Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI

Background: The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI. Methods: Six DCE-MRI and three 18F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K-trans, v(p), and v(e)) were examined for correlation with FDG-PET (SUVmax) and association with drug exposure, and evaluated with clinical outcome. Results: Ktrans (P = 0.041) and vp (P = 0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in vp at day 5 (P = 0.04) and week 10 (P = 0.02). A lower Ktrans at week 10 was associated with greater percent necrosis (P = 0.024) and longer event-free survival (P = 0.034). Conclusions: This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.