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

  • Molecular Imaging
  • Published:
European Radiology Aims and scope Submit manuscript

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.

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Abbreviations

RRS:

radiogenomic risk score

SOMA:

surrogate of molecular assay

WHO:

World Health Organization

SPC:

supervised principal component

ccRCC:

clear cell renal cell carcinoma

mRCC:

metastatic renal cell carcinoma

GO:

gene ontology

MSKCC:

Memorial Sloan Kettering Cancer Center

RECIST:

response evaluation criteria in solid tumours

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Acknowledgments

MDK is the scientific guarantor of this publication. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. MZ, NJ, and MDK have significant statistical expertise. Institutional review board approval was obtained from Umea Hospital and the MD Anderson Cancer Center. Written informed consent was obtained from all subjects in this study. None of the study cohort imaging findings or results have been previously reported in the literature. This is a retrospective, diagnostic/prognostic, single institution study.

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Authors and Affiliations

  1. Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA

    Neema Jamshidi, Matthew Zapala & Michael D. Kuo

  2. Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Eric Jonasch

  3. Department of Radiology, University of California-San Diego, San Diego, CA, USA

    Matthew Zapala

  4. Scottsdale Medical Imaging, Scottsdale, AZ, USA

    Ronald L. Korn

  5. Department of Urology, Stanford University School of Medicine, Stanford, CA, USA

    James D. Brooks

  6. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea Hospital, Umea, Sweden

    Borje Ljungberg

Authors
  1. Neema Jamshidi
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  2. Eric Jonasch
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Correspondence to Michael D. Kuo.

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Jamshidi, N., Jonasch, E., Zapala, M. et al. The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial. Eur Radiol 26, 2798–2807 (2016). https://doi.org/10.1007/s00330-015-4082-8

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  • DOI: https://doi.org/10.1007/s00330-015-4082-8

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