Letter to the Editor Regarding Article "Prior to Initiation of Chemotherapy, Can We Predict Breast Tumor Response? Deep Learning Convolutional Neural Networks Approach Using a Breast MRI Tumor Dataset".

The cited article reports on a convolutional neural network trained to predict response to neoadjuvant chemotherapy from pre-treatment breast MRI scans. The proposed algorithm attains impressive performance on the test dataset with a mean Area Under the Receiver-Operating Characteristic curve of 0.98 and a mean accuracy of 88%. In this letter, I raise concerns that the reported results can be explained by inadvertent data leakage between training and test datasets. More precisely, I conjecture that the random split of the full dataset in training and test sets did not occur on a patient level, but rather on the level of 2D MRI slices. This allows the neural network to "memorize" a patient's anatomy and their treatment outcome, as opposed to discovering useful features for treatment response prediction. To provide evidence for these claims, I present results of similar experiments I conducted on a public breast MRI dataset, where I demonstrate that the suspected data leakage mechanism closely reproduces the results reported on in the cited work.

Brunekreef J 《-》

Prior to Initiation of Chemotherapy, Can We Predict Breast Tumor Response? Deep Learning Convolutional Neural Networks Approach Using a Breast MRI Tumor Dataset.

Ha R ，Chin C ，Karcich J ，Liu MZ ，Chang P ，Mutasa S ，Pascual Van Sant E ，Wynn RT ，Connolly E ，Jambawalikar S ... -  《-》

New Explainable Deep CNN Design for Classifying Breast Tumor Response Over Neoadjuvant Chemotherapy.

To reduce breast tumor size before surgery, Neoadjuvant Chemotherapy (NAC) is applied systematically to patients with local breast cancer. However, with the existing clinical protocols, it is not yet possible to have an early prediction of the effect of chemotherapy on a breast tumor. Predicting the response to chemotherapy could reduce toxicity and delay effective treatment. Computational analysis of Dynamic Contrast-Enhanced Magnetic Resonance Images (DCE-MRI) through Deep Convolution Neural Network (CNN) has proved a significant performance in classifying responders and no responder's patients. This study intends to present a new explainable Deep Learning (DL) model predicting the breast cancer response to chemotherapy based on multiple MRI inputs. In this study, a cohort of 42 breast cancer patients who underwent chemotherapy was used to train and validate the proposed DL model. This dataset was provided by the Jules Bordet institute of radiology in Brussels, Belgium. 14 external subjects were used to validate the DL model to classify responding or non-responding patients on temporal DCE-MRI volumes. The model performance was assessed by the Area Under the receiver operating characteristic Curve (AUC), accuracy, and features map visualization according to pathological complete response (Ground truth). The developed deep learning architecture was able to predict the responding breast tumors to chemotherapy treatment in the external validation dataset with an AUC of 0.93 using parallel learning MRI images acquired at different moments. The visual results showed that the most important extracted features from non-responding tumors are in the peripheral and external tumor regions. The model proposed in this study is more efficient compared to those proposed in the literature. Even with a limited training dataset size, the developed multi-input CNN model using DCE-MR images acquired before and following the first chemotherapy was able to predict responding and non-responding tumors with higher accuracy. Thanks to the visualization of the extracted characteristics by the DL model on the responding and non-responding tumors, the latter could be used henceforth in clinical analysis after its evaluation based on more extra data.

Adoui ME ，Drisis S ，Benjelloun M 《Current Medical Imaging》

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

El Adoui M ，Drisis S ，Benjelloun M 《-》

Convolutional Neural Network Using a Breast MRI Tumor Dataset Can Predict Oncotype Dx Recurrence Score.

Oncotype Dx is a validated genetic analysis that provides a recurrence score (RS) to quantitatively predict outcomes in patients who meet the criteria of estrogen receptor positive / human epidermal growth factor receptor-2 negative (ER+/HER2-)/node negative invasive breast carcinoma. Although effective, the test is invasive and expensive, which has motivated this investigation to determine the potential role of radiomics. We hypothesized that convolutional neural network (CNN) can be used to predict Oncotype Dx RS using an MRI dataset. Institutional Review Board (IRB)-approved retrospective study from January 2010 to June 2016. In all, 134 patients with ER+/HER2- invasive ductal carcinoma who underwent both breast MRI and Oncotype Dx RS evaluation. Patients were classified into three groups: low risk (group 1, RS <18), intermediate risk (group 2, RS 18-30), and high risk (group 3, RS >30). 1.5T and 3.0T. Breast MRI, T1 postcontrast. Each breast tumor underwent 3D segmentation. In all, 1649 volumetric slices in 134 tumors (mean 12.3 slices/tumor) were evaluated. A CNN consisted of four convolutional layers and max-pooling layers. Dropout at 50% was applied to the second to last fully connected layer to prevent overfitting. Three-class prediction (group 1 vs. group 2 vs. group 3) and two-class prediction (group 1 vs. group 2/3) models were performed. A 5-fold crossvalidation test was performed using 80% training and 20% testing. Diagnostic accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) area under the curve (AUC) were evaluated. The CNN achieved an overall accuracy of 81% (95% confidence interval [CI] ± 4%) in three-class prediction with specificity 90% (95% CI ± 5%), sensitivity 60% (95% CI ± 6%), and the area under the ROC curve was 0.92 (SD, 0.01). The CNN achieved an overall accuracy of 84% (95% CI ± 5%) in two-class prediction with specificity 81% (95% CI ± 4%), sensitivity 87% (95% CI ± 5%), and the area under the ROC curve was 0.92 (SD, 0.01). It is feasible for current deep CNN architecture to be trained to predict Oncotype DX RS. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:518-524.

Ha R ，Chang P ，Mutasa S ，Karcich J ，Goodman S ，Blum E ，Kalinsky K ，Liu MZ ，Jambawalikar S ... -  《-》