Prognosis

The most important prognostic factor is whether or not the tumor can be removed surgically. Other significant prognostic for patients with neuroendocrine tumor include the the size of the tumor, the grade of the tumor (how fast the cells are dividing), and the presence or absence of metastases to lymph nodes or other organs (also known as stage).

John Cameron

Surgical Treatment

Surgical resection remains the best hope for a cure for patients with well-differentiated (“low grade) neuroendocrine tumors. Many well-differentiated neuroendocrine tumors can be cured if they can be completely removed, and some patients with metastases (tumors that have spread beyond the gland or organ in which the tumor arose) can achieve long-term survival after their metastases are surgically resected. The surgical team at Johns Hopkins has decades of experience removing neuroendocrine tumors. The undifferentiated neuroendocrine carcinomas (small cell carcinomas or high-grade neuroendocrine carcinomas) are often best treated with chemotherapy.

If you have an neuroendocrine tumor of the pancreas and would like to be treated at Johns Hopkins, please contact us at 410-955-8964.

Medical Treatment

The best medical treatment for patients with a neuroendocrine tumor depends on the grade of the tumor. Low-grade tumors are so slow growing that they do not respond to conventional chemotherapy (which usually targets fast growing cells). Instead, they are best treated with specific targeted therapies. High-grade neuroendocrine carcinoma (such as small cell carcinomas) are best treated with chemotherapy.

Medications

Low-grade Tumors

There are several relatively new and exciting chemotherapy options available to patients with some types of neuroendocrine tumors. For example, the U.S. Food and Drug Administration (FDA) has approved the drugs Sutent (sunitinib) and Afinitor (Everolimus) for the treatment of advanced neuroendocrine tumors. Sutent is manufactured by Pfizer, and Afinitor by Novartis. It is exciting to see that the options available for patients with neuroendocrine tumors is growing!

Afinitor was approved for the treatment of patients with progressive pancreatic neuroendocrine tumors that are not resectable surgically, that are locally advanced or metastatic. This approval by the FDA was based on a phase III clinical trial of Afinitor, in which the drug was shown to prolong progression free survival in patients with advanced pancreatic neuroendocrine tumors. This phase III trial was reported in the New England Journal of Medicine (N Engl J Med. 2011 Feb 10;364(6):514-23.). The research team at Johns Hopkins has played a role in understanding the likely mechanism by which Afinitor works. The team sequenced all of the known human genes in a series of pancreatic neuroendocrine tumors and found that one in six of these tumors harbors an activating mutation (DNA change) in the mTOR pathway. (Jiao, Shi, Edil, de Wilde, Klimstra, Maitra, Schulick, Tang, Wolfgang, Choti, Velculescu, Diaz, Jr., Vogelstein, Hruban & Papadopoulos, Science, 2011). This is the very pathway that Afinitor targets, and it is likely that Afinitor will be most effective in patients with a tumor with an mTOR pathway gene mutation.

Sunitinib belongs to the class of drugs called "tyrosine kinase inhibitors," and it has both effects against blood vessels in tumors (antiangiogenic) and effects against the tumor itself (antitumor properties). In a phase III clinical trial treatment with Sunitinib has been shown to significantly improve progression free survival in patients with metastatic pancreatic neuroendocrine tumors (PNETs) (Reviewed in: Cancer Metastasis Rev, 2011, Suppl 1:19-26).

In some instance metastases to the liver can be treated by destroying their blood supply using techniques such as hepatic artery embolization, chemoembolization or embolization using radionucleotides Radioembolization (Yttrium-90).

These approaches involve the selective cannulation of the blood vessels leading to the tumor. The vessels feeding the metastases are identified and then destroyed (embolized).

In some instances drugs can be used to block the symptoms causes by the release of hormones from the neuroendocrine tumor. For example, proton pump inhibitors can be used to counteract the high levels of stomach acid produced in patients with gastrinomas. Finally, in selected patients response rates as high as 70% have been reported following the treatment of islet cell tumors / pancreatic endocrine neoplasms with the drug streptozocin.

Clearly, there are a lot of options for the medical treatment of neuroendocrine tumors. If you would like to be seen by one of our oncologists, please contact our multi-disciplinary clinic coordinator, Suzanne Smallwood-Massey, at 877-LIVER99 (548-3799) or by e-mail: hopkinslivercenter@jhmi.edu.

High-grade Neuroendocrine Carcinomas

High-grade neuroendocrine carcinomas are best treated with multiagent chemotherapy, and published studies have shown that the treatment at academic centers is associated with improved survival (see PMID: 32395915).

Interventional Radiology

An exciting relatively new approach to the treatment of neuroendocrine tumors is “interventional radiology.” As the name suggests, this is the medical field in which radiologists with advanced training deliver treatments that are guided by imaging (radiology). This approach can be used to deliver a variety of therapies, including:

  1. Chemoembolization is a method of blocking the blood vessels that feed the tumor. It is particularly used to treat tumors that have metastasized (spread) to the liver. Chemoembolization can also be used to deliver high doses of chemotherapy directly to neuroendocrine tumors in the liver. Good results have been obtained using chemoembolization on patients who are not candidates for standard therapy. A small catheter from the blood vessel in the patient’s groin is placed into the artery that supplies blood to the liver. Chemotherapeutic drugs can then be delivered through the catheter along with a blood vessel occluding agent to the blood vessels supplying the tumor. As a result, highly concentrated chemotherapy is delivered and, at the same time, the blood vessels supplying the tumor are partially blocked with the occluding agent starving the tumor of it's blood supply. This "double-punch" can slow or stop tumor growth, and in some cases can even result in significant shrinkage of the tumor.
  2. Radioembolization is a method similar to chemoembolization, only radioactive (Yttrium-90) beads are delivered instead of chemotherapy. These radioactive beads deliver radiation directly to the tumor, minimizing systemic side effects while maximizing local delivery to the tumor.
  3. Radio Frequency Ablation (RFA) is another technique that can be used to treat tumors, particularly tumors that have metastasized (spread) to the liver. Radio frequency ablation, as the name suggests, uses radio frequency waves to destroy tumors. Basically, under radiology guidance, a long a needle-like probe is inserted through the skin and the tip placed inside the tumor. The operator then activates the device passing radio frequency waves through the probe into the tumor. These waves greatly increase the temperature within neuroendocrine tumor and the increased heat kills the tumor. This approach can also be used intraoperatively, in which case the probe is place directly by the surgeon.

As you can see there are a host of new options available for the treatment of neuroendocrine tumors. Determining which of the many options available is right for a particularly patient requires an experienced multidisciplinary team such as the team assembled at Johns Hopkins.