Abramson Cancer Center

Neuroendocrine Tumor Risk Factors

There may be hereditary reasons for developing NETs. People with:

• Multiple endocrine neoplasia type I (MEN-1)
• Multiple endocrine neoplasia type 2 (MEN-2)
• Phacomatoses (neurocutaneous syndromes)

 
Other reasons for developing NETs are sporadic, meaning they are isolated in a family and acquired over a lifetime.

Neuroendocrine Tumor Prevention

There are no known prevention measures for neuroendocrine tumors. Some studies have suggested that smoking doubles the risk of carcinoid tumors in the small intestine so quitting smoking, or not starting to smoke, may reduce risk.

People who have hereditary conditions that may predispose them to developing neuroendocrine tumors should be screened for tumors on a regular basis. Genetic testing may be useful under special circumstances.

Neuroendocrine Tumor Risk Assessment

The Gastrointestinal Cancer Risk Evaluation Program and the Cancer Risk Evaluation Programs at Penn Medicine offers knowledge about the presence of genetic risk factors for cancer and provides patients with important, sometimes life-saving options.

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• Gastrointestinal neuroendocrine tumors
  • Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
    • Alimentary tract carcinoid tumors
      • Functioning vs. non-functioning
    • Pancreatic endocrine tumors (PETs)
      • Functioning vs. non-functioning
• Adrenal neuroendocrine tumors
  • Pheochromocytomas/paragangliomas (PHEOs)
• Others

Gastrointestinal Neuroendocrine Tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

GEP-NETs occur in the digestive tract. They can be classified as alimentary tract carcinoid tumors or pancreatic endocrine tumors (PETs). GEP-NETs are rare, and account for less than 2 percent of all GI tumors. But, their prevalence is high because they are generally inactive tumors.

Alimentary tract tumors can occur anywhere within the digestive tract including the esophagus, stomach, small and large intestine and rectum. Physicians may refer to this area as the “gut” and further classify a tumor, by its location, as being in the foregut, midgut or hindgut.

Alimentary tract tumors are further classified into two groups:

• Tumors that are functional, or secrete hormones.
• Tumors that are non-functional, or do not secrete hormones.

Most alimentary tract tumors are initially non-functional.

Foregut tumors occasionally are functional and can produce an atypical carcinoid syndrome; midgut tumors often are functional, but the carcinoid syndrome may only develop after metastases have developed; hindgut tumors are generally non-functional.

Pancreatic endocrine tumors originate within the pancreas, or in some cases, in nearby tissues.

PETs are also classified into two groups: those tumors that are functional, or secrete hormones, and those that do not.

If the tumors secrete a hormone, they are classified by the type of hormone they produce. Some of these include:

• Gastrinomas: Release gastrin leading to excessive gastric acid production, abdominal pain and ulcers.
• Insulinomas: Release insulin leading to low blood sugar levels.
• Glucagonomas: Release glucagon leading to high blood sugar levels and a typical rash.
• VIPomas: Release vasoactive intestinal polypeptide leading to severe diarrhea and abnormal electrolyte levels.
• Growth hormone producing tumors: Release growth hormone causing acromegaly.
• PPomas and Non-functioning tumors: No identifiable hormone is released such that these tumors are functionally silent.

Adrenal Neuroendocrine Tumors

Pheochromocytomas/Paragangliomas (PHEOs)

PHEOs are rare tumors found in both the adrenal and extra-adrenal locations, located above the kidneys.

Because the adrenal glands produce hormones, tumors on these glands can create an overproduction of hormones causing side effects such as high blood pressure and a rapid heart rate. People with PHEOs are often diagnosed with hypertension.

PHEOs are even more rare than GEP-NETs and account for less than two in 100,000 people with neuroendocrine tumors. Only about 800 people in the United States are diagnosed each year with these tumors. Penn Medicine treats 30 to 40 of these patients per year. These patients often have very high blood pressure.

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Neuroendocrine tumors are usually slow to develop, and may not cause hormonal symptoms, making the condition difficult to diagnose and stage. Also, because most of the symptoms that do occur are often vague and intermittent, they can be easily confused with other more common conditions.

Carcinoid Syndrome Symptoms

• Wheezing
• Flushing
• Diarrhea
• Heart palpitations
• Cardiac disease

Gastrinoma Symptoms

• Pain
• Ulcers
• Heartburn
• Diarrhea

Insulinoma Symptoms

• Low glucose levels
• Confusion
• Shakiness
• Weight gain

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Staging and Prognosis of Neuroendocrine Tumors

Staging systems provide doctors with a common language for describing tumors. After a NET is first diagnosed, a series of tests are used to determine the extent of the tumor and to see whether it has spread to other parts of the body from where it started. Staging is a way of recording the size and growth of a tumor, and developing the plan for treatment. By understanding the stage of their tumor, patients can make informed decisions about their treatment.

Cancer specialists at Penn use the TNM staging method as generally accepted by the World Health Organization.

Cancer specialists may also classify each gastrointestinal carcinoid tumor into one of three general stages:

• Localized. The tumor has not spread outside of the wall of the primary organ, such as the stomach, colon, or intestine.
• Regional spread. The tumor has spread through the wall of the primary organ and to nearby tissues, such as fat, muscle, or lymph nodes.
• Distant spread. The tumor has spread to tissues or organs far away from the primary organ, such as the liver, bones, or lungs.

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After being diagnosed with a neuroendoctine tumor, patients at the Abramson Cancer Center may be evaluated through the Neuroendocrine Tumor Center, which provides expert support and evaluation to discuss treatment options and individualized treatment plans.

Patients with NETs are treated by a multidisciplinary team of cancer specialists who see more patients with gastrointestinal (GI) cancers in one year than many doctors see in their careers.

In addition, the Neuroendocrine Tumor Center at Penn offers patients:

• A tumor board: A treatment planning approach in which the NET team reviews and discusses the medical condition and treatment options of a patient.
• Nurse navigators: Specialty nurses available to guide patients through the appointment and treatment process.
• A single point of contact.

The Penn Neuroendocrine Tumor Treatment Program is an interdisciplinary program centered on the diagnosis, staging and treatment of neuroendocrine tumors.

GEP-NETs and PHEOs are extremely rare. The tumors are usually slow to develop and difficult to diagnose. Symptoms can be as vague as wheezing, flushing, diarrhea, heart palpitations and cardiac disease. Due to the rarity and slow development of GEP-NETs and PHEOs and their possibly life-threatening complications, early diagnosis depends largely on the experience and expertise of physicians and access to advanced imaging and laboratory facilities, genetic testing and multidisciplinary treatments: A combination of advantages unique to Penn Medicine.

The NET program at Penn was developed under the direction of David C. Metz, MD, professor of medicine, a Penn gastroenterologist and associate chief of the GI division, and Debbie Cohen, MD, associate professor of medicine and a Penn nephrologist. Together with the nurse coordinator, they provide a comprehensive, interdisciplinary approach to the diagnosis, staging, and medical and surgical treatment of NETs.

Penn Medicine offers one of the only dedicated NET programs in the country with the combined expertise to treat both GEP-NETs and PHEOs. In addition, Penn’s program is the first and only one of its kind in the Philadelphia region.

The dedicated NET management team at Penn encompasses a variety of clinical disciplines, including:

• Gastroenterology
• Medical  oncology
• Renal hypertension
• Nuclear medicine
• Endocrine and surgical oncology
• Gastrointestinal surgery
• Neurology
• Neurosurgery
• Radiation oncology
• Interventional radiology
• Pathology
• Endocrinology
• Genetic counseling

Patients also benefit from the resources of the Ruth and Raymond Perelman Center for Advanced Medicine and the Abramson Cancer Center. Adjacent to the Hospital of the University of Pennsylvania, the Perelman Center links Penn physicians and researchers in a common commitment to translational medicine and excellence in care.

Oncology Navigation Specialists

Every step of cancer treatment – from cancer diagnosis, to surgery and treatment to forming a survivorship plan – comes with different needs and issues that should be addressed.

Oncology Navigation Specialists at the Abramson Cancer Center are available to make a patient’s experience as seamless as possible. As experts in navigating complex health care situations, patient support specialists serve as a consistent point of contact and a reliable source for advice, support and direction for patients and families. They can help in a variety of ways including; provide emotional support, identify resources, and ensure access to information, support services, educational programs and community resources.

Learn more about Patient Navigation specialists at the Abramson Cancer Center.

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Penn Medicine’s multidisciplinary treatment team includes nationally recognized pathologists and radiologists who are experts at finding and diagnosing tumors.
After a thorough medical exam, if a physician suspects a patient may have a NET, he might order one or more of these diagnostic tests:

• Blood/urine tests. Blood and urine samples may indicate abnormal levels of hormones and other substances. Specific tests are available to identify both carcinoid and pheochromocytomas.
• Imaging tests. Pictures of the inside of the body can help find out whether a suspicious area might be cancerous, learn how far cancer may have spread, and to help determine if treatment is working.
  • Computed tomography (CT) scan. A CT scan creates a 3-D X-ray of the inside of the body. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A CT scan is used to see if the tumor has spread to the liver and to detect a carcinoid tumor in lymph nodes within the abdomen. Sometimes, a contrast medium (dye) is used to provide better detail.
  • Magnetic resonance imaging (MRI). An MRI uses magnetic fields to produce detailed images of the body. A contrast medium may be injected into a patient’s vein to create a clearer picture.
  • Radionuclide scanning (OctreoScan). A small amount of a radioactive hormone-like substance that is attracted to neuroendocrine tumors is injected into a vein. A special camera is then used to show where the radioactivity accumulates.
  • MIBG scan. An imaging test that uses a radioactive substance (called a tracer) and a special scanner to find or confirm the presence of pheochromocytoma and neuroblastoma, which are tumors of specific types of nervous tissue.
  • Endoscopy. Endoscopy allows the doctor to see the lining of the upper or lower digestive system with a thin, lighted, flexible tube called an endoscope. A patient may be sedated as the tube is inserted through the mouth, down the esophagus, into the stomach and small bowel, or through the anus into the rectum. If an abnormality is found, a fine needle aspiration biopsy may be performed.
  • Endoscopic ultrasound. An ultrasound uses sound waves to create a picture of the internal organs. This procedure is often done at the same time as the upper endoscopy. The endoscopic ultrasound can show enlarged lymph nodes, which may indicate a tumor or advanced disease. If identified, a fine needle aspiration biopsy may be performed.
  • Bone scan. A bone scan uses a radioactive tracer to look at the inside of the bones. The tracer is injected a vein. It collects in areas of the bone and is detected by a special camera.
  • Positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. The tumor absorbs the radioactive substance, and a scanner detects this substance to produce images.
  • Barium imaging. Barium coats the lining of the esophagus, stomach, and intestines, so abnormalities are easier to see on X-rays. If there is an abnormality, an endoscopic biopsy can help make the diagnosis of cancer. Barium may be given through a swallow test or an enema.
• Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. A pathologist, who is a doctor that specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease, analyzes the tissue. A biopsy can tell a pathologist the grade and differentiation of the tumor.

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Staging is a way of describing a tumor: Where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the tumor’s stage, so staging may not be complete until all the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's chance of recovery.

Physicians at Penn Medicine use the TNM staging system.

T Stage

The T stage represents the extent of the primary tumor itself.

• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• T1-4: Increasing degrees of size, number or invasion of the primary tumor.

N Stage

The N stage represents the degree of the involvement of the lymph nodes.

• NX: The regional lymph nodes cannot be assessed
• N0: No evidence of spread to the lymph node
• N1: Regional lymph nodes are involved with tumor

M Stage

The M stage represents whether or not there is spread of cancer to other parts of the body.

• M0: No evidence of distant spread of the cancer
• M1: Evidence of distant spread of the cancer including spread to non-regional lymph node chains

The “staging diagnosis” combines the T, N and M groups into four stages (Stage I-IV); some of which have subtypes (a or b) according to overall tumor burden.

Cancer specialists at Penn often classify tumors by whether or not they can be resected, or removed with surgery. There are three ways physicians look at tumors:

• Localized resectable tumors: These are tumors that can be completely removed by surgery. This would include most stage I and some stage II cancers in the TNM system.
• Localized unresectable tumors: Cancers that have not spread to the lymph nodes or distant organs, but cannot be completely removed by surgery are classified as localized unresectable. This would include some early stage cancers, as well as stage IIIA and IIIB cancers in the TNM system. For NETs, debulking, removing some of all of the tumor, surgery may still be an option.
• Advanced tumors: Cancers that have spread to lymph nodes or other organs, especially the liver, are classified as advanced. These would include stage IIIC and stage IV cancers in the TNM system. Most advanced tumors cannot be cured with surgery, though debulking surgery may be done to improve overall outcome.

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Many carcinoid tumors are successfully treated with surgery, and surgery is the first line of treatment for patients with NETs. Complete removal of the entire tumor is the standard treatment whenever possible. When complete removal of the tumor is not possible, surgeons often remove as much of the tumor as they can to provide some relief from symptoms and possibly improve outcomes.

Penn Medicine has one of the largest gastrointestinal surgical programs in the United States with a nationally recognized record for high-quality patient care and survivorship. Penn Medicine has better outcomes for patients with resection surgeries.

There are two types of surgery:

• Resection (to cut off or remove the tumor)  for a cure
• Debulking (to remove by cutting the major part of a tumor that cannot be completely removed surgically), to control symptoms or improve outcomes

Local and local-regional excision

Surgeons remove the primary tumor and a margin of tissue around the primary location in local NETs. Lymph nodes may also be removed in local-regional surgeries. Most localized tumors can be surgically removed through a skin incision, but rectal or gastroduodenal carcinoid tumors may be removed using an endoscope.

Debulking surgery, including liver resection

Debulking surgery removes resectable (able to be removed) sections of the tumor, in particular areas of metastases or where the tumor has spread. It often helps relieve or reduce hormonal or tumor symptoms and may improve outcomes.

Liver transplantation

A liver transplant removes the entire liver and replaces it with a healthy donated liver. Liver transplantation is rarely used in the treatment of carcinoid tumors, but it may help younger patients whose tumors cannot be removed by resection.

Radiofrequency ablation

Sometimes used for carcinoid tumors and metastases, radiofrequency ablation destroys the tumor by heating it with an electric current.

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Penn Medicine specializes in a team approach to chemotherapy treatment with interdisciplinary care and innovative approaches to target tumors prior to surgery.

Hormonal therapy

Hormonal therapy manipulates the endocrine system. Because NETs derive from hormonally responsive tissues, and may produce secretions that affect hormone levels in the body, this treatment may alleviate symptoms and inhibit tumor growth.

Octreotide
Octreotide is a synthetic hormone that inhibits the release of multiple peptides in the body relieving symptoms from NETs.

Proton pump inhibitors (PPIs)
PPIs are a group of drugs that reduce gastric acid production .

Liver-directed therapy

Chemoembolization of the hepatic artery
Injecting an anticancer drug into the hepatic artery, which supplies blood to the liver, blocks blood flow to the liver and disrupts the blood supply to the tumor.

Targeted therapies

Penn’s medical oncologists are combining personalized care with personalized medicine to create targeted therapies for the treatment of cancer. Targeted therapies act as certain molecular pathways leading to tumor suppression.

Chemotherapy

Chemotherapy uses drugs delivered through the bloodstream to kill cancer cells throughout the body. Chemotherapy for a carcinoid tumor is most often used when the tumor has spread to other organs or is causing severe symptoms. This type of tumor rarely responds to chemotherapy alone, and other treatments may be necessary.

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Because NETs can occur in multiple locations, and may be different types of tumors (functioning vs. non-functioning) the type of radiation therapy used for NETs depends on the type of tumor.

Radiation oncologists at Penn Medicine are recognized for developing and using techniques that target radiation precisely to the disease site while sparing nearby tissue.

External beam radiation therapy, most common type of radiation treatment, is delivered by a machine outside the body.  A radiation therapy schedule usually consists of a specific number of treatments given over a specific time. External-beam radiation therapy is the most common radiation treatment for carcinoid tumors, and it is most often used to relieve symptoms from cancer that has spread to the bone.

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Today, more and more people are surviving cancer. Clinical trials, many of which are conducted at Penn Medicine, benefit patients through breakthrough therapies and treatments. These new advances in cancer treatment are occurring every day, giving patients hope that even greater discoveries lie ahead. Through clinical trials:

• Diagnosing cancer has become more precise.
• Radiation and surgical techniques have advanced.
• Medications are more successful.
• Combinations of medical, surgical and radiation therapy are improving treatment effectiveness and enhancing outcomes.
• Strategies to address the late effects of cancer and its treatment are improving quality of life.

Penn Medicine is the only health care facility in the country that is using proton therapy to treat recurrent gastrointestinal tumors in clinical trials. Also, radiation oncologists at Penn Medicine will soon use proton therapy to treat gastrointestinal cancers in the upper digestive tract.

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In addition to standard treatments and clinical trials, patients at Penn Medicine may wish to add additional therapies and treatments such as massage therapy, acupuncture and art therapy. These therapies do not have curative intent, and are designed to complement standard treatments, not take their place.

Integrative Medicine and Wellness Programs

At Penn Medicine, integrative medicine and wellness services can supplement traditional cancer treatments such as chemotherapy, surgery and radiation therapy. While conventional medicine plays a critical role in eradicating cancer, integrative medicine and wellness programs offer patients ways to enhance the quality of their lives, minimize or reduce the side effects of cancer and cancer treatment, and promote healing and recovery.

Cancer specialists at Penn Medicine are knowledgeable and supportive of complementary cancer treatments. The cancer team works with patients and families to integrate these supportive programs into the overall care plan, while ensuring the safety and health of patients.

The Abramson Cancer Center’s range of integrative supportive services is designed to help patients cope with the cancer experience and improve their overall sense of well-being. Services include:

• Acupuncture
• Diet and nutrition
• Mindfulness-based stress reduction therapy
• Reiki therapy
• Yoga
• Exercise and rehabilitation

The Joan Karnell Cancer Center at Pennsylvania Hospital offers a variety of supportive care programs for patients and families, from diagnosis through survivorship. These programs are available at no cost to the patients treated at Pennsylvania Hospital, and some are open to patients treated elsewhere. These services include social work counseling, nutrition counseling, psychological counseling and spiritual counseling.

The Cancer Appetite and Rehabilitation Clinic focuses on patients experiencing loss of appetite and weight.

The Supportive Care Clinic helps to manage cancer-related symptoms. Integrative support programs include:

• Music therapy
• Art therapy
• Shiatsu massage
• Mindfulness meditation

Support groups and educational programs are available at Pennsylvania Hospital throughout the year.

Palliative Care

Palliative care provides medical and non-medical interventions to ease the symptoms of cancer and its treatment. Palliative care includes physical, emotional and spiritual care that can enhance the quality of life for cancer patients.

Palliative care can be used to complement traditional cancer therapies, to treat symptoms or to improve quality of life and when curative therapies are no longer an option.

Palliative care is an approach to patient care that can be integrated with curative therapies at any point from diagnosis to survivorship or end-of-life care.

Palliative care services include chemotherapy, radiation therapy and surgery as well as psychological counseling, art therapy and support groups for patients and families. The goals of palliative care are to enhance the quality of life for cancer patients and their families, and provide emotional and spiritual support to enhance personal growth.

Palliative care services are offered at Pennsylvania Hospital, and at the Hospital of the University of Pennsylvania.  

Penn Home Care and Hospice Services

Penn Home Care and Hospice Services offer a full range of home health care needs by partnering three top-level home health care services under one roof:

• Penn Wissahickon Hospice
• Penn Care at Home
• Penn Home Infusion Therapy

Penn Home Care and Hospice Services offer an array of specialized therapies and medications for patients with cancer and cancer-related conditions.

Oncology Navigation Specialists

Every step of cancer treatment – from cancer diagnosis, through treatment to forming a survivorship plan – comes with different needs and issues that should be addressed.

Oncology Navigation Specialists at the Abramson Cancer Center are available to the experience as seamless as possible. As experts in navigating complex health care situations, Patient Navigation specialists serve as a consistent point of contact and a reliable source for advice, support and direction for patients and families. They can help in a variety of ways including provide emotional support, identify resources, and ensure access to information, support services, educational programs and community resources.

Learn more about Patient Navigation specialists at the Abramson Cancer Center.

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At the end of treatment, neuroendocrine tumor patients should schedule a survivorship visit with their nurse navigator. At this time, patients are provided with a summary of the treatment received as well as a plan for follow-up care.

The survivorship care plan includes information on:

• Potential long-term or late side effects of cancer treatment, the symptoms and treatment.
• Recommendations for cancer screening for disease recurrence or a new cancer.
• Psychosocial effects, including relationships and sexuality.
• Planning follow-up visits.
• Genetic screening for other family members.

A survivorship care plan encourages patients to review the information with their health care team and become active participants in their follow-up care.

Penn also offers neuroendocrine tumor patients a number of support programs and groups to enhance their survivorship care plans.

Oncology Navigation Specialists

Every step of cancer treatment; from a cancer diagnosis, through treatment, to forming a survivorship plan; comes with different needs and issues that should be addressed.

Oncology Navigation Specialists at the Abramson Cancer Center are available to make the patient experience as seamless as possible. As experts in navigating complex health care situations, patient support specialists serve as a consistent point of contact and a reliable source for advice, support and direction for patients and families. They can help in a variety of ways including; provide emotional support, identify resources, and ensure access to information, support services, educational programs and community resources.

Learn more about patient navigation specialists at the Abramson Cancer Center.

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Penn Medicine’s Living Well After CancerTM Program is a nationally recognized program that focuses on issues facing cancer survivors. In 2007, the Abramson Cancer Center was designated a LIVESTRONG ™ Survivorship Center of Excellence Network.  The Abramson Cancer Center is only one of eight LIVESTRONG centers in the United States, and is the only LIVESTRONG Survivorship Center of Excellence in the Philadelphia region. The program focuses on survivorship, a distinct phase of care.

Prescription for Living: The Cancer Survivorship Program at the Joan Karnell Cancer Center at Pennsylvania Hospital, provides patients with a summary of important information about specific cancer diagnoses and treatments, as well as follow-up information and steps to take towards recovery, supportive care and education to help patients adjust to their lives as cancer survivors.

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Penn offers cancer patients support programs and groups to enhance their survivorship care plans.

The Abramson Cancer Center and Joan Karnell Cancer Center at Pennsylvania Hospital provide materials and host a wide range of activities for education and support to address key areas of concern including survivorship for cancer patients and their loved ones.

Focus On: Gastrointestinal Cancers and Focus On: Neuroendocrine Tumors are day-long conferences that addresses issues for patients with neuroendocrine tumors, as well as their loved ones.

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