TY - JOUR
T1 - Dose-Finding Study of a CEA-Targeting Agent, SGM-101, for Intraoperative Fluorescence Imaging of Colorectal Cancer
AU - de Valk, Kim S.
AU - Deken, Marion M.
AU - Schaap, Dennis P.
AU - Meijer, Ruben P.
AU - Boogerd, Leonora S.
AU - Hoogstins, Charlotte E.
AU - van der Valk, Maxime J.
AU - Kamerling, Ingrid M.
AU - Bhairosingh, Shadhvi S.
AU - Framery, Bérénice
AU - Hilling, Denise E.
AU - Peeters, Koen C.
AU - Holman, Fabian A.
AU - Kusters, Miranda
AU - Rutten, Harm J.
AU - Cailler, Françoise
AU - Burggraaf, Jacobus
AU - Vahrmeijer, Alexander L.
N1 - Funding Information: The study was funded by Surgimab (Montpellier, France). The company Quest Medical Imaging BV (Middenmeer, the Netherlands) provided the near-infrared Quest Spectrum Platform imaging system. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - Background: Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC. Methods: Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose. Results: Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients. Conclusions: The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.
AB - Background: Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC. Methods: Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose. Results: Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients. Conclusions: The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.
UR - http://www.scopus.com/inward/record.url?scp=85092351518&partnerID=8YFLogxK
U2 - https://doi.org/10.1245/s10434-020-09069-2
DO - https://doi.org/10.1245/s10434-020-09069-2
M3 - Article
C2 - 33034788
SN - 1068-9265
VL - 28
SP - 1832
EP - 1844
JO - Annals of surgical oncology
JF - Annals of surgical oncology
IS - 3
ER -