Trial Outcomes & Findings for DWI in Assessing Treatment Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy (NCT NCT01564368)

NCT ID: NCT01564368

Last Updated: 2024-04-15

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 406 participants
• Primary outcome timeframe: Surgery
• Results posted on: 2024-04-15

Participant Flow

Participant milestones

Measure	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 (pathological Complete Response: pCR) in neoadjuvant treatment for breast cancer.
Overall Study STARTED	406
Overall Study Randomized in Parent Study	272
Overall Study Acceptable Baseline Imaging	263
Overall Study Acceptable Post Baseline Image	242
Overall Study Baseline and Early Treatment Usable	227
Overall Study Baseline and Mid-treatment Usable	210
Overall Study Baseline and Post-Treatment Usable	186
Overall Study Usable Re-test Scan	71
Overall Study COMPLETED	242
Overall Study NOT COMPLETED	164

Reasons for withdrawal

Measure	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 (pathological Complete Response: pCR) in neoadjuvant treatment for breast cancer.
Overall Study Ineligible	18
Overall Study Not Randomized in Parent study	116
Overall Study Baseline Imaging failed QC requirements	9
Overall Study No Acceptable post-baseline imaging	21

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Diffusion Weighted-MRI n=242 Participants Participants on all arms of the I-SPY II trial with both a diffusion-weighted magnetic resonance imaging (DWI-MRI) scan at baseline and 1 post-baseline timepoint (early-treatment, mid-treatment, or post-treatment). The experimental component/intervention is whether DW-MRI can predict therapeutic response in women receiving neoadjuvant treatment for breast cancer.
Age, Continuous	48.1 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex/Gender, Customized Female	242 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	154 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	65 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	26 Participants n=5 Participants
Race (NIH/OMB) White	173 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=227 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change n=210 Participants Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change n=186 Participants Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Pathologic Complete Response (pCR) Pathological Complete Responders (pCR)	71 Participants	70 Participants	63 Participants
Pathologic Complete Response (pCR) Non-Responders(pCR-)	156 Participants	140 Participants	123 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=227 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change n=210 Participants Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change n=186 Participants Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Functional Tumor Volume (FTV) as a Predictor of Pathologic Complete Response (pCR) Non-Responders(pCR-)	156 Participants	140 Participants	123 Participants
Functional Tumor Volume (FTV) as a Predictor of Pathologic Complete Response (pCR) Pathological Complete Responders (pCR)	71 Participants	70 Participants	63 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Early Treatment Change n=86 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change n=86 Participants Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change n=86 Participants Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Determine the Accuracy of Predictive Models Including Covariates for Combined Measurement of Change in Tumor ADC Value, Change in Tumor Volume, and Other Variables	0.71 probability Interval 0.59 to 0.84	0.72 probability Interval 0.61 to 0.83	0.57 probability Interval 0.44 to 0.7

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=71 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Repeatability Coefficient (RC)Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	0.16 10E-3 mm/sec^2 Interval 0.13 to 0.19	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=71 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Within-subject Coefficient of Variation (wCV) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	4.8 coefficient of variation Interval 4.0 to 5.7	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=71 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
ICC Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	0.97 correlation coefficient Interval 0.95 to 0.98	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Early Treatment Change n=71 Participants Participants who had both the pre-treatment (baseline) and the early-treatment (after 3 weekly doses of paclitaxel/taxane-based therapy) scans	Mid-Treatment Change Participants who had both the pre-treatment (baseline) and the mid-treatment (after 12 weeks, between taxane and anthracycline regimens) scans	Post-Treatment Change Participants who had both the pre-treatment (baseline) and the post-treatment (post-treatment after all chemotherapy, prior to surgery) scans
Agreement Index (AI) Test-retest Metric for Reproducibility of ADC as Applied to Breast Tumors	0.83 probability Interval 0.76 to 0.87	—	—

Adverse Events

Diffusion Weighted-MRI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Director Clinical Research Administration

American College of Radiology

Phone: 215-574-3150

Email: info@acr.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place