Neuroendocrine Tumors: An Evidence-Based Discussion - Episode 1

Clinical and Biological Distinctions in Neuroendocrine Tumors

Transcript:Matthew H. Kulke, MD: Hello, and thank you for joining us for this OncLive Peer Exchange. The clinical presentation and the biology of neuroendocrine tumors varies widely and impacts both the prognosis and management of this disease. More recently, evidence has emerged regarding additional benefits with somatostatin analogs, with chemotherapy, as well as with a number of new targeted treatment approaches.

This OncLive Peer Exchange will focus on understanding the clinical and biological distinctions in neuroendocrine tumors, symptom management, the role of surgery, and some of the latest research that is likely to impact clinical practice.

My name is Dr. Matthew Kulke. I direct the program in Neuroendocrine and Carcinoid Tumors at Dana-Farber/Brigham and Women's Cancer Center. I’m also an associate professor of medicine at Harvard Medical School. I’m joined today by: Dr. Jennifer Eads, who is an assistant professor of medicine in the Division of Hematology and Oncology at University Hospitals Seidman Cancer Center, Case Western Reserve University, Case Comprehensive Cancer Center. I’m also joined by Dr. Eric Liu, who is a surgical oncologist at the Rocky Mountain Cancer Center; Dr. Diane Reidy-Lagunes, an assistant attending physician at Memorial Sloan-Kettering Cancer Center; and Dr. James Yao, who is professor and chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. Thanks for participating in this discussion. Let’s get started.

My first question is going to go to Dr. Yao. James, you’ve been in this field for a while, and when we first started treating neuroendocrine tumors, we thought they were all the same disease. I think that understanding has changed over the years. In your perspective, how has our understanding changed?

James C. Yao, MD: Well, that’s a great question. As you mentioned, way back when, when we were early in this disease, we used terms like apudoma and carcinoid tumor, atypical carcinoid, and thought of this as a pretty homogeneous, but rare disease. But what we’re understanding is they’re a little more common than we thought and, actually, it’s a group of different diseases that are in some way similar.

We know now that primary site makes a big difference in terms of prognosis, as well as response to some types of treatment. For example, we have diseases like gastric carcinoid and rectal carcinoid tumor where most of the time they’re localized, have great prognosis, and they don’t recur. But they are actually malignant, and when they do spread, they tend to have a very aggressive course.

Matthew H. Kulke, MD: One of the biggest differences is if you just take a step back and think about what are called carcinoid tumors and pancreatic neuroendocrine tumors, they look identical under the microscope but they responded really differently to treatments.

James C. Yao, MD: Absolutely. With pancreatic neuroendocrine tumors, they tend to be much more responsive to cytotoxic chemotherapy. We also have phase III data for VEGF inhibitors such as sunitinib, a trial that you were very involved in developing, a drug you’re very involved in developing. And we also understand, underlying some of these differences, there are real differences in terms of the molecular biology.

For example, in pancreatic neuroendocrine tumors, you see a lot of somatic mutations in the MEM1 gene. Along with that, we also see mutation in DAXX, ATRX, and the mTOR pathway. And, along with that, we also understand that now they have a lot of recurrent chromosomal copy number changes. With small bowel carcinoid tumor, another large group, it’s actually quite different. We see very few somatic mutations that recur. Ten percent were p27 involving the cell cycle.

But generally, on a genomic sequencing level, they are pretty bland. They do have recurrent copy number variations and loss of one copy of chromosome 18. And the value of that, in terms of prognostic features, is still an area under investigation. There are some hints that that may be a prognostic marker in this group of patients. But as we move forward, we’re going to find more and more of these molecular differences that drive the biology and clinical course difference that we see.

Diane Reidy-Lagunes, MD: I would add to that too, James, as you said, we have the pancreatic neuroendocrine tumors that we say is a different entity, and then we have the so-called carcinoid. For the last 5 to 10 years, we have sort of lumped all extra pancreatic neuroendocrine tumors into one lump sum of carcinoid. As you were saying, that’s probably not the right thing to do. And back in the olden days when we used to have the foregut, midgut, and hindgut, now as we’re learning about the genetics, in fact, foregut may be different than the so-called midgut.

So, the lung, gastric, and pancreatic neuroendocrine may have common genetic findings, as well as clinical findings. So, it’s really interesting that in many ways, we’re going back to the old day’s nomenclature in thinking about, genetically, how these cancers may arise and not necessarily lumping them together as all carcinoids.

Transcript Edited for Clarity