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

Abstract

PurposeTo 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.MethodsIn 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 (10th, 25th, 50th, 75th, and 90th 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.ResultsA statistically significant difference existed in the 10th and 25th 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 10th 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).ConclusionsOur findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.

Whole Volume Apparent Diffusion Coefficient (ADC) Histogram as a Quantitative Imaging Biomarker to Differentiate Breast Lesions: Correlation with the Ki-67 Proliferation Index

“…Various ADC histogram parameters were calculated: 10th percentile, mean, 50th percentile (median), 90th percentile, skewness (a measure of asymmetry of the histogram about its mean), kurtosis (a measure of the peakedness of the histogram), and entropy (measure of the variation in the histogram distribution). We followed the methods of Tang et al [ 12 ].…”

“…The ADC measurements in the previous study were mostly based on traditional 2D regions of interest (ROIs) manually drawn from a single representative slice of the breast lesion, which might limit these ADC measurements in their ability to reflect whole tumour characteristics [4,[8][9][10][11]. Assessments with whole volume histogram analyses of the ADC might provide more reliable results to reflect the biological characteristics of the heterogeneous breast lesions [3,[8][9][10][11][12].…”

Radiomics Assessment of the Tumor Immune Microenvironment to Predict Outcomes in Breast Cancer

“…While image-based assessments will likely neither supplant nor substitute for the current gold standard of tissue-based assessment, we posit that our radiographic methodology would be helpful in promoting long-term evaluation and in vivo surveillance of the TME. In fact, some researchers have surveyed the relationship between radiographic features and tumor-invading lymphocytes (10)(11)(12), and the ability of radiomic features to predict prognosis (12). Fertéet al correlated both on-tumor and peri-tumor radiomic features with CD8 expression at the central tumor area and suggested that imaging features might help assess the CD8 cell population and also forecast the clinical response for those patients receiving antibody therapy (11).…”

“…Analysis of radiologic images by quantified radiomics methods can reveal associations between particular images with molecular phenotypes (9). And some investigators have already begun exploring the relationships between imaging features and tumor-infiltrating lymphocytes (10)(11)(12)(13).…”

Whole-Lesion Apparent Diffusion Coefficient Histogram Analysis: Significance for Discriminating Lung Cancer from Pulmonary Abscess and Mycobacterial Infection

“…For the breast, ADC histogram analysis also revealed ADC kurtosis to be higher in breast cancer of triple-negative than breast cancer of estrogen receptor-positive subtype [ 34 ]. Whole-lesion histogram analysis of the ADC could be used as a qualitative imaging biomarker for the tumor-infiltrating lymphocyte levels in breast cancer [ 35 ]. Maximum whole tumor ADC values may be used to differentiate luminal cancers from other molecular subtypes of breast tumors [ 36 ].…”