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A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

ABSTRACT: Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

SUBMITTER: Tadayyon H

PROVIDER: S-EPMC5388850 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

Tadayyon Hadi H Sannachi Lakshmanan L Gangeh Mehrdad J MJ Kim Christina C Ghandi Sonal S Trudeau Maureen M Pritchard Kathleen K Tran William T WT Slodkowska Elzbieta E Sadeghi-Naini Ali A Czarnota Gregory J GJ

Scientific reports 20170412

Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS ...[more]

PMID: 28401902

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Project description:BackgroundPathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer.MethodsThe study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.ResultsOf the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology.ConclusionsThis work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients.

Project description:BackgroundAngiogenic activity of cancerous breast tumors can be impacted by neoadjuvant chemotherapy (NAC), thus potentially serving as a marker for response monitoring. While different imaging modalities can aid in evaluation of tumoral vascular changes, ultrasound-based approaches are particularly suitable for clinical use due to their availability and noninvasiveness. In this paper, we make use of quantitative high-definition microvasculature imaging (qHDMI) based on contrast-free ultrasound for assessment of NAC response in breast cancer patients.MethodsPatients with invasive breast cancer recommended treatment with NAC were included in the study and ultrafast ultrasound data were acquired at pre-NAC, mid-NAC, and post-NAC time points. Data acquisitions also took place at two additional timepoints - at two and four weeks after NAC initiation in a subset of patients. Ultrasound data frames were processed within the qHDMI framework to visualize the microvasculature in and around the breast tumors. Morphological analyses on the microvasculature structure were performed to obtain 12 qHDMI biomarkers. Pathology from surgery classified response using residual cancer burden (RCB) and was used to designate patients as responders (RCB 0/I) and non-responders (RCB II/III). Distributions of imaging biomarkers across the two groups were analyzed using Wilcoxon rank-sum test. The trajectories of biomarker values over time were investigated and linear mixed effects models were used to evaluate interactions between time and group for each biomarker.ResultsOf the 53 patients included in the study, 32 (60%) were responders based on their RCB status. The results of linear mixed effects model analysis showed statistically significant interactions between group and time in six out of the 12 qHDMI biomarkers, indicating differences in trends of microvascular morphological features by responder status. In particular, vessel density (p-value: 0.023), maximum tortuosity (p-value: 0.049), maximum diameter (p-value: 0.002), fractal dimension (p-value: 0.002), mean Murray's deviation (p-value: 0.034), and maximum Murray's deviation (p-value: 0.022) exhibited significantly different trends based on responder status.ConclusionsWe observed microvasculature changes in response to NAC in breast cancer patients using qHDMI as an objective and quantitative contrast-free ultrasound framework. These finding suggest qHDMI may be effective in identifying early response to NAC.

Project description:Locally advanced breast cancer (LABC) is a severe type of cancer with a poor prognosis, despite advancements in therapy. As the disease is often inoperable, current guidelines suggest upfront aggressive neoadjuvant chemotherapy (NAC). Complete pathological response to chemotherapy is linked to improved survival, but conventional clinical assessments like physical exams, mammography, and imaging are limited in detecting early response. Early detection of tissue response can improve complete pathological response and patient survival while reducing exposure to ineffective and potentially harmful treatments. A rapid, cost-effective modality without the need for exogenous contrast agents would be valuable for evaluating neoadjuvant therapy response. Conventional ultrasound provides information about tissue echogenicity, but image comparisons are difficult due to instrument-dependent settings and imaging parameters. Quantitative ultrasound (QUS) overcomes this by using normalized power spectra to calculate quantitative metrics. This study used a novel transfer learning-based approach to predict LABC response to neoadjuvant chemotherapy using QUS imaging at pre-treatment. Using data from 174 patients, QUS parametric images of breast tumors with margins were generated. The ground truth response to therapy for each patient was based on standard clinical and pathological criteria. The Residual Network (ResNet) deep learning architecture was used to extract features from the parametric QUS maps. This was followed by SelectKBest and Synthetic Minority Oversampling (SMOTE) techniques for feature selection and data balancing, respectively. The Support Vector Machine (SVM) algorithm was employed to classify patients into two distinct categories: nonresponders (NR) and responders (RR). Evaluation results on an unseen test set demonstrate that the transfer learning-based approach using spectral slope parametric maps had the best performance in the identification of nonresponders with precision, recall, F1-score, and balanced accuracy of 100, 71, 83, and 86%, respectively. The transfer learning-based approach has many advantages over conventional deep learning methods since it reduces the need for large image datasets for training and shortens the training time. The results of this study demonstrate the potential of transfer learning in predicting LABC response to neoadjuvant chemotherapy before the start of treatment using quantitative ultrasound imaging. Prediction of NAC response before treatment can aid clinicians in customizing ineffectual treatment regimens for individual patients.

Project description:PurposeWe develop a multi-centric response predictive model using QUS spectral parametric imaging and novel texture-derivate methods for determining tumour responses to neoadjuvant chemotherapy (NAC) prior to therapy initiation.Materials and methodsQUS Spectroscopy provided parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average-scatterer-diameter (ASD), and average-acoustic-concentration (AAC) in 78 patients with locally advanced breast cancer (LABC) undergoing NAC. Ultrasound radiofrequency data were collected from Sunnybrook Health Sciences Center (SHSC), University of Texas MD Anderson Cancer Center (MD-ACC), and St. Michaels Hospital (SMH) using two different systems. Texture analysis was used to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS, texture- and texture-derivate parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis for developing a response predictive model to classify responders versus non-responders. Model performance was assessed using leave-one-out cross-validation. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest-neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated.ResultsA combination of tumour core and margin classification resulted in a peak response prediction performance of 88% sensitivity, 78% specificity, 84% accuracy, 0.86 AUC, 84% PPV, and 83% NPV, achieved using the SVM-RBF classification algorithm. Other parameters and classifiers performed less well running from 66% to 80% accuracy.ConclusionsA QUS-based framework and novel texture-derivative method enabled accurate prediction of responses to NAC. Multi-centric response predictive model provides indications of the robustness of the approach to variations due to different ultrasound systems and acquisition parameters.

Dataset Information

A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

Publications

A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

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