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DWI in Assessing Treatment Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy

Not Applicable
Completed
Conditions
Breast Cancer
Interventions
Procedure: diffusion-weighted magnetic resonance imaging
Registration Number
NCT01564368
Lead Sponsor
American College of Radiology Imaging Network
Brief Summary

RATIONALE: Imaging procedures, such as diffusion-weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), may help in evaluating how well patients with breast cancer respond to treatment.

PURPOSE: This research trial studies DWI and DCE-MRI in assessing treatment response in patients with breast cancer undergoing neoadjuvant chemotherapy.

Detailed Description

OBJECTIVES:

Primary

* To determine if the change in tumor apparent diffusion coefficient (ADC) value measured from each treatment timepoint to baseline is predictive of pathologic complete response (pCR).

Secondary

* To determine if the combined measurement of change in tumor ADC value, change in tumor volume, and change in peak signal-enhancement ratio (SER) is predictive of pCR.

* To investigate the relative effectiveness of the individual measurements, change in tumor ADC value, change in tumor volume, and change in peak SER for predicting pCR in experimental treatment arms.

* To assess the test-retest reproducibility of ADC metrics applied to breast tumors.

OUTLINE: This is a multicenter study.

Patients undergo diffusion-weighted magnetic resonance imaging (DWI) at baseline, after week 3 of neoadjuvant paclitaxel regimen, and prior to and after completion of 4 courses of neoadjuvant chemotherapy. Patients then undergo surgery. Patients undergo DWI prior to contrast administration for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

After completion of treatment procedure, patients are followed up for 5 years on the I-SPY 2 TRIAL.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
406
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Diffusion Weighted-MRIdiffusion-weighted magnetic resonance imagingParticipants on all arms of the I-SPY II trial will undergo diffusion-weighted magnetic resonance imaging as described in the ACRIN 6698 protocol. The experimental component/intervention is whether DW-MRI can predict therapeutic response in neoadjuvant treatment for breast cancer.
Primary Outcome Measures
NameTimeMethod
Pathologic Complete Response (pCR)Surgery

Pathologic complete response (pCR) is defined as the lack of all signs of cancer in tissue samples removed during surgery after Neoadjuvant treatment for Breast cancer.

ie., no residual invasive disease in either breast or axillary lymph nodes after neoadjuvant therapy (ypT0/is, ypN0) Histopathologic analysis was performed using the Residual Cancer Burden system

Secondary Outcome Measures
NameTimeMethod
Within-subject Coefficient of Variation (wCV) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumorsbaseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)

within-subject standard deviation (wSD) Within-subject coefficient of variation (wCV): \[wCV = 100%\*wSD/mean\]

Smaller values of wCV bounded for \[0,...) represent better agreement

Repeatability Coefficient (RC)Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumorsbaseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)

within-subject standard deviation (wSD) Repeatability coefficient (RC): \[RC = 2.77\*wSD\] (units: 10E-3 mm/sec\^2)

Smaller values of RC, bounded \[0, ...), represent agreement

Agreement Index (AI) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumorsbaseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)

Test and retest DWI measurements for a given patient were performed on the same day in a single imaging session.

Agreement index (AI): (Zhang, Wang, Duan - 2014) is based on the data's overall ranking. AI confidence intervals were obtained via bootstrap method Larger values AI (bounded \[0.5,1\]) represent agreement

Functional Tumor Volume (FTV) as a Predictor of Pathologic Complete Response (pCR)Surgery

Pathologic complete response (pCR) is defined as the lack of all signs of cancer in tissue samples removed during surgery after Neoadjuvant treatment for Breast cancer.

ie., no residual invasive disease in either breast or axillary lymph nodes after neoadjuvant therapy (ypT0/is, ypN0) Histopathologic analysis was performed using the Residual Cancer Burden system Functional tumor volume (FTV) (units cm3) was computed by summing all tumor voxels meeting specific enhancement criteria, with customized thresholds for each site to account for variability in MR imaging systems

ICC Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumorsbaseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)

Test and retest DWI measurements for a given patient were performed on the same day in a single imaging session.

Intraclass correlation coefficient (ICC) is derived from the analysis of variance (ANOVA) model estimates (Barnhart,Haber, Lin 2007),

Larger values of ICC (bounded \[-1,1\]) represent agreement

Determine the Accuracy of Predictive Models Including Covariates for Combined Measurement of Change in Tumor ADC Value, Change in Tumor Volume, and Other Variablesbaseline and mid-treatment

Accuracy will be measured as the Area under the Receiver Operating Characteristic Curve (AUC) Predictive logistic regression modeling was performed in 207 patients with complete mid-treatment ΔADC and ΔFTV data.

To build prediction models with ADC and other variables, a data-splitting approach was used where a randomly selected 60% of participants (124 patients), stratified according to pCR status and tumor subtype, were selected as the training data set and the rest (86 patients) as the test set. Logistic regression with backward variable selection was used to construct the prediction models, which were then applied to the remaining 40% of the data to obtain predictive scores for each participant.

Trial Locations

Locations (7)

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

University of Texas M.D. Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University of Washington/SCCA

🇺🇸

Seattle, Washington, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

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