AUTHOR=Tang Wen-jie , Jin Zhe , Zhang Yan-ling , Liang Yun-shi , Cheng Zi-xuan , Chen Lei-xin , Liang Ying-ying , Wei Xin-hua , Kong Qing-cong , Guo Yuan , Jiang Xin-qing 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.611571

DOI=10.3389/fonc.2020.611571

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>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.</p></sec><sec><title>Methods</title><p>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<sup>th</sup>, 25<sup>th</sup>, 50<sup>th</sup>, 75<sup>th</sup>, and 90<sup>th</sup> 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.</p></sec><sec><title>Results</title><p>A statistically significant difference existed in the 10<sup>th</sup> and 25<sup>th</sup> percentile ADC values between the low and high TIL groups in breast cancer (<italic>P</italic>=0.012 and 0.027). For the luminal subtype of breast cancer, the 10<sup>th</sup> percentile ADC value was significantly lower in the low TIL group (<italic>P</italic>=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (<italic>P</italic>=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (<italic>P</italic>=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (<italic>P</italic>=0.029).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>