The Lancet Gastroenterology and Hepatology





① 剂量递增组包括9例诊断时血清癌胚抗原(CEA)升高的初治结直肠癌,拟开腹或内镜手术切除,扩展组包括17例复发或腹膜转移结直肠癌,拟行开腹手术;② 3+3剂量递增设计,SGM-101分别为5 mg、7.5 mg和10 mg,术前2-4天静脉注射30分钟;③ SGM-101未引起任何治疗相关性不良事件,剂量递增组术前4天给药10mg的肿瘤-背景比最高;④ 扩展组荧光成像额外检出43%病灶,改变了35%患者的治疗策略;⑤ 扩展组的敏感性98%,特异性62%,荧光强度准确率84%。

结直肠癌 癌胚抗原 荧光成像


Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study


Abstract & Authors展开

Tumour-targeted fluorescence imaging has the potential to advance current practice of oncological surgery by selectively highlighting malignant tissue during surgery. Carcinoembryonic antigen (CEA) is overexpressed in 90% of colorectal cancers and is a promising target for colorectal cancer imaging. We aimed to assess the tolerability of SGM-101, a fluorescent anti-CEA monoclonal antibody, and to investigate the feasibility to detect colorectal cancer with intraoperative fluorescence imaging.We did an open-label, pilot study in two medical centres in the Netherlands. In the dose-escalation cohort, we included patients (aged ≥18 years) with primary colorectal cancer with increased serum CEA concentrations (upper limit of normal of ≥3 ng/mL) since diagnosis, who were scheduled for open or laparoscopic tumour resection. In the expansion cohort, we included patients (aged ≥18 years) with recurrent or peritoneal metastases of colorectal cancer, with increasing serum concentrations of CEA since diagnosis, who were scheduled for open surgical resection. We did not mask patients, investigators, or anyone from the health-care team. We assigned patients using a 3 + 3 dose design to 5 mg, 7·5 mg, or 10 mg of SGM-101 in the dose-escalation cohort. In the expansion cohort, patients received a dose that was considered optimal at that moment of the study but not higher than the dose used in the dose-escalation cohort. SGM-101 was administered intravenously for 30 min to patients 2 or 4 days before surgery. Intraoperative imaging was done to identify near-infrared fluorescent lesions, which were resected and assessed for fluorescence. The primary outcome was tolerability and safety of SGM-101, assessed before administration and continued up to 12 h after dosing, on the day of surgery, the first postoperative day, and follow-up visits at the day of discharge and the first outpatient clinic visit. Secondary outcomes were effectiveness of SGM-101 for detection of colorectal cancer, assessed by tumour-to-background ratios (TBR); concordance between fluorescent signal and tumour status of resected tissue; and diagnostic accuracy in both cohorts. This trial is registered with the Nederlands Trial Register, number NTR5673, and, number NCT02973672.Between January, 2016, and February, 2017, 26 patients (nine in the dose-escalation cohort and 17 in the expansion cohort) were included in this study. SGM-101 did not cause any treatment-related adverse events, although three possibly related mild adverse events were reported in three (33%) of nine patients in the dose-escalation cohort and five were reported in three (18%) of 17 patients in the expansion cohort. Five moderate adverse events were reported in three (18%) patients in the expansion cohort, but they were deemed unrelated to SGM-101. No changes in vital signs, electrocardiogram, or laboratory results were found after administration of the maximum dose of 10 mg of SGM-101 in both cohorts. A dose of 10 mg, administered 4 days before surgery, showed the highest TBR (mean TBR 6·10 [SD 0·42] in the dose-escalation cohort). In the expansion cohort, 19 (43%) of 43 lesions were detected using fluorescence imaging and were not clinically suspected before fluorescent detection, which changed the treatment strategy in six (35%) of 17 patients. Sensitivity was 98%, specificity was 62%, and accuracy of fluorescence intensity was 84% in the expansion cohort.This study presents the first clinical use of CEA-targeted detection of colorectal cancer and shows that SGM-101 is safe and can influence clinical decision making during the surgical procedure for patients with colorectal cancer.

All Authors:
Leonora S F Boogerd, Charlotte E S Hoogstins, Dennis P Schaap, Miranda Kusters, Henricus J M Handgraaf, Maxime J M van der Valk, Denise E Hilling, Fabian A Holman, Koen C M J Peeters, J Sven D Mieog, Cornelis J H van de Velde, Arantza Farina-Sarasqueta, Ineke van Lijnschoten, Bérénice Framery, André Pèlegrin, Marian Gutowski, Simon W Nienhuijs, Ignace H J T de Hingh, Grard A P Nieuwenhuijzen, Harm J T Rutten, Francoise Cailler, Jacobus Burggraaf, Alexander L Vahrmeijer

First Authors:
Leonora S F Boogerd, Charlotte E S Hoogstins

Alexander L Vahrmeijer