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PLoS One. 2015 Mar 27;10(3):e0122151. doi: 10.1371/journal.pone.0122151. eCollection 2015.

Multi-site clinical evaluation of DW-MRI as a treatment response metric for breast cancer patients undergoing neoadjuvant chemotherapy.

Author information

1
Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
2
Centre for MR Investigations, Hull York Medical School, University of Hull, Hull, United Kingdom.
3
Departments of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
4
Department of Radiology, University of California San Francisco, San Francisco, California, United States of America.
5
Departments of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
6
Departments of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.

Abstract

PURPOSE:

To evaluate diffusion weighted MRI (DW-MR) as a response metric for assessment of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer using prospective multi-center trials which provided MR scans along with clinical outcome information.

MATERIALS AND METHODS:

A total of 39 patients with locally advanced breast cancer accrued from three different prospective clinical trials underwent DW-MR examination prior to and at 3-7 days (Hull University), 8-11 days (University of Michigan) and 35 days (NeoCOMICE) post-treatment initiation. Thirteen patients, 12 of which participated in treatment response study, from UM underwent short interval (<1hr) MRI examinations, referred to as "test-retest" for examination of repeatability. To further evaluate stability in ADC measurements, a thermally controlled diffusion phantom was used to assess repeatability of diffusion measurements. MRI sequences included contrast-enhanced T1-weighted, when appropriate, and DW images acquired at b-values of 0 and 800 s/mm2. Histogram analysis and a voxel-based analytical technique, the Parametric Response Map (PRM), were used to derive diffusion response metrics for assessment of treatment response prediction.

RESULTS:

Mean tumor apparent diffusion coefficient (ADC) values generated from patient test-retest examinations were found to be very reproducible (|ΔADC|<0.1x10-3mm2/s). This data was used to calculate the 95% CI from the linear fit of tumor voxel ADC pairs of co-registered examinations (±0.45x10-3mm2/s) for PRM analysis of treatment response. Receiver operating characteristic analysis identified the PRM metric to be predictive of outcome at the 8-11 (AUC = 0.964, p = 0.01) and 35 day (AUC = 0.770, p = 0.05) time points (p<.05) while whole-tumor ADC changes where significant at the later 35 day time interval (AUC = 0.825, p = 0.02).

CONCLUSION:

This study demonstrates the feasibility of performing a prospective analysis of DW-MRI as a predictive biomarker of NAC in breast cancer patients. In addition, we provide experimental evidence supporting the use of sensitive analytical tools, such as PRM, for evaluating ADC measurements.

PMID:
25816249
PMCID:
PMC4376686
DOI:
10.1371/journal.pone.0122151
[Indexed for MEDLINE]
Free PMC Article

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