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Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.

ABSTRACT: PURPOSE:Identifying imaging phenotypes and understanding their relationship with prognostic markers and patient outcomes can allow for a noninvasive assessment of cancer. The purpose of this study was to identify and validate intrinsic imaging phenotypes of breast cancer heterogeneity in preoperative breast dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans and evaluate their prognostic performance in predicting 10 years recurrence. EXPERIMENTAL DESIGN:Pretreatment DCE-MRI scans of 95 women with primary invasive breast cancer with at least 10 years of follow-up from a clinical trial at our institution (2002-2006) were retrospectively analyzed. For each woman, a signal enhancement ratio (SER) map was generated for the entire segmented primary lesion volume from which 60 radiomic features of texture and morphology were extracted. Intrinsic phenotypes of tumor heterogeneity were identified via unsupervised hierarchical clustering of the extracted features. An independent sample of 163 women diagnosed with primary invasive breast cancer (2002-2006), publicly available via The Cancer Imaging Archive, was used to validate phenotype reproducibility. RESULTS:Three significant phenotypes of low, medium, and high heterogeneity were identified in the discovery cohort and reproduced in the validation cohort (P < 0.01). Kaplan-Meier curves showed statistically significant differences (P < 0.05) in recurrence-free survival (RFS) across phenotypes. Radiomic phenotypes demonstrated added prognostic value (c = 0.73) predicting RFS. CONCLUSIONS:Intrinsic imaging phenotypes of breast cancer tumor heterogeneity at primary diagnosis can predict 10-year recurrence. The independent and additional prognostic value of imaging heterogeneity phenotypes suggests that radiomic phenotypes can provide a noninvasive characterization of tumor heterogeneity to augment personalized prognosis and treatment.

SUBMITTER: Chitalia RD

PROVIDER: S-EPMC7024654 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.

Chitalia Rhea D RD Rowland Jennifer J McDonald Elizabeth S ES Pantalone Lauren L Cohen Eric A EA Gastounioti Aimilia A Feldman Michael M Schnall Mitchell M Conant Emily E Kontos Despina D

Clinical cancer research : an official journal of the American Association for Cancer Research 20191115 4

<h4>Purpose</h4>Identifying imaging phenotypes and understanding their relationship with prognostic markers and patient outcomes can allow for a noninvasive assessment of cancer. The purpose of this study was to identify and validate intrinsic imaging phenotypes of breast cancer heterogeneity in preoperative breast dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans and evaluate their prognostic performance in predicting 10 years recurrence.<h4>Experimental design</h4>Pretreatme ...[more]

PMID: 31732521

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Project description:BACKGROUND: The UK's National Institute for Health and Care Excellence (NICE) has recommended contrast-enhanced ultrasound (CEUS) for the characterisation of focal liver lesions where the results of standard unenhanced ultrasound are inconclusive. A further recommendation is for CEUS to replace other imaging modalities. However, little is currently known about the diagnostic pathways in the National Health Service (NHS) followed by patients with potential liver lesions. The aim of this study was to identify the diagnostic pathways for a number of representative hospital trusts and record the clinicians' views on patient experiences of these processes through a series of semi-structured interviews with UK clinicians (radiologists and sonographers) (N?=?7). This study was undertaken in the broader context of a larger research project where the overarching research question is focused on patient preferences for CEUS and other imaging modalities, and how these impact on patient quality of life (QOL). RESULTS: The results from the semi-structured interviews with UK clinicians revealed that there is a great deal of heterogeneity in diagnostic pathways followed by patients with potential liver lesions which differ both within and between hospitals. In terms of the patient experience, the clinicians believed that a combination of the more patient-friendly ultrasound process, and the fact that scan results are given to patients in 80-90% of cases on the day, as well as the problems inherent to other scan modalities (claustrophobia, anxiety) would lead to patients preferring ultrasound compared with other imaging modalities (CT or MR). However, current clinical practice means that patient choice is virtually non-existent. CONCLUSIONS: The significant variation in diagnostic pathways across the NHS will require further standardisation through local agreements if contrast-enhanced ultrasound is to replace other imaging modalities in characterising focal liver lesions in line with NICE Diagnostics Guidance. The gradual development of patient choice of modalities may necessitate a change of practice in radiology processes.

Project description:Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features. A network strategy was used to integrate all image features and classify patients into different risk groups. The prognostic value of imaging-based stratification was evaluated in relation to clinical-pathologic factors with multivariable Cox regression. Results Three intratumoral subregions with high, intermediate, and low MR perfusion were identified and showed high consistency between the two cohorts. Patients in both cohorts were stratified according to network analysis of multiregional image features regarding RFS (log-rank test, P = .002 for both). Aggressive tumors were associated with a larger volume of the poorly perfused subregion as well as interaction between poorly and moderately perfused subregions and surrounding parenchyma. At multivariable analysis, the proposed MSI-based marker was independently associated with RFS (hazard ratio: 3.42; 95% confidence interval: 1.55, 7.57; P = .002) adjusting for age, estrogen receptor (ER) status, progesterone receptor status, human epidermal growth factor receptor type 2 (HER2) status, tumor volume, and pathologic complete response (pCR). Furthermore, imaging helped stratify patients for RFS within the ER-positive and HER2-positive subgroups (log-rank test, P = .007 and .004) and among patients without pCR after neoadjuvant chemotherapy (log-rank test, P = .003). Conclusion Breast cancer consists of multiple spatially distinct subregions. Imaging heterogeneity is an independent prognostic factor beyond traditional risk predictors.

Project description:Breast tumor morphological and vascular characteristics can be changed during neoadjuvant chemotherapy (NACT). The early changes in tumor heterogeneity can be quantitatively modeled by longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is useful in predicting responses to NACT in breast cancer. In this retrospective analysis, 114 female patients with unilateral unifocal primary breast cancer who received NACT were included in a development (n = 61) dataset and a testing dataset (n = 53). DCE-MRI was performed for each patient before and after treatment (two cycles of NACT) to generate baseline and early follow-up images, respectively. Feature-level changes (delta) of the entire tumor were evaluated by calculating the relative net feature change (deltaRAD) between baseline and follow-up images. The voxel-level change inside the tumor was evaluated, which yielded a Jacobian map by registering the follow-up image to the baseline image. Clinical information and the radiomic features were fused to enhance the predictive performance. The area under the curve (AUC) values were assessed to evaluate the prediction performance. Predictive models using radiomics based on pre- and post-treatment images, Jacobian maps and deltaRAD showed AUC values of 0.568, 0.767, 0.630 and 0.726, respectively. When features from these images were fused, the predictive model generated an AUC value of 0.771. After adding the molecular subtype information in the fused model, the performance was increased to an AUC of 0.809 (sensitivity of 0.826 and specificity of 0.800), which is significantly higher than that of the baseline imaging- and Jacobian map-based predictive models (p = 0.028 and 0.019, respectively). The level of tumor heterogeneity reduction (evaluated by texture feature) is higher in the NACT responders than in the nonresponders. The results suggested that changes in DCE-MRI features that reflect a reduction in tumor heterogeneity following NACT could provide early prediction of breast tumor response. The prediction was improved when the molecular subtype information was combined into the model.

Dataset Information

Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.

Publications

Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.

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