C159
Temporal evolution and duration of anti-vascular properties of bevacizumab in metastatic colorectal carcinoma (CRC): evaluation by DCE-MRI and tumour volumetrics
James O'Connor1, Geoff Parker1, Andrew Clamp2, Alan Jackson1, Chris Rose1, Claire Mitchell2, Yvonne Watson1, Sue Cheung1, Giovanni Buonaccorsi1, Lynn Hope2, Paula Thorton2, Caleb Roberts1, Olivia del Puerto3, Jurgees Hasan2, Gordon Jayson2
1Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK, 2CR-UK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK, 3Roche Products Limited, Welwyn Garden City, UK
Background
The addition of bevacizumab to conventional cytotoxic chemotherapy prolongs progression free and overall survival in patients with metastatic CRC. Bevacizumab reduces tumour blood flow, so may impair delivery of subsequent cytotoxic chemotherapy. We present the first detailed data that describe the temporal anti-vascular effects of bevacizumab and evaluate the role of size-change metrics in detecting treatment response.
Method
Ten patients with newly diagnosed CRC liver metastases underwent DCE-MRI. Patients were imaged at baseline (twice), 4 hours after single agent 10mg/kg bevacizumab, at 48 hours and at days 8 and 12. Tumour size and enhancing fraction (EF) were measured. Plasma volume (vp) and Ktrans were calculated using the extended Tofts model. Parameter change from baseline was tested for significance using paired t-tests.
Results
Thirty-four tumors were identified. Significant reductions in EF (p=0.007), Ktrans and vp (both p<0.001) were present within 4 hours. All parameter reductions were maximal at 48 hours (all p≤0.001) and persisted until day 8. De-coupling of parameter changes was observed at day 12 – Ktrans returned to baseline but vp remained reduced. Mean tumour volume gradually reduced reaching significance by day 12 (p<0.001), when 12/34 tumours had >25% volume reduction (beyond 95% CI for repeatability).
Conclusion
These data demonstrate a rapid reduction in blood flow and vascular shutdown following bevacizumab administration, implying that cytotoxic chemotherapy should be administered before bevacizumab, rather than concurrently. Volumetric MRI is sensitive at detecting individual and group change in tumour size following one dose of anti-VEGF antibodies.
