Over a period of about ten years, I had been mentioning symptoms to my family practice doctor at my annual physicals – flushing and hot flashes, itching and changing bowel habits. These ‘dots’ were never connected and over this period the cancer inside my small intestines slowly spread to my liver and started growing.“You have a carcinoid tumor or a Neuroendocrine Tumor (NET). The flushing and other symptoms you’ve experienced are referred to as“Carcinoid Syndrome.” I learned that Carcinoids occur in about 1 of 100,000 people – it is the rarest of rare diseases, is frequently misdiagnosed and is incurable when it spreads to the liver. At first I was mad about the misdiagnosis, but then I realized misdiagnosis is almost always the case. A Mayo Oncologist said he received about 20 minutes of classroom discussion of NETs in medical school. The government classifies it as an orphan disease because it gets so little attention from the medical community, pharmaceutical companies and government. Its also sometimes referred to as the ‘looking good disease’ because many who have it, don’t show any or many outward signs of distress’ because it's so slow growing or indolent.
NET Cancer Day - November 10
 |
| November 10 is National Neuroendocrine Tumor Day |
“Watch & Wait”
After a liver biopsy and a 3 day scan called an OctreoScan ($8800), the diagnosis was confirmed in June 2015. My local oncologist suggested a ‘watch and wait’ strategy which I later learned is referred to as the ‘Wait and Worry’ strategy. My husband immediately went into a complete research mode and within 6-weeks we attended a patient directed conference 5 hours away where NET experts from clinics throughout the middle part of the U.S. presented. What did we learn? If you have this, you need to see a NET expert. I live in Wisconsin and there is no one who is an expert – not in the entire state. My gastroenterologist told me in no uncertain terms, “If I were you, I’d go to Mayo.” (generically meaning a center of excellence for NETs). After the conference, I talked with experts in Rochester, MN, Kenner, LA and Iowa City, Iowa. There are a handful of other clinics and speciality groups in other cities, but I didn’t want to have to travel to either of the coasts, especially if surgery were involved.
The first key learning was that the ‘watch and wait’ strategy my local oncologist prescribed was 100% wrong for me. Every expert told me that right off. It became clear to me that she was out of her league and didn’t have the intellectual curioscity to learn more about this disease, even when I presented her with facts from my research.
One size does not fit all
Each NET case is different and there is no one size fits all. In most cases there is tumor growth where it started (in my case, the ileum or end of the small intestine), the lymph nodes and the liver. They are all treated uniquely. If they’re all treated the same, you’ll go down in flames. A NET expert will devise a strategy to tackle each area. It's all about individualized care and a team approach where Oncologists, Surgeons and many other specialities work together. There are quite a few tools they can employ. Surgery to ‘get rid of it’ if it's possible is the first choice. In my case, it was possible and that is what I elected. Because I was in good physical (and mental) shape, the liver metastases were few, small and contained to only the right side of my liver, I was a good candidate for surgery. The surgeons said they could get it all (the visible part) and that I would not need monthly injections of Octreotide that cost about $10,000 each… following surgery.
Earlier I mentioned “it's incurable”. If it spreads to the liver, this is true. It almost always does spread to the liver because it's allowed to sit, fester and spread due to misdiagnosis. If there is any good news, is that it is usually (not always) slow growing. Where lung cancer may grow at 80% per year, a NET may only grow at 1 to 2%. So you have a little time to develop a plan.
Now let me introduce the Zebra.
 |
| A Zebra is a rare disease. |
Why the Zebra? “When you hear hoofbeats, think horses, not zebras.”
In the medical field, the term “zebra” is used in reference to a rare disease or condition. Doctors are taught to assume that the simplest explanation is usually the best, so as not to go around diagnosing patients with all sorts of exotic illnesses that are highly unlikely. Common diseases are what doctors should expect to encounter.
But many doctors seem to forget that ‘zebras” exist, and so getting a diagnosis and getting treatment can be more difficult for sufferers of rare diseases.
NET Newby Checklist
The information below was prepared and written in its original form by Gary Murfin, a NET patient himself. I modified it a bit for my particular case. If you would like a link to Gary's 'Newby' list you can reach him at gmurfin@covad.net. I thank him for the use of his original material.
Record Keeping – get copies of everything. Office visits, scans and bloodwork.
Digitize your records – name them so they can be sorted in chronological sequence. A file might say 100 – CT 11/10/15. I number the record in chronological sequence like 1000, 1010, 1020, etc. It makes it easy to sort. Get a scanner or go to a print shop.
Get copies of scans on CD’s. Learn how to make copies or take them to a FedEx Office store.
Record visits to Doctors. I’ve never been told no. Purchase a recorder or download a free app on a smartphone. With the app on my iPhone, I can easily email the recording to family, etc. I own an app named Voice Record.
Resources & Research – I have a file that’s about 100 pages long (after only 6 months). It is a bullet point summary of every event – Doctor Office visits, scans, biopsy, etc. It also contains:
A list of contacts including addresses, phone, fax, email, etc.
A list of medications and allergies to medicines. Clinics will ask for this information often… it's easier just to email, fax or mail a document.
A spreadsheet of blood tests, and scans. What they are for and what were the results. Over 100 so far.
A scan of your insurance card and driver’s license
Websites, List Serves, YouTube videos of presentations
Links to relevant peer reviewed articles on Pubmed.gov
Resources & Research
- Carcinoid.org
- Neuroendocrine Tumor Research Foundation
- Dr. Liu's Zebras
- Northwoods NETS
- Other NET and Carcinoid sites
- NETs support groups
- International Neuroendocrine Cancer Alliance
- The NET Alliance
- NetCancerBlog
- HealingNetFoundation
The Diagnosis - Testing/Scanning - Prior to my surgery, my first inexperienced, local oncologist ran several tests to confirm the diagnosis.
Needle biopsy of one of the tumors in the liver to confirm that it was a NET.
Urinalysis called the 5-HIAA where you lug around a gallon jug of urine for over a day. She should have ordered the plasma version of this test which is far less inconvenient), but was likely not aware.
OctreoScan. This is a nuclear scan (uses a radioisotope tracer) that detects the presence of carcinoid tumors anywhere in the body. However, there is one caveat to using this type of scan. Not all carcinoid tumors are the same. Some have special receptors that facilitate the absorption of the radioisotope and some tumors do not have these receptors. If you have the receptors then the O-scan will work. If not, then it will not show anything. This type of scan does not show specific tumors, but rather lights up (shows bright spots) in the area or areas where neuroendocrine tumors exist (those with receptors).
Because she was not experienced with carcinoids (which I didn’t realize at the time), she failed to order a Chromogranin A (CgA) test or pancreastatin (more sensitive than CgA). These are some of the best biomarkers for determining the presence of carcinoid tumor.
Inter Science Institute, located in California does these tests . The web address is interscienceinstitute.com. ISI offers a free guideline manual for NETs that they will send you or your doctor for free. Just call them. The guide is considered by many to be the gold standard and is authored by a number of recognized experts -- and updated regularly.
For the past few years there have been clinical trials offered in the US for a scan known as the Gallium-68 PET/CT scan. This scan has been used for years in Europe and is the Gold Standard for detecting NETS (with receptors). They are much more detailed, take significantly less time than an OctreoScan and use far less radiation. Why they are taking so long to get approved in the U.S. is anyone's guess.
Where carcinoid tumors start
Most carcinoid tumors start in the gastrointestinal tract to include the stomach and the appendix. The pancreatic type of neuroendocrine cancer can develop in or on the pancreas. Carcinoid seems to start almost anywhere in the gastrointestinal tract. A less common point of origin is in the lung. The development of the cancer starts with what is called the primary tumor. This is usually a small tumor that sends out seeds that go to other parts/organs of the body. The liver is the most common place to find the metastases along with the lymph nodes.
My diagnosis was a primary in my ileum of the small intestine which had spread to four adjacent lymph nodes and two sections of my liver. The original scans of my liver showed 3 tumors. Upon removal, it was found one of the tumors was horseshoe shaped and two tumors came out at the same time.
Ki-67 Index
This is an important test, but can only be done on tumor tissue. The Ki-67 index is a stain test that tells the Docs how quickly (or not) your type of tumor will spread in the body. It is technically known as a Proliferation Index.
The Ki-67 stain can be done even years after surgery, if that tissue was retained. Hospitals are supposed to keep cubes of the tissue from the primary tumor as well as the mets for a number of years.
This test is run on resected tumor tissue, metastasized tissue and biopsy material. The test is done to determine how likely your form of carcinoid is to proliferate (grow-spread). The scale is on a 1-100 percent basis. An index of below 2% is good. The norm for most carcinoid patients is 1-2% and this means it is slow growing. The lower the Ki-67 index, the slower growing the tumor cells.
The results of this test are now categorized into THREE Grades:
- Grade 1 - < 2%
- Grade 2 - 3 to 20%
- Grade 3 - > 20%
If you don’t have this Ki-67 test result, call your surgeon and ask him to have it run on your tissue.
A similar test that is like the Ki-67 and measures cell mitotic activity is called the MIB-1 or Mitotic test. This is a proliferation index too. This is sometimes run in place of the Ki-67 depending upon the form of cancer involved.
If either of these tests were done, it should be reported in your pathology report which you should have a copy of.
Creating Your Strategy
Remove the primary tumor. The first and most important step in dealing with a newly diagnosed carcinoid is to get the primary tumor taken out. One of the general rules about this cancer is that most of the time it takes a long time for this cancer to grow and so it is thought that most people have this cancer in their body for an average of 9.2 years before a diagnosis is made. This means that the cancer has had time to spread. The definitive work on the importance of removing the primary (if it can be found) was done by a team of Docs at Oregon Health Sciences University in Portland OR. The team was led by Dr. Rod Pommier. Here is what you might expect with this type of open surgery.
Another theory is that the primary tumor sends out very small tumors (sometimes called micro-lesions) to all parts of the body via the bloodstream. This continues to happen until that primary tumor is taken out. The other part of this theory is that most people, by the time they are diagnosed, have already had their cancer metastasize (spread) to other parts of the body. When the primary tumor is in the gastrointestinal tract this usually means that the cancer spreads to nearby lymph nodes and most always to the liver. The tumors in the liver can remain quite small for a long time, but be aware that tumor size does not equate to tumor activity in terms of the release of the hormones that cause symptoms (if you have symptoms). You can have a few or even a lot of very small tumors that release a lot of bad hormones and these tumors may not show up on your scans.
Another general rule for this cancer is that is it not curable. Only under certain circumstances has it been found that surgery could be a cure. This is only when the cancer has been found to not have spread. This is just a fact of life that the majority of us with this cancer must face. The bad news is we can't be cured, but the good news is that this cancer generally grows slowly and there are treatments that will slow the development of the tumors in the body. This means that usually a person has the time to what treatment could be best for them. Bottom line is that this cancer is treated like a chronic illness. You just keep controlling the tumor load, doing treatments that have good benefit but that are low risk.
Interpreting test results
When evaluating test results (blood, urine, etc) you have to look at two things…one is the test value in relation to the normal range and the other is the trend of the test values over time (usually at least 3 tests over time). The first thing you need to know is that normal is normal. All of these tests have a normal range. A test number at the low end of the range is considered to be the same as the test number at the high end of the normal range. If the test number falls below the lowest normal number then the result is abnormal. The same is true if the test number is higher than the highest value in the normal range. Abnormal low or abnormal high usually has a different interpretation, depending upon what is being tested.
A lot of people get excited if they get a test number that is very high or very low compared to the normal range, but the real importance of the testing is the trend. If over 3 or more tests the values for one kind of test changes in one direction (by a significant enough amount) then that is an indicator of something going on. It could mean that things are getting better or things are getting worse. The best values are those that fall within the normal range. If the trend is a change within the normal range, then usually this means nothing….normal is normal. Also, there can be a trend, but the magnitude of change from one test to another may not be much, so the significance is not much either.
Some people get tests done at different labs and this can cause complications in the interpretation of the test values. Each lab may have its own normal range, so you must have the normal range from each lab for each test run. If a test was done multiple times over a period of time at the same lab, then the norm range will be the same. If not, then the range may vary according to the lab and the interpretation of the test values and the trend may have a different meaning.
The real question to be asked is will the test results change my treatment plan? For me the value is in knowing if there is something going on with my tumors. If the answer is yes, then it means I must be diligent in monitoring my cancer.
The reality is that these kind of test results do not tell you where the activity is in the body. The other reality is that until tumors get to be of a size that they can be found on some kind of scan, they cannot be accurately treated. The only exception to this would be the case where tumor load is spread throughout the body and a “systemic” form of treatment, like Chemo or PRRT, needs to be used.
Scans in Use
The CT and MRI scans done in the US have limitations in terms of the size of tumor that can be found by the scans. The Tri-phasic MRI or 4-Phase CT are the best in the US for finding lesions in the liver, but even the best do not get below 5mm. This is pretty small (0.2”), but you could have lesions in the 1-4mm range that are producing lots of hormone. The fact that your liver may still look good on an MRI or CT scan may not be good enough to declare that there are no tumors there. They may be there, but are too small to find.
Morphological vs Functional scans
There are two types of scans…one is called a morphological scan and the other is a functional scan. The first type includes the MRI and the CT scans that most patients experience during the course of dealing with NETS. These scans show tumor structure, so tissue masses must be large enough to be identified by the scanner. The purpose is to determine size, volume and location of tumors. Depending upon the vascularity of the tumor, a radiologist may be able to conclude that the tumor is a NET or not. Note - MRI does not use radiation, the CT does.
The second type of scan (functional) is able to find active tumors through the use of radioactive tracers that may be absorbed into the tumor. This kind of scan looks at the whole body and if tumors are large enough or have the right receptors or the right cellular metabolism they can be detected on the scan. For NETS, the Octreotide Scan can be done in the US. A relatively new scan for the US, that is currently in clinical trials here, is the Gallium-68 PET/CT. Another type of scan that can be used for faster growing tumors is the FDG-PET scan. It uses a tracer attached to glucose. Fast growing tumor cells consume the glucose and thereby absorb the tracer and the tumor shows up. There are other scans, some actually more effective than the Ga-68, but they are not offered in the US.
Sando LAR and Somatuline Depot / Sub Q Octreotide - Octreotide comes in two forms…a short acting form that is given by subcutaneous shot and a long acting formula called Sandostatin LAR which is given as an Intramuscular shot. At present the company making the LAR is Novartis. The short acting is made by a variety of companies. For many years the Sando LAR formulation was prescribed for NETS patients to control the syndrome symptoms. In early 2009, a study, called the PROMID Study, was released by Novartis. This study showed that the medication could slow tumor growth for some patients with certain characteristics, in addition to stopping symptoms. This finding got many Docs to start prescribing this med to slow tumor growth for patients who had no symptoms.
Another drug also on the market to stop syndrome symptoms is Lanreotide. This drug is made by Ipsen Pharma. As of 2015, this drug comes in only one formulation — a long acting formula called Somatuline Depot that is given as a subcutaneous shot. In July of 2014, Ipsen did a press release announcing the results of a study called CLARINET. The results of this study showed that Lanreotide in the long acting form (Somatuline Depot), like Sandostatin LAR, could slow tumor growth.
For both drugs, there are side effects that can potentially affect patients. One is to pre-dispose a person for Type II diabetes since the med can influence blood glucose levels. Another possible side effect is to cause the gallbladder to produce gallstones. This typically leads to resection of the gallbladder which is a standard of care currently when NET surgery is performed.
The timing of treatments. The first objective first after diagnosis is to remove the primary tumor. My first oncologist prescribed a ‘wait and worry’ strategy. That instinctively, did not sound right to me. The type of surgery performed depends on the location of the primary. Depending on the location of any metastases, a doctor may choose to reduce a patient’s tumor load by taking metastases out of the liver or in areas of the mesentery at the time of primary resection. There can be an order to the treatments in that doing one treatment might preclude the use of another type of treatment. That is why it is important to seek out a NET expert and develop a strategy that addresses the primary, lymph nodes and other metastases You don't necessarily treat them all the same, if you do, you can go down in flames (Dr. Gene Woltering).
In my particular case, my primary was in the distal ileum with metastases to four of 22 lymph nodes and 3 small metastases to the liver, all on the right side (which is a good thing). Add to this my age (62) and general health (no diabetes, not a smoker, not overweight, etc.) made me an excellent candidate for surgery. Because the tumor had metastasized to my liver, the odds of it recurring sometime in the future is high - but it could be 10 to 20 years. By then there will be new developments.
I studied this disease until I knew it much better than my original, local oncologist (and certainly my Family Practice doctor). Keep in mind that the typical F.P. doctor might only see one person with a NET during their entire career. I went to a patient directed seminar on NETs with presentations by a range of NET experts from various clinics throughout the midwest. I arranged a meeting with three of them to get opinions. After meeting with and talking to two and getting the same answer, I decided on the clinic that was closest to home - a four hour car ride. Both the Oncologist and Surgeon are recognized experts. The surgeon had done more liver surgeries than any other doctor at Mayo.
The Five Es — it is well-known in the NETS community that there are a number of things that
can trigger the syndrome.
- Epinephrine – or Epi: It is extremely dangerous for us as it can precipitate a carcinoid crisis. Novocaine as used by most dentists can come in two forms…one with Epi and one that is “plain” with no Epi. When talking to your dentist make sure he is using the plain form. There are "caines" without epinephrine (like Mepivacaine). Make sure your dentist and others know that you cannot tolerate Epinephrine. If you have a medical ID bracelet or necklace, NO EPI should be prominently displayed on that.
- Ethanol (Alcohol): Hardly any carcinoid patients can tolerate wine or beer. That is because those contain amines. They set off flushing, hot flashes, etc. On the other hand, many people can still drink "hard liquor". That is, rum, vodka, gin, bourbon, etc. Some people cannot tolerate any of these. If you drink, you may have to discover your own level.
- Exercise: The trick here is not to overdo. If not used to a particular exercise regime, take it slowly and work up your tolerance. Lots of carcinoid patients are regulars at gyms, walk, run, ski, etc. Mostly because that is something they have always done and so are used to it. But when starting something new or taking it to a higher level, increase the activity slowly.
- Eating: Large meals are difficult for most of us, especially those who have had gastrointestinal surgeries. Please do read through the section on Nutrition on the Carcinoid Foundation website. There is a list of "forbidden foods" - which does not mean you have to avoid them exactly. Some can indulge in those foods and some cannot. For instance, sauerkraut is on the forbidden list but some eat it frequently and have no problem. Here again, it is a case of testing out things. Most of us cannot eat an entire "regular" meal. You might want to eat six small meals instead of three big ones. You may want to "graze" instead, e.g. eat a little bit many times through the day.
- Emotions: Stress! It is difficult to avoid all stress - at work, family conflicts, worry. Learn meditation (transcendental - prayer - whatever form helps you). Take time off and get a massage, sit by the ocean, lake, river, and relax.
3 comments:
This was great!! Thank you for the time and energy that you put into this. I am a lung NET.
Awesome info and the easiest to digest I've ever seen. Thank you so much!
Excellent information -- Very grateful for this clear, well-presented resource! Thank you! (appendiceal carcinoid)
Post a Comment