The Underlying Biology and Prevalence of NETs

Video

Transcript:

Simron Singh, MD: The treatment landscape of neuroendocrine tumors (NETs) has experienced exponential growth with the addition of several new agents after decades of limited therapeutic options. Now clinicians must focus on how to optimally sequence these therapies.

In this OncLive® Peer Exchange, we will discuss the importance of multidisciplinary care for affected patients as well as available treatment options and emerging therapies.

My name is Dr Simron Singh. I’m a medical oncologist and co lead of the Susan Leslie Clinic for Neuroendocrine Cancers at the Sunnybrook Health Sciences Centre in Toronto, Ontario. I’m also an associate professor at the University of Toronto.

Joining me today is Dr Jonathan Strosberg, head of the Neuroendocrine [Tumor] Division and chair of the Gastrointestinal Department of Research Program at the Moffitt Cancer Center and an associate professor at the University of South Florida College of Medicine.

Thank you for joining us.

So Jon, maybe we’ll start by talking about the biological mechanisms that drive neuroendocrine cancers. What do you think about that?

Jonathan R. Strosberg, MD: The underlying biology of NETs is unique compared with most cancers. It is probably best characterized for pancreatic neuroendocrine tumors, where most of the genetic mutations seem to involve chromatin remodeling—so things like MEN1, which is present in 40% of pancreatic NETs as a somatic mutation. In addition to MEN1, hereditary genes such as DAXX and ATRX are also involved in chromatin remodeling. About 15% involve the mTOR pathway—things like PIK3CA, PTEN, and things of that nature. Overall, the mutational burden in well-differentiated NETs tends to be quite low.

As you know, in small bowel neuroendocrine tumors, we know much less about underlying genetic mutations. Epigenetic changes seem to be the driver of carcinogenesis, but there are very few targetable mutations. Generally, we’re talking about tumors with a very low mutational burden. Of course, on the other end of the spectrum are poorly differentiated neuroendocrine carcinomas with mutations that are much more common, such as p53, RB, and RAS. And so it’s a very heterogeneous family of cancers. Each primary site in well versus poorly differentiated has its own unique biological mechanisms.

Maybe you can talk a bit about the incidence and prevalence of NETs. It seems to have increased quite a bit over the past couple of years.

Simron Singh, MD: Yes. It’s interesting. As you know, we’ve been seeing more and more cases of neuroendocrine cancers. Dr Yao’s paper from 2008, which was published in the Journal of Clinical Oncology, first described this phenomenon. An update then showed that the rate continued to rise. In Canada, we also did a very similar study in which we basically found similar results—an increasing incidence of NETs. When you look around the world, a lot of registries have seen the same phenomenon of more neuroendocrine cancers. I don’t know what the real cause of that is. I speculate it’s probably due to better classification and a better understanding of the disease. Even the Nordic registries are showing an increase. As you know, in the Nordic areas, they were quite advanced in classifying these tumors quite early on.

Jonathan R. Strosberg, MD: Right.

Simron Singh, MD: And so there may be something in there, as well, about an increase in incidence.

Jonathan R. Strosberg, MD: So you think there might be a real increase in disease?

Simron Singh, MD: There might be. It might be both. I clearly think a better understanding and classification has helped us understand that there are more of these tumors out there than we ever thought.

Jonathan R. Strosberg, MD: We’re obviously picking up a lot of small incidental tumors as patients undergo routine scans and routine endoscopies. Sometimes it’s a bit of a conundrum—how to deal with really small, low-grade, potentially not clinically significant tumors but tumors that cause a lot of anxiety among patients. We know from autopsy series that the actual incidence of neuroendocrine neoplasms, if you look carefully enough, is well in excess of 1%. So there are a lot of really small, clinically insignificant neuroendocrine tumors out there. We’re definitely picking up more of those.

Simron Singh, MD: I think that’s going to be a big area for us in the future. We need to try to understand, as you alluded to, what to do with these small lesions. Would it affect people’s lives? Do we need to treat them? If so, how? And what is the most patient-centered, least invasive way that we can deal with these lesions if we need to?

Jonathan R. Strosberg, MD: Exactly. When it comes to prevalence, because patients with metastatic disease can live for many years, I think it’s been shown that the prevalence of NETs is well over 100,000 in the United States. This makes it the second-most-prevalent gastrointestinal cancer after colorectal cancer. So NETs are often thought of as very rare, but when you think of prevalence, they’re quite common.

Simron Singh, MD: Yes, I think that’s a really important point. I think we need to realize that there are many patients living with neuroendocrine cancer, much like a chronic cancer. We need to meet their needs when we’re talking about what kinds of treatments we want to develop. I think it’s also important for our colleagues to understand that there are a lot of patients living with neuroendocrine cancers who are maintaining their daily lives.

Transcript Edited for Clarity

Related Videos
Katrina S. Pedersen, MD, MS, associate professor, John T. Milliken Department of Medicine, Division of Oncology, Medical Oncology program leader, cofounder, Young Onset Colorectal Cancer Program, Washington University School of Medicine in St. Louis, Siteman Cancer Center
Riccardo Lencioni, MD, FSIR, EBIR
Manish A. Shah, MD
Dae Won Kim, MD, Gastrointestinal Oncology Program, Moffitt Cancer Center
Michael J. Overman, MD, The University of Texas MD Anderson Cancer Center,
John Michael Bryant, MD,
Jacob Shreve, MD, MS, hematology/oncology fellow, Mayo Clinic
Efrat Dotan, MD, Fox Chase Cancer Center
A panel of 4 experts on gastrointestinal cancers
A panel of 4 experts on gastrointestinal cancers