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Classifying NETs Versus NECs in Gastrointestinal Cancer

Danielle Bucco
Published: Thursday, Jan 18, 2018

Jennifer Eads, MD
Jennifer Eads, MD
Patients with gastrointestinal cancers who have aggressive grade 3 (G3) neuroendocrine neoplasms can have either neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs), which should be specifically classified as 2 separate entities, according to Jennifer Eads, MD.

“Determining the pathologic differentiation status of these G3 tumors can have a significant impact on the prognosis and treatment decision of the patient,” says Eads.

Appropriate classification can lead to more precise therapeutic approaches. There is a phase II study (NCT02595424) investigating cisplatin, carboplatin, and etoposide versus temozolomide and capecitabine in patients with metastatic GI NECs. Certain NECs may respond better to treatments other than the current standard of care, which is a regimen of cisplatin and etoposide. The primary objective of the study is to determine the progression-free survival (PFS) of platinum-based therapy and etoposide versus the PFS of temozolomide and capecitabine in this patient population. This trial is currently accruing patients.

In an interview with OncLive, Eads, an assistant professor of medicine, senior clinical instructor, Department of Medicine, University Hospitals Cleveland Medical Center, discusses the classification of NETs versus NECs.

OncLive: What is the current classification of NETs?

Eads: Within the neuroendocrine population of patients, there is an aggressive category that is grade 3. Within that subcategory, there are NETs and NECs. The current classification system for NETs includes many tumors in the G3 category that are heterogeneous and should be classified as 2 separate entities. The features of G3 NETs and NECs, such as the pathology, genetics, and clinical presentation distinguish a less aggressive, well-differentiated G3 tumor from a more aggressive or poorly differentiated G3 tumor.

Can you discuss those characteristics and how they present differently?

The current classification scheme for GI neuroendocrine neoplasms involves using both the tumor histology, Ki-67, and the mitotic index as parameters for placing a tumor within a category and guiding us in terms of what to do. There is a separate classification scheme that is used for neuroendocrine neoplasms of the lung, which uses mitotic index and the presence or absence of necrosis as their main distinguishing features. Their classification system does not include Ki-67. 

We hope to understand how Ki-67 contributes to the GI component. What the pathologic and clinical studies have indicated is that the tumor differentiation status is the most important factor when determining if a patient is likely to be in the less aggressive G3 category versus the more aggressive G3 category. It makes a difference in terms of patient presentation because, often, the patients with more aggressive G3 tumors do not do as well. Those patients have a median overall survival (OS) that is quite poor and usually die in less than 1 year. However, patients who are in the well-differentiated category and have Ki-67 on the lower end of the G3 range often have a better median OS outcome of several years.

There is also a difference in their response to therapies, such as platinum-based therapy. Platinum-based therapy is the standard for G3 NECs, but is probably not appropriate for patients who have well-differentiated tumors or who may have Ki-67 in the lower end of the G3 pathology category. 

Are there difficulties in detecting that specific diagnosis?

It requires a lot of pathologic knowledge. You rely heavily on the pathologist to make the correct diagnosis. Pathologists who do this often are able to make these very detailed subtle distinctions, whereas pathologists who do not see as many neuroendocrine neoplasms may be unsure.

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