Kate Johnson

June 11, 2015

BALTIMORE, MD — An investigative radiotracer used to image neuroendocrine cancer patients who have metastatic tumors can successfully locate their previously elusive primary disease and change clinical management, according to a new study presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2015 Annual Meeting here.

"Many times patients first present with metastatic disease…and the primary site of metastatic neuroendocrine tumors (NETs) may go undetected in up to 20% of cases despite extensive work-up," said lead investigator Yusuf Menda, MD, associate professor of radiology and radiation oncology at the University of Iowa Carver College of Medicine in Iowa City.

This is because symptoms of NET are vague, making the duration from symptom onset to diagnosis an average of 9.2 years, he explained at a press briefing.

Positron emission tomography/computed tomography (PET/CT) scanning with gallium 68 DOTATOC (Ga-68 DOTATOC) has proven effective in locating the primary tumor, but although this radiotracer has been used in Europe for more than a decade, it is not approved by the US Food and Drug Administration (FDA), Dr Menda said.

In fact, compared with octreotide, which is the current FDA-approved diagnostic agent for NETs, Ga-68 DOTATOC imaging performs better, according to a meta-analysis ( Eur J Nucl Med Mol Imaging. 2007 Oct;34:1617-1626), with a pooled sensitivity and specificity of 93% and 91%, respectively, he said.

So in a patient who already has metastatic disease, why is it important to find the primary tumor?

"Because depending on where the primary is, the surgical and medical treatment are different," Dr Menda said, adding that resection of the primary tumor, even in the presence of hepatic metastases, improves overall survival.

In light of this, the study aimed to assess the efficacy of Ga-68 DOTATOC PET/CT in 37 patients (median age 55 years) with metastatic disease and unknown primary site.

It found that Ga-68 DOTATOC PET/CT identified the primary site in 13 patients (eight in the small bowel and five in the pancreas), which was confirmed by histology or conventional imaging, and prompted a significant change in management for eight patients (seven had resection of the primary tumor).

"Our results show that in patients with well-differentiated NET metastases, Ga-68 DOTATOC PET-CT is an effective modality to identify the site of unknown primary tumor and may change the management in these patients, primarily by allowing surgical resection of the primary tumor," Dr Menda concluded.

Asked to comment on the findings, Damian Wild, MD, PhD, professor and head of nuclear medicine at the University of Basel Hospital, Switzerland, said, "It has been shown before that somatostatin receptor PET/CT (e.g. 68Ga-DOTATOC PET/CT) is superior to other imaging modalities in the detection of neuroendocrine tumors. In the current study Menda et al. showed that 68Ga-DOTATOC PET/CT can localize the primary neuroendocrine tumor in most patients who present with metastases and unknown primary site. This finding is clinically relevant as previous studies suggest a survival advantage in patients with metastatic neuroendocrine tumors, who undergo resection of the primary tumor."

Additionally, Yuji Nakamoto, MD, PhD, from Kyoto University Graduate School of Medicine, Japan, told Medscape Medical News that while the study results are not surprising, the clinical implications have not caught on outside Europe.

"Unfortunately, US and Japan are relatively behind, more than 10 years, as compared with the status in Europe," he said.

"Neuroendocrine tumors are not often FDG-avid, so it is usually difficult to detect primary and/or metastatic sites with PET/CT with 18F-FDG. Therefore, somatostatin receptor scintigraphy, including PET/CT with 68Ga-DOTATOC, is expected [to be useful] since many NETs express somatostatin receptors," Dr Nakamoto said. He also expressed the hope that "this imaging technique and therapeutic options would be widely accepted in clinical even in US and Japan."

Dr Menda has disclosed no relevant financial relationships.

Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2015 Annual Meeting: Abstract 599. Presented June 8, 2015.

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