Tumor-targeted fluorescence may help pinpoint colorectal cancer during surgery

Last Updated: 2018-02-08

By Marilynn Larkin

NEW YORK (Reuters Health) - SGM-101, a fluorescent antibody that targets carcinoembryonic antigen (CEA), may help detect colorectal cancer metastases intraoperatively, according to a small, open-label, phase-2 pilot study.

CEA, overexpressed in 90% of colorectal cancers, is a promising target for imaging, according to Dr. Alexander Vahrmeijer of Leiden University Medical Center, in the Netherlands, and colleagues.

To investigate, the team included two cohorts in their Netherlands-based pilot: the nine patients in the dose-escalation cohort had primary colorectal cancer with increased serum CEA concentrations since their diagnosis, and were scheduled for open or laparoscopic tumor resection; the 17 patients in the expansion cohort had recurrent or peritoneal metastases of colorectal cancer, with increasing CEA concentration since diagnosis, and were scheduled for open surgical resection.

The dose-escalation cohort received 5 mg, 7.5 mg, or 10 mg of SGM-101 administered intravenously for 30 minutes either two or four days before surgery; the expansion cohort received a dose considered optimal at that moment, but not higher than the dose used in the dose-escalation study.

Intraoperative imaging was used to identify near-infrared fluorescent lesions, which were resected and assessed for fluorescence.

As reported online January 17 in The Lancet Gastroenterology and Hepatology, the antibody did not cause any treatment-related adverse events (AEs). However, three possibly related mild AEs were reported in three (33%) patients in the dose-escalation cohort, and five were reported in three (18%) patients in the expansion cohort. Five moderate AEs deemed to be unrelated to SGM-101 were reported in three (18%) patients in the expansion cohort.

No changes in vital signs, electrocardiogram, or laboratory results were found in either cohort after the maximum 10-mg SGM-101 dose was administered.

In the dose-escalation cohort, the 10-mg dose given four days before surgery was associated with the highest tumor-to-background ratios (mean TBR, 6.10).

In the expansion cohort, imaging detected 19 (43%) of 43 lesions that had not been clinically suspected previously. This detection changed the treatment strategy for six (35%) of the patients. In this cohort, fluorescence imaging detected lesions with 98% sensitivity, 62% specificity, and 84% accuracy.

Dr. Vahrmeijer told Reuters Health, "The key findings from our paper are that we were able to identify colorectal cancer and metastases in real time (and) that in about (35%) of our patients with either recurrent or locally advanced rectal cancers, the surgical plan was changed based on the intraoperative findings."

"However," he said by email, "this is still a pilot study and more data are needed to show the full capabilities of this technique."

"A phase-3 pivotal trial is expected to start in a few months," he added.

Dr. Steven Wexner of Cleveland Clinic Florida in Weston, author of a related commentary, told Reuters Health by email, "CEA-targeted fluorescence seems to be a safe, potentially accurate, and easy-to-use method of identifying malignant foci, which is a natural extension of our rapidly expanding indications for intraoperative fluorescence imaging."

Several other U.S. colorectal cancer experts commented in emails to Reuters Health.

Dr. Edward Levine, chief, Surgical Oncology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, said, "This preliminary study is encouraging in that approximately 40% of patients had some additional site of cancer found using the technique."

"However," he noted, "this approach will be useful for only about half of patients at best because only about half of patients with colon cancer have significantly elevated CEA levels."

"It is far too early to start planning to use this approach until much larger safety and efficacy research trials confirm (its) utility," he concluded.

Dr. Scott Strong, chief, Division of Gastrointestinal Surgery at Northwestern University Feinberg School of Medicine and surgical director, Digestive Health Center of Northwestern Medical Group in Chicago, said, "Despite the use of standard preoperative imaging to determine the areas involved by (the) colorectal tumor, unanticipated tumors detected only by SGM-101 altered the planned procedure in six patients in the study's 'expansion cohort'."

"This group was at especially high risk for tumor to be located outside the normal confines because many of the patients were undergoing surgery for cancer that had recurred or diffusely spread in the abdominal cavity," he noted.

"The true impact of this modality will not be known until longer follow-up is available and we see how recurrence and survival rates are influenced," Dr. Strong concluded.

Like the other commentators, Dr. Anton Bilchik, chief of gastrointestinal research at John Wayne Cancer Institute and chief of general surgery at Providence Saint John's Health Center in Santa Monica, California, observed that this is a small pilot study "and, while promising, larger studies are needed to validate (the findings)."

"The ability to find small tumors missed by conventional imaging has great therapeutic value," he said. "Many attempts have been made, but none has been particularly successful."

The study was funded by Surgimab, Montpellier, France, which owns the SGM-101 conjugate. Two authors are employees and three (including one of the employees) are Surgimab founders and stockholders.

SOURCES: http://bit.ly/2GEsaLq and http://bit.ly/2ExHj0B

Lancet Gastroenterol Hepatol 2018.