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

Breast Cancer Clinical Trial

— ACRIN6698  

Official title:

Diffusion Weighted MR Imaging Biomarkers for Assessment of Breast Cancer Response to Neoadjuvant Treatment: A Sub-study of the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And MoLecular Analysis)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01564368
• Other study ID #: CDR0000729174
• Secondary ID: ACRIN-6698U01CA0
• Status: Completed
• Phase: N/A
• Start date: August 27, 2012
• Est. completion date: January 14, 2020

Study information

• Verified date: March 2024
• Source: American College of Radiology Imaging Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: January 14, 2020
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Meets I-SPY 2 TRIAL inclusion criteria

• High-risk for recurrent disease

PATIENT CHARACTERISTICS:

• Able to tolerate imaging required by protocol

PRIOR CONCURRENT THERAPY:

• Not specified

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• diffusion-weighted magnetic resonance imaging
diffusion-weighted magnetic resonance imaging examination and subsequent radiologist interpretation

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington/SCCA	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
American College of Radiology Imaging Network	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (7)

DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988 Sep;44(3):837-45. — View Citation

Li W, Partridge SC, Newitt DC, Steingrimsson J, Marques HS, Bolan PJ, Hirano M, Bearce BA, Kalpathy-Cramer J, Boss MA, Teng X, Zhang J, Cai J, Kontos D, Cohen EA, Mankowski WC, Liu M, Ha R, Pellicer-Valero OJ, Maier-Hein K, Rabinovici-Cohen S, Tlusty T, O — View Citation

Newitt DC, Amouzandeh G, Partridge SC, Marques HS, Herman BA, Ross BD, Hylton NM, Chenevert TL, Malyarenko DI. Repeatability and Reproducibility of ADC Histogram Metrics from the ACRIN 6698 Breast Cancer Therapy Response Trial. Tomography. 2020 Jun;6(2):1 — View Citation

Newitt DC, Tan ET, Wilmes LJ, Chenevert TL, Kornak J, Marinelli L, Hylton N. Gradient nonlinearity correction to improve apparent diffusion coefficient accuracy and standardization in the american college of radiology imaging network 6698 breast cancer tr — View Citation

Newitt DC, Zhang Z, Gibbs JE, Partridge SC, Chenevert TL, Rosen MA, Bolan PJ, Marques HS, Aliu S, Li W, Cimino L, Joe BN, Umphrey H, Ojeda-Fournier H, Dogan B, Oh K, Abe H, Drukteinis J, Esserman LJ, Hylton NM; ACRIN Trial Team and I-SPY 2 TRIAL Investiga — View Citation

Partridge SC, Steingrimsson J, Newitt DC, Gibbs JE, Marques HS, Bolan PJ, Boss MA, Chenevert TL, Rosen MA, Hylton NM. Impact of Alternate b-Value Combinations and Metrics on the Predictive Performance and Repeatability of Diffusion-Weighted MRI in Breast — View Citation

Partridge SC, Zhang Z, Newitt DC, Gibbs JE, Chenevert TL, Rosen MA, Bolan PJ, Marques HS, Romanoff J, Cimino L, Joe BN, Umphrey HR, Ojeda-Fournier H, Dogan B, Oh K, Abe H, Drukteinis JS, Esserman LJ, Hylton NM; ACRIN 6698 Trial Team and I-SPY 2 Trial Inve — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response (pCR)	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	Surgery
Secondary	Functional Tumor Volume (FTV) as a Predictor of Pathologic Complete Response (pCR)	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	Surgery
Secondary	Determine the Accuracy of Predictive Models Including Covariates for Combined Measurement of Change in Tumor ADC Value, Change in Tumor Volume, and Other Variables	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 ?ADC and ?FTV 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.	baseline and mid-treatment
Secondary	Repeatability Coefficient (RC)Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	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	baseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)
Secondary	Within-subject Coefficient of Variation (wCV) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	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	baseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)
Secondary	ICC Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	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	baseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)
Secondary	Agreement Index (AI) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	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	baseline (pre-treatment) or after 3 weeks of taxane-based treatment (early-treatment)

External Links

•   National Cancer Institute's Clinical trial database