P-289 - Preliminary data of a pilot study of combined stereotactic body radiotherapy (SBRT) and bevacizumab as a radiosensitizer for colorectal liver metast...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter H. Chung
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H. Chung1, L. Milot1, W. Chu1, G. Czarnota1, Y.-. Ko2
  • 1University of Toronto, Toronto/CA
  • 2Sunnybrook Research Institute (SRI), Toronto/CA

Abstract

Introduction

Bevacizumab, an anti-VEGF, has been shown to normalize vasculature of tumors by changing tumor blood perfusion and tumor microvessel density, and therefore improve its oxygenation. This may have potential benefits as a radiosensitizer and indeed has been reported in several clinical trials with chemoradiation for locally advanced rectal cancer. To explore the effects of tumour perfusion, blood flow and cell death in vivo (on liver metastasis) as measured by dynamic contrast-enhanced (DCE-) CT and contrast-enhanced ultrasound (CEUS), efficacy and toxicities after bevacizumab and post-SBRT in patients with colorectal liver metastases.

Methods

This was a single-centre, single-arm, open-label proof-of-concept study. Ethics approval was received by our institution. Eligible patients included any patient with metastatic colorectal cancer to liver (1-3 lesions) that was to receive SBRT. Patients received 2 doses of bevacizumab (5mg/kg) separated by 2 weeks. SBRT was commenced within 48 hours of the second dose of bevacizumab, and was up to 60 Gy in 6 fractions (alternating weekdays). DCE-CT and CEUS were performed at baseline, after the second dose of bevacizumab (but before SBRT) and within 7 days of completing SBRT. Toxicities were assessed by NCI CTCAE v4.0. Efficacy of the SBRT was measured by CT and/or MRI and used RECIST v1.1 criteria.

Results

This study enrolled 11 patients. One patient withdrew consent shortly after accrual. Median follow-up was 329 days (8-426). Median age was 64 (44-94) years. There were 7 males and 4 females. All 10 patients completed the bevacizumab and SBRT (median 60 Gy, range 36-60) without dose modifications. Adverse events attributable to bevacizumab included one grade 3 (hypertension), two grade 2 (hypertension, paresthesia) toxicities. For SBRT, there were two grade 2 (fatigue, nausea), but no grade 3 toxicities. By RECIST criteria, the response to the SBRT treated lesions was (n): stable disease (5), partial response (2), progressive disease (2), and not evaluable (2). To date, 5 have died. Eight patients underwent all 3 DCE-CT and were available for analyses. From baseline, median tumor perfusion decreased by 24.8% (-64%-120%) after bevacizumab (but before SBRT) and decreased by 3.3% (-40%-247%) after SBRT. Similarly, median blood flow decreased by 25% (-70%-163%) and 50.2% (-70-24%), respectively.

Conclusion

In our pilot study, we found that bevacizumab can be safely given immediately prior to SBRT for colorectal liver metastases with little toxicities. Tumor perfusion and blood flow decreased after bevacizumab and SBRT, though significant heterogeneity was seen.