frontiers in Handwriting Recognition.

[19]  Stylianos Drisis,et al.  Breast Cancer Heterogeneity Analysis as Index of Response to Treatment Using MRI Images: A Review , 2017 .

[20]  Sidi Ahmed Mahmoudi,et al.  MRI Breast Tumor Segmentation Using Different Encoder and Decoder CNN Architectures , 2019, Comput..

[21]  T. Metens,et al.  Total choline quantification measured by 1H MR spectroscopy as early predictor of response after neoadjuvant treatment for locally advanced breast cancer: The impact of immunohistochemical status , 2018, Journal of magnetic resonance imaging : JMRI.

[22]  W. London,et al.  Response Evaluation Criteria in Solid Tumors (RECIST) following neoadjuvant chemotherapy in osteosarcoma , 2018, Pediatric blood & cancer.

[23]  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.

[24]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[25]  Thomas Grill,et al.  Exploring Data Augmentation for Improved Singing Voice Detection with Neural Networks , 2015, ISMIR.

[26]  R. Gillies,et al.  Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy. , 2004, Neoplasia.

[27]  M. Piccart,et al.  Neoadjuvant therapy for breast cancer. , 2015, Annual review of medicine.

[28]  Jeffrey E. Lee,et al.  Characterization of Anthropometric Changes that Occur During Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer , 2015, Annals of Surgical Oncology.

[29]  J. Kładny,et al.  Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients , 2009, Breast Cancer Research and Treatment.

[30]  D. Yee,et al.  Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response with in vivo (1)H MR spectroscopy--a pilot study at 4 T. , 2004, Radiology.

[31]  Mohammed Benjelloun,et al.  Analyzing breast tumor heterogeneity to predict the response to chemotherapy using 3D MR images registration , 2017, ICSDE.

[32]  Luca Maria Gambardella,et al.  Fast image scanning with deep max-pooling convolutional neural networks , 2013, 2013 IEEE International Conference on Image Processing.

[33]  Mohammed Benjelloun,et al.  Predict Breast Tumor Response to Chemotherapy Using a 3D Deep Learning Architecture Applied to DCE-MRI Data , 2019, IWBBIO.