DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6

J. P B O'Connor, C. J. Rose, A. Jackson, Y. Watson, S. Cheung, F. Maders, B. J. Whitcher, C. Roberts, G. A. Buonaccorsi, G. Thompson, A. R. Clamp, G. C. Jayson, G. J M Parker

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    Background:There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases.Methods:Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan.Results:In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (v e), tumour enhancing fraction (E F), and microvascular uniformity (assessed with the fractal measure box dimension, d 0) (R 2 0.86, P0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan.Conclusion:Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers. © 2011 Cancer Research UK All rights reserved.
    Original languageEnglish
    Pages (from-to)139-145
    Number of pages6
    JournalBritish Journal of Cancer
    Issue number1
    Publication statusPublished - 28 Jun 2011


    • angiogenesis
    • biomarker
    • heterogeneity
    • MRI
    • outcome
    • personalised medicine


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