A special focus on carcinoid tumors

By Anna E. Mazzucco, Ph.D.
2013

Although textbooks call them rare, the incidence of carcinoid tumors is on the rise.  In 1973, carcinoid tumors were diagnosed in only 8.5 people per million; by 1994 this number more than quadrupled to 38.4 per million.1 This increase could be due to several factors, such as more sensitive detection, increased awareness, and the larger number of Americans over the age of 50.2   However, the cause of the increase is unclear, and these tumors can be life-threatening.  When they grow and spread, these tumors often affect organs that show no symptoms until late in the disease. Like almost all cancers, earlier diagnosis is very important for the overall prognosis.

Carcinoid tumors belong to a larger medical category called neuroendocrine tumors, which are named for their “neural” (i.e. information-sensing) and “endocrine” (i.e. hormone-related) functions.  Carcinoid tumors are a particular type of neuroendocrine tumor, named to reflect being “carcinoma-like” or “carcinoid” due to their microscopic similarities to more aggressive cancers.  They are considered distinct types of tumors because they are usually very slow-growing.3  Instead of being named for the organ in which they occur, the unifying feature of carcinoid tumors is that they start in a particular kind of neuroendocrine cell, which can be found in several different organs.  That is why carcinoid tumors can be found in the stomach, appendix, colon, lung, and other organs, and also why the symptoms, treatment and prognosis of carcinoid tumors can also vary so much between patients.  The location and size of the tumor determine a lot about its characteristics and also which treatments are best.

Risk Factors

Scientists and physicians are still working to understand carcinoid tumors.  We know that there are a few traits which can increase a person’s risk of having a carcinoid tumor.  These include:

  • Age (50 and older)
  • Gender (female)
  • Family history of multiple endocrine neoplasia type I (MEN1)
  • Conditions which cause low stomach acid production, such as Zollinger-Ellison syndrome, pernicious anemia, and atrophic gastritis
  • Smoking (for atypical lung carcinoid tumors)

Symptoms

As carcinoid tumors can form in many different organs, symptoms vary by location, and can be similar to those of other health issues.  However, if you experience any of these symptoms for several days, call your doctor.

For carcinoid tumors of the gastrointestinal system, symptoms may include:

  • diarrhea or constipation
  • nausea
  • abdominal or rectal pain
  • rectal bleeding

For carcinoid tumors of the lungs, symptoms may include:

  • chest pain
  • wheezing or shortness of breath
  • skin discloration that looks like stretch marks
  • unexplained weight gain in the midsection or upper back

Another feature of carcinoid tumors which makes them different from other tumors is that they can cause symptoms which at first may seem unrelated to each other.  In these rare cases (only about five percent of all carcinoid tumor cases), the tumor can cause unusually high amounts of hormones in the blood.4  This situation, called carcinoid syndrome, could result in symptoms such as:

  • flushing
  • heart palpitations
  • large changes in blood pressure
  • swelling of legs and feet

Diagnosis

Diagnosis may rely on several sources of information, such blood and urine tests, imaging tests such as CT or MRI, endoscopy, or biopsy.  Endoscopy allows closer visual examination of the tumor with a tiny camera passed through the digestive tract.  During an endoscopy, a biopsy sample may be collected, which is very small amount of tissue removed for analysis.  Based on this information, physicians will often classify carcinoid tumors as either typical or atypical.  They will also define a tumor as having “local”, “regional spread”, or “distant spread”, based on how far a tumor may have grown beyond its original location.

Treatment

Surgery is often used as the first treatment for carcinoid tumors.  If the tumor hasn’t spread, surgery can cure the cancer.  Surgery may also be combined with other treatments to reduce the tumor and the symptoms.  If the tumor has spread to the liver, which is quite common, it can be surgically treated by blocking the artery to the liver with chemotherapy or injected polymer beads. Liver tumors can also be treated by radiofrequency (radiowaves) or cryotherapy (using cold to destroy cancer cells).2

The drugs most commonly used to treat carcinoid tumors are hormone therapies called somatostatin analogues, such as octreotide (Sandostatin) and lanreotide (Somatuline Depot), which are given as daily or monthly injections, respectively.  These drugs work to block the growth of the tumor and the hormones it may produce, and can be effective for long periods of time, although the dose may need to be increased over time.  Newer versions of these drugs, such as pasireotide, are being developed and compared to the older drugs to determine which are more effective, and for whom.   Other treatments are being developed that use these same drugs to deliver radiation directly to cancer cells, such as in MIBG therapy.   A different drug also used to treat carcinoid tumors is interferon (Intron A, Pegasys), which uses the body’s own immune defenses against the tumor.2  New studies are evaluating the safety and effectiveness of combining hormone therapies such as octreotide with interferon to see if they work better together.  Radiation and traditional chemotherapies are not usually helpful for slow-growing carcinoid tumors.  However, some carcinoid tumors (often called “atypical”) with higher growth rates (or high “proliferation index”) may respond to them.  Studies of combinations of chemotherapy drugs are being conducted to find out which are most effective.

As scientists are learning more about carcinoid tumors, new drugs called “targeted therapies” are being developed, which are based on a detailed biological understanding of the tumor.  Clinical trials are being done to investigate these new drugs for carcinoid tumors, such as everolimus (Afinitor), sunitinib (Sutent), azaspirane (Atiprimod), IGF-R1 blockers (AMG 479), and VEGFR and Akt inhibitors (such as Tricirinine, Axitinib, Votrient, Avastin, Cometriq, Ziv-aflibercept) 2,5  Everolimus and sunitinib have been approved by the Food and Drug Administration for the treatment of advanced pancreatic neuroendocrine tumors, but FDA will not approve these drugs for carcinoid tumors until clinical trials are completed to show whether they are safe and effective for those tumors.   Studies have shown that carcinoid tumors produce high amounts of particular proteins related to cell growth, including IGF-R1 and VEGFR2, and new drugs are being developed to block these molecules.6   Another new treatment, YF476, is being tested specifically for stomach carcinoid tumors.

If you are undergoing treatment for a carcinoid tumors, up-to-date information about clinical trials can be found here.   A healthy diet, exercise, and emotional support can also be helpful during treatment for cancer.  If you have questions about your treatment or want to know more about your treatment options, ask your doctor lots of questions and consider seeking another opinion until you receive the information you need.

  1. Maggard et al., Annals of Surgery. 2004: 240(1): 117-122.  
  2. Gustafsson B et al., Curr Opin Oncol. 2008; 20:1–12.  
  3. Pinchot et al., Oncologist. 2008; 13(12): 1255–1269.  
  4. Gastrointestinal carcinoid tumors treatment (PDQ). National Cancer Institute. http://cancer.gov/cancertopics/pdq/treatment/gastrointestinalcarcinoid/Patient  
  5. Dong et al., Clin Cancer Res. 2012.  
  6. Bowen et al., J Gastrointest Surg. 2009.