562P - Bevacizumab beyond progression: how to monitor treatment efficacy? Results of a functional imaging study in murine colorectal cancer

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Basic Science
Colon Cancer
Rectal Cancer
Presenter Linda Heijmen
Authors L. Heijmen1, E.E.G.W. Ter Voert2, C.J.A. Punt3, L. De Geus-Oei4, A. Heerschap2, J. Bussink5, V. Zerbi2, W.J.G. Oyen6, O. Boerman4, H. van Laarhoven3
  • 1Medical Oncology, Radboud University Medical Centre, 6500 HB - Nijmegen/NL
  • 2Radiology, Radboud University Medical Centre, Nijmegen/NL
  • 3Department Of Medical Oncology, Academic Medical Center, Amsterdam/NL
  • 4Nuclear Medicine, Radboud University Medical Centre, Nijmegen/NL
  • 5Radiation Oncology, Radboud University Medical Centre, Nijmegen/NL
  • 6Department Of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB - Nijmegen/NL

Abstract

Introduction

The BRiTE study suggested that bevacizumab beyond progression to first line therapy is beneficial for survival in advanced stage colorectal cancer. However, since response to bevacizumab cannot always be predicted by tumor size measurements, we studied utility of several functional imaging modalities to assess efficacy of bevacizumab beyond progression (BBP).

Methods

26 BALB/c nude mice with s.c. LS174T xenografts (diameter >0.4 cm) were treated with daily capecitabine (200 mg/kg), weekly oxaliplatin (3mg/kg) and 2x/weekly bevacizumab (5 mg/kg). Tumor volume was assessed using caliper measurements. Tumors were considered progressive on the treatment regimen when volume was ≥1.5 times initial volume at 2 succeeding measurements. In 13 mice bevacizumab treatment was continued (BBP group), while the control group received saline injections. Within 3 days after progression, imaging was performed: FDG-PET, diffusion weighted imaging (DWI), T2*, dynamic contrast enhanced MRI (DCE-MRI). Measurements were repeated 7 and 10 days after the first measurements. Linear mixed models were used to assess differences between the 2 groups over time. After the last measurement, tumors were snap-frozen and immunohistochemically examined for 9F1 (vasculature), glucose transporter 1 (GLUT-1), carbonic anhydrase IX (CAIX) and Ki67 (proliferation) expression.

Results

Tumor growth after progression was more pronounced in the control group (p < 0.01). FDG-PET showed a trend towards higher FDG uptake in the control group (p = 0.08). DWI, T2* and DCE-MRI parameters were not significantly different in the 2 groups. Immunohistochemical analyses showed a trend towards lower Ki67 expression (fraction 0.027 vs 0.041 p = 0.05) and higher CAIX fraction (0.21 vs. 0.10 p < 0.01) in the BBP group. The relative vascular area was lower in the BBP group (0.029 vs. 0.042 p = 0.03). Vascular density (104 vs. 127 vessels/mm2 p = 0.16) and GLUT-1 expression (0.08 vs 0.11 p = 0.48) did not significantly differ.

Conclusion

Bevacizumab after progression had significant effects on tumor microenvironment. FDG-PET may be a sensitive functional imaging technique to assess the effects of bevacizumab.

Disclosure

All authors have declared no conflicts of interest.