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.

Savannah C Partridge,Nola M Hylton,Jessica E Gibbs,Jon Steingrimsson,Thomas L Chenevert,David C Newitt,Michael A Boss,Patrick J Bolan,Helga S Marques,Mark A Rosen

doi:10.3390/tomography8020058

Abstract

In diffusion-weighted MRI (DW-MRI), choice of b-value influences apparent diffusion coefficient (ADC) values by probing different aspects of the tissue microenvironment. As a secondary analysis of the multicenter ECOG-ACRIN A6698 trial, the purpose of this study was to investigate the impact of alternate b-value combinations on the performance and repeatability of tumor ADC as a predictive marker of breast cancer treatment response. The final analysis included 210 women who underwent standardized 4-b-value DW-MRI (b = 0/100/600/800 s/mm2) at multiple timepoints during neoadjuvant chemotherapy treatment and a subset (n = 71) who underwent test–retest scans. Centralized tumor ADC and perfusion fraction (fp) measures were performed using variable b-value combinations. Prediction of pathologic complete response (pCR) based on the mid-treatment/12-week percent change in each metric was estimated by area under the receiver operating characteristic curve (AUC). Repeatability was estimated by within-subject coefficient of variation (wCV). Results show that two-b-value ADC calculations provided non-inferior predictive value to four-b-value ADC calculations overall (AUCs = 0.60–0.61 versus AUC = 0.60) and for HR+/HER2− cancers where ADC was most predictive (AUCs = 0.75–0.78 versus AUC = 0.76), p < 0.05. Using two b-values (0/600 or 0/800 s/mm2) did not reduce ADC repeatability over the four-b-value calculation (wCVs = 4.9–5.2% versus 5.4%). The alternate metrics ADCfast (b ≤ 100 s/mm2), ADCslow (b ≥ 100 s/mm2), and fp did not improve predictive performance (AUCs = 0.54–0.60, p = 0.08–0.81), and ADCfast and fp demonstrated the lowest repeatability (wCVs = 6.71% and 12.4%, respectively). In conclusion, breast tumor ADC calculated using a simple two-b-value approach can provide comparable predictive value and repeatability to full four-b-value measurements as a marker of treatment response.

Highlights

As oncologic approaches move increasingly towards personalization of therapies, improved methods for early assessment of breast cancer response to neoadjuvant chemotherapy (NAC) are needed to enable timely modification of therapeutic regimens
Of the 406 consecutive women enrolled in the ACRIN 6698 trial at 10 institutions, 196 were excluded from this secondary analysis: 134 (33.0%) were not randomized to treatment on I-SPY 2 and 62 (15.3%) had missing or non-evaluable diffusion-weighted magnetic resonance imaging (MRI) (DW-MRI) scans at pre- and/or mid-treatment timepoints (Figure 1); further details were previously reported [14]
From the full cohort of 406 ACRIN 6698 patients, a subset of 89 patients consented to the test/retest substudy (Figure 1), of which 71 patients from 8 institutions had analyzable repeat DW-MRI scans (Table 1)

Summary

Introduction

As oncologic approaches move increasingly towards personalization of therapies, improved methods for early assessment of breast cancer response to neoadjuvant chemotherapy (NAC) are needed to enable timely modification of therapeutic regimens. Consensus recommendations from the European Society of Breast Radiology were recently published to facilitate standardization and to provide best practices for achieving an adequate signal-to-noise ratio while minimizing artifacts and distortions [10]. These recommendations are largely based on expert opinions; more data are needed to refine optimal methods for implementation of ADC as a quantitative imaging biomarker in breast cancer clinical trials. Test–retest data indicating similar repeatability with the use of fewer b-values would allow for shorter acquisitions

Objectives

Methods

Results

Conclusion