PET Scans Help Detect Difficult-to-treat Tumors in Ectopic Cushing’s Syndrome, Study Suggests

Positron emission tomography (PET) scans help identify neuroendocrine tumors causing ectopic Cushing’s syndrome in patients whose disease persisted or recurred after initial treatment, a new study suggests.

The research, “68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing’s syndrome,” was published in the journal Endocrine.

Paraneoplastic (meaning “associated with cancer”) Cushing’s syndrome, also known as ectopic Cushing’s syndrome, results from the overproduction of adrenocorticotropic hormone by a malignant tumor outside the pituitary gland.

These tumors — called neuroendocrine tumors — are mostly found in the lungs, but may also be located in the thymus, thyroid, adrenal gland, or pancreas. Early detection is key to improve patient survival, but 20% of these cases remain undetectable for years using conventional imaging methods.

PET is an imaging technique that measures tissue metabolism. It uses small amounts of radioactive labels, called radiotracers, along with a special camera and computer to help evaluate organ and tissue function.

As neuroendocrine tumors have high levels of somatostatin receptors — proteins that bind the hormone somatostatin — PET radiotracers targeting these receptors could improve early tumor detection. One of these radiotracers is called 68Ga-edotreotide (DOTATOC).

Researchers from France analyzed 19 patients (14 women and five men, between 26 and 71 years old) who underwent DOTATOC PET scans from January 2011 to June 2017.

Thirteen patients underwent scans to detect a primary (initial) neuroendocrine tumor over a median 14 months after their ectopic Cushing’s syndrome diagnosis. PET scans identified the tumors in six of these patients, with four tumors located in the lungs. Seven patients were ruled as having negative PET scans.

However, one patient developed a pituitary adenoma — tumors normally slow-growing and benign found in the pituitary gland — which was detected on a magnetic resonance imaging scan 14 years after diagnosis. Two other patients with negative PET scans also revealed a pituitary adenoma during follow-up. The other four negative PET results corresponded to false negatives, the researchers noted.

In patients undergoing scans to detect a primary tumor, the DOTATOC-PET scan’s sensitivity — the ability to correctly identify a tumor — was 50%, and its accuracy was 56%.

Three patients had undergone PET scans for persistent disease while four had the scans for recurrent disease after surgery. The time between surgery and PET scan ranged from one month to 11 years (median of 40 months). A tumor was found in six of these cases. Surgery confirmed the presence of metastasis — cancer spreading — to lymph nodes in the other case.

Overall, the scan’s sensitivity was 90%, and its accuracy was 82% in these patients.

In addition, all six patients who underwent the scan as a surveillance measure had undergone surgery to remove a neuroendocrine tumor, then identified with the DOTATOC-PET scan. This subsequent assessment three to 55 months after surgery (median of 17 months) identified all cases as true negatives.

Altogether, these results suggest the DOTATOC PET scan “is a particularly valuable tool for detection of the NET [neuroendocrine tumor] responsible for persistent or recurrent [paraneoplastic Cushing’s syndrome] after surgery, even more effective than for detection of the initial causal tumor,” the scientists wrote.