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

Research output: Contribution to journalArticlepeer-review

Abstract

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, P<0.00005). 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.

Original languageEnglish
Pages (from-to)139-45
Number of pages7
JournalBritish Journal of Cancer
Volume105
Issue number1
DOIs
Publication statusPublished - 28 Jun 2011

Keywords

  • Aged
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab
  • Biomarkers, Tumor
  • Colorectal Neoplasms
  • Contrast Media
  • Drug Therapy, Combination
  • Female
  • Fluorouracil
  • Gadolinium DTPA
  • Humans
  • Leucovorin
  • Liver Neoplasms
  • Magnetic Resonance Imaging
  • Male
  • Organoplatinum Compounds
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome

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