Somatostatin Analogues--Octreotide and Lanreotide

Octreotide and lanreotide are medicines that are called somatostatin analogues (SSAs). They are synthetic versions of a natural hormone we all make called somatostatin. It's like the brake pedal of your body in that it slows digestion, hormonal function, and a lot more. Unfortunately, the natural stuff is broken down quickly. Octreotide and lanreotide, on the other hand can last for 4-6 hours, and when given in the depot version, last for a month. Both medicines bind to the somatostatin receptor on NETs and help decrease hormone secretion and growth. Their bindings are very similar, but not exactly the same, so they may have slightly different effects in individuals.

In my opinion, it is best to have options. If you've been on octreotide and it's working, no need to rock the boat. If it has been difficult to mix, administer, and absorb, then lanreotide might be a better option. If you've had a reaction to one of them, the other might work better.

Eric Liu, M.D.

Carcinoid Crisis: A Dangerous Complication of Invasive Procedures

Carcinoid crisis is an uncommon dangerous situation that arises from a sudden over-release of hormones from your tumors, causing intense flushing, wheezing, and dangerous fluctuations in blood pressure. It is different from the excess hormone release that causes carcinoid syndrome, and even if your tumors are non-functioning, you are at risk. Surgical or dental procedures require anesthetics and can involve severe stress to the body, both of which are known causes of crisis. Always reduce this risk by informing your doctor or dentist of your situation prior to surgery or dental procedures. The swift administration of octreotide and/or other medications (held on standby during procedures) can treat this crisis should it occur. Octreotide can also be administered preventively during invasive treatments to avoid this complication.

Carcinoid Heart Disease--Taking Precautions

Carcinoid heart disease is one of the major features of carcinoid syndrome and occurs in 50 to 70 percent of people with carcinoid syndrome. It is caused by excessive release of serotonin, usually by metastatic tumors in the liver. When carried through the bloodstream into the heart, the excessive serotonin can cause scarring of the heart’s inner lining, including the two right heart valves, the tricuspid and pulmonary. Symptoms may or may not be apparent and can include: fatigue, difficult or labored breathing, and/or fluid build up and swelling in the body. It is important for you to report ALL of your symptoms to your doctors. This condition may be treated by medications and, if needed, cardiac surgery. Follow this link for more detailed information.

All patients with a neuroendocrine tumor should have a baseline echocardiogram; the echocardiogram is 100% sensitive and specific for diagnosing carcinoid heart disease, and that test can determine the presence or absence of other important cardiac problems which, when treated, can prolong one’s survival. --Jerome S. Zacks, MD

Managing Carcinoid Syndrome Symptoms--The 5 E's

EATING
Large meals, spicy foods, and foods high in nitrogen-containing compounds called amines can trigger symptoms of carcinoid syndrome. Tomato-based foods, caffeine, chocolate, nuts and raw vegetables are common triggers.

EXERCISE
This trigger is highly variable from person to person, but in general physical stress may activate symptoms. The trick here is not to overdo. If you are not used to a particular exercise regimen, take it slowly and work up your tolerance.

EMOTIONS
Strong emotions such as anger, stress and anxiety can trigger symptoms. While it is impossible to completely avoid stress in everyday life, patients with carcinoid syndrome should work to reduce stress levels.

EPINEPHRINE
Certain medical or dental procedures may require numbing agents or anesthetics, which could contain epinephrine. In small doses it is usually quite safe, but epinephrine could trigger symptoms. Inform providers of your carcinoid syndrome diagnosis so they are aware and can consider alternatives.

ETHANOL (ALCOHOL)
Some people cannot tolerate any alcohol because it can exacerbate carcinoid syndrome. Monitor your own reaction and adjust accordingly.

Finding ways to cope with the anxiety and worry that can accompany carcinoid syndrome may aid in decreasing symptoms and how much they affect your life. Incorporating self care activities to reduce stress, such as journaling, enjoying your favorite hobby, spending quality time with loved ones, meditation and/or just resting and pausing when needed, can make a difference. These things, coupled with your medical interventions, can greatly improve your quality of life. --Dana Stafford RN, BSN

Functional Tumor Syndromes

CARCINOID SYNDROME usually arises from NETs in the small intestine or lung due to the overproduction of serotonin, which may trigger severe diarrhea, dry flushing of the skin, night sweats, and/or wheezing. Carcinoid syndrome diarrhea and its treatments can lead to pellagra, a niacin-deficiency disorder.

ZOLLINGER ELLISON SYNDROME results from a NET of the pancreas or duodenum and produces excessive levels of the digestive hormone gastrin. This tumor is also called a gastrinoma. Symptoms include diarrhea, severe ulceration of the stomach or small bowel, heartburn and abdominal pain.

GLUCAGONOMA usually begins in the pancreas. The overproduction of the hormone glucagon raises the concentration of glucose and fatty acids in the blood and can cause diabetes, severe weight loss, severe rashes, and blood clots.

INSULINOMA almost always begins in the pancreas. It over produces the hormone insulin. Uncontrolled insulin levels can cause low blood sugar (hypoglycemia), which can lead to serious medical conditions.

VIPOMA usually arises in the pancreas and may overproduce a hormone that can cause prolonged watery diarrhea and dehydration. Patients may experience muscle weakness, nausea, vomiting and crampy abdominal pain.

PHEOCHROMOCYTOMA arises in the adrenal glands and can release hormones that may raise blood pressure and cause heart palpitations, headaches and excessive sweating.

PARAGANGLIOMA appears in the head, neck, or torso and may secrete hormones that can cause episodes of high blood pressure, a rapid heartbeat, sweating, headache and tremors.

Functional Tumors--The Challenge of Hormonal Imbalances

A certain proportion of NET patients will have to adjust to living with symptoms that the cancer is actively causing. NETs can upset your normal hormone balance; your doctor can help discern if your symptoms result from your tumors and, if so, how best to address them. It can take a long time to sort this out, which can be frustrating, but keep at it.

NETs that actively produce and release excess hormones into the body are called functional tumors. It is generally understood that about 20 to 35% of all patients may have some level of functional disease. This causes imbalances that affect your body and how it functions and may create dangerous, health threatening issues.

Non-functional tumors do not cause imbalances, either because they do not release hormones or they release such small amounts. However, it has been observed that some tumors that are originally non-functional can change after a while and begin to produce and release hormones.

Excess hormones can cause a myriad of symptoms referred to as a syndrome. Symptoms will differ depending upon where the tumor arises and which hormone is overproduced. The most common is carcinoid syndrome caused by excess serotonin. Patients will differ in the frequency and intensity of symptoms they experience. Some may require constant management of their symptoms while others may experience symptoms only occasionally. If you have any of the syndromes that can be caused by a functional NET, you may need the attention and care of a knowledgeable endocrinologist (a specialist in the endocrine, or hormone-releasing system) to help your oncologist sort out, treat and monitor your symptoms.

A typical treatment for the syndromes caused by functional NETS is prescribing somatostatin analogues (SSAs). Your doctor can discuss all the available variations of these medications with you. A medication called telotristat ethyl can be given along with SSAs to help control carcinoid syndrome diarrhea that is not managed by SSAs alone. In some cases, surgery to remove as much of the tumor load as possible is recommended. This is referred to as de-bulking surgery, and this can help reduce the effects of functional tumors.

Surveillance and Monitoring--Essential Practices

Most likely you will be dealing with NET cancer in some way or another for the rest of your life. It is important to understand that NETs recur very often, sometimes years later, even if a patient is determined to have no evidence of disease (NED). Patients should be checked at regular intervals for any changes. A provider with NET expertise will know what to look for and how often to check.

Surveillance is watching for disease recurrence once all visible signs of the cancer have been removed by surgery or other therapy and the patient is considered to be NED. Even in this case, there should always be a physician-monitored schedule of surveillance. This schedule of surveillance may differ in how (which modalities) and when (how often) depending on individual circumstances.

Monitoring is watching existing disease by comparing the results from the latest tests and scans to prior results. How you are monitored will depend on the type of NET you have and the location and extent of the cancer in your body. It may include blood tests, 24-hour urine collections, and imaging scans such as CT, MRI and/or nuclear medicine scans such as the Ga-68 or Cu-64 DOTATATE PET scan.

If you have any questions about your monitoring plan, ask your doctor. It is important to have confidence that you are being managed well. Experiencing bouts of anxiety can occur as part of having these regular scans and check-ins with your oncologist. Support groups often discuss the ups and downs of living between scans. It is part of the reality that you will adjust to in your own way, which is not to say it is easy. Keep in mind that the same adage “knowledge is power” is as true here as well as during your first diagnostic work-up. When you are worried, remind yourself that early detection of changes leads to earlier intervention, which offers the best shot at controlling disease!

What Are Grade, Stage, and Differentiation?

GRADE

These tumors do not all behave or grow in the same way.

Grade refers to how fast or how slow the tumor is growing. Doctors use a sample of the tumor obtained through a biopsy or through surgery and examine it to determine how quickly the tumor cells are multiplying. The result is the Ki-67 index or the mitotic index, and the higher the measure, the higher the grade, on a range from Grade 1 or G1 (slower growing) to Grade 3 or G3 (faster growing).

Ki-67 is a protein in cells that is involved in cell replication, so if many cells are expressing it, the tumor is growing quickly. The pathologist needs to count about a thousand cells and determine the percentage of cells that are Ki-67 positive. The devil is in the details. Since it is not routine, it is often not done on specimens. Also, tiny little samples may not have enough cells to make it meaningful. And where was the sample taken from? We stained many tumors from several patients and found there is "heterogeneity" in the patients. In other words, one patient could have Ki67 of 1% in the primary tumor but 30% in a liver metastasis. Well, that certainly makes things more complicated. --Eric Liu, MD, FACS

STAGE

A tumor can start in one place and then spread (metastasize) to other parts of the body.

Stage refers to how advanced the cancer is--how far it has spread, or traveled, from where it began in the body. Using scans or imaging (CTs, MRIs, or various types of PET scans), doctors can “see” where the tumors are in your body. The stages range from Stage 1 (has not spread) to Stage 4 (spread to other organs or parts of the body).

DIFFERENTIATION

The structure of the cells that make up NET tumors is variable.

Differentiation refers to how the tumor cells look when compared to normal cells. Well-differentiated means the cells generally resemble normal cells, and these are usually slower growing tumors. Poorly-differentiated means the cell structures appear abnormally jumbled or disordered as compared to normal cells, and these are typically faster growing, more aggressive tumors. In lung NETs there are additional classifications: welldifferentiated lung NETs are further classified as typical or atypical, with the typical ones being more slow growing than the atypical ones. Atypical lung tumors are sometimes called moderately differentiated or poorly differentiated. Poorly differentiated lung neuroendocrine tumors may also be called large cell neuroendocrine tumors of the lung.

Terms Describing Neuroendocrine Cancer

Tumors that occur in this disease all come from hormone-producing cells. There are many types of these cells making different hormones, and they are in many different parts of the body. What we know about this disease, and the words used to describe it, continues to change over time. An older term for these tumors which is still being used is carcinoid, or cancer-like, but all tumors in this disease are now understood to be cancer. They can and do spread to other parts of the body after starting in one place. “Tumor” and “lesion” are basically the same thing: an abnormal growth of cells in your body.

NEN: Neuroendocrine Neoplasm is an umbrella term that medical professionals may use to refer to these kinds of tumors.

NET: Neuroendocrine Tumor is the term generally used to refer to the most common form of these tumors.

NEC: Neuroendocrine Carcinoma refers to a more aggressive (it spreads faster) and more harmful version of the disease.

Medical Assessment of Neuroendocrine Cancer

Having a thorough assessment of your condition at diagnosis and finding the right care are interrelated and essential to optimal treatment. A full assessment can help you determine what constitutes the best physician choice for you, but sometimes it takes finding the right physician before you get a true full assessment.

It is not possible to generalize, for example, what a Stage 4 diagnosis of NETs means until as much information as possible is gathered. Many NET patients have metastatic disease at the time of diagnosis, but where are all the tumors and metastases? How aggressive is their growth (grade), and are they growing in a location that interferes with important functions? Is the tumor releasing hormones (functional) and does it have receptors (a characteristic of the cells that impacts diagnosis and treatment)? Every part of the assessment informs your eventual treatment plan. In many situations, given limited disease and indolent or slow-growing tumors, even Stage 4 disease can be controlled for years if not decades. However, aggressive tumors, or tumors impacting vital structures, usually require intervening vigorously and with urgency. Patients are always best served by comprehensive assessments that provide the complete picture.

Assessment tools can include biomarkers in blood and urine, tissue analysis (biopsy), and imaging (CT, MRI, and PET or other nuclear imaging). If a certain test or scan has not been ordered for you, don’t hesitate to ask your health care provider why. These tools may not all be available at your local care center, and some may not be covered by your insurance without an appeal from your doctor. Tests, biopsies and scans alone may not give the whole picture. In certain cases, your doctor may want to observe your disease status over a period of time; watching can be informative.

“When establishing a treatment plan, it is very important to know as much as possible about the tumor itself—grade, origin, stage, organs involved by the cancer, whether the tumor makes any biochemical substances (hormones) and if the patient has any symptoms from the cancer. Additionally it is important to consider any previous history of cancer and related treatments, as well as the patient’s overall state of health.”
--Boris Naraev, MD, PhD

Being Diagnosed with Neuroendocrine Cancer: An Unexpected Journey

There are some journeys in life that we plan for meticulously and others, like cancer, that are unexpected, immediate and scary. We refer to cancer as a journey because the diagnosis is just the beginning, the first step of many to follow. At the outset, you will likely have more questions than answers. There will be stops and starts along the way as you learn to navigate the complexities of the medical system and the twists and turns of tests and treatments. At each fork in the road, you will need to decide which course is best for you.

The Special Case of a Rare Cancer

When it comes to cancer journeys, neuroendocrine cancer is definitely one of the roads less traveled. Neuroendocrine cancer refers to all forms of this disease, both neuroendocrine tumors (NETs) and neuroendocrine carcinoma (NEC). Most patients have never before heard of neuroendocrine cancer at the time of their diagnosis. Many primary care doctors are unaware of the signs and symptoms of this cancer. Slower-growing neuroendocrine tumors can remain “silent,”undetected and without causing noticeable symptoms, for a long time. Consequently, diagnosis is often delayed, and as many as half of all NET patients have metastatic disease at the time of their initial diagnosis. Since gastrointestinal NETs can produce symptoms similar to Crohn’s disease and irritable bowel syndrome, some patients have been treated for months, if not years, for a condition they did not have. Sometimes NETs may be mistaken for another cancer that commonly occurs in the same location, such as the lung or pancreas. But a NET in the pancreas is not pancreatic cancer, and a NET in the lung is not lung cancer. This concept can be hard to understand and a challenge to communicate to others.

Because neuroendocrine cancer is rare, it is essential that you learn as much as you can. Arming yourself with information will help you choose the best medical care team to guide you. It is critical to understand that there is no one size fits all or even one size fits most when it comes to this disease. The rule of thumb for NET patients is that everybody is different. Keep this in mind when you are reviewing information, seeking support and speaking to other patients.

You are one of a kind...Like fingerprints and zebra stripes, no two neuroendocrine patients are exactly alike. That’s why many organizations that advocate on behalf of these patients display zebra stripes as their symbol. Another reason we use the zebra symbol is to raise awareness in the medical profession. During their medical school training, doctors are taught the old adage, “If you hear hoofbeats, think horses, not zebras,” meaning that common symptoms usually are caused by common diseases. In NETS, however, we need our doctors to be prepared to “think zebra” as well.