TY - JOUR
T1 - Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI
AU - Guo, J.
AU - Glass, J. O.
AU - McCarville, M. B.
AU - Shulkin, B. L.
AU - Daryani, V. M.
AU - Stewart, C. F.
AU - Wu, J.
AU - Mao, S.
AU - Dwek, J. R.
AU - Fayad, L. M.
AU - Madewell, J. E.
AU - Navid, F.
AU - Daw, N. C.
AU - Reddick, W. E.
N1 - Publisher Copyright:
© 2015 Cancer Research UK. All rights reserved.
PY - 2015/11/3
Y1 - 2015/11/3
N2 - 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 18 F-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 (SUV max) and association with drug exposure, and evaluated with clinical outcome.Results:K trans (P=0.041) and v p (P=0.001) significantly dropped from baseline at 24h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in v p at day 5 (P=0.04) and week 10 (P=0.02). A lower K trans 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.
AB - 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 18 F-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 (SUV max) and association with drug exposure, and evaluated with clinical outcome.Results:K trans (P=0.041) and v p (P=0.001) significantly dropped from baseline at 24h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in v p at day 5 (P=0.04) and week 10 (P=0.02). A lower K trans 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.
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U2 - 10.1038/bjc.2015.351
DO - 10.1038/bjc.2015.351
M3 - Article
C2 - 26461056
AN - SCOPUS:84946493879
SN - 0007-0920
VL - 113
SP - 1282
EP - 1288
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 9
ER -
