MR spectroscopy of breast cancer for assessing early treatment response: Results from the ACRIN 6657 MRS trial

Abstract

Purpose: To estimate the accuracy of predicting response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer using MR spectroscopy (MRS) measurements made very early in treatment.

Materials and methods: This prospective Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol was approved by the American College of Radiology and local-site institutional review boards. One hundred nineteen women with invasive breast cancer of ≥3 cm undergoing NACT were enrolled between September 2007 and April 2010. MRS measurements of the concentration of choline-containing compounds ([tCho]) were performed before the first chemotherapy regimen (time point 1, TP1) and 20-96 h after the first cycle of treatment (TP2). The change in [tCho] was assessed for its ability to predict pathologic complete response (pCR) and radiologic response using the area under the receiver operating characteristic curve (AUC) and logistic regression models.

Results: Of the 119 subjects enrolled, only 29 cases (24%) with eight pCRs provided usable data for the primary analysis. Technical challenges in acquiring quantitative MRS data in a multi-site trial setting limited the capture of usable data. In this limited data set, the decrease in tCho from TP1 to TP2 had poor ability to predict either pCR (AUC = 0.53, 95% confidence interval [CI]: 0.27-0.79) or radiologic response (AUC = 0.51, 95% CI: 0.27-0.75).

Conclusion: The technical difficulty of acquiring quantitative MRS data in a multi-site clinical trial setting led to a low yield of analyzable data, which was insufficient to accurately measure the ability of early MRS measurements to predict response to NACT.

Level of evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:290-302.

Keywords: breast cancer; choline; magnetic resonance spectroscopy; treatment response.

Figure 1

Representative case showing imaging and MRS data. Voxel positioning for a) TP1 (pre-treatment) and c) TP2 is shown on the first post-contrast T1-weighted image. The corresponding spectra are shown in b) and d) show a decrease in [tCho] from 1.81 mmol/kg to 1.17 mmol/kg. This patient was considered a non-responder by both pathologic and radiologic criteria.

Figure 2

Concentrations of tCho at time points 1 and 2, separated out by pathologic response (a,b) and radiologic response (c,d). Box plots indicate median (red line), mean (black diamond), and 25^th and 75^th percentiles (box limits).

Figure 3

Relationship between Δ[tCho]_1→2 and %ΔFTV_1→4, showing no significant correlation (Spearman ρ = −0.07; p = 0.72). The vertical dotted line is the median volume change (−94.75%); the horizontal dotted line is the optimal cutoff for Δ[tCho]_1→2 (0.562 mmol/kg). The five cases with the largest increase in tCho are indicated by filled circles (see text for details).