Radiolabeled Peptide Offers Surgical Method for Assessing NETs

Radioguided surgery (RGS) using gallium 68 (⁶⁸Ga) dota peptides offers a highly sensitive method for detecting neuroendocrine tumors (NETs), according to a new study. Researchers determined a tumor to background ratio (TBR) that can be used as a cutoff for NETs that warrant surgical resection.

“A unique and important feature of NETs is that they express somatostatin receptors, which can be targeted with radiolabeled peptides for imaging and treatment,” wrote study authors led by Mustapha El Lakis, MD, of the National Cancer Institute in Bethesda, Maryland. “Positron emission tomography with computed tomography using somatostatin analogues labeled with positron-emitting ⁶⁸Ga dota peptides has been shown to be more accurate than other agents for detecting many types of NETs.”

A previous pilot study showed that RGS using ⁶⁸Ga-dotatate is safe and feasible in patients with gastroenteropancreatic NETs; the new study aimed to evaluate intraoperative criteria using the same technique that could define positive lesions and warrant resection. The results were published in JAMA Surgery.

The study included a total of 44 patients (22 women, 22 men) with a total of 133 lesions detected on preoperative imaging. Of that group, 43% had a diagnosis of a pancreatic NET, 50% had a gastrointestinal NET, and 7% had pheochromocytoma or paraganglioma. The primary outcome measure was the TBR, which was obtained by normalizing to the omentum (in 106 lesions) or other solid organs (27 lesions).

Lesions that contained NETs had a higher TBR than those that did not, at 18.9 compared with 4.4 (P < .001). A receiver operating curve analysis found that a TBR of 2.5 yielded a sensitivity for determining a NET of 90% and a specificity of 25%. Using a TBR of 16, meanwhile, offered a sensitivity of 54% and a specificity of 81%.

A total of 49 of the 133 lesions (36.8%) were seen on preoperative MRI scans, and 88% of those were NETs, with a significantly higher TBR compared with lesions seen on MRI with negative histologic findings (21.0 vs 2.7; P = .04).

“A TBR of 2.5 or more is a highly sensitive threshold for guided surgical resection of suspicious lesions,” the authors concluded. “Long-term follow-up and comparison with patients who did not have ⁶⁸Ga-dotatate RGS are needed to determine if such a surgical approach reduces the rate of persistent or recurrent disease.”

In an accompanying editorial, James R. Howe, MD, of the University of Iowa Hospitals and Clinics in Iowa City, wrote that this was an “important study” showing the utility of RGS in this setting, but that several important questions remain. “These questions include how many additional lesions are found using RGS vs imaging and exploration alone, and whether RGS reduces operative time or incomplete resections, which will further define its clinical utility,” he wrote.

Thomas Clancy, MD, of the division of surgical oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was not involved with this research, told Cancer Network that the novel peptide is "a potentially exciting tool to allow surgeons to address known surgical challenges with NETs: localization of both small functional tumors and occult nonfunctional metastases." He noted that it is unclear if there is an absolute benefit to the technique over careful operative dissection, and that any correlation with imaging was not documented. "Further work is needed to see whether the technique is sufficiently sensitive to identify all tumors seen on imaging, and follow-up studies using postoperative ⁶⁸Ga-dotatate/PET after radioguided surgery would be useful," he said. "The technique therefore is not practice-changing at present, but certainly offers promise worthy of further investigation."