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.
In a prospective, institutional review board-approved single-center study, 40 patients (13 female/27 males, 60.4±10.7 years) 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.
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 [Formula: see text]) for malignancy. ccLS had the highest [Formula: see text] for overall detection of ccRCC, and mpMRI distinguished ccRCC from non-ccRCC with increased IVIM D and ADC with [Formula: see text].
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.
Journal for immunotherapy of cancer. 2025 Dec 05*** epublish ***
Mira M Liu, Octavia Bane, Xin Mu, Haitham Al-Mubarak, Ghadi Abboud, Arthi M Reddy, Paul Kennedy, Philip Robson, Kirolos Meilika, Laura Zuluaga, Amir Horowitz, Bernd Kuhn, Tin Htwe Thin, Monica Garcia-Barros, Rachel Brody, Ketan Badani, Bachir Taouli, Sara Lewis
Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Department of Diagnostic, Molecular and Interventional Radiology, Mount Sinai Hospital, New York, New York, USA., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Siemens Healthineers AG, Erlangen, BY, Germany., Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Department of Diagnostic, Molecular and Interventional Radiology, Mount Sinai Hospital, New York, New York, USA .