Immuno-oncologic profiling of renal masses using multiparametric MRI: a pilot study

Purpose Preoperative characterization of renal mass malignancy, subtype, and immuno-oncologic pathology could inform and improve tailored management decisions. We examine multiparametric MRI (mpMRI) for (1) sensitivity to immuno-oncologic markers of the tumor immune microenvironment and (2) classification of tumor malignancy, subtype, and grade. Methods and materials In a prospective, institutional review board-approved single-center study, 40 patients (13 female/27 males, 60.4±10.7years) scheduled to undergo surgical management of solid renal masses underwent preoperative 1.5T MRI. This included T1, multi-b-value diffusion-weighted imaging (DWI as intravoxel incoherent motion (IVIM), and apparent diffusion coefficient (ADC)), R2*, arterial spin labeling (ASL), and dynamic contrast-enhanced (DCE-)MRI. Clear cell likelihood scores (ccLS) were assigned using clinical MR images. Tumor diagnoses were extracted from the surgical histopathology. Logistic regression models were built with leave-one-out cross-validation and bootstrapping. Interobserver measurements were obtained in a subset of 27 patients, and tests–retests were run for 2 patients. Tumors from 18 patients with clear cell renal cell carcinoma (ccRCC) underwent immunohistochemistry for CD3, CD4, CD8, CD68, PD-L1, NKp46, HIF-1α, and CD31. MR biomarkers of immunohistochemistry stains were identified with Pearson’s r correlation, and diagnostic OR for >5%or >15% cells stained positive, by cross-validated univariate logistic regression. Results Of the 40 solid renal masses (mean (range)=32 (8–68) mm), 22 were clear cell, 9 non-clear cell and 9 benign, with 10 Grade 1. IVIM f, D*, and fD* correlated with T cells (CD4, CD3, CD8), while R2* correlated positively with macrophage presence (CD68) and negatively with angiogenesis (CD31). DCE-MRI and ASL negatively correlated with CD68. ASL negatively correlated with CD8 T cells. IVIM D* returned a significant OR for CD68-positive stains (OR=55.0, p<0.001), while ASL renal blood flow returned a significant OR for CD8-positive stains (OR=24.0, p=0.03). mpMRI tumor volume and IVIM D heterogeneity returned the highest A U C 95 % C I = 0.84 ( 0.70,0.98 )) for malignancy. ccLS had the highest A U C ( 95 % C I ) = 0.75 ( 0.56 , 0.92 ) for overall detection of ccRCC, and mpMRI distinguished ccRCC from non-ccRCC with increased IVIM D and ADC with A U C ( 95 % C I ) = 0.95 ( 0.86,1.0 ) ). Conclusion In this pilot study, mpMRI was sensitive to immuno-oncologic biomarkers supporting preoperative MRI as a method of characterizing tumor immune microenvironment, malignancy, and subtype for informed and tailored treatment management.