The science and art of diagnosing and treating neuroendocrine tumors

Neuroendocrine tumors (NETs) pose unique obstacles for oncologists and radiologists. Many people with this rare condition often do not experience symptoms. Others show signs similar to other diseases, making diagnosis difficult. And treatment requires carefully calibrated techniques to achieve the best possible outcomes.

Radiologist A physician who has special training in creating and interpreting pictures of areas inside the body. The pictures are made with X-rays, sound waves or other types of energy. Sign In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. In medicine, a sign is something found during a physical exam or from a laboratory test that shows that a person may have a condition or disease. Some examples of signs are fever, swelling, skin rash, high blood pressure and high blood glucose. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.
radiologist Dr. Delphine Chen and oncologist Dr. David Zhen
Drs. David Zhen and Delphine Chen

That is where Seattle Cancer Care Alliance (SCCA) radiologist Dr. Delphine Chen and oncologist Dr. David Zhen are helping to make a difference. Among the nation’s top NET experts, Dr. Chen and Dr. Zhen combine leading-edge science and deep clinical experience to artfully navigate the care of patients with these complex tumors.

“We see neuroendocrine tumors that range from slow growing, indolent tumors to aggressive carcinomas. Managing them can be very nuanced,” says Dr. Chen.

Along with their SCCA colleagues, they provide:

  • Expertise that spans the NET spectrum
  • Advanced imaging techniques, including dotatate PET imaging
  • Innovative therapies, such as off-label PRRT for patients with non-GI NETs 
  • Access to emerging treatments through clinical trials 
  • Making a difficult diagnosis 

Though NETs are considered a rare cancer, their incidence is rising. Between 1973 and 2012, the number of NET diagnoses increased more than sixfold. Researchers attribute this rise to an increase in screening colonoscopies and improved imaging technologies, and yet many cases of NETs still go undiagnosed. 

In many cases, radiologists detect tumors while imaging for other conditions. Research also shows NETs are often found more than two years after symptoms develop. "Finding these tumors can be difficult and is frequently delayed," says Dr. Zhen.

As a specialized cancer center, SCCA has advanced tools to evaluate neuroendocrine tumors, and physicians are learning what works best. NETs don’t always show up well on CT scans, especially using standard venous phase contrast. CT scans that capture the arterial phase of contrast are more likely to detect tumors. 

“Even without the extra phases of CT, you can sometimes see the tumors in certain areas of the body if you know what to look for. This is where experience comes in,” Dr. Chen says.  

Evaluating NETs for treatment planning

Diagnostic tools give physicians information about tumors that guides patient prognosis and treatment options. That helps them counsel patients with accuracy and compassion.

“Patients are very anxious about their diagnosis," says Dr. Zhen. "When we have a good understanding of the type and extent of the tumor, we can ease their anxiety and better prepare them for what’s to come.” 

Dr. Zhen relies on a multidisciplinary team's expertise to develop customized treatment plans. The SCCA NET tumor board includes surgeons, oncologists, radiologists and endocrinologists with specialized expertise in multiple body systems where NETs occur (GI tract, lungs, prostate).

Diagnostic tests they use include:

  • Biopsies: Tissue samples aid in the classification of two main types of neuroendocrine cancers—well differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC).
  • Dotatate PET scan: This is an effective, high-resolution tool for evaluating the full extent of the tumor. Dotatate is a radiotracer that binds to a tumor’s somatostatin receptors. 
  • FDG PET scan: FDG is best for imaging poorly differentially neuroendocrine carcinomas. 
  • Biomarker testing: The most common biomarker for NETs is Chromogranin A. But since it fluctuates with other conditions, Chromogranin A is only useful along with other tests to evaluate or track NETs.

Delaying treatment in well differentiated NETs

For low grade NETs that are slow growing, Dr. Zhen discusses that close observation over immediate treatment may be an option. Hormone-producing tumors respond well to somatostatin analogs (octreotide and lanreotide) and help alleviate symptoms. If the tumor is not producing hormones, he counsels patients that a watch and wait may be appropriate but considers each patient’s personal goals as well “In medicine, we're trained to intervene,” says Dr. Zhen.

“But with some NETs, immediate treatment may not provide a benefit. Considering this, as well as the cost, time and potential side effects of treatment, I may counsel patients that close monitoring may be the best option.”

New treatments for neuroendocrine tumors

Treatment options for metastatic NETs range from surgery and chemotherapy to newer targeted therapies and nuclear medicine options.

Peptide receptor radionuclide therapy (PRRT), for instance, is an exciting new systemic radiation treatment that delivers radiation directly to the tumor. SCCA is one of only a few centers in the Northwest that offers PRRT, including LutatheraÒ. This PPRT combines dotatate that binds to the cancer cells, with lutetium 177, that delivers radiation to destroy them. 

FDA approval of PRRT is for gastrointestinal (GI) NETs. However, Dr. Chen uses PRRT off label for other tumors based on results from smaller studies that suggest it is effective.

SCCA interventional radiologists also have extensive experience with liver-directed therapies for patients with NETs. These include:

  • Hepatic artery embolization
  • Radioembolization
  • Radiofrequency ablation

The future of neuroendocrine tumor treatment

Knowing when to deliver treatments is part of the challenge of any treatment plan. Ongoing research at SCCA means physicians are learning more and more about these latest advances.  

“Even though we have standards of care, the bigger question is often which treatment to give up front and which to reserve for later," says Dr. Zhen. "Through our research, we are trying to better understand the fine distinctions of all these available treatments.”

SCCA physicians belong to an active community of NET researchers worldwide. They are involved in current initiatives such as:

  • An upcoming clinical trial aimed at improving treatment options for patients with poorly differentiated extrapulmonary small cell NEC. The trial will evaluate the addition of the immunotherapy drug atezolizumab to standard chemotherapy. 
  • A clinical trial investigating whether abemaciclib, a cyclin-dependent kinase (CDK) inhibitor used in breast cancer treatment, slows cell growth in well differentiated NET. 

Dr. Chen and Dr. Zhen are currently evaluating SCCA patient data to determine whether PRRT drug doses can be tailored to a patient’s tumor burden. SCCA is also a lead site for a repository of NET patient data from major centers across the U.S. aimed at developing guidelines for improved care. 

Partnering with SCCA in neuroendocrine tumor care

As leaders in the field of NET research and clinical care, SCCA doctors partner with clinicians across the northwestern U.S., Alaska and Hawaii. They consult on diagnosis and treatment while also offering patients access to the latest NET therapies and clinical trials. 

SCCA seeks to advance the understanding of these rare and complex tumors and improve patient care. Learn more about neuroendocrine tumor care at SCCA. 

To refer a patient, (206) 606-1024, or use the referral tools available on the SCCA website.

Chemotherapy Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments. Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy. Clinical trial A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis or treatment of a disease. Computed tomography A procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body. The pictures are used to create three-dimensional (3-D) views of tissues and organs. A procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create three-dimensional (3-D) views of tissues and organs. A dye may be injected into a vein or swallowed to help the tissues and organs show up more clearly. This scan may be used to help diagnose disease, plan treatment or find out how well treatment is working. Gastrointestinal Refers to the stomach and intestines. Also called GI. Grade In cancer, a grade is a description of a tumor based on how abnormal the cancer cells and tissue look under a microscope and how quickly the cancer cells are likely to grow and spread. In cancer, a grade is a description of a tumor based on how abnormal the cancer cells and tissue look under a microscope and how quickly the cancer cells are likely to grow and spread. Low-grade cancer cells look more like normal cells and tend to grow and spread more slowly than high-grade cancer cells. Grading systems are different for each type of cancer. They are used to help plan treatment and determine prognosis. Also called histologic grade and tumor grade. Imaging In medicine, a process that makes pictures of areas inside the body. Imaging uses methods such as X-rays (high-energy radiation), ultrasound (high-energy sound waves) and radio waves. Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Indolent Slow-growing. Metastatic A metastatic cancer is a cancer that has spread to other areas of the body by way of the lymph system or bloodstream. Oncologist A physician who has special training in diagnosing and treating cancer. Some oncologists specialize in a particular type of cancer treatment, such as treating cancer with radiation. A physician who has special training in diagnosing and treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. Prognosis A statement about the likely outcome of a disease in a patient. Radiologist A physician who has special training in creating and interpreting pictures of areas inside the body. The pictures are made with X-rays, sound waves or other types of energy. Radiologist A physician who has special training in creating and interpreting pictures of areas inside the body. The pictures are made with X-rays, sound waves or other types of energy. Screening Checking for disease when there are no symptoms. Because screening may find diseases at an early stage, there may be a better chance of curing the disease Checking for disease when there are no symptoms. Because screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (for breast cancer), colonoscopy (for colon cancer) and Pap and HPV tests (for cervical cancer). Screening can also include a genetic test to check for a person’s risk of developing an inherited disease. Side effects A problem that occurs when treatment affects healthy tissues or organs. Some side effects of cancer treatment are nausea, vomiting, fatigue, pain, decreased blood cell counts, hair loss and mouth sores. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain. Targeted therapy A type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells while causing less harm to normal cells. A type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells while causing less harm to normal cells. Some targeted therapies block the action of certain enzymes, proteins or other molecules involved in the growth and spread of cancer cells. Other types of targeted therapies help the immune system kill cancer cells, or they deliver toxic substances directly to cancer cells and kill them. Targeted therapy may have fewer side effects than other types of cancer treatment. Most targeted therapies are either small molecule drugs or monoclonal antibodies. Treatment plan A detailed plan with information about a patient’s disease, the goal of treatment, the treatment options for the disease and the possible side effects and expected length of treatment. A detailed plan with information about a patient’s disease, the goal of treatment, the treatment options for the disease and the possible side effects and expected length of treatment. A treatment plan may also include information about how much the treatment is likely to cost and about regular follow-up care after treatment ends. Watchful waiting Closely watching a patient’s condition but not giving treatment unless symptoms appear or change. During watchful waiting, patients may be given certain tests and exams. Closely watching a patient’s condition but not giving treatment unless symptoms appear or change. Watchful waiting is sometimes used in conditions that progress slowly. It is also used when the risks of treatment are greater than the possible benefits. During watchful waiting, patients may be given certain tests and exams. Watchful waiting is sometimes used in prostate cancer. It is a type of expectant management.