Role of the Intravoxel Incoherent Motion Diffusion Weighted Imaging in the Pre-treatment Prediction and Early Response Monitoring to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Abstract

The aim of this study was to explore whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can probe pre-treatment differences or monitor early response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Thirty-six patients with locally advanced breast cancer were imaged using multiple-b DWI with 12 b values ranging from 0 to 1000 s/mm(2) at the baseline, and 28 patients were repeatedly scanned after the second cycle of NAC. Subjects were divided into pathologic complete response (pCR) and nonpathologic complete response (non-pCR) groups according to the surgical pathologic specimen. Parameters (D, D*, f, maximum diameter [MD] and volume [V]) before and after 2 cycles of NAC and their corresponding change (Δparameter) between pCR and non-pCR groups were compared using the Student t test or nonparametric test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic curve analysis. Before NAC, the f value of pCR group was significantly higher than that of non-pCR (32.40% vs 24.40%, P = 0.048). At the end of the second cycle of NAC, the D value was significantly higher and the f value was significantly lower in pCR than that in non-pCR (P = 0.001; P = 0.015, respectively), whereas the D* value and V of the pCR group was slightly lower than that of the non-pCR group (P = 0.507; P = 0.676, respectively). ΔD was higher in pCR (-0.45 × 10(-3) mm(2)/s) than that in non-pCR (-0.07 × 10(-3) mm(2)/s) after 2 cycles of NAC (P < 0.001). Δf value in the pCR group was significantly higher than that in the non-pCR group (17.30% vs 5.30%, P = 0.001). There was no significant difference in ΔD* between the pCR and non-pCR group (P = 0.456). The prediction performance of ΔD value was the highest (AUC [area under the curve] = 0.924, 95% CI [95% confidence interval] = 0.759-0.990). When the optimal cut-off was set at -0.163 × 10(-3) mm(2)/s, the values for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were up to 100% (95% CI = 66.4-100), 73.7% (95% CI = 48.8-90.9), 64.3% (95% CI = 35.6-86.0), and 100% (95% CI = 73.2-99.3), respectively. IVIM-derived parameters, especially the D and f value, showed potential value in the pre-treatment prediction and early response monitoring to NAC in locally advanced breast cancer. ΔD value had the best prediction performance for pathologic response after NAC.

FIGURE 1

A 51-year-old woman with invasive ductal carcinoma who was enrolled into the pCR group. Images in each vertical row are from 2 measurement time-points: before NAC (NAC-pre) and after 2 cycles of NAC (NAC-mid). A, The tumor shrunk obviously after 2 NAC cycles. B, The D value increased significantly from 0.906 × 10^–3 to 1.310 × 10^–3 mm²/s after the therapy. C, The D^∗ value decreased significantly from 40.4 × 10^–3 to 13.8 × 10^–3 mm²/s after 2 cycles of NAC. D, The f value significantly decreased to 14.2% after the NAC initiation, which was 35.7% before NAC.

FIGURE 2

A 75-year-old woman with invasive ductal carcinoma who was classified as the non-pCR group. Images in each vertical row are from 2 measurement time-points: before NAC (NAC-pre) and after 2 cycles of NAC (NAC-mid). A, The tumor reduced mildly after 2 NAC cycles. B, The D value increased slightly from 1.110 × 10^–3 to 1.410 × 10^–3 mm²/s after the therapy. C, The D^∗ value increased from 14.8 × 10^–3 to 27.4 × 10^–3 mm²/s after 2 cycles of NAC. D, The f value slightly decreased to 21.4% after the NAC initiation, which was 29.2% before NAC.

FIGURE 3

Box and whisker plot shows the parameters (D, D^∗, and f) before and after 2 cycles of NAC, and their corresponding change (Δparameter) and the shrinkage of mass (ΔMD% and ΔV%) between pCR and non-pCR groups. The dotted line represents a cutoff value calculated by the ROC analysis. The f-pre and D-mid in pCR were significantly higher than that in non-pCR. The f-mid in pCR was significantly lower than that in non-pCR. The f, MD, and V values were decreased more in pCR than in non-pCR. By contrast, the D was increased more in pCR than in non-pCR.

FIGURE 4

Receiver-operating characteristic curve analyses of parameters deriving from IVIM model and their changes for the prediction of the pathologic responses. The area under the curve (AUC) of the D, D^∗, and f value in pretreatment (D-pre, D^∗-pre, f-pre) was 0.600, 0.538, and 0.701, respectively. The AUC of the D, D^∗, and f value after 2 cycles of NAC (D-mid, D^∗-mid, f-mid) was 0.851, 0.579, and 0.772, respectively. The AUC of the change of parameters (Δparameter) after the chemotherapy was 0.924 for ΔD, 0.550 for ΔD^∗, and 0.906 for Δf.

FIGURE 5

Scatter plots of the mass shrinkage percentage versus D-pre(A), f-pre(B), D-mid(C), f-mid(D), ΔD(E), and Δf(F). The P values and corresponding correlation coefficient (r value) for the spearman correlation tests were represented for each plot. The linear least-squares fit was depicted if there was a significant correlation.