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Eur Radiol. 2016 Aug;26(8):2798-807. doi: 10.1007/s00330-015-4082-8. Epub 2015 Nov 11.

The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial.

Author information

1
Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
2
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
3
Department of Radiology, University of California-San Diego, San Diego, CA, USA.
4
Scottsdale Medical Imaging, Scottsdale, AZ, USA.
5
Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
6
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea Hospital, Umea, Sweden.
7
Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. michaelkuo@mednet.ucla.edu.

Abstract

OBJECTIVES:

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.

KEYWORDS:

Bevacizumab; Imaging biomarker; Imaging surrogate; Radiogenomics; Renal cell carcinoma

PMID:
26560727
DOI:
10.1007/s00330-015-4082-8
[Indexed for MEDLINE]

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