DWI in Assessing Treatment Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy (ACRIN6698)

• ClinicalTrials.gov Identifier: NCT01564368
• Recruitment Status: Completed
• First Posted: March 27, 2012
• Results First Posted: February 10, 2023
• Last Update Posted: April 15, 2024
• Sponsor: American College of Radiology Imaging Network
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): American College of Radiology Imaging Network

Tracking Information

• First Submitted Date: March 24, 2012
• First Posted Date: March 27, 2012
• Results First Submitted Date: January 12, 2023
• Results First Posted Date: February 10, 2023
• Last Update Posted Date: April 15, 2024
• Actual Study Start Date: August 27, 2012
• Actual Primary Completion Date: July 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2023)

Pathologic Complete Response (pCR) [ Time Frame: 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

Original Primary Outcome Measures (submitted: March 24, 2012)

• Pathologic complete response (pCR)
• Change in ADC value as measured by area under the receiver operating characteristic curve from each treatment timepoint to baseline

Current Secondary Outcome Measures (submitted: March 18, 2024)

• Functional Tumor Volume (FTV) as a Predictor of Pathologic Complete Response (pCR) [ Time Frame: 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
• Determine the Accuracy of Predictive Models Including Covariates for Combined Measurement of Change in Tumor ADC Value, Change in Tumor Volume, and Other Variables [ Time Frame: baseline 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.
• Repeatability Coefficient (RC)Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors [ Time Frame: baseline (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
• Within-subject Coefficient of Variation (wCV) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors [ Time Frame: baseline (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
• ICC Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors [ Time Frame: baseline (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
• Agreement Index (AI) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors [ Time Frame: baseline (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

Original Secondary Outcome Measures (submitted: March 24, 2012)

• Changes in ADC value, DCE-MRI tumor volume, and SER
• Effectiveness of the individual measurement's changes in ADC value, DCE-MRI tumor volume, and SER
• Test-retest reproducibility of DW-MRI ADC metric

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DWI in Assessing Treatment Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy
• 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)

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Breast Cancer

Intervention

Procedure: diffusion-weighted magnetic resonance imaging

diffusion-weighted magnetic resonance imaging examination and subsequent radiologist interpretation

Other Names:

• functional MRI
• DWI
• diffusion-weighted MRI
• DW-MRI

Study Arms

Experimental: Diffusion Weighted-MRI

Participants 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.

Intervention: Procedure: diffusion-weighted magnetic resonance imaging

Publications *

• 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.
• 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, Ozery-Flato M, Parekh VS, Jacobs MA, Yan R, Sung K, Kazerouni AS, DiCarlo JC, Yankeelov TE, Chenevert TL, Hylton NM. Breast Multiparametric MRI for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: The BMMR2 Challenge. Radiol Imaging Cancer. 2024 Jan;6(1):e230033. doi: 10.1148/rycan.230033.
• 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 Investigators. Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial. Radiology. 2018 Dec;289(3):618-627. doi: 10.1148/radiol.2018180273. Epub 2018 Sep 4.
• 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):177-185. doi: 10.18383/j.tom.2020.00008.
• 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 Investigators. Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial. J Magn Reson Imaging. 2019 Jun;49(6):1617-1628. doi: 10.1002/jmri.26539. Epub 2018 Oct 22.
• 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 Cancer Treatment: Results from the ECOG-ACRIN A6698 Trial. Tomography. 2022 Mar 4;8(2):701-717. doi: 10.3390/tomography8020058.
• 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 trial. J Magn Reson Imaging. 2015 Oct;42(4):908-19. doi: 10.1002/jmri.24883. Epub 2015 Mar 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2023): 406
• Original Estimated Enrollment (submitted: March 24, 2012): 304
• Actual Study Completion Date: January 14, 2020
• Actual Primary Completion Date: July 19, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01564368
• Other Study ID Numbers: CDR0000729174; ACRIN-6698 ( Other Identifier: NCI CIP ); U01CA080098 ( U.S. NIH Grant/Contract ); U01CA079778 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: See ACRIN data sharing Policy https://www.acrin.org/RESEARCHERS/POLICIES/DATAANDIMAGESHARINGPOLICY.aspx
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 6mo post publication
• Access Criteria: upon request
• URL: https://www.acrin.org/RESEARCHERS/POLICIES/DATAANDIMAGESHARINGPOLICY.aspx

• Current Responsible Party: American College of Radiology Imaging Network
• Original Responsible Party: Mitchell Schnall, American College of Radiology Imaging Network
• Current Study Sponsor: American College of Radiology Imaging Network
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nola M. Hylton, PhD; University of California, San Francisco

• PRS Account: American College of Radiology Imaging Network
• Verification Date: March 2024