Newly Diagnosed With a Neuroendocrine Tumor: First Steps

Neuroendocrine tumors, or NETs, start in a scattered set of hormone-making cells. Those cells sit all over the body. NCI calls these tumors rare and slow-growing.

You may see the older word carcinoid on your report. It means the same family of tumors.

The scale is small. Worldwide, about 2 people per 100,000 are diagnosed each year. NETs make up about 0.5 percent of all new cancers. The average age at diagnosis is 61.4.

NCI groups them by the part of the embryonic gut they came from:

• Foregut, up to 25 percent of cases. Lung, thymus, stomach, or upper duodenum.
• Midgut, up to 50 percent. Small intestine, appendix, or proximal colon.
• Hindgut, about 15 percent. Distal colon or rectum.

Other sites include the gallbladder, kidney, liver, pancreas, ovary, and testis.

Site predicts behavior. NCI reports that people with NETs of the appendix and rectum live longer. Those with tumors of the stomach, small intestine, or colon do worse. Small intestine NETs spread more readily than those of the appendix, colon, or rectum. That holds even when they are small.

One more fact worth knowing. A second, unrelated cancer shows up in roughly 29 percent of people with small intestinal NETs. It may come at the same time or later.

A functional tumor makes hormones that cause symptoms. A nonfunctional one does not.

In the pancreas, NCI names five functional types. They are gastrinoma, insulinoma, glucagonoma, somatostatinoma, and VIPoma. VIPoma is also called Verner-Morrison syndrome. About 15 percent of islet cell tumors are nonfunctional. Those look much like ordinary pancreatic cancer.

Two of these have distinctive pictures. Zollinger-Ellison syndrome comes from a gastrinoma. It means stubborn peptic ulcers, diarrhea, and high stomach acid. NCI notes it causes under 1 percent of all peptic ulcer disease. Of gastrinomas, 15 to 35 percent are linked to MEN1 syndrome, and up to half are malignant. Diagnosis rests on serum gastrin ten times normal, or above 500 pg/mL. Insulinomas are the opposite. They are far more often benign than malignant.

MEN1 is multiple endocrine neoplasia type 1. It is inherited, and it causes tumors of the pituitary, parathyroid, and endocrine pancreas. If it applies to you, there may be several pancreatic tumors. Your relatives should be checked.

Carcinoid syndrome hits fewer than 20 percent of people with NETs. It starts when vasoactive amines reach the bloodstream. Those are hormone-like substances the tumor makes. The result is flushing, belly pain and diarrhea, tight airways, and heart disease.

There is a reason it usually signals liver spread. The liver normally breaks these substances down. So the syndrome rarely appears without liver metastases. Exceptions include lung and ovarian primaries, pelvic or retroperitoneal spread, and wide bone spread.

Carcinoid heart disease develops in more than one third of those with the syndrome. Scarring thickens the heart valves. The tricuspid and pulmonic valves are hit harder than the mitral and aortic. That causes leaking valves, a narrowed pulmonary valve, and irregular heart rhythms. NCI links severe carcinoid heart disease to shorter survival.

Ask for an echocardiogram if you have flushing or diarrhea. This is a cardiology problem hiding inside an oncology diagnosis.

24-hour urinary 5-HIAA. This measures a breakdown product of serotonin. Specificity is about 88 percent. Sensitivity is reported as low as 35 percent. Prep matters. You must avoid foods rich in serotonin, such as bananas, tomatoes, and eggplant.

Plasma chromogranin A, or CgA. Very sensitive, but not specific. It also rises in pancreatic and small cell lung cancers. NCI calls it a better marker than urinary 5-HIAA. Its level tracks with how advanced the disease is.

One trap deserves emphasis. Proton pump inhibitors are common acid-reducing drugs. They cause false-positive CgA results. NCI notes this happens even at a low dose, taken briefly. Tell whoever orders the test if you take one.

Most NETs carry somatostatin receptors on their surface. NCI reports that more than 70 percent of gut and pancreatic NETs carry several subtypes. Subtype 2 and subtype 5 dominate.

Scans use that. A radiolabeled somatostatin analogue is injected, and receptor-rich tumors light up. Sensitivity of the octreotide scan is reported as high as 90 percent. Misses come from small tumors, technical problems, or too few receptors.

For bone, technetium-99m MDP scintigraphy is the main tool, with detection rates of 90 percent or higher.

One exception matters. Receptor imaging works less well for insulinomas. They often carry few somatostatin receptors.

Somatostatin analogues are the backbone. Octreotide came first. NCI describes its benefit as limited to symptom relief. About 70 percent of patients see their diarrhea or flushing clear. Lanreotide is long-acting and given every 10 to 14 days. It works about as well, with 75 to 80 percent reporting less diarrhea and flushing.

Depot forms exist for both. One study set short-acting octreotide under the skin against monthly long-acting octreotide. Median survival was measured from the date of metastatic diagnosis. It was 143 months with the short-acting form and 229 months with the long-acting form. That is a 66 percent lower risk of death.

Four radionuclide conjugates are used most. They are iodine I 131-MIBG, indium In 111, yttrium Y 90, and lutetium Lu 177. The last three are bound to somatostatin analogues. That is how they find the tumor.

NCI calls 177Lu-octreotate the most promising advance here. The largest series reported covered 131 patients. Remission rates tracked with two things: high uptake on the scan beforehand, and limited tumor in the liver.

By contrast, median tumor response to 131I-MIBG is under 5 percent, though roughly 70 percent achieve tumor stability.

For advanced pancreatic NETs, NCI lists several chemotherapy drugs. They include streptozocin, doxorubicin, fluorouracil, dacarbazine, and temozolomide.

Two targeted drugs have randomized evidence of longer progression-free survival. One is sunitinib, a tyrosine kinase inhibitor. The other is everolimus, an mTOR inhibitor.

• Call 911 or go to an emergency department if intense flushing arrives together with wheezing, a racing heart, or fainting. That combination can be a carcinoid crisis, and it is most dangerous around anaesthesia or a procedure. Wheezing that your usual inhaler will not touch also counts.
• Call your care team the same day if diarrhea leaves you lightheaded when you stand, or you cannot hold fluids down. Fluid and potassium losses here get out of hand quickly.
• Call your care team within a day or two if flushing episodes are becoming more frequent, your ankles are swelling, or breathlessness lying flat or on stairs is new. Those point to the heart valves rather than the gut.

• Where did my tumor start, and is it well or poorly differentiated?
• What is my Ki-67 index, and what grade does that make it?
• Has somatostatin receptor imaging been done? Did the tumor light up?
• Was my chromogranin A drawn while I was taking a proton pump inhibitor?
• Do I need an echocardiogram to check my heart valves?
• Should I be tested for MEN1?

https://www.cancer.gov/types/gi-neuroendocrine-tumors/hp/gi-neuroendocrine-treatment-pdq

https://www.cancer.gov/types/pancreatic/hp/pnet-treatment-pdq