Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer

Wen-Jie Tang; Zhe Jin; Yan-Ling Zhang; Yun-Shi Liang; Zi-Xuan Cheng; Lei-Xin Chen; Ying-Ying Liang; Xin-Hua Wei; Qing-Cong Kong; Yuan Guo; Xin-Qing Jiang

doi:10.3389/fonc.2020.611571

Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer

Front Oncol. 2021 Jan 8:10:611571. doi: 10.3389/fonc.2020.611571. eCollection 2020.

Authors

Affiliations

¹ Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² Department of Ultrasound, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
³ Department of Pathology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁴ Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Abstract

Purpose: To assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer.

Methods: In total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29-85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10^th, 25^th, 50^th, 75^th, and 90^th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student's t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests.

Results: A statistically significant difference existed in the 10^th and 25^th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10^th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029).

Conclusions: Our findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.

Keywords: apparent diffusion coefficient; breast cancer; magnetic resonance imaging; molecular subtypes; tumor-infiltrating lymphocytes.