Quantitative Apparent Diffusion Coefficients From Peritumoral Regions as Early Predictors of Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer

Abstract

Background: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC.

Purpose: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC.

Study type: Prospective.

Population/subjects: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020.

Field strength/sequence: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI).

Assessment: Three scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels.

Statistical tests: ADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant.

Results: Fifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm² /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans.

Data conclusion: Quantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC.

Evidence level: 1 TECHNICAL EFFICACY: Stage 4.

Keywords: apparent diffusion coefficient; neoadjuvant therapy; peritumoral edema; prediction of treatment response; quantitative MRI; triple negative breast cancer.

Figure 1.

Peritumoral region segmentation in a 48-year-old woman with triple-negative breast cancer of the right breast. A, ADC map showing known 4.8 cm cancer at 9 o’clock position 8 cm from the nipple (red arrow). B, ADC maps with fat-inclusive peritumoral regions. C, ADC maps with fat-exclusive peritumoral regions. The solid red lines in B and C show the tumor boundary; the outer lines show boundaries of different peritumoral region thicknesses: solid yellow line – 20 mm, the inner dashed orange line – 15 mm, dashed red line – 10 mm, and dashed maroon line - 5 mm.

Figure 2.

Dot plots and Mann Whitney p-values of the 4 volume-independent peritumoral region (PTR) apparent diffusion coefficient (ADC) features compared using the area under the receiver operating characteristic curve (AUC) between patients with a pathologic complete response (pCR) and without a pCR (“non-pCR”) for both the training and testing sets. A, Cycle 4 fat-inclusive 5-mm ADC standard deviation (SD). B, Cycle 4 fat-inclusive 10-mm ADC SD. C, Cycle 4 fat-inclusive 15-mm ADC SD. D, Cycle 4 fat-inclusive 20-mm ADC SD.