Noninvasive imaging surrogate of angiogenesis in osteosarcoma.
OBJECTIVE
Measurement of tumor angiogenesis by qualitative analysis of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI), and its association with diffusion-weighted (DW)-MRI and glucose metabolism using positron emission tomography-computerized tomography (PET-CT) scan has not been explored in osteosarcoma. Present study was aimed to evaluate the potential of these surrogates.


METHODS
Thirty-one treatment naive patients with osteosarcoma underwent MRI and PET-CT preceding and following three cycles of neoadjuvant chemotherapy (NACT) and surgery. Time intensity curves (TICs) representing low microvascular permeability is persistent type while that of high permeability are plateau and washout types. Vascular endothelial growth factor (VEGF) expression was assessed in biopsy and resected specimens by immunohistochemistry. The sample was considered VEGF positive when intensive positive staining of VEGF was observed in >10% of the tumor cells in biopsy or resection specimens.


RESULTS
TIC could correctly identify all 28 VEGF positive samples at baseline and 24/25 (96%) of VEGF positive samples and 5/6 (83%) of VEGF negative samples after NACT. The change in curve pattern from washout/plateau to persistent type was in agreement with corresponding decrease in microvascular permeability, that is, VEGF expression. For persistent type of TIC, mean change in VEGF was 73.3 +/- 43.2% and for plateau and washout type of TIC it was 19.54 +/- 45% and 16.66 +/- 28.86%, respectively (P <or= 0.04). VEGF expression did not correlate with DW-MRI and PET-CT parameters.


CONCLUSIONS
This study suggests an important role of DCE-MRI as a noninvasive imaging surrogate of tumor angiogenesis in osteosarcoma based on visual inspection of TIC.
Bajpai
Jyoti
J
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Gamanagatti
Shivanand
S
Sharma
Mehar C
MC
Kumar
Rakesh
R
Vishnubhatla
Sreenivas
S
Khan
Shah Alam
SA
Rastogi
Shishir
S
Malhotra
Arun
A
Bakhshi
Sameer
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012516:Osteosarcoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D055815:Young Adult
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A