OBJECTIVE - To characterize a radiogenomic risk score (RRS), a previously defined biomarker, and to evaluate its potential for stratifying radiological progression-free survival (rPFS) in patients with metastatic renal cell carcinoma (mRCC) undergoing pre-surgical treatment with bevacizumab.
METHODOLOGY - In this IRB-approved study, prospective imaging analysis of the RRS was performed on phase II clinical trial data of mRCC patients (n = 41) evaluating whether patient stratification according to the RRS resulted in groups more or less likely to have a rPFS to pre-surgical bevacizumab prior to cytoreductive nephrectomy. Survival times of RRS subgroups were analyzed using Kaplan-Meier survival analysis.
RESULTS - The RRS is enriched in diverse molecular processes including drug response, stress response, protein kinase regulation, and signal transduction pathways (P < 0. 05). The RRS successfully stratified rPFS to bevacizumab based on pre-treatment computed tomography imaging with a median progression-free survival of 6 versus >25 months (P = 0. 005) and overall survival of 25 versus >37 months in the high and low RRS groups (P = 0. 03), respectively. Conventional prognostic predictors including the Motzer and Heng criteria were not predictive in this cohort (P > 0. 05).
CONCLUSIONS - The RRS stratifies rPFS to bevacizumab in patients from a phase II clinical trial with mRCC undergoing cytoreductive nephrectomy and pre-surgical bevacizumab.
KEY POINTS • The RRS SOMA stratifies patient outcomes in a phase II clinical trial. • RRS stratifies subjects into prognostic groups in a discrete or continuous fashion. • RRS is biologically enriched in diverse processes including drug response programs.
European radiology. 2015 Nov 11 [Epub ahead of print]
Neema Jamshidi, Eric Jonasch, Matthew Zapala, Ronald L Korn, James D Brooks, Borje Ljungberg, Michael D Kuo
Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. , Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. , Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. , Scottsdale Medical Imaging, Scottsdale, AZ, USA. , Department of Urology, Stanford University School of Medicine, Stanford, CA, USA. , Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea Hospital, Umea, Sweden. , Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.