TY - JOUR
T1 - Fluorescence-Guided Visualization of Soft-Tissue Sarcomas by Targeting Vascular Endothelial Growth Factor A
T2 - A Phase 1 Single-Center Clinical Trial
AU - Steinkamp, Pieter Jan
AU - Pranger, Bobby Klaas
AU - Li, Meifang
AU - Linssen, Matthijs D
AU - Voskuil, Floris Jan
AU - Been, Lukas B
AU - van Leeuwen, Barbara L
AU - Suurmeijer, Albert J H
AU - Nagengast, Wouter B
AU - Kruijff, Schelto K
AU - van Ginkel, Robert J
AU - van Dam, Gooitzen Michell
N1 - Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Resection of soft-tissue sarcoma (STS) is accompanied by a high rate of tumor-positive surgical margins (14%-34%), which potentially lead to decreased disease-free survival. Vascular endothelial growth factor A is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety, and optimal dose of bevacizumab-800CW for fluorescence-guided surgery in STS for in vivo and ex vivo tumor detection. Methods: Patients with a histopathologic diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 d before surgery (10, 25, and 50 mg; n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab800CW at the optimal dose. Fluorescence images were obtained in vivo and ex vivo during all stages of standard care. The optimal dose was determined by calculating in vivo and ex vivo tumor-to-background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in vivo and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg, with a median in vivo TBR of 2.0 (+/- 0.58) and a median ex vivo TBR of 2.67 (+/- 1.6). All 7 tumor-positive margins could be observed in real time after surgical resection. Conclusion: GS using 10 mg of bevacizumab-800CW is feasible and safe for intraoperative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase 2 study is needed to confirm the diagnostic accuracy.
AB - Resection of soft-tissue sarcoma (STS) is accompanied by a high rate of tumor-positive surgical margins (14%-34%), which potentially lead to decreased disease-free survival. Vascular endothelial growth factor A is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety, and optimal dose of bevacizumab-800CW for fluorescence-guided surgery in STS for in vivo and ex vivo tumor detection. Methods: Patients with a histopathologic diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 d before surgery (10, 25, and 50 mg; n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab800CW at the optimal dose. Fluorescence images were obtained in vivo and ex vivo during all stages of standard care. The optimal dose was determined by calculating in vivo and ex vivo tumor-to-background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in vivo and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg, with a median in vivo TBR of 2.0 (+/- 0.58) and a median ex vivo TBR of 2.67 (+/- 1.6). All 7 tumor-positive margins could be observed in real time after surgical resection. Conclusion: GS using 10 mg of bevacizumab-800CW is feasible and safe for intraoperative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase 2 study is needed to confirm the diagnostic accuracy.
KW - soft-tissue sarcoma
KW - fluorescence-guided surgery
KW - molecular imaging
KW - vascular endothelial growth factor A
KW - tumor targeting
KW - near-infrared fluorescence
KW - LOCAL RECURRENCE
KW - NAVIGATION
KW - SURGERY
KW - SAFETY
KW - MARGIN
KW - SERIES
KW - 1ST
U2 - 10.2967/jnumed.120.245696
DO - 10.2967/jnumed.120.245696
M3 - Article
C2 - 32680922
SN - 0161-5505
VL - 62
SP - 342
EP - 347
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -