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Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

ABSTRACT: Pathological 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.The 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.Of 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.This 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.

SUBMITTER: Sannachi L

PROVIDER: S-EPMC5751990 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNeoadjuvant chemotherapy (NAC) is used in patients with breast cancer to reduce tumor focus, metastatic risk, and patient mortality. Monitoring NAC effects is necessary to capture resistant patients and stop or change treatment. The existing methods for evaluating NAC results have some limitations. The aim of this study was to assess the tumor response at an early stage, after the first doses of the NAC, based on the variability of the backscattered ultrasound energy, and backscatter statistics. The backscatter statistics has not previously been used to monitor NAC effects.MethodsThe B-mode ultrasound images and raw radio frequency data from breast tumors were obtained using an ultrasound scanner before chemotherapy and 1 week after each NAC cycle. The study included twenty-four malignant breast cancers diagnosed in sixteen patients and qualified for neoadjuvant treatment before surgery. The shape parameter of the homodyned K distribution and integrated backscatter, along with the tumor size in the longest dimension, were determined based on ultrasound data and used as markers for NAC response. Cancer tumors were assigned to responding and non-responding groups, according to histopathological evaluation, which was a reference in assessing the utility of markers. Statistical analysis was performed to rate the ability of markers to predict the final NAC response based on data obtained after subsequent therapeutic doses.ResultsStatistically significant differences (p<0.05) between groups were obtained after 2, 3, 4, and 5 doses of NAC for quantitative ultrasound markers and after 5 doses for the assessment based on maximum tumor dimension. Statistical analysis showed that, after the second and third NAC courses the classification based on integrated backscatter marker was characterized by an AUC of 0.69 and 0.82, respectively. The introduction of the second quantitative marker describing the statistical properties of scattering increased the corresponding AUC values to 0.82 and 0.91.ConclusionsQuantitative ultrasound information can characterize the tumor's pathological response better and at an earlier stage of therapy than the assessment of the reduction of its dimensions. The introduction of statistical parameters of ultrasonic backscatter to monitor the effects of chemotherapy can increase the effectiveness of monitoring and contribute to a better personalization of NAC therapy.

Project description:AimCancer treatments with radiation present a challenging physical toll for patients, which can be justified by the potential reduction in cancerous tissue with treatment. However, there remain patients for whom treatments do not yield desired outcomes. Radiomics involves using biomedical images to determine imaging features which, when used in tandem with retrospective treatment outcomes, can train machine learning (ML) classifiers to create predictive models. In this study we investigated whether pre-treatment imaging features from index lymph node (LN) quantitative ultrasound (QUS) scans parametric maps of head & neck (H&N) cancer patients can provide predictive information about treatment outcomes.Methods72 H&N cancer patients with bulky metastatic LN involvement were recruited for study. Involved bulky neck nodes were scanned with ultrasound prior to the start of treatment for each patient. QUS parametric maps and related radiomics texture-based features were determined and used to train two ML classifiers (support vector machines (SVM) and k-nearest neighbour (k-NN)) for predictive modeling using retrospectively labelled binary treatment outcomes, as determined clinically 3-months after completion of treatment. Additionally, novel higher-order texture-of-texture (TOT) features were incorporated and evaluated in regards to improved predictive model performance.ResultsIt was found that a 7-feature multivariable model of QUS texture features using a support vector machine (SVM) classifier demonstrated 81% sensitivity, 76% specificity, 79% accuracy, 86% precision and an area under the curve (AUC) of 0.82 in separating responding from non-responding patients. All performance metrics improved after implementation of TOT features to 85% sensitivity, 80% specificity, 83% accuracy, 89% precision and AUC of 0.85. Similar trends were found with k-NN classifier.ConclusionBinary H&N cancer treatment outcomes can be predicted with QUS texture features acquired from index LNs. Prediction efficacy improved by implementing TOT features following methodology outlined in this work.

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Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

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