Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

Breast cancer risk prediction combining a convolutional neural network-based mammographic evaluation with clinical factors.

PURPOSE: Deep learning techniques, including convolutional neural networks (CNN), have the potential to improve breast cancer risk prediction compared to traditional risk models. We assessed whether combining a CNN-based mammographic evaluation with clinical factors in the Breast Cancer Surveillance Consortium (BCSC) model improved risk prediction. METHODS: We conducted a retrospective cohort study among 23,467 women, age 35-74, undergoing screening mammography (2014-2018). We extracted electronic health record (EHR) data on risk factors. We identified 121 women who subsequently developed invasive breast cancer at least 1 year after the baseline mammogram. Mammograms were analyzed with a pixel-wise mammographic evaluation using CNN architecture. We used logistic regression models with breast cancer incidence as the outcome and predictors including clinical factors only (BCSC model) or combined with CNN risk score (hybrid model). We compared model prediction performance via area under the receiver operating characteristics curves (AUCs). RESULTS: Mean age was 55.9 years (SD, 9.5) with 9.3% non-Hispanic Black and 36% Hispanic. Our hybrid model did not significantly improve risk prediction compared to the BCSC model (AUC of 0.654 vs 0.624, respectively, p = 0.063). In subgroup analyses, the hybrid model outperformed the BCSC model among non-Hispanic Blacks (AUC 0.845 vs. 0.589; p = 0.026) and Hispanics (AUC 0.650 vs 0.595; p = 0.049). CONCLUSION: We aimed to develop an efficient breast cancer risk assessment method using CNN risk score and clinical factors from the EHR. With future validation in a larger cohort, our CNN model combined with clinical factors may help predict breast cancer risk in a cohort of racially/ethnically diverse women undergoing screening.

Use of a convolutional neural network-based mammographic evaluation to predict breast cancer recurrence among women with hormone receptor-positive operable breast cancer.

PURPOSE: We evaluated whether a novel, fully automated convolutional neural network (CNN)-based mammographic evaluation can predict breast cancer relapse among women with operable hormone receptor (HR)-positive breast cancer. METHODS: We conducted a retrospective cohort study among women with stage I-III, HR-positive unilateral breast cancer diagnosed at Columbia University Medical Center from 2007 to 2017, who received adjuvant endocrine therapy and had at least two mammograms (baseline, annual follow-up) of the contralateral unaffected breast for CNN analysis. We extracted demographics, clinicopathologic characteristics, breast cancer treatments, and relapse status from the electronic health record. Our primary endpoint was change in CNN risk score (range, 0-1). We used two-sample t-tests to assess for difference in mean CNN scores between patients who relapsed vs. remained in remission, and conducted Cox regression analyses to assess for association between change in CNN score and breast cancer-free interval (BCFI), adjusting for known prognostic factors. RESULTS: Among 848 women followed for a median of 59 months, there were 67 (7.9%) breast cancer relapses (36 distant, 25 local, 6 new primaries). There was a significant difference in mean absolute change in CNN risk score from baseline to 1-year follow-up between those who relapsed vs. remained in remission (0.001 vs. - 0.022, p = 0.030). After adjustment for prognostic factors, a 0.01 absolute increase in CNN score at 1-year was significantly associated with BCFI, hazard ratio = 1.05 (95% Confidence Interval 1.01-1.09, p = 0.011). CONCLUSION: Short-term change in the CNN-based breast cancer risk model on adjuvant endocrine therapy predicts breast cancer relapse, and warrants further evaluation in prospective studies.

Deep learning prediction of axillary lymph node status using ultrasound images.

OBJECTIVE: To investigate the ability of our convolutional neural network (CNN) to predict axillary lymph node metastasis using primary breast cancer ultrasound (US) images. METHODS: In this IRB-approved study, 338 US images (two orthogonal images) from 169 patients from 1/2014-12/2016 were used. Suspicious lymph nodes were seen on US and patients subsequently underwent core-biopsy. 64 patients had metastatic lymph nodes. A custom CNN was utilized on 248 US images from 124 patients in the training dataset and tested on 90 US images from 45 patients. The CNN was implemented entirely of 3 × 3 convolutional kernels and linear layers. The 9 convolutional kernels consisted of 6 residual layers, totaling 12 convolutional layers. Feature maps were down-sampled using strided convolutions. Dropout with a 0.5 keep probability and L2 normalization was utilized. Training was implemented by using the Adam optimizer and a final SoftMax score threshold of 0.5 from the average of raw logits from each pixel was used for two class classification (metastasis or not). RESULTS: Our CNN achieved an AUC of 0.72 (SD ± 0.08) in predicting axillary lymph node metastasis from US images in the testing dataset. The model had an accuracy of 72.6% (SD ± 8.4) with a sensitivity and specificity of 65.5% (SD ± 28.6) and 78.9% (SD ± 15.1) respectively. Our algorithm is available to be shared for research use. (https://github.com/stmutasa/MetUS). CONCLUSION: It's feasible to predict axillary lymph node metastasis from US images using a deep learning technique. This can potentially aid nodal staging in patients with breast cancer.

Deep Learning of Computed Tomography Virtual Wedge Resection for Prediction of Histologic Usual Interstitial Pneumonitis.

Rationale: The computed tomography (CT) pattern of definite or probable usual interstitial pneumonia (UIP) can be diagnostic of idiopathic pulmonary fibrosis and may obviate the need for invasive surgical biopsy. Few machine-learning studies have investigated the classification of interstitial lung disease (ILD) on CT imaging, but none have used histopathology as a reference standard.Objectives: To predict histopathologic UIP using deep learning of high-resolution computed tomography (HRCT).Methods: Institutional databases were retrospectively searched for consecutive patients with ILD, HRCT, and diagnostic histopathology from 2011 to 2014 (training cohort) and from 2016 to 2017 (testing cohort). A blinded expert radiologist and pulmonologist reviewed all training HRCT scans in consensus and classified HRCT scans based on the 2018 American Thoracic Society/European Respriatory Society/Japanese Respiratory Society/Latin American Thoracic Association diagnostic criteria for idiopathic pulmonary fibrosis. A convolutional neural network (CNN) was built accepting 4 × 4 × 2 cm virtual wedges of peripheral lung on HRCT as input and outputting the UIP histopathologic pattern. The CNN was trained and evaluated on the training cohort using fivefold cross validation and was then tested on the hold-out testing cohort. CNN and human performance were compared in the training cohort. Logistic regression and survival analyses were performed.Results: The CNN was trained on 221 patients (median age 60 yr; interquartile range [IQR], 53-66), including 71 patients (32%) with UIP or probable UIP histopathologic patterns. The CNN was tested on a separate hold-out cohort of 80 patients (median age 66 yr; IQR, 58-69), including 22 patients (27%) with UIP or probable UIP histopathologic patterns. An average of 516 wedges were generated per patient. The percentage of wedges with CNN-predicted UIP yielded a cross validation area under the curve of 74% for histopathological UIP pattern per patient. The optimal cutoff point for classifying patients on the training cohort was 16.5% of virtual lung wedges with CNN-predicted UIP and resulted in sensitivity and specificity of 74% and 58%, respectively, in the testing cohort. CNN-predicted UIP was associated with an increased risk of death or lung transplantation during cross validation (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P = 0.03).Conclusions: Virtual lung wedge resection in patients with ILD can be used as an input to a CNN for predicting the histopathologic UIP pattern and transplant-free survival.

Dynamic Changes of Convolutional Neural Network-based Mammographic Breast Cancer Risk Score Among Women Undergoing Chemoprevention Treatment.

INTRODUCTION: We investigated whether our convolutional neural network (CNN)-based breast cancer risk model is modifiable by testing it on women who had undergone risk-reducing chemoprevention treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients diagnosed with atypical hyperplasia, lobular carcinoma in situ, or ductal carcinoma in situ at our institution from 2007 to 2015. The clinical characteristics, chemoprevention use, and mammography images were extracted from the electronic health records. We classified two groups according to chemoprevention use. Mammograms were performed at baseline and subsequent follow-up evaluations for input to our CNN risk model. The 2 chemoprevention groups were compared for the risk score change from baseline to follow-up. The change categories included stayed high risk, stayed low risk, increased from low to high risk, and decreased from high to low risk. Unordered polytomous regression models were used for statistical analysis, with P < .05 considered statistically significant. RESULTS: Of 541 patients, 184 (34%) had undergone chemoprevention treatment (group 1) and 357 (66%) had not (group 2). Using our CNN breast cancer risk score, significantly more women in group 1 had shown a decrease in breast cancer risk compared with group 2 (33.7% vs. 22.9%; P < .01). Significantly fewer women in group 1 had an increase in breast cancer risk compared with group 2 (11.4% vs. 20.2%; P < .01). On multivariate analysis, an increase in breast cancer risk predicted by our model correlated negatively with the use of chemoprevention treatment (P = .02). CONCLUSIONS: Our CNN-based breast cancer risk score is modifiable with potential utility in assessing the efficacy of known chemoprevention agents and testing new chemoprevention strategies.

A novel CNN algorithm for pathological complete response prediction using an I-SPY TRIAL breast MRI database.

PURPOSE: To apply our convolutional neural network (CNN) algorithm to predict neoadjuvant chemotherapy (NAC) response using the I-SPY TRIAL breast MRI dataset. METHODS: From the I-SPY TRIAL breast MRI database, 131 patients from 9 institutions were successfully downloaded for analysis. First post-contrast MRI images were used for 3D segmentation using 3D slicer. Our CNN was implemented entirely of 3 × 3 convolutional kernels and linear layers. The convolutional kernels consisted of 6 residual layers, totaling 12 convolutional layers. Dropout with a 0.5 keep probability and L2 normalization was utilized. Training was implemented by using the Adam optimizer. A 5-fold cross validation was used for performance evaluation. Software code was written in Python using the TensorFlow module on a Linux workstation with one NVidia Titan X GPU. RESULTS: Of 131 patients, 40 patients achieved pCR following NAC (group 1) and 91 patients did not achieve pCR following NAC (group 2). Diagnostic accuracy of our CNN two classification model distinguishing patients with pCR vs non-pCR was 72.5 (SD ± 8.4), with sensitivity 65.5% (SD ± 28.1) and specificity of 78.9% (SD ± 15.2). The area under a ROC Curve (AUC) was 0.72 (SD ± 0.08). CONCLUSION: It is feasible to use our CNN algorithm to predict NAC response in patients using a multi-institution dataset.

Prospective Analysis Using a Novel CNN Algorithm to Distinguish Atypical Ductal Hyperplasia From Ductal Carcinoma in Situ in Breast.

INTRODUCTION: We previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm. MATERIALS AND METHODS: In this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The "positive class" was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases. RESULTS: Area under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively. CONCLUSION: Prospectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.

Channel width optimized neural networks for liver and vessel segmentation in liver iron quantification.

INTRODUCTION: MRI T2* relaxometry protocols are often used for Liver Iron Quantification in patients with hemochromatosis. Several methods exist to semi-automatically segment parenchyma and exclude vessels for this calculation. PURPOSE: To determine if inclusion of multiple echoes inputs to Convolutional Neural Networks (CNN) improves automated liver and vessel segmentation in MRI T2* relaxometry protocols and to determine if the resultant segmentations agree with manual segmentations for liver iron quantification analysis. METHODS: Multi echo Gradient Recalled Echo (GRE) MRI sequence for T2* relaxometry was performed for 79 exams on 31 patients with hemochromatosis for iron quantification analysis. 275 axial liver slices were manually segmented as ground truth masks. A batch normalized U-Net with variable input width to incorporate multiple echoes is used for segmentation, using DICE as the accuracy metric. ANOVA is used to evaluate significance of channel width changes in segmentation accuracy. Linear regression is used to model the relationship of channel width on segmentation accuracy. Liver segmentations are applied to relaxometry data to calculate liver T2* yielding liver iron concentration(LIC) derived from literature based calibration curves. Manual and CNN based LIC values are compared with Pearson correlation. Bland altman plots are used to visualize differences between manual and CNN based LIC values. RESULTS: Performance metrics are tested on 55 hold out slices. Linear regression indicates that there is a monotonic increase of DICE with increasing channel depth (p = 0.001) with a slope of 3.61e-3. ANOVA indicates a significant increase segmentation accuracy over single channel starting at 3 channels. Incorporation of all channels results in an average DICE of 0.86, an average increase of 0.07 over single channel. The calculated LIC from CNN segmented livers agrees well with manual segmentation (R = 0.998, slope = 0.914, p«0.001), with an average absolute difference 0.27 ± 0.99 mg Fe/g or 1.34 ± 4.3%. CONCLUSION: More input echoes yields higher model accuracy until the noise floor. Echos beyond the first three echo times in GRE based T2* relaxometry do not contribute significant information for segmentation of liver for LIC calculation. Deep learning models with three channel width allow for generalization of model to protocols of more than three echoes, effectively a universal requirement for relaxometry. Deep learning segmentations achieve a good accuracy compared with manual segmentations with minimal preprocessing. Liver iron values calculated from hand segmented liver and Neural network segmented liver were not statistically different from each other.

Potential Role of Convolutional Neural Network Based Algorithm in Patient Selection for DCIS Observation Trials Using a Mammogram Dataset.

RATIONALE AND OBJECTIVES: We investigated the feasibility of utilizing convolutional neural network (CNN) for predicting patients with pure Ductal Carcinoma In Situ (DCIS) versus DCIS with invasion using mammographic images. MATERIALS AND METHODS: An IRB-approved retrospective study was performed. 246 unique images from 123 patients were used for our CNN algorithm. In total, 164 images in 82 patients diagnosed with DCIS by stereotactic-guided biopsy of calcifications without any upgrade at the time of surgical excision (pure DCIS group). A total of 82 images in 41 patients with mammographic calcifications yielding occult invasive carcinoma as the final upgraded diagnosis on surgery (occult invasive group). Two standard mammographic magnification views (CC and ML/LM) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D Slicer and resized to fit a 128 × 128 pixel bounding box. A 15 hidden layer topology was used to implement the neural network. The network architecture contained five residual layers and dropout of 0.25 after each convolution. Five-fold cross validation was performed using training set (80%) and validation set (20%). Code was implemented in open source software Keras with TensorFlow on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: Our CNN algorithm for predicting patients with pure DCIS achieved an overall diagnostic accuracy of 74.6% (95% CI, ±5) with area under the ROC curve of 0.71 (95% CI, ±0.04), specificity of 91.6% (95% CI, ±5%) and sensitivity of 49.4% (95% CI, ±6%). CONCLUSION: It's feasible to apply CNN to distinguish pure DCIS from DCIS with invasion with high specificity using mammographic images.

Accuracy of Distinguishing Atypical Ductal Hyperplasia From Ductal Carcinoma In Situ With Convolutional Neural Network-Based Machine Learning Approach Using Mammographic Image Data.

OBJECTIVE. The purpose of this study was to test the hypothesis that convolutional neural networks can be used to predict which patients with pure atypical ductal hyperplasia (ADH) may be safely monitored rather than undergo surgery. MATERIALS AND METHODS. A total of 298 unique images from 149 patients were used for our convolutional neural network algorithm. A total of 134 images from 67 patients with ADH that had been diagnosed by stereotactic-guided biopsy of calcifications but had not been upgraded to ductal carcinoma in situ or invasive cancer at the time of surgical excision. A total of 164 images from 82 patients with mammographic calcifications indicated that ductal carcinoma in situ was the final diagnosis. Two standard mammographic magnification views of the calcifications (a craniocaudal view and a mediolateral or lateromedial view) were used for analysis. Calcifications were segmented using an open-source software platform and images were resized to fit a bounding box of 128 × 128 pixels. A topology with 15 hidden layers was used to implement the convolutional neural network. The network architecture contained five residual layers and dropout of 0.25 after each convolution. Patients were randomly separated into a training-and-validation set (80% of patients) and a test set (20% of patients). Code was implemented using open-source software on a workstation with an open-source operating system and a graphics card. RESULTS. The AUC value was 0.86 (95% CI, ± 0.03) for the test set. Aggregate sensitivity and specificity were 84.6% (95% CI, ± 4.0%) and 88.2% (95% CI, ± 3.0%), respectively. Diagnostic accuracy was 86.7% (95% CI, ± 2.9). CONCLUSION. It is feasible to apply convolutional neural networks to distinguish pure atypical ductal hyperplasia from ductal carcinoma in situ with the use of mammographic images. A larger dataset will likely result in further improvement of our prediction model.

Predicting Breast Cancer Molecular Subtype with MRI Dataset Utilizing Convolutional Neural Network Algorithm.

To develop a convolutional neural network (CNN) algorithm that can predict the molecular subtype of a breast cancer based on MRI features. An IRB-approved study was performed in 216 patients with available pre-treatment MRIs and immunohistochemical staining pathology data. First post-contrast MRI images were used for 3D segmentation using 3D slicer. A CNN architecture was designed with 14 layers. Residual connections were used in the earlier layers to allow stabilization of gradients during backpropagation. Inception style layers were utilized deeper in the network to allow learned segregation of more complex feature mappings. Extensive regularization was utilized including dropout, L2, feature map dropout, and transition layers. The class imbalance was addressed by doubling the input of underrepresented classes and utilizing a class sensitive cost function. Parameters were tuned based on a 20% validation group. A class balanced holdout set of 40 patients was utilized as the testing set. Software code was written in Python using the TensorFlow module on a Linux workstation with one NVidia Titan X GPU. Seventy-four luminal A, 106 luminal B, 13 HER2+, and 23 basal breast tumors were evaluated. Testing set accuracy was measured at 70%. The class normalized macro area under receiver operating curve (ROC) was measured at 0.853. Non-normalized micro-aggregated AUC was measured at 0.871, representing improved discriminatory power for the highly represented Luminal A and Luminal B subtypes. Aggregate sensitivity and specificity was measured at 0.603 and 0.958. MRI analysis of breast cancers utilizing a novel CNN can predict the molecular subtype of breast cancers. Larger data sets will likely improve our model.

Fully Automated Convolutional Neural Network Method for Quantification of Breast MRI Fibroglandular Tissue and Background Parenchymal Enhancement.

The aim of this study is to develop a fully automated convolutional neural network (CNN) method for quantification of breast MRI fibroglandular tissue (FGT) and background parenchymal enhancement (BPE). An institutional review board-approved retrospective study evaluated 1114 breast volumes in 137 patients using T1 precontrast, T1 postcontrast, and T1 subtraction images. First, using our previously published method of quantification, we manually segmented and calculated the amount of FGT and BPE to establish ground truth parameters. Then, a novel 3D CNN modified from the standard 2D U-Net architecture was developed and implemented for voxel-wise prediction whole breast and FGT margins. In the collapsing arm of the network, a series of 3D convolutional filters of size 3 × 3 × 3 are applied for standard CNN hierarchical feature extraction. To reduce feature map dimensionality, a 3 × 3 × 3 convolutional filter with stride 2 in all directions is applied; a total of 4 such operations are used. In the expanding arm of the network, a series of convolutional transpose filters of size 3 × 3 × 3 are used to up-sample each intermediate layer. To synthesize features at multiple resolutions, connections are introduced between the collapsing and expanding arms of the network. L2 regularization was implemented to prevent over-fitting. Cases were separated into training (80%) and test sets (20%). Fivefold cross-validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX Titan X GPU. In the test set, the fully automated CNN method for quantifying the amount of FGT yielded accuracy of 0.813 (cross-validation Dice score coefficient) and Pearson correlation of 0.975. For quantifying the amount of BPE, the CNN method yielded accuracy of 0.829 and Pearson correlation of 0.955. Our CNN network was able to quantify FGT and BPE within an average of 0.42 s per MRI case. A fully automated CNN method can be utilized to quantify MRI FGT and BPE. Larger dataset will likely improve our model.

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

BACKGROUND: 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. HYPOTHESIS: We hypothesized that convolutional neural network (CNN) can be used to predict Oncotype Dx RS using an MRI dataset. STUDY TYPE: Institutional Review Board (IRB)-approved retrospective study from January 2010 to June 2016. POPULATION: 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). FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T. Breast MRI, T1 postcontrast. ASSESSMENT: 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. STATISTICAL TESTS: 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. RESULTS: 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). DATA CONCLUSION: It is feasible for current deep CNN architecture to be trained to predict Oncotype DX RS. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:518-524.

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

We hypothesize that convolutional neural networks (CNN) can be used to predict neoadjuvant chemotherapy (NAC) response using a breast MRI tumor dataset prior to initiation of chemotherapy. An institutional review board-approved retrospective review of our database from January 2009 to June 2016 identified 141 locally advanced breast cancer patients who (1) underwent breast MRI prior to the initiation of NAC, (2) successfully completed adriamycin/taxane-based NAC, and (3) underwent surgical resection with available final surgical pathology data. Patients were classified into three groups based on their NAC response confirmed on final surgical pathology: complete (group 1), partial (group 2), and no response/progression (group 3). A total of 3107 volumetric slices of 141 tumors were evaluated. Breast tumor was identified on first T1 postcontrast dynamic images and underwent 3D segmentation. CNN consisted of ten convolutional layers, four max-pooling layers, and dropout of 50% after a fully connected layer. Dropout, augmentation, and L2 regularization were implemented to prevent overfitting of data. Non-linear functions were modeled by a rectified linear unit (ReLU). Batch normalization was used between the convolutional and ReLU layers to limit drift of layer activations during training. A three-class neoadjuvant prediction model was evaluated (group 1, group 2, or group 3). The CNN achieved an overall accuracy of 88% in three-class prediction of neoadjuvant treatment response. Three-class prediction discriminating one group from the other two was analyzed. Group 1 had a specificity of 95.1% ± 3.1%, sensitivity of 73.9% ± 4.5%, and accuracy of 87.7% ± 0.6%. Group 2 (partial response) had a specificity of 91.6% ± 1.3%, sensitivity of 82.4% ± 2.7%, and accuracy of 87.7% ± 0.6%. Group 3 (no response/progression) had a specificity of 93.4% ± 2.9%, sensitivity of 76.8% ± 5.7%, and accuracy of 87.8% ± 0.6%. It is feasible for current deep CNN architectures to be trained to predict NAC treatment response using a breast MRI dataset obtained prior to initiation of chemotherapy. Larger dataset will likely improve our prediction model.

Convolutional Neural Network Based Breast Cancer Risk Stratification Using a Mammographic Dataset.

RATIONALE AND OBJECTIVES: We propose a novel convolutional neural network derived pixel-wise breast cancer risk model using mammographic dataset. MATERIALS AND METHODS: An institutional review board approved retrospective case-control study of 1474 mammographic images was performed in average risk women. First, 210 patients with new incidence of breast cancer were identified. Mammograms from these patients prior to developing breast cancer were identified and made up the case group [420 bilateral craniocaudal mammograms]. The control group consisted of 527 patients without breast cancer from the same time period. Prior mammograms from these patients made up the control group [1054 bilateral craniocaudal mammograms]. A convolutional neural network (CNN) architecture was designed for pixel-wise breast cancer risk prediction. Briefly, each mammogram was normalized as a map of z-scores and resized to an input image size of 256 × 256. Then a contracting and expanding fully convolutional CNN architecture was composed entirely of 3 × 3 convolutions, a total of four strided convolutions instead of pooling layers, and symmetric residual connections. L2 regularization and augmentation methods were implemented to prevent overfitting. Cases were separated into training (80%) and test sets (20%). A 5-fold cross validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: The average age of patients between the case and the control groups was not statistically different [case: 57.4years (SD, 10.4) and control: 58.2years (SD, 10.9), p = 0.33]. Breast Density (BD) was significantly higher in the case group [2.39 (SD, 0.7)] than the control group [1.98 (SD, 0.75), p < 0.0001]. On multivariate logistic regression analysis, both CNN pixel-wise mammographic risk model and BD were significant independent predictors of breast cancer risk (p < 0.0001). The CNN risk model showed greater predictive potential [OR = 4.42 (95% CI, 3.4-5.7] compared to BD [OR = 1.67 (95% CI, 1.4-1.9). The CNN risk model achieved an overall accuracy of 72% (95%CI, 69.8-74.4) in predicting patients in the case group. CONCLUSION: Novel pixel-wise mammographic breast evaluation using a CNN architecture can stratify breast cancer risk, independent of the BD. Larger dataset will likely improve our model.

Prediction of Lymph Node Maximum Standardized Uptake Value in Patients With Cancer Using a 3D Convolutional Neural Network: A Proof-of-Concept Study.

OBJECTIVE: The purpose of this study is to determine whether a convolutional neural network (CNN) can predict the maximum standardized uptake value (SUVmax) of lymph nodes in patients with cancer using the unenhanced CT images from a PET/CT examination, thus providing a proof of concept for potentially using deep learning to diagnose nodal involvement. MATERIALS AND METHODS: Consecutive initial staging PET/CT scans obtained in 2017 for patients with pathologically proven malignancy were collected. Two blinded radiologists selected one to 10 lymph nodes from the unenhanced CT portion of each PET/CT examination. The SUVmax of the lymph nodes was recorded. Lymph nodes were cropped and used with the primary tumor histology type as input for a novel 3D CNN with predicted SUVmax as the output. The CNN was trained using one cohort and tested using a separate cohort. An SUVmax of 2.5 or greater was defined as FDG avid. Two blinded radiologists separately classified lymph nodes as FDG avid or not FDG avid on the basis of unenhanced CT images and separately using a short-axis measurement cutoff of 1 cm. Logistic regression analysis was performed. RESULTS: A total of 400 lymph nodes (median SUVmax, 6.8 [interquartile range {IQR}, 2.7-11.6]; median short-axis, 1.1 cm [IQR, 0.9-1.6 cm]) in 136 patients were used for training. A total of 164 lymph nodes (median SUVmax, 3.5 [IQR, 1.9-8.6]; median short-axis, 1.0 cm [IQR, 0.7-1.4 cm]) in 49 patients were used for testing. The predicted SUVmax was associated with the real SUVmax (ß estimate = 0.83, p < 0.0001). The predicted SUVmax was associated with FDG avidity (p < 0.0001), with an ROC AUC value of 0.85, and it improved when combined with radiologist qualitative assessment and short-axis criteria. CONCLUSION: A CNN is able to predict with moderate accuracy the SUVmax of lymph nodes, as determined from the unenhanced CT images and tumor histology subtype for patients with cancer.

Predicting Post Neoadjuvant Axillary Response Using a Novel Convolutional Neural Network Algorithm.

OBJECTIVES: In the postneoadjuvant chemotherapy (NAC) setting, conventional radiographic complete response (rCR) is a poor predictor of pathologic complete response (pCR) of the axilla. We developed a convolutional neural network (CNN) algorithm to better predict post-NAC axillary response using a breast MRI dataset. METHODS: An institutional review board-approved retrospective study from January 2009 to June 2016 identified 127 breast cancer patients who: (1) underwent breast MRI before the initiation of NAC; (2) successfully completed Adriamycin/Taxane-based NAC; and (3) underwent surgery, including sentinel lymph node evaluation/axillary lymph node dissection with final surgical pathology data. Patients were classified into pathologic complete response (pCR) of the axilla group and non-pCR group based on surgical pathology. Breast MRI performed before NAC was used. Tumor was identified on first T1 postcontrast images underwent 3D segmentation. A total of 2811 volumetric slices of 127 tumors were evaluated. CNN consisted of 10 convolutional layers, 4 max-pooling layers. Dropout, augmentation and L2 regularization were implemented to prevent overfitting of data. RESULTS: On final surgical pathology, 38.6% (49/127) of the patients achieved pCR of the axilla (group 1), and 61.4% (78/127) of the patients did not with residual metastasis detected (group 2). For predicting axillary pCR, our CNN algorithm achieved an overall accuracy of 83% (95% confidence interval [CI] ± 5) with sensitivity of 93% (95% CI ± 6) and specificity of 77% (95% CI ± 4). Area under the ROC curve (0.93, 95% CI ± 0.04). CONCLUSIONS: It is feasible to use CNN architecture to predict post NAC axillary pCR. Larger data set will likely improve our prediction model.

Axillary Lymph Node Evaluation Utilizing Convolutional Neural Networks Using MRI Dataset.

The aim of this study is to evaluate the role of convolutional neural network (CNN) in predicting axillary lymph node metastasis, using a breast MRI dataset. An institutional review board (IRB)-approved retrospective review of our database from 1/2013 to 6/2016 identified 275 axillary lymph nodes for this study. Biopsy-proven 133 metastatic axillary lymph nodes and 142 negative control lymph nodes were identified based on benign biopsies (100) and from healthy MRI screening patients (42) with at least 3 years of negative follow-up. For each breast MRI, axillary lymph node was identified on first T1 post contrast dynamic images and underwent 3D segmentation using an open source software platform 3D Slicer. A 32 × 32 patch was then extracted from the center slice of the segmented tumor data. A CNN was designed for lymph node prediction based on each of these cropped images. The CNN consisted of seven convolutional layers and max-pooling layers with 50% dropout applied in the linear layer. In addition, data augmentation and L2 regularization were performed to limit overfitting. Training was implemented using the Adam optimizer, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. Code for this study was written in Python using the TensorFlow module (1.0.0). Experiments and CNN training were done on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Two class axillary lymph node metastasis prediction models were evaluated. For each lymph node, a final softmax score threshold of 0.5 was used for classification. Based on this, CNN achieved a mean five-fold cross-validation accuracy of 84.3%. It is feasible for current deep CNN architectures to be trained to predict likelihood of axillary lymph node metastasis. Larger dataset will likely improve our prediction model and can potentially be a non-invasive alternative to core needle biopsy and even sentinel lymph node evaluation.

Genetic dysregulation in recurrent respiratory papillomatosis.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a devastating disease, caused by infection of the upper aerodigestive tract with human papillomavirus types 6 and 11. There is no cure for RRP, and surgical removal is the mainstay of treatment. The purpose of this project was to compare genes of cell cycle, apoptosis, and inflammatory cytokines in laryngeal papilloma versus normal tissue for a better understanding of the molecular mechanisms of the disease to discover novel therapies. STUDY DESIGN: Basic science research study. METHODS: Papilloma tissue was obtained from patients requiring surgical debridement. For comparison, normal mucosa was obtained from the excised uvula of patients undergoing uvulopalatopharyngoplasty. Total RNA was extracted from both groups and then probed using customized reverse transcriptase real time polymerase chain reaction gene arrays. RESULTS: The custom arrays examine expression of 84 separate genes within the cell cycle, apoptosis, and inflammatory cytokine pathways. Our findings based on 11 papilloma samples run in comparison to normal mucosa shows that the MCL-1 gene of the apoptosis pathway is significantly downregulated. cytokine genes IL1-A, IL-8, IL-18, and IL-31 are also significantly dysregulated. CONCLUSIONS: Genes of cell cycle and apoptosis are generally upregulated and downregulated, respectively, as expected in papilloma tissue, with MCL-1 achieving significance when compared to normal tissue. The finding of particular interest is that inflammatory cytokine genes were significantly downregulated, including IL1-A, IL-18, and IL-31. This finding may explain why patients infected with the virus are unable to mediate a T-cell immune clearance of their disease.