Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically-integrated radiogenomics co-localization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives.
We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially co-localized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 metastatic RCC patients (39 metastases) treated with first-line anti-angiogenic drugs or checkpoint inhibitors.
DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of anti-angiogenic and immuno-therapies. Our vertically-integrated analyses show that angiogenesis and inflammation frequently co-exist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to anti-angiogenic therapy among metastatic RCC patients.
These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Jul 01 [Epub ahead of print]
Durga Udayakumar, Ze Zhang, Yin Xi, Durgesh K Dwivedi, Michael Fulkerson, Sydney Haldeman, Tiffani McKenzie, Qurratulain Yousuf, Allison Joyce, Asghar Hajibeigi, Hollis Notgrass, Alberto Diaz de Leon, Qing Yuan, Matthew A Lewis, Ananth J Madhuranthakam, Robert C Sibley, Roy Elias, Junyu Guo, Alana Christie, Renée M McKay, Jeffrey A Cadeddu, Aditya Bagrodia, Vitaly Margulis, James Brugarolas, Tao Wang, Payal Kapur, Ivan Pedrosa
Radiology, The University of Texas Southwestern Medical Center., Department of Clinical Sciences, The University of Texas Southwestern Medical Center., Department of Radiology, The University of Texas Southwestern Medical Center., Radiology, The University of Texas Southwestern Medical Center & King George's Medical University, Lucknow, India., Department of Internal Medicine, The University of Texas Southwestern Medical Center., Internal Medicine - Hematology-Oncology Division, The University of Texas Southwestern Medical Center., Internal Medicine, The University of Texas Southwestern Medical Center., Department of Pathology, The University of Texas Southwestern Medical Center., Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center., Urology, The University of Texas Southwestern Medical Center., Urology, University of Texas Southwestern Medical Center at Dallas., Department of Population and Data Sciences, The University of Texas Southwestern Medical Center., Department of Radiology, The University of Texas Southwestern Medical Center .