Pancreatic cancer has been in the national spotlight lately with "Jeopardy" host Alex Trebek revealing his diagnosis. For the majority of all pancreatic cancer cases, the cancer begins in the ducts of the pancreas. This is known as pancreatic ductal adenocarcinoma and is the deadliest form of the disease. The other 5%-10% fall under the category of pancreatic neuroendocrine tumors (pNETs). While rare form, pNETS are still potentially deadly. Two prominent people who succumbed to pNETs include Aretha Franklin and Steve Jobs.
To learn more about pNETs and how they differ from other types of pancreatic cancer, we spoke with Xavier Keutgen, MD, the director of University of Chicago Neuroendocrine Tumor Program and one of the few surgeons in the country with advanced expertise in extensive removal of neuroendocrine tumors. Keutgen is also a lead investigator on several clinical trials focusing on new diagnostic and therapeutic methods for endocrine and neuroendocrine tumors.
What is the best way to understand what a neuroendocrine tumor (NET) is? Why is it called "neuro?"
Neuroendocrine tumors are tumors that develop from neuroendocrine cells. These are cells that can be found in almost every organ in the body yet, despite the word "neuro," they have nothing to do with the brain. Their name stems from the cells' connection to the autonomic nervous system (the nervous system that you cannot control). Neuroendocrine tumors can develop in any organ that has neuroendocrine cells. These cells produce hormones or proteins that can be secreted in our bloodstream. For example, in the pancreas, you can find these cells in pancreatic islets, which secrete hormones like insulin that regulate our blood sugar. Although pancreatic neuroendocrine tumors develop from these islet cells that normally secrete hormones, about 75% of the tumors are nonfunctional and do not produce hormones.
How common are NET tumors? What is the most common NET tumor you see at UChicago Medicine?
Currently, 170,000 people live with a NET tumor in the United States. Each year, 400-700 people in the Chicagoland area are diagnosed with a neuroendocrine tumor. It's not as rare as most people think and is even getting more common. That's most likely due to a combination of being able to better diagnose these tumors and just a general increase in occurrence. I think that, overall, the most common NETs we see in a clinical setting at UChicago Medicine are NETs of the lung, small bowel and pancreas.
What is the difference between pancreatic ductal adenocarcinomas and pancreatic neuroendocrine tumors (pNET)?
The most common mistake is that "pancreatic cancer" is confused with "pancreatic neuroendocrine tumors." Usually pancreatic cancer is defined as adenocarcinoma of the pancreas (derived from pancreatic ductal cells), which has a bad prognosis. Only 5% to 10% of pancreatic tumors are pNETs. They behave differently, have a much better prognosis and are treated completely differently. Unlike the more common type of pancreatic cancer, 50% of patients that have metastasized pNET (or cancer that has spread to other parts of the body) live five years or longer after diagnosis.
What is the treatment for pNETs?
The most common treatment is surgery. If the tumor is still localized and has not spread, we remove tumors greater than 2 centimeters. We recently published a study examining the correlation between tumor size and surgery and what size is best to perform surgery for. If the tumor secretes hormones (~10-25% of patients), the tumor is resected regardless of size. If the tumor has spread, surgery is still common. Here at UChicago Medicine, we are very good at and specialized in this type of surgery.
For example, if the tumor has spread to the liver, we can remove the primary tumor from the pancreas, while also taking out all or almost all of the disease in the liver with very specialized techniques to prevent harm to the remaining sections of healthy liver. This is called parenchymal-sparing resection, which allows us to take out parts of the tumor carefully, one-by-one. The deeper tumors can be burned with microwave ablation. With this technique, we can resect 30, 40 or sometimes up to 50 lesions out of the liver without damaging liver function.
What are the other treatment options?
Unlike adenocarcinoma, classic chemotherapy is rarely used to treat pNETs. In addition to or instead of surgery, some patients received intramuscular injections or a daily oral pill to slow down the tumor growth, which sometimes is successful for many years. Recent, more advanced therapies include the new and promising PRRT therapy, or peptide receptor radionuclide therapy. PRRT is a radioactive infusion given every other month for eight months that targets the tumor cells without having to affect other organs. It has minimal side effects and is a promising therapy because it can shrink the tumor in up to 30-40% of patients with pancreatic neuroendocrine tumors.
How are pNETs and other neuroendocrine cancers diagnosed? What are the symptoms?
Since most tumors do not secrete hormones, most patients are asymptomatic. That means they have no obvious symptoms like weight loss and abdominal pain. They also don't turn yellow (jaundice). These tumors grow slowly over months and years without ever being noticed. In many cases, the patients may get a CT scan or ultrasound for another condition, which is how their tumor is found. If the tumors do secrete hormones such as insulin or gastrin, they are typically diagnosed more quickly. That's because they can cause hypoglycemia, leading to low glucose levels and passing out or lead to stomach acidity and ulcers.
Who is most at risk? How can you lower your risk?
There are some rare inherited genetic conditions that make some people more susceptible to having NETs. Besides rare genetic syndromes, we do not currently know of a reason why people develop these tumors.
What are the latest research efforts focused on?
Here at the UChicago Medicine Comprehensive Cancer Center, my laboratory focuses on understanding why some people respond better to certain therapies than others. We are studying how to improve the effectiveness of PRRT to make it better for pancreatic and other NET patients. We also specialize in trying combination therapies, such as combining PRRT with surgery. Also, next year, we will be starting a clinical trial specifically examining these combination therapies for patients with pancreatic neuroendocrine tumors.