Matthew H. Kulke, MD
When it comes to neuroendocrine tumors (NETs), there is no shortage of nomenclature. Broad categories, such as “carcinoid,” belie the true heterogeneous nature of this group of diseases and the complexity of their management.
During the past several years, a wealth of positive clinical trials coupled with an evolution in understanding of the cancer type has altered the treatment landscape. At a recent OncLive
Peer Exchange session entitled “Neuroendocrine Tumors: An Evidence-Based Discussion,” a panel of experts examined the latest evidence in NETs and provided valuable insight into how these advances are likely to impact clinical practice.
Although carcinoid tumors and pancreatic NETs look identical under the microscope, they respond differently to treatments, said moderator Matthew H. Kulke, MD. This is due to biological differences at the molecular level.
Pancreatic NETs have somatic mutations that have a lot of recurrent chromosomal copy number changes, agreed James C. Yao, MD. Small bowel carcinoid tumors, by contrast, have very few somatic mutations that recur.
“We know now that primary site makes a big difference in terms of prognosis as well as response to some types of treatment,” Yao said. “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,” he said. “But they are actually malignant, and when they do spread, they tend to have a very aggressive course.”
James C. Yao, MD
It is important to note, however, that what was formerly lumped into a single “carcinoid” category is now being recognized as multiple diseases, said Diane Reidy Lagunes, MD. “Now as we’re learning about the genetics, in fact, foregut may be different than the so-called midgut,” she said. The lung, gastric, and pancreatic tumors may have common genetics and seem to have clinical similarities as well, Lagunes said.
In addition to primary site, NETs are classified according to whether they are well differentiated or poorly differentiated, and the treatment options for these tumor types also differ, explained, Jennifer Eads, MD. Within the poorly differentiated tumors, there are further distinctions: large cell and small cell histologies.
Systemic chemotherapy is the standard of care for poorly differentiated tumors, and no targeted agents have been found to be useful in this setting. “It’s very difficult to do clinical trials in this population,” Eads stated. “And historically, because the histology under the microscope has been similar to that seen in small cell lung cancer, we’ve really just extrapolated data from the small cell lung cancer literature to guide our treatments for the poorly differentiated population.”
Diane Reidy Lagunes, MD
For patients with well-differentiated NETs, there are more options, noted Eads. These include somatostatin analogues (SSAs), targeted therapies such as VEGF or mTOR inhibitors, and cytotoxic therapies based on primary site.
In order to more fully define the classification, Eads uses supplementary features such as the Ki67 proliferative index. Poorly differentiated tumors typically are defined by a Ki67 of at least 20% up to 100%, said Eads.
However, the panelists agreed that there are gray areas where disease burden trumps this proliferative index. “There’s this borderline in between where sometimes patients can have a well-differentiated histology but may have a Ki67 that technically classifies them as a high-grade or poorly differentiated tumor,” Eads said. “I think that gray area is difficult.”