I offer you two subjects in one article but they are overlapping and very related. The piece of research in the 2nd half of the article is very exciting – did you know researchers have found there are two main sub-types of pNETs, one less likely to recur and metastasise than the other? This will hopefully lead to similar research in other types of Neuroendocrine Neoplasm.
I’ve written before about pancreatic NETs (pNETs), much of which has been on the awareness side of my advocacy work, particularly emphasising the differences with core Pancreatic Cancer (adenocarcinoma).
Pancreatic NETs are quite difficult to diagnose and treat, some of that difficulty is due to the location of the pancreas and accessibility for surgeons and radiographers. It’s not helped by the fact that most pNETs are non-functional making diagnosis more difficult as there is little clinical suspicion to scan, but also results in more late diagnoses.
Although biopsies are possible, mainly via endoscopic ultrasound or laparoscopy, it can still be difficult to reach. In some cases biopsies are not done until after surgical removal of tumours. The latter scenario plus surgery after a positive biopsy result does present an increased risk of morbidity and mortality. Consequently physicians (and patients) often have difficult decisions to make. I discussed some of these issues in my article “To cut or not to cut” which covers all types of NETs, but it’s particularly relevant to pNETs
To cut or not to cut
There are guidelines for treatment of pNETs and most seem to have tumour size thresholds to aid decision making but that is just one factor. I’ve listened to many presentations by NET specialists talking about the dilemma of cutting or not cutting and the ‘debate’ is still happening 3 years since I took an interest in the subject. Most guidelines seem to use 2cm as a threshold for surgical removal (>2cm) or watch and wait (<2cm) but there are other factors which could also indicate surgical removal such as a functioning tumour producing one of the pNET syndromes (i.e. palliative surgery) or the tumour threatening important vessels (i.e. pre-emptive surgery). These guidelines include ENETS, NANETS and NCCN. Currently it’s difficult for physicians to know how aggressive a pNET could become over time and this hinders decision making.
For those interested in this debate, you may like a recent article from the 2019 Society of Surgical Oncology Annual Cancer Symposium where Cristina R. Ferrone, MD, the surgical director of the liver program in the Division of General Surgery at Massachusetts General Hospital, in Boston, and Peter J. Allen, MD, the chief of surgical oncology at Duke Cancer Institute, in Durham, N.C., describe the benefits of resection versus observation in small neuroendocrine tumors of the pancreas and outlined the risks of under- and over-treatment, respectively. Click here.
Better and more accurate prognostic data is required to help therapy decisions
What we really need is more information from biopsies and blood tests to help make the right decisions. I’ve been watching articles discussing the use of liquid biopsies (essentially a blood test) which not only provide the conventional biopsy information but also molecular DNA measurements which an lead to data analysis indicating prognostic trends in those with particular levels. For example, in one study for Pancreatic Cancer, higher levels of plasma Cell-free nucleic acid (cfNAs) were found to significantly correlate with metastasis and recurrences. Work continues on liquid biopsies for many different cancer types, in some cases multiple types.
Latest Neuroendocrine research 2019
In a study sponsored by the NET Research Foundation, researchers used molecular analytic methods to describe new subtypes of pNETs that differ in the expression of specific regulatory proteins and found that the differences correlated with the risk of recurrence following surgical treatment. The regulatory proteins ARX and PDX1 are epigenetic modifiers that are involved in development of the pancreas.
The scientists found that tumors whose cells exclusively expressed the protein ARX had more than a 35% risk of recurrence following surgery, compared to less than a 5% risk if the tumor lacked ARX but expressed PDX1. Among study participants whose tumors showed high ARX levels, cancers recurred in the liver within 1 to 4 years, compared to the rare recurrence of tumors that expressed PDX1.
Dr. Shivdasani and his colleagues studied molecular findings first in about a dozen pNETs and then analyzed the molecular profiles of another 142 pNET specimens. They found that about half of the pNETs expressed the regulatory protein ARX and resembled normal alpha cells in the pancreas, whereas the other half expressed the PDX1 regulatory protein and resembled normal beta pancreatic cells. The presence or absence of those proteins was strongly correlated with outcomes: among 103 cases the researchers studied, distant metastatic relapses occurred almost exclusively in patients whose tumors expressed the ARX protein but not the PDX1 protein.
“This robust molecular stratification provides insight into cell lineage correlates of nonfunctional pNETs, accurately predicts disease course, and can inform postoperative clinical decisions,” the authors wrote.
On the basis of these findings, said Dr. Shivdasani, pathologists could easily test specimens of pNET tumors to classify them as type A (expressing ARX) or type B (expressing PDX1). “Now you can tell patients with type B that their recurrence risk after surgery is very small…,” said Dr. Shivdasani. For patients whose tumors are type A, with a higher risk of recurrence, close follow-up could be undertaken to detect new metastases, which may be treatable with chemotherapy or other methods.
To summarise this really important piece of research, the key points are:
Tumors whose cells exclusively expressed the protein ARX had more than a 35% risk of recurrence following surgery, compared to less than a 5% risk if the tumor lacked ARX but expressed another regulatory protein, PDX1.
Among study participants whose tumors showed high ARX levels, cancers recurred in the liver within 1 to 4 years, compared to the rare recurrence of tumors that expressed PDX1.
Distant metastatic relapses occurred almost exclusively in patients whose tumors expressed the ARX protein but not the PDX1 protein
These proteins can be measured by standard biopsy stains as used by pathologists in determining conventional prognostic data such as Ki67 and differentiation. At this time, there is no plans to introduce a new stain and routinely measure all pNET biopsies. It’s also envisaged that larger trials would need to be completed before such a change could happen. Nonetheless, this is very positive news.
Hopefully similar research will follow on other types of Neuroendocrine Neoplasms.
Thanks for reading.
In addition to linked articles above, resources used to compile this article:
1. Subtypes of Pancreatic Neuroendocrine Tumors and Effect on Disease Recurrence – By The ASCO Post, posted: 15 Jul 2019.
2. Robust molecular stratification provides insights into cell lineage correlates – By ESMO posted 09 Jul 2019.
3. NET Research Blog – NETRF-Funded Finding May Help Predict Pancreatic NET (pNET) Recurrence posted 1 Jul 2019.
4. Surgeons Debate Management of Small Pancreatic Neuroendocrine Tumors. Resect or Observe? – By Clinical Oncology News posted 17 Jul 2019.
Proton pump inhibitors (PPIs) reduce the production of acid by blocking the enzyme in the wall of the stomach that produces acid. Acid is necessary for the formation of most ulcers in the oesophagus, stomach, and duodenum, and the reduction of acid with PPIs prevents ulcers and allows any ulcers that exist in the oesophagus, stomach, and duodenum to heal. PPIs are prescribed to treat acid related conditions such as:
Esophageal duodenal and stomach ulcers
Gastroesophageal reflux disease (GERD)
Zollinger-Ellison Syndrome – ZES (note this is a syndrome associated with a functioning duodenal or pancreatic NET known as a Gastrinoma)
They also are used in combination with antibiotics for eradicating Helicobacter pylori, a bacterium that together with acid causes ulcers of the stomach and duodenum for eradicating H. pylori, a bacterium that together with acid causes ulcers of the stomach and duodenum.
Although this should not be considered a full list applicable to all countries, the drugs tend to be prescribed or purchased under the following names:
Aspirin and Omeprazole (Yosprala)
Dexlansoprazole (Dexilent, Dexilent Solutab)
Esomeprazole (Nexium, Nexium IV, Nexium 24 HR)
Esomeprazole magnesium/naproxen (Vimovo)
Lansoprazole (Prevacid, Prevacid IV, Prevacid 24-Hour, Zoton FasTab)
Omeprazole and sodium bicarbonate (Zegerid, Zegerid OTC)
Pantoprazole (Protonix, Pantoloc Control)
Rabeprazole (Aciphex, Aciphex Sprinkle, Pariet)
PPIs have revolutionized the management of acid-related diseases and there is evidence supporting their superior efficacy and overall safety profile. Unfortunately, it would appear this has possibly led to their overuse and inappropriate use. When used appropriately, the overall benefits significantly outweigh the potential risks in most patients.
One US pharmacist magazine has stated that almost half of all patients taking a PPI do not have a clear indication. It follows that PPIs may not be the appropriate treatment for many people. The American Gastro Journal nicely covers this issue – click here.
What is the connection with NETs?
Millions of people will have been prescribed these drugs for the various reasons listed above and as I said above quoting from a reputable US Pharmacist magazine, perhaps many do not have a clear indication for their use. So this issue is much wider than NETs.
Above, you can see a direct link to duodenal/pancreatic NET syndrome – ZES. However, there is also a known link between the use of PPIs and the effect on the Chromogranin A blood test, the most common tumour marker used in the diagnosis and surveillance of many types of NET. Several studies have concluded that PPIs falsely elevate Chromogranin A but there is another option – read more here.
Any other risks of using PPIs?
There are several well-known risks of using PPIs in the long-term. However, many drugs have side effects, often the risks of not taking a particular drug can be outweighed by taking it. I will not comment further but leave you with some references to read yourself:
1. From the UK National Health Service (NHS). They took a balanced view adding the risk element I described above. Importantly they stated that PPIs are not usually intended to be taken long-term. Read more here. The British Medical Journal (BMJ) published the study referred to by the NHS here.
2. The NHS also published an article based on the results of a US study. Again, they indicated the study had similar limitations to the one above. Read more here (links to the study contained within).
3. There are literally dozens of similar articles but most seem to point to these two studies. However, it should also be noted that the US FDA has issued safety warnings about long-term use of PPIs. This is covered in the aforementioned US Pharmacist magazine article here.
Are there alternatives to PPIs?
Firstly, you should NEVER stop taking PPIs without speaking to the doctor who prescribed them.
There’s a class of drugs known as Histamine H2 Receptor Antagonists (H2RA) that reduce the amount of acid produced by the cells in the lining of the stomach. They are also commonly called H2 blockers. They include Cimetidine (Tagamet, Tagamet HB), Famotidine (Pepcid, Pepcid AC), Nizatidine (Axid) and Ranitidine (Zantac). Brand names may differ from country to country. From what I read, they are not as powerful as PPIs but for some people they may prove adequate. Read more about H2 blockers here.
So I can just stop taking PPIs and start taking H2 blockers?
NO. As I said above, you should never discontinue a prescription for PPI without talking to your doctor. However …. it’s not common knowledge that suddenly stopping PPIs is not a good idea – you must gradually reduce (i.e. taper off).
Why taper? PPIs block the production of acid in your stomach which can help with the symptoms but that also turns on the release of gastrin. This is not ideal for two reasons according to NOLANETS:
When you try to get off of PPI, the gastrin stimulates acid production and stays elevated, potentially for several months (depending on how long you were on the PPIs). This makes your reflux worse than before and makes getting off of this medication very difficult. Gastrin also stimulates Chromogranin A thus why this can be elevated in patients who have been taking PPIs.
Gastrin also acts like a growth factor and stimulates the growth of ECL cells (enterochromaffin like cells). Clearly this does not happen to everyone on PPIs. However, and as per the NHS advice above, PPIs should not be considered a long-term solution except for conditions for which they are clinically indicated (e.g. Barrett’s oesophagus, Gastrinoma (Zollinger Ellison Syndrome).
What are NET Specialists saying about this?
The best source of information on this seems to be in two main areas:
1. One is NOLANETS (Dr Eugene Woltering et al) who appear to be leading the way on identifying those who may have a clinical indication for use of H2 blockers rather than PPI and this NET Specialist organisation has produced a sheet showing how to taper people off the drug and onto the less risky H2 blockers. Read the NOLANETS “Get off PPIs” Sheet by clicking here. They state that PPI use increases circulating gastrin which in turn increases the amount of acid in the stomach. The increase in gastrin also stimulates the enterochromaffin like cells (ECL) of the stomach to produce Chromogranin A and this explains why it can be elevated in PPI users. The US Pharmacy magazine quoted above, appears to confirm this thinking.
2. The European NET Society (ENETS) discusses the issue in their guidelines but only in relation to Zollinger-Ellison Syndrome (ZES). This is a direct quote from ENETS 2016 Guidance – “The widespread use of PPIs is a major problem for the diagnosis of ZES because these drugs have an extended duration of action (up to one week), they cause hypergastrinemia in 80-100% of all normal subjects, and can confound the diagnosis. Furthermore, if PPIs are abruptly stopped in a true ZES patient, anti-peptic complications can rapidly develop, and therefore some expert groups have recently recommended that the diagnosis of ZES should be established without stopping the PPIs or by attempting to taper the dose. Unfortunately, as suggested in a number of recent papers, in most patients, the diagnosis cannot be easily established without an interruption of the PPIs. Furthermore, a secretin test cannot be used while a patient is taking PPIs because it can result in a false positive test. Other tumour markers such as serum chromogranin A were found to be not reliable for the diagnosis of ZES patients, as up to 30% have normal plasma chromogranin A levels. PPIs also lead to increased chromogranin A levels on their own. It is therefore recommended that if the diagnosis is unclear, the patient should be referred to a centre of excellence and if this is not possible, PPI withdrawal should be cautiously performed (in an asymptomatic patients with no active acid-peptic disease or damage) and with adequate cover by H2 blockers and careful patient monitoring”.
PPIs and PERT
I have anecdotal evidence that people are being prescribed PPIs alongside Pancreatic Enzymes Replacement Therapy (e.g. Creon, Nutrizym etc). While most types of PERT are gastro-resistant, a high acid environment may impair their efficacy. The rationale behind using PPI (or H2 blocker) is to decrease the acid level and allow the PERT to work better. Given the research behind this article, I would certainly challenge the use of PPI alongside long-term use of PERT.
The aim of this article is not to scare anyone, I’ve been careful with the sources, quotes and facts. Like anything in life (including the medical world), there are risks and knowing about them allows us to manage these risks in conjunction with our doctors and healthcare specialists. If you are concerned about anything you find inside this article, I suggest you speak directly to your doctor/specialist for advice.
Personally speaking, I would like to see more from the NET Specialist community on this issue.
When you live with any illness, getting through the day can be tough. Trying to get a diagnosis, dealing with a diagnosis, undergoing treatment and then learning to recover and adapt.
I’ve been living with my condition for almost 8 years and I’m a big advocate of keeping busy, keeping active and keeping my mind occupied. Despite this, there are times with a chronic disease, an invisible disease, an incurable and long-term disease including cancer, occasionally just doing nothing can be very productive in the long term!
Of course, sometimes you have little choice if you’re ill from your condition or something routine.
So now and then, I just breathe in and breathe out (then repeat). It’s very enjoyable!
From other posts, you’ll be aware of the thyroid lesion (now 17x19mm) which I’ve been tracking since 2013. The surveillance has included routine thyroid blood tests, mainly TSH, T3 and 4. Due to trends in TSH and T4, it’s been suggested I’m borderline hypothyroidism. I’m out of range in TSH (elevated) but the T4 is currently at the lower end of the normal range. On 20 March 2018, following an Endocrine appointment, I was put on a trial dose of 50mcg of Levothyroxine to counter the downwards trend in results indicating hypothyroidism. Levothyroxine is essentially a thyroid hormone (thyroxine) replacement. One month after taking these drugs, my thyroid blood levels are now normal for the first time in 4 years (since there are records of test results – it might be longer).
The NET Connection?
To put things into context, hypothyroidism is an extremely common condition and the main treatment is administration of thyroid hormone replacement therapy (i.e. Lewvothyroxine). This is in the top 5 of the most commonly prescribed medication in USA and UK.
However, there are connections with NETs. Firstly there is one type of cancer known as Medullary Thyroid Cancer (MTC) and it also has a familial version known as Familial MTC or FMTC.
There are also connections between regular Neuroendocrine Tumours (NETs) and the thyroid. It can often be a site for metastasis, something I have not yet written off given it lights up on nuclear scanning – although my biopsy was inconclusive. You can see a summary of the connections and my own thyroid issue in more detail in my article “Troublesome Thyroids”. Please note the parathyroid glands are beyond the scope of this article.
Thyroid Function – the Lanreotide/Octreotide connection
Before I continue talking about hypothyroidism, here’s something not very well-known: Somatostatin analogues might cause a “slight decrease in Thyroid function”(a quote from the Lanreotide patient leaflet). The Octreotide patient leaflet also states “Underactive thyroid gland (hypothyroidism)” as a side effect. Many sources indicate that thyroid function should be monitored when on long-term use of somatostatin analogues. It’s also possible and totally feasible that many NET patients will have thyroid issues totally unrelated to their NETs. Remember, NET patients can get regular illnesses too!
What is Hypothyroidism?
Hypothyroidism is a condition in which your thyroid gland doesn’t produce enough of thyroxine. This leads to an underactive thyroid. It seldom causes symptoms in the early stages, but over time, untreated hypothyroidism can cause a number of health problems, such as obesity, joint pain, infertility and heart disease. Both men and women can have an underactive thyroid, although it’s more common in women. In the UK, it affects 15 in every 1,000 women and 1 in 1,000 men. Children can also develop an underactive thyroid.
What causes Hypothyroidism?
Autoimmune thyroid disease sometimes called Hashimoto’s thyroiditis
Radioactive iodine or surgery to correct hyperthyroidism or cancer
Over-treatment of hyperthyroidism with anti-thyroid drugs
A malfunction of the pituitary gland
What are the symptoms of Hypothyroidism?
The signs and symptoms of hypothyroidism vary, depending on the severity of the hormone deficiency. But in general, any problems you have tend to develop slowly, often over a number of years. At first, you may barely notice the symptoms of hypothyroidism, such as fatigue and weight gain, or you may simply attribute them to getting older. But as your metabolism continues to slow, you may develop more-obvious signs and symptoms. Hypothyroidism signs. Below are major symptoms associated with hypothyroidism:
Weight gain or difficulty losing weight (despite reduced food intake)
Coarse, dry hair and dry skin
Sensitivity to cold
Muscle cramps and aches
Abnormal menstrual cycles
Slowed speech (severe cases)
Jaundice (severe cases)
Increase in tongue size (severe cases)
Check out this excellent short video from WebMD – click here or the picture below. It’s based on USA but most of it is relevant globally.
You don’t have to encounter every one of these symptoms to be diagnosed with hypothyroidism. Every patient’s experience with the disorder is different. While you may notice that your skin and hair have become dry and rough, another patient may be plagued more by fatigue and depression.
When hypothyroidism isn’t treated, signs and symptoms can gradually become more severe. Constant stimulation of your thyroid gland to release more hormones may lead to an enlarged thyroid (goiter). In addition, you may become more forgetful, your thought processes may slow, or you may feel depressed.
Now ….. some of these symptoms look very familiar to me and they also look very familiar to some of the comments I see on patient forums related to somatostatin analogues and some of the NET syndromes – that jigsaw thing again. I guess it’s possible that people are borderline hypothyroidism prior to taking somatostatin analogues and the drug pushes them out of range (similar to what it’s known to do with blood glucose levels and diabetes). I’m not suggesting a direct clinical link in all cases but what I am suggesting is that perhaps some of the answers might be found in checking Thyroid hormone levels.
What are the Thyroid Hormone tests for Hypothyroidism?
A high thyroid stimulating hormone (TSH) level with a low thyroxine (T4) level indicates hypothyroidism. Rarely, hypothyroidism can occur when both the TSH and T4 are low. A slightly raised TSH with a normal T4 is called subclinical, mild, or borderline hypothyroidism. Subclinical hypothyroidism can develop into clinical or overt hypothyroidism
Routine ‘Thyroid blood tests’ from your doctor will confirm whether or not you have a thyroid disorder. I now test for TSH (thyroid-stimulating hormone), T4 every 6 months. Mostly in range but recently TSH is spiking out of range and T4 is consistently at the lower end of normal range.
Can hypothyroidism be treated?
Yes. A synthetic version of thyroxine taken daily as prescribed. e.g. Levothyroxine tablets
OK that’s Hypothyroidism – what is Hyperthyroidism?
Hyperthyroidism is a condition where the thyroid gland produces too much thyroid hormone for the body’s needs. It is also known as an overactive thyroid or thyrotoxicosis. An overactive thyroid can affect anyone, but it’s about 10 times more common in women than men and it typically starts between 20 and 40 years of age.
Hyper – means “over -“
Hypo – means “under -“
The terms “hyperthyroid” and “thyrotoxic” are interchangeable
Graves’ disease – the most common cause
A toxic nodular goitre (a goitre is an enlarged thyroid gland)
A solitary toxic thyroid adenoma (an adenoma is a clump of cells)
Thyroiditis (infection or inflammation of the thyroid gland) which is temporary
A speeding up of mental and physical processes of the whole body, such as
weight loss, despite an increased appetite
palpitations / rapid pulse
sweating and heat intolerance
tiredness and weak muscles
nervousness, irritability and shakiness
mood swings or aggressive behaviour
looseness of the bowels
warm, moist hands
passing larger than usual amounts of urine
an enlarged thyroid gland
If the cause is Graves’ disease, you may also have ‘thyroid eye disease’. Smokers are up to eight times more likely to develop thyroid eye disease than non-smokers.
By a physical examination and blood tests
A low thyroid stimulating hormone (TSH) level with a high thyroxine (T4) level indicate hyperthyroidism
Surgery to remove all or part of the thyroid gland
Radioactive iodine to destroy most of the thyroid tissue
Diarrhea is a huge subject for NET patients, whether it’s caused by the tumor itself (i.e. a syndrome), due to treatment, knock on effects of treatment, or some other reason, it can dramatically limit qualify of life. Working out the root cause can be problematic even for medical teams. I wrote about these issues before in my article Neuroendocrine Cancer – the diarrhea jigsaw. So when I saw the data from a trial of something called enterade®, I was immediately drawn to investigate. I don’t normally write articles on over the counter commercial products but this one is an exception given that it has been classed as a medical food since 2012 and is also used to rehydrate patients undergoing radiotherapy and chemotherapy for cancer (so not just for NETs).
What is enterade® ?
It’s a drink currently produced in 8oz bottles. It’s a first-in-class, glucose-free medical food i.e. it is intended to be used under the supervision of a healthcare provider. The solution comprises five critical amino acids – Valine, Aspartic Acid, Serine, Threonine, Tyrosine and electrolytes – potassium and sodium.
What does it do?
It’s designed to help manage debilitating gastrointestinal (GI) side effects. With no sugar to exacerbate the GI tract, enterade® supports the small bowel’s ability to absorb fluids, nutrients, and electrolytes and leads to improved digestive function. By helping to restore normal GI function, enterade® reduces diarrhea and dehydration, leading to a significant improvement in the patient’s overall quality of life and a healthier GI tract.
Is there evidence that it works?
Since May 2017, it’s been trialled by University of Kentucky Markey Cancer Center (MCC) for potential use by NET patients – trial coordinators include the well-known NET specialist Dr Lowell Anthony. The results so far are very interesting. The recent conference reported revised data as follows:
33 of 41 patients (80%) reported subjective improvement in diarrheal symptoms.
51% (21/41) reported more than 50% reduction in diarrhea frequency.
click here or on the poster below to see the trial poster data output.
As you will see from the poster, there were a wide range of patient types including (but not limited to) small intestinal NETs, bronchial NETs, NETs of unknown primary, gastric NETS, pancreatic NETs and one high grade neuroendocrine carcinoma of the prostate.
A follow on Phase 2 trial is now recruiting with the following detail available:
1. Up to 30 patients will be recruited.
2. The trial is coordinated by Markey Cancer Centre, Kentucky.
3. There will be two cohorts, those with carcinoid syndrome and those without.
4. The trial will run from December 2018 to August 2020.
Click here to see the trial information – important to note the inclusion and exclusion criteria.
Please also note there’s a plan for a follow on trial covering more locations. I will update further when known.
Can I buy Enterade now?
The product is available in North America on Amazon.com, www.enterade.com and 1-855-enterade. However, the parent company (Entrinsic Health) recently announced a partnership with global company Nestlé Health Science to provides worldwide commercial license and supply agreement for enterade®. The announcement is linked here:
NORWOOD, Mass., November 15, 2018 – Entrinsic Health Solutions (EHS), an innovative health sciences company, today announced that they have entered into a partnership with Nestlé Health Science (NHSc), a global innovative leader pioneering premium-quality, science-based nutritional health solutions. The partnership gives NHSc the exclusive rights to market EHS’s enterade® product.
Please note this is not a recommendation to go out and buy the product. It is actually described as a ‘medical food’ and is formulated to be consumed or administered under the supervision of a physician.
3. Recent output from ASCO 2018 – click here. (contact data update for 2018)
4. If you are interested in more information about how enterade® works, check out this short video
Please note this is not a recommendation to go out and buy the product. It is actually described as a ‘medical food’ and is formulated to be consumed or administered under the supervision of a physician.
If you want to strike up a friendly conversion with a Brit, ask him or her about the weather – we’re really famous for our weather conversations and they normally focus on rain or clouds! However, despite the famous British ‘reserve’ and ‘stiff upper lip’, they also frequently talk about being ‘under the weather’, a phrase meaning slightly unwell or in low spirits.
I find myself smiling at some of the conversations I hear in medical establishment waiting rooms, particularly the potentially long wait for blood tests. Here, conversations bypass the weather and focus on being under the weather! I thought I was a regular when I started to recognise people in the queue (line!) and their pill conversations. Statements such as “Yes, I just started a ‘blue chap’ ” (medical names are sometimes hard to pronounce). Normally followed by “I’m on that one too and I take it along with my yellow and white chaps“. Some people seem to be taking a veritable rainbow of ‘chaps’. Strangely, some people appear to be quite proud of how many ‘chaps’ they take. I tend to maintain the traditional British reserve and a stiff upper lip in waiting rooms, so I keep quiet (actually I’m just happy to be inside away from the weather!).
I might join in one day and I wonder if they would be impressed with my tally of chaps? I have a funny feeling my tally of drugs is nothing compared to some of you guys and hope you will comment to prove me right! I don’t think I’m proud to give you my list but here’s my ‘chaps’, some prescription, some over the counter:
Apixaban (Eliquis). To prevent a recurrence of pulmonary emboli (PE). Unfortunately, I had PE after my big surgery in 2010. 2 per day.
Pancreatic Enzyme Replacement Therapy (Creon). Recently added, anything between 6 and 12 per day depending on what I eat. Check out this article on PERT. Check out this article on Malabsorption with references to NET dietitians.
Multi-Vitamin (50+ age). I’ve actually been taking these since a few years before diagnosis in 2010. NET patients can be at risk of vitamin and mineral deficiencies. Check out this article on the issues and with references to NET dietitians.
Vitamin B Complex. This was added in 2013 to mainly tackle low B12 (despite my multi-vit containing 400% RDA) and it seemed to help with fatigue. Read more here.
Vitamin D3. This was also added in 2013 to tackle low Vit D levels (again, despite my multi-vit containing 200% RDA). 10µg (400iu). D3 is normally the recommended form of Vitamin D to take, easiest to absorb and more natural. Vitamin D3 is also known as cholecalciferol. Many people who do not live in sunny countries are probably deficient or borderline already.
Probiotic. This was also added in 2013 to try to offset some of the abdominal issues that many NET patients seem to have. I take a 5 billion dose and it seems to help. Check out this article with references to NET dietitians.
Omega 3. This is also something I had been taking since before my diagnosis. I think I took it for a couple of reasons, my diet did not really include foodstuffs containing Omega 3 and I was experiencing some joint pain in my hands. I just never stopped taking it. Dose size 1000mg.
Lanreotide (Somatuline Autogel). An injection rather than a pill/capsule. Quite a big chap! You can read all about my relationship with Lanreotide by clicking here.
Levothyroxine. One 50mcg tablet each morning. My blood tests are indicating hypothyroidism – check out my whole thyroid story by clicking here. All NET patients need to keep an eye on thyroid levels. Read why here.
Seretide and Ventolin. These are asthma drugs, a preventer and a reliever respectively. I hardly ever take the latter nowadays. I had mild asthma as a child, it went at 16 and came back at 35. I take 2 puffs of Seretide night and day. Seems to help. Ventolin seems to be only required if I have a cold or flu thing going on.
Of course, most people have lots of other stuff in the ‘medicine box’ ready for ad hoc issues as they arise (pain killers, imodium, cough mixture, anti-histamines, indigestion, etc etc). I could go on forever.
Please always consult your specialists or dietitian about the requirements for drugs and supplements. You may not actually need them. I only take my supplements after very careful consideration, in reaction to low blood vitamin/mineral tests and listening to what ‘NET aware’ dietitians say (you’ll find references in some of the articles above).
Warning: You should always think carefully about over the counter stuff (including online) as there’s a lot of ‘scammers’ out there selling counterfeit supplements. Always buy from a reputable source. With supplements, remember in most countries they are not regulated in the same way as medicines so it’s worthwhile checking they are compliant with regional food supplements directives. The supplements provider I use is actually approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) covering UK. I’m sure there will be similar approval organisations where you live. Also be careful of some claims about the miracle cure of certain food supplements. There are plenty sites with fake health news online (check out my article on this – click here).
You should be clear why you take supplements and try to consult with a specialist or dietitian for advice.
Finally, don’t forget to take your chaps, they should help you keep well!
After 7 years of avoiding pancreatic enzyme replacement therapy (PERT), I finally asked for some on a trial basis at the end of 2017. To be honest, for some time, I thought they were really only needed in the NET world for those with pancreatic issues (pNETs). I’ve always known I’ve had some digestive issues related to malabsorption. However, I’m not losing weight – this has been stable for some years (but see below). Plus my key vitamin levels (B12 and D) are in range. However, I had been struggling with a lot of bloating issues, thus the trial. You know me, I like to research and analyse such things! I’ve actually written about a lot of these issues in my Nutrition series ….. so this is now ‘Article Number 5’.
Crash Course.We eat food, but our digestive system doesn’t absorb food, it absorbs nutrients. Food has to be broken down from things like steak and broccoli into its nutrient pieces: amino acids (from proteins), fatty acids and cholesterol (from fats), and simple sugars (from carbohydrates), as well as vitamins, minerals, and a variety of other plant and animal compounds. Digestive enzymes, primarily produced in the pancreas and small intestine, break down our food into nutrients so that our bodies can absorb them.
Some of the common symptoms of NETs are gas, bloating, cramping and abdominal pain and the root cause of these issues can sometimes be as a result of insufficient ‘digestive’ enzymes. They are primarily produced in the pancreas (an exocrine function) and the small intestine but also in the saliva glands and the stomach. This post will focus on pancreas and to a certain extent, the small intestine. There are actually some key tell-tale signs of a pancreatic enzyme deficiency, such as steatorrhoea which is described as an excess of fat in faeces, the stool may float due to trapped air, the stool can be pale in colour, may be foul-smelling, and you may also notice droplets of oil or a ‘slick’ in the toilet pan. Steatorrhoea is mainly (but not always) due to malabsorption of fat from the diet and this can actually be caused or made worse by somatostatin analogues which are known to inhibit the supply of pancreatic enzymes. Of course if fat is not being absorbed, then the key nutrients your body needs to function properly might not be either. The signs from that might not be so noticeable but can be even more problematic over time. Please see Article 1.
Those who have had surgery, in particular, in GI tract/digestive system, are at risk of malabsorption; as are those prescribed somatostatin analogues (Lanreotide/Octreotide) as these drugs can inhibit digestive enzymes, causing or adding to the malabsorption effect. For those who need to read more, see Article 2.
One way to combat these issues when they are caused by pancreatic insufficiency is with Pancreatic Enzyme Replacement Therapy (PERT) which can mimic the normal digestive process. However, this is not the whole story as there could be numerous reasons for these issues, perhaps even some which are unrelated to NETs. If you are in doubt about whether you suffer from malabsorption and/or any form of digestive enzyme insufficiency, you should consult your doctors.
Pancreatic Enzyme Replacement Therapy
Many NET patients succumb to malabsorption due to pancreatic insufficiency and are prescribed Pancreatic Enzyme Replacement Therapy, or PERT for short. There are various brands available (e.g. Creon®, Nutrizym®, Pancrease HL® or Pancrex®). Most are in capsule form in various doses.
How does PERT work? Most people experiencing the issues above are going to benefit from a multiple-enzyme replacement which tend to include the key ones such as:
lipase which break down fats (e.g from many different foods)
amylase which breaks down starchy carbohydrates (e.g. potatoes, bread, rice, pasta, cereals, fruits, fibre, etc).
The dose sizes tend to be based on the amount of lipase, i.e. a 25,000 strength would mean 25,000 units of lipase and (normally) a lesser amount of amylase and protease. The entire mix of enzymes may be given a name, e.g. ‘Pancreatin’ or ‘Pancrealipase’. You will be given a number of capsules to be used from your prescribing doctor.
The pancreatic enzyme capsule is swallowed along with food and digests food as they pass through the gut. If your capsules contain an enteric coat or enteric coated granules (delayed release), they should not be affected by stomach acid. The replacement enzymes will help to break down food allowing the nutrients to be absorbed beyond the stomach (i.e. in the small intestine). Do not be alarmed at the dose sizes, a healthy pancreas will release about 720,000 lipase units during every meal!
Frequently Asked Questions (FAQ)
When I first started taking the supplements, I thought of numerous questions, many of which I could not find definitive answers to! Different sites say different (and contradictory) things. Clearly, you should always consult your prescribing doctor and the medicine patient information leaflet. That said, I found the patient information leaflet which came with the capsules is just not detailed enough for an inquisitive patient such as myself!
I always like to refer to best practice which is why I’ve consulted one of the top NET Dietitians, Tara Whyand of Royal Free London. She agreed to an online Q&A session on 28 Feb 2018. This took place on my private Facebook group click here or search Facebook for this group “Neuroendocrine Cancer – Ronny Allan’s Group“. Join, answer some simple questions and then your application will be processed.
The output from the online with with Tara Whyand is below:
Thanks for attending the online event. Here is a tidy summary of the many comments. I hope this is also useful for those who were unable to attend.
Why would I need PERT and are there any tests that can be done to validate this?
“Somatostatin analogues, pancreatic surgery, pancreatitis and cystic fibrosis can cause exocrine pancreatic insufficiency (EPI). This means that the pancreas does not produce enough enzymes to break down food. It results in fatty loose stools called steatorrhoea.
Patients who have exocrine pancreatic insufficiency (EPI) require PERT (pancreatic enzyme replacement therapy) to break down food (fat, protein and carbohydrate). There are many brands of pancreatic enzymes, the most commonly used are Creon and Nutrizyme. Both have different dose levels to choose from.
The fecal elastase test was traditionally used to test the function of the pancreas, although it may not be that useful in NETs. This is because a NET team in Wales found that some NET patients who reported steatorrhoea had a false negative result.
Steatorrhoea may also be a result of bile acid malabsorption and small intestinal bacterial overgrowth which can co-exist and are common especially after surgery. They can both be tested for at a hospital.”
1a. Would the treatment be different for both EPI and bile acid malabsorption? If not how different?
“Yes BAM requires bile acid sequestrants rather than PERT”.
1b. would this be something you would take in general to help overall digestion and absorption of nutrients?
“No only if you have reasons for EPI to occur”.
PERT dosage. Is there a set dosage for all patients or does it depend on type of NET or surgery? And can I overdose on PERT?
“It depends on what you eat. PERT dose is normally tailored on fat content (the more fat you have, the more enzymes you need), but patients who have had a total pancreatectomy will have to have PERT for all food and drink (apart from water) as carbohydrate and protein needs to be broken down too.”
2a. “What about when taking medication such as Cholesteramine or pills in the morning and evening. Do I need to take it to absorb these?”
“see question 5”.
2b. I had a total pancreatectomy and was told I do not need PERT for fruit and veg?
“there’s carbs in all fruit and veg and often fat and protein too, so no different really.”
Some sources say to take the capsules at the beginning of a meal, some say it’s also at the end of a meal is also OK. How critical is this?
“You must always take the capsules at the beginning of the meal and if the meal goes on longer than ~30 minutes, or there are several courses, you will need to have another capsule/tablet/scoop of enzymes. If you don’t, food will pass by the pancreas undigested and ‘malabsorption occurs. This leads to fatty stools (steatorrhoea), fat soluble vitamin deficiency and weight loss. Unbroken down food can also feed bacteria and you can develop small intestinal bacterial overgrowth as a result.”
3a. so if my oncologist says to take four capsules per meal, then I should take all four at the same time?
“see question 11”
3b. if you have had a total gastrectomy (total removal of the stomach), is there a different procedure for taking PERT? I am on Creon and have heard that perhaps I need to open up the capsules as I can not break down the gelatin casing. Not sure if this is true or not.
“See question 11”
What is a meal? Is it multiple courses, or is there a strategy for each individual course? What about snacks? (i.e. a single biscuit with a cup of tea)
“The standard starting dose for snacks: 22-25,000 units lipase, titrating up when symptoms have not resolved. Most people end up taking 44,000-50,000 for snacks.
For main meals start on 44,000/50,000 and most people will need 66,000-100,000 units lipase/meal for the long term.”
4a. I have to eat multiple small meals a day (like every 3 hours, so 7 to 8 small meals). Is there a limit on the amount of Creon I can take in a day?
“see question 11”
4b. What is a snack?
“No official definition. Something with a little fat and maybe 50-200kcals.
Are there any problems taking PERT at the same time as other drugs? e.g. I like to take my vitamin supplements with food. And it’s recommended that some drugs be taken with food.
“PERT only breaks down food, but it is important to take your PERT to ensure food and drugs are absorbed. If you do not take you PERT with the meal, it is likely that food and drugs will rush through your bowel without being absorbed. There is no problem taking vitamins and minerals with food and PERT.
5a. I take a probiotic also, when is best time to take this, before, during or after food?
“Timing doesn’t matter”
I heard PERT is a porcine produce but I’m a vegan? Is there anything else for me?
“There are no other recommended products, and you should only have prescription PERT’s. This is for safety and reliability. Other off the shelf enzymes are unlikely to work.
Pigs are not slaughtered for PERT, they are slaughtered for meat and enzymes are a by-product if that makes anyone feel more comfortable with the idea.”
I heard PERT is a porcine produce but my religion does not allow me to eat such produces. Is there anything else for me?
“PERT are only sourced from a pigs pancreas but Jewish and Muslim patients have been granted approval to take the enzymes on medical grounds from their religious leaders because there is no alternative.”
Some doctors are prescribing PPIs along with PERT claiming that they help the PERT do the job. Do you have a view on this and are there any general diet tips to support the job of PERT without resorting to other drugs?
“Yes if you have had a whipples operation or you have acid reflux you must take an anti-acid (proton-pump inhibitor-PPI) drug to reduce the acid level. If left untreated it can cause ulcers, and when they bleed it can sometimes lead to a life threatening situation. PERT are gastro-resistant-they do not work in too high an acid environment. Sometimes a PPI / H2 blocker can decrease the acid level and allow the PERT to work better. There is no other reliable way of reducing stomach acid.
Note: Ronny Allan input that there is information published about the over-subscribing of PPI for long term use. Additionally that some NET specialists are suggesting a preference for H2 Blockers rather than PPI for NET Patients. H2 Receptor Blockers include Nizatidine (Axid), Famotidine (Pepcid, Pepcid AC), Cimetidine (Tagamet, Tagamet HB), Ranitidine (Zantac). The exceptions would be for PPI therapy necessary for Barrett’s Esophagus and Zollinger Ellison Syndrome (Gastrinoma). Read my article on PPIs by clicking here.
8a. I had a whipples two and a half years ago and have recently stopped taking omperazole as I didn’t seem to need them. Do you think I should still be taking something to reduce acid level anyway?
“yep think you should be on Ranitadine or a PPI long term.”
8b. Is it possible to suffer from excess acid without even knowing it? I also take probiotics, is it possible they could be minimising any excess acid? Also, I seem to be able to eat whatever I want without consequence but am worried now in case I am doing wrong and storing up trouble for myself.
“yes you can have silent reflux but after a total pancreatectomy you needs lots of adjustments and insulin dosing advice.”
9. How will I know the PERT is working for me? And are there any tests to validate this?
“You will know if your PERT is working well if your symptoms improve – i.e. you get normal (mid brown and formed) stools.
Patients taking enough PERT will not become fat soluble vitamin deficient or lose weight in the long term.
You could do a fecal elastase test (if stools are not liquid), but this is not a very reliable test especially for patients with NETs.
If symptoms do not resolve entirely, there may be a co-existing cause of malabsorption e.g. bile acid malabsorption or small intestinal bacterial overgrowth.”
9a. With regards to Question 9, how would you know if you have bile acid malabsorption or SIBO? Can you be tested for those?
“If PERT doesn’t resolve things, SIBO testing is another thing to look at using a lactulose drink and hydrogen breath test. If the NET is in the terminal ileum, bile acid malabsorption (BAM) is likely. The test is a SeHCAT scan and treatment usually Questran or Colesevelam.
If I need to stop taking PERT, do I just stop or do I need to taper off consumption over time?
“No, just stop. But only do so if it has caused a side effect and report the reaction to the doctor and pharmaceutical company. If you don’t think they are working, speak with a specialist Dietitian and you may need a PPI or H2 blocker or change brand/dose.”
If someone has had a total gastrectomy, can they take Creon? If so, do they need to open up the pill to remove the gelatin to help the enzymes to work?
“They are to be taken as normally directed. You can open capsules but only into an acidic fruit juice (a pH of 4.5 or below) and swallow immediately. It could be argued that PERT will work most easily in patients having a gastrectomy as you cannot get too high a stomach acid level without stomach P-cells. By the way, shouldn’t be any gelatin in the prescribed PERT”
11a. Are there any problems with taking too much in a day? I have to have 7 to 8 meals (minimum). I am losing weight. Take with every snack and meal?
“You can overdose – for Creon this is 6000 units lipase per kg of body weight. If you are still losing weight, PERT is not working or something else is the cause of malabsorption”
SUPPLEMENTARY QUESTIONS AT THE END
12A. My steatorrhoea only occurs once/twice a month. Is PERT indicated if steatorrhoea is not chronic?
“Yes, probably need to take all month as steatorrhoea is only a sign of extreme malabsorption, small amounts of malabsorption aren’t noticeable visibly but will reflect in weight and blood vitamin levels.”
12B. I do not need Creon as I am a Lung NET; although I have had my gall bladder removed.
“May need PERT if on somatostatin analogues. Some people take a bile acid sequestrants after gall bladder removal. PERT won’t work for that.”
I’ve always known about issues such as steatorrhoea and vitamin/mineral deficiency. My weight is fine but very happy to trial PERT to see the differences. I made a mistake of starting the capsules on Dec 23rd just before Christmas – it made for an interesting week! Early days so far but I’m getting used to taking them (and remembering to take them ….). Still seeing signs of steatorrhoea but am tracking this against diet. Not seeing any change to stool frequency. I would appear to be belching more though! I will keep this post live as I learn more.
You may wish to see the output from an online chat I carried out, the link is above.
UPDATE 1st Feb 2019. After 1 year, I’m not sure if there has been any difference to signs of malabsorption with Creon, although the supplement did help with weight gain in the period Oct – Dec 2018 after a dose increase. I had lost weight earlier in 2018 due to a bad chest infection and was having trouble regaining it. Despite the success with the weight gain, that is no long an issue, so I commenced a 3 month trial of Nutrizym to see any change in intermittent but frequent steatorrhea, which potentially indicates a continuing malabsorption issue.
If I had a pound for every time I’ve said “make sure you get good surveillance and follow up”, I’d have a lot of pounds! Most Neuroendocrine Tumours are slow-growing and they can be difficult to diagnose due to their sneaky nature. Some can be just as sneaky beyond diagnosis though. The best way to combat that is through regular surveillance or ‘follow-up’. There are actually guidelines and recommendations for follow-up on the main NET specialist societies such as ENETS, NANETS and UKINETS. There’s others including in USA, the NCCN also have a set (and no surprises that the different organisation guidelines can often differ due to the healthcare systems in place). For more detailed or the latest guidelines content, you may need a login or in one instance (ENETS) a membership subscription.
The type and frequency of surveillance will depend on a number of factors, including but not limited to; NET type, primary location, stage and grade. Worth also noting that these are guidelines and physicians will often take many factors into account in deciding on the frequency and content of follow up surveillance.
Let me also tell you that there isn’t really total common ground on exactly what that should be, although to be fair there’s much more agreement than disagreement. There’s even occasional mentions of “not enough data” to be able to say what the surveillance should be in certain scenarios – it’s not an exact science. So surveillance can be anything from monthly to recommended intervals such as 3 months, 6 months, 12 months, 3 years and I’ve even read something which said “no specific follow-up strategy has been recommended” (e.g. ENETS “curative resection of an Appendiceal NET less than 1cm by simple appendectomy“). Often a patient will need to advocate to get the right attention. Knowing what the guidelines are for your situation is a good start.
So what sort of surveillance might be needed?
I think the definition of surveillance is actually wider than the guidelines infer. In addition to the planned follow-up surveillance, I also think there are checks that might be described as ‘opportunistic’. A simple example … if a nurse visits you at home, he or she might ask how things are. Similarly if you visit a GP/PCP, this could be an opportunity to assess the issue you are having against your medical history. Again, if you call your NET specialist or NET Specialist Nurse, this could be another opportunity to assess a problem, albeit over the phone. The other surveillance I would like to see more ‘formalised’ would be the surveillance of the consequences of cancer and it’s treatment – this is a huge unmet need in many cancers. Examples include (but are not limited to) the issues of vitamin & mineral deficiencies and gastrointestinal malabsorption.
However, the documented and objective surveillance methods are really important and can be very similar to those which were used to diagnose you. These are…..
Scanning is very important because the locations of tumours should already be documented and can therefore be tracked, or in the case of an unknown primary, continue to look. Scans are looking for tumours or suspicious objects and any progression of known tumour sites. There are different scans for different purposes and even for different parts of the body and NET type. Check out my article “If you can see it – you can detect it“ – click here. The Ga68 PET scan is becoming more available – click here.
Tumour Markers and Hormone Levels
You will have baseline test results which will be compared at each planned surveillance opportunities. Whilst there are common tests available, some types of NETs may need particular tests, especially if you have one or more of the NET Syndromes producing one or more of the offending hormones. These tests may even be required on an ad hoc basis if symptoms worsen. I have a fairly comprehensive article on this subject – click here. It’s also possible that a new biopsy might be necessary (perhaps following a scan) and this may even lead to a new grading on the basis that the score might turn out be higher than the baseline grade.
NETs are a heterogeneous group of malignancies so I guess some people have additional tests alongside their main tumour markers and hormone levels. I have the routine blood levels alongside my markers, that’s pretty standard I think. I also get my thyroid levels checked due to a lesion currently under watch and wait. Read about his here. Due to surgery and malabsorption issues, I also get regular vitamin checks, in particular B12 and D. Read here to see why this is important. As someone who was initially diagnosed with ‘Carcinoid Syndrome’ alongside my NET, I normally get an annual Echocardiogram to check for Carcinoid Heart Disease – they had removed that earlier this year from my surveillance but it’s now back as a precaution due to the discovery of some fibrosis growth in my retroperitoneal area. You may also be monitored for ‘at risk’ or comorbidity checks such as the thyroid.
Listen to your body
I also have a personal theory that patients are doing surveillance on a daily basis. For example, I actually maintain a diary briefly listing things such as sleeping patterns, what I’ve eaten, bathroom activity, weight, and some other stuff including particular comorbidities that might or might not be related (if not, then it’s also useful for any resulting GP/PCP appointment). That sounds like a lot of work but actually only takes me one minute each day. I’m really looking for patterns. If I think there is a pattern or a connection, I take this data to any appointment or contact the NET Nurse for advice or even just a sounding board. I can’t beat up my medical team for not spotting something where my input would have been important. I already learned that lesson prior to diagnosis.
A lot of people don’t like living in a surveillance society. Me? I’m perfectly happy about it – it will keep me alive longer. And if ‘Big Brother’ is a NET specialist, even better!
Always ask what your follow-up regime will be – this cancer can be SNEAKY.
Thanks for reading
You may also enjoy my article “10 Questions to ask your Doctor” – click here.
This is an excellent and positive video based overview of where we are with the Management of NETs. This is a presentation from a NET Specialist (who some of you may know) presenting to a “GI Malignancies” conference. This is therefore not only awareness of NETs, it’s also some good education for non NET GI experts who may only know the very basics. Useful for patients too! I met Dr Strosberg in Barcelona (ENETS 2017) and thanked him for his presentational and scientific paper output which I often use in my articles.
The classification picture is good as it explains the different facets of NETs and how NETs are classified and categorised in a general way – not seen it done this way before. Slightly out of date as it does not adequately convey the possibility of a well differentiated high grade recently classified by the World Health Organisation – read more here.
Amazingly it is delivered without using the word ‘carcinoid’ other than in reference to syndrome, indicating it can be done and is something also being reflected in all my posts to ensure they are up to date with the latest nomenclature. It’s also a good example for GI doctors as this branch of medicine is often involved in NET diagnostics and surveillance.
Excellent update of all the trials which have introduced treatments in the last decade.
Great update and worth the 30 minutes it takes to watch – you can view it CLICK HERE.
I quite like the Facebook memory thing. This morning I got a reminder of a post I made from 7 years ago whilst I was in hospital recovering from my 9 Nov surgery. It had taken 12 days for me to feel strong enough to venture onto social media with a simple message “I’m feeling perkier”. For those not familiar with English localisms, it just means lively, spirited, bright, sunny, cheerful, animated, upbeat, buoyant, bubbly, cheery, bouncy, genial, jaunty, chirpy, sprightly, vivacious, in fine fettle, full of beans, bright-eyed and bushy-tailed. I guess I met some of these descriptors most of the time! I had gotten through the worst and the light at the end of the tunnel was now a faint glimmer.
I’ve recently had a ton of ‘7 years ago cancerversaries’ and there’s still a few to go! I’m currently being reminded of an issue that started just after my initial treatment and by coincidence (perhaps?) the commencement of my Lanreotide (Somatuline Autogel). Itching! However, for me, it’s mainly the right leg below the knee (go figure!). Much less frequently on my arms and sides. I know many people have the same issue but no-one ever seems to find out why – I guess it’s that Neuroendocrine jigsaw thing again?
Initially, I put the issue down to Lanreotide, as this is mentioned in the side effect list on the drug instructions. The initial connection was made because it seemed to be happening immediately after my monthly ‘dart’. A really annoying itch mostly around my ankles and which had to be scratched! An application of a general emollient cream for a few days seemed to do the trick and after a week it was gone (until the next injection …..). However, after a few years, I sensed the issue was drifting away from the injection cycle and adopting a different and more random pattern. I’m also suspicious of a nutritional connection and checking my article Nutrition for NETs -Vitamins and Mineral Challenges, I can see Vit B3 (Niacin) and Vit E are mentioned in regards skin issues. I’d be confused if this was an issue today as I now take plenty supplements to offset GI malabsorption. However, I probably wasn’t taking sufficient between surgery and 2013 as I lacked the knowledge to do so at the time. So nutritional deficiency remains a possibility or at least an added complication. The most recent outbreak has unusually gone on for the last 4 weeks.
I also seem to have had an eczema type issue in my right ear and mild rosacea for more than 7 years (pre diagnosis). As you can imagine my ‘inner detective’ is working overtime! One thing is clear – this itchy leg issue has plagued me for 7 years.
I know that many people have real issues with rashes and skin itching, I’ve seen this so many times with some people describing it as severe. Clearly when this is the case, a doctor’s intervention is generally required. I’ve seen the following connections to NETs and skin issues:
Glucagonoma – a type of functioning pNET can often come with dermatological issues.
Of course there is a Neuroendocrine Carcinoma of the skin known as Merkel Cell Carcinoma – more of a skin lesion effect than regular dermatological issues.
Edit: 2019. Winter in UK has made my itching seem worse, perhaps the cold weather plays a factor. Maybe I just currently have what many people have – dry flaky skin and the onset of winter probably isn’t helping?
There’s a lot of scary diseases in this world but some of them are particularly spooky. One such spooky disease is the lesser known type of cancer that infiltrated my body – Neuroendocrine Cancer (aka Neuroendocrine Tumors or NET for short). Not only is it scary and spooky, but it’s also cunning, devious, misleading, double-crossing, and it likes nothing better than to play tricks on you.
It will grow in your body without you knowing. It finds places to hide, mainly the small intestine, appendix, lungs, stomach, pancreas, rectum and a host of other places. It can be fiendishly small to avoid being seen. Once it’s established in the primary location (….or locations), it will try to break out via your blood and lymphatic systems. It wants to establish other bases in your mesentery, your liver, your lymph nodes, your bones and any other place it can get to.
It can often be uncannily quiet, not showing any symptoms. However, sometimes it wants to have fun by over-secreting certain hormones to add or introduce symptoms which mimic many other conditions such as IBS, asthma, abdominal upset, diarrhea, flushing. These are just more tricks up its sleeve. You will go to your doctor, perhaps many times, to report what looks like routine/regular symptoms. Unfortunately, it’s also really good at tricking your doctors. After several visits and despite your concerns, your doctors could become so frustrated that nothing serious is obvious, they might even start to think it’s all in your head. This is exactly what Neuroendocrine Cancer wants, it’s just getting started.
One particular type of NET has a wicked trick up its sleeve. This one will over-secrete a hormone called Serotonin which can often cause fibrosis in your abdominal area, potentially causing obstructions and damage to major organs and blood vessels. It’s not finished though, it will also try to introduce fibrosis to the right side of your heart causing more life threatening issues. In addition to common symptoms of flushing, this type and others will also make you feel weak, fatigued, pain, agitated, anxious, dizzy, nauseous, jaundiced, acid reflux, skin irritation, anemic, lose weight and give you heart palpitations. It’s a real Witch’s Brew of symptoms and living with it is often not easy. Its main trick is to prevent you from being correctly diagnosed and it’s pretty good at it.
However, it has a ‘finale’ trick. Neuroendocrine Cancer actually wants to kill you, and if it’s left to plough its relentless path throughout your body, that’s exactly what it will do, slowly but surely.
It’s not just slow and scary, it can also be deadly. Spread the word and help save a life.
If you are suspicious you have Neuroendocrine Cancer but not yet formally diagnosed, you may appreciate this article.
NANETS (North American Neuroendocrine Tumor Society) is one of the biggest NET conferences, bringing together NET Specialists from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field of Neuroendocrine Neoplasms (Tumors and Carcinomas). This is fairly complex stuff but much of it will be familiar to many. I’ve filtered out several outputs from the conference which I think are both relevant and topical to patients. The list is below allowing you to easily peruse and read further via linkages if you need to read more. Remember, some of these are extracts so do not contain all the details of the research or study – although some of the linkages will take you to in-depth information if that’s your bag. Where applicable, I’ve also linked to some of my blog posts to add context and detail in patient speak. The list comprises articles which were published in medical news media and for which I received alerts. It does not comprise the entire schedule of NANETS 2017. I may add more to the list if other relevant and interesting articles are published downstream.
Please note: Some of the output from the conference is in ‘study form’ and has not yet been published as peer-reviewed data (important notice to readers).
NANETS to Bring All Specialties in the NETs Community Together for 10th Annual Symposium
Interview with Michael Soulen MD. Nice introduction.
PFS and OS After Salvage Peptide Receptor Radionuclide Therapy (PRRT) with 177-Lu[Dota⁰,Tyr³] octreotate in Patients with GastroEnteroPancreatic or Bronchial NeuroEndocrine Tumours (GEP-NETs) – The Rotterdam Cohort
“Cured” – In cancer, this word can evoke a number of emotions. Interestingly, not all these emotions will be as positive as you might think. If you want to spark a heated debate on a Neuroendocrine Cancer patient forum, just mention that you’ve been cured.
I’ve been living with Neuroendocrine Cancer for 8 years so I must be cured, right? Unfortunately not as straightforward as this, and I’m guessing this is the case for many cancers. Doctors clearly need to be careful when saying the word “cured‘ even if there is a small likelihood that a cancer will recur. There’s plenty of ‘conservative’ and alternative terms that can be used, such as ‘stable’, ‘no evidence of disease (NED)’, ‘in remission’ or ‘complete response’. However, I don’t see the latter two much in Neuroendocrine disease circles.
So with all these ‘ifs’ and ‘buts’, what exactly is a cure?
Answering this question isn’t a simple case of ‘yes’ or ‘no’, because it depends on the way that the term ‘cancer’ is defined. It should actually be viewed as an umbrella term for a collection of hundreds of different diseases. They all share the fundamental characteristic of rogue cells growing out of control, but each type of cancer, and each person’s individual cancer, is unique and comes with its own set of challenges.
That’s why it’s very unlikely that there will be one single cure that can wipe out all cancers. That doesn’t mean individual cases of cancer can’t be cured. Many cancers in fact already can be. Scientists aren’t actually on the hunt for a ‘silver bullet’ against all cancers, Quite the opposite. The more scientists get to know each type of cancer inside and out, the greater the chance of finding new ways to tackle these diseases so that more people can survive. Thanks to a much deeper understanding of cell biology and genetics, there exist today a growing number of targeted therapies that have been designed at a molecular level to recognise particular features specific of cancer cells. Along with chemotherapy, surgery and radiotherapy, these treatments—used singly and in combination—have led to a slow, but steady, increase in survival rates. You can definitely count Neuroendocrine Cancer in that category.
Cancer is seen today less as a disease of specific organs, and more as one of molecular mechanisms caused by the mutation of specific genes. The implication of this shift in thinking is that the best treatment for, say, colorectal cancer may turn out to be designed and approved for use against tumors in an entirely different part of the body, such as the breast. We’re certainly seeing that with certain targeted therapies and more recently with Immunotherapy.
Surely a cure is more possible if cancer is diagnosed earlier?
To a certain extent this is true for many types of cancer, not just for NETs. In fact the same scientists did say ….”We detect those attacks when they’re still early, before the cancers have widely spread, at a time when they can still be cured simply by surgery or perhaps surgery and adjuvant therapy, which always works better on smaller tumors.”.
What about Neuroendocrine Tumors (NETs)? Clearly I’m not qualified to make such statements except to say that I am of the opinion that earlier diagnosis is better for any curative scenario. When you read NET guidelines (ENETS/NANETS etc), the word ‘cure’ and ‘curative’ is mentioned in relation to surgery. Bearing in mind that our most expert NET specialists are involved in the drafting of these guidelines, perhaps we should pause and think before dismissing these claims. Having checked ENETS publications, I can see it’s related to certain conditions and factors such as localisation within the organ, tumour size, good resection margins, and a suitable follow-up surveillance.
Clearly with advanced disease, the cancer becomes incurable but treatment for many being palliative to reduce tumor bulk and reduce any symptoms and/or syndrome effects. Despite this, the outlook for metastatic NETs at the lower grades is good. While we’re talking about palliative care, do not confuse this with end of life, that is only one end of the palliative spectrum. It can and is used at the earliest stage of cancer.
Immunotherapy will eventually cure cancer, right?
Immunotherapy will play a huge part in cancer treatment in the future, that we know. But to suggest that it’s a cure is probably overstating its current success. Neuroendocrine Cancer has not been forgotten – you can read more about Neuroendocrine Cancer and Immunotherapy here.
I heard the Oncolytic Virus at Uppsala is a cure for NETs?
There is currently no scientific evidence that the Oncolytic Virus (AdVince) can cure humans with Neuroendocrine Cancer. So far it has only been proven in destroying neuroendocrine tumours in mice. The Oncolytic Viruses developed in Uppsala are now being evaluated in phase I clinical trials for neuroendocrine cancer. If you’re not up to speed with this trial, read more here – Oncolytic Virus Uppsala
Isn’t prevention better than a cure?
This old adage is still relevant BUT latest thinking would indicate it is not applicable to all cancers. Scientists claim that 66% of cancer is simply a form of ‘bad luck’ and if the claim is accurate, it follows that many cancers are simply inevitable. The thinking suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development confirming that “bad luck” explains a far greater number of cancers than do hereditary and environmental factors. This scientific thinking is a tad controversial so it’s worth remembering that even if, as this study suggests, most individual cancer mutations are due to random chance, the researchers also admit that the cancers they cause may still be preventable. It’s complex!
The newspapers are always talking about breakthroughs and cures for cancer?
Newspapers looking for a good headline will use words such as ‘cure’. Sadly, headlines are generally written by sub-editors who scan the article and look to find a ‘reader-oriented angle’ for the heading. They either can’t or don’t have time to understand what’s actually being said. Unfortunately this then leads to people sharing what is now a misleading article without a thought for the impact on those who are worried about the fact they have cancer and whether it can be cured or not. There’s also a lot of fake health news out there – check out my article series about the problems with the internet and ‘Miracle Cures’.
To cure, they must know the cause?
To a certain extent, that’s very accurate. Have you ever wondered what caused your NETs? I did ponder this question in an article here. The only known cause of NETs is currently the proportion of patients with heredity syndromes – see my article of Genetics and Neuroendocrine Cancer. Interestingly, the NET Research Foundation recently awarded funding to look at the causes of Small Intestine (SI) NETs (one of the most common types). A scientific collaboration between UCL, Dana-Farber Cancer Institute, UCSF Medical Centre and the UCL Cancer Institute / Royal Free Hospital London. The team’s approach has the potential to identify inherited, somatic (non-inherited) genetic, epigenetic and infectious causes of SI-NETs. The research is questioning whether SI-NETs are caused by DNA changes in later life or by aberrant genes inherited at birth; environmental influences or infectious agents – or is it a combination of all these factors? Very exciting. Read more here.
What would a cure mean to those living with NETs?
This is something that has crossed my mind, even though I don’t believe it will happen in my lifetime. I guess it would be good to get rid of the known remnant tumors left behind from my treatment (and any micrometastases currently not detectable). However, many NET patients are living with the consequences of cancer and its treatment, including surgery, chemotherapy, biological therapy, somatostatin analogues, radionuclide therapy, liver directed therapy, and others. Many of these effects would remain – let’s face it, a cure is not going to give me back bits of my small and large intestine, liver and an army of lymph nodes. So support for those living with NETs would need to remain despite a cure.
The emotional aspect of the word ‘cured’ seems to be an issue across many cancers and it’s certainly very controversial in NET circles. The world has still not cured the many cancers that exist. But over the next five to ten years the era of personalised medicine could see enormous progress in making cancer survivable. I think both doctors and patients need to take a pragmatic view on the ‘cured’ word and to end this article I wanted to share an interesting quote I found whilst researching.
Firstly, let me say that I have no intention of advising you how to lose or gain weight! Rather, I’d like to discuss what factors might be involved and why people with NETs might lose or gain weight either at diagnosis or after treatment. Clearly I can talk freely about my own experience and associated weight issues. If nothing else, it might help some in thinking about what is causing their own weight issues.
I wrote a patient story for an organisation over 3 years ago and it started with the words “Did you mean to lose weight”. Those were actually the words a nurse said to me after I nonchalantly told her I thought I’d lost some weight (….about half a stone). I answered the question with “no” and this response triggered a sequence of events that led to all the stories in all the posts in this blog (i.e. my diagnosis).
I annoyingly can’t remember at which point I started to lose the weight but I was initially reported to have Iron Deficiency Anemia due to a low hemoglobin result and my subsequent iron test (Serum Ferritin) was also low and out of normal range. This, combined with the weight loss, the GP was spot on by referring me to a clinic. The sequence of events during the referral led to a diagnosis of metastatic NETs (Small Intestine Primary). If I had been a betting man, I would have put money on my GP thinking “Colorectal Cancer”. So my adage “If your doctors don’t suspect something, they won’t detect anything” applies.
I can also tell you that I weigh myself most days at the same time using the same scales. Weight loss or gain needs to be recorded. Clearly 2 or 3 pounds is nothing to worry about, I found you could put on or lose that amount in a day, depending on time of weighing and food intake. I’m looking for downwards or upwards trends of 7lbs or more (3kg).
Why did I lose weight?
The drop from 12st to 11st was clearly something to do with the anemia symptom (the NETs). But after diagnosis, I had major surgery about 10 weeks later. When I left the hospital after my 19 day stay, I was a whole stone lighter (14 lbs or 6.3 kg). I guess 3 feet of intestine, the cecum, an ascending colon, a bit of a transverse colon together with an army of lymph nodes and other abdominal ‘gubbins’ actually weighs a few pounds.
However, add the gradual introduction of foods to alleviate pressure on the ‘new plumbing’, and this is also going to have an effect on weight. I remember my Oncologist after the surgery saying to use full fat milk – the context is lost in memory but I guess he was trying to help me put weight back on. I also vividly remember many of my clothes not fitting me after this surgery. In fact, since 2010, I’ve actually dropped 2 trouser sizes and one shirt/jumper size. I did spend a lot of time in the toilet over the coming months, so I guess that also had an impact! However, what I wasn’t aware of was the side effect of my surgery. I started to put on some weight in time for my next big surgery – a liver resection. The average adult liver weighs 1.5 kg so I lost another 1 kg in one day based on a 66% liver resection.
However, what was also going on was something that took me a while to figure out – malabsorption and vitamin/mineral deficiency. My new ‘plumbing’ wasn’t really as efficient as my old one, so the malabsorption. issues caused by a lack of terminal ileum was slowly starting to have an effect. The commencement of Lanreotide in Dec 2010 added to this complication. That knowledge led me to understand some of the more esoteric nutritional issues that can have a big effect on NET patients and actually lead to a host of side effects that might be confused with one of the several NET syndromes. What it also confirmed to me was that I could still eat foods I enjoy without worrying too much about the effect on my remnant tumours or the threat of a recurrence of my carcinoid syndrome, something I was experiencing prior to and after diagnosis.
Armed with the ‘consequences of NETs’ knowledge, I did eventually adjust my diet and my weight has now ‘flat-lined’ at around 10 st 7 lbs (give or take 1 or 2 lbs fluctuation). Amazingly, the same weight I was when I left hospital after major surgery, looking thin and gaunt and not very well at all! The difference to day is that I have adapted to my new weight and look fit and healthy.
I actually lost another half a stone (7 lbs or 3.5 kg) in 2014 whilst training for an 84 mile charity walk – many commented that I looked thin and gaunt despite being extremely fit from all the training. Perspectives. It took several months to put the weight back on but at least I knew what had caused the loss and then subsequent gain.
I don’t have any appetite issues although I try to avoid big meals due to a shorter gut, so I snack more. With the exception of the 4 months of intense training for the 84 mile hike, I cannot seem to lose or gain weight. As my current weight is bang in the middle of the BMI green zone (healthy), I’m content.
Why do NET patients lose weight?
That’s a tricky one but any authoritative resource will confirm fairly obvious things such as (but not limited to) loss of appetite and side effects of cancer treatments. NETs can be complex so I resorted to researching the ISI Book on NETs, a favourite resource of mine. I wanted to check out any specific mentions of weight and NETs whether at diagnosis or beyond. Here’s some of the things I found out:
Carcinoid Syndrome. Weight loss is listed but not as high a percentage as I thought – although it tends to be tied into those affected most with diarrhea.
Gastrinoma/Zollinger-Ellison Syndrome. Up to half of these patients will have weight loss at diagnosis.
Glucagonoma. 90% will have weight loss.
Pheochromocytoma. Weight loss is usual.
Somatostatinoma. Weight loss in one-third of pancreatic cases and one-fifth in intestinal cases.
VIPoma. Weight loss is usual.
MEN Syndromes. One of the presentational symptoms can be weight loss.
Secondary Effects of NETs.
Many NETs can result in diabetes (particularly certain pNETs) and as somatostatin analogues can inhibit insulin, it could push those at borderline levels into formal diabetic levels (including any type of NET using long term somatostatin analogues). In people with diabetes, insufficient insulin prevents the body from getting glucose from the blood into the body’s cells to use as energy. When this occurs, the body starts burning fat and muscle for energy, causing a reduction in overall body weight.
It must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above.
Suggested reading for putting weight back after surgery
An excellent reference document produced by Royal Free Hospital, authored by Tara Whyand and distributed via the NET Patient Foundation – hints and tips for different types of NET by anatomy: click here
What about weight gain?
You always associate weight loss with cancer patients but there are some types of NETs and associated syndromes which might actually cause weight gain. Here’s what I found from ISI and other sources (as mentioned):
Cushing’s Syndrome. Centripetal weight gain is mentioned. (Centripetal – tends to the centre of the body). I also noted that Cushing’s Syndrome tends to be much more prevalent in females. Cushing’s syndrome comprises the signs and symptoms caused by excessive amounts of the hormone cortisol (hypercortisolism) or by an overdosage of drugs known as glucocorticoids.
Insulinoma. Weight gain occurs in around 40% of cases, because patients may eat frequently to avoid symptoms. However, according to an Insulinoma support group site, I did note that after treatment (some stability), things can improve.
Again, it must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above. As in weight loss scenarios, the Secondary Effects of NETs can have an effect.Hypothyroidism is another potential issue and weight gain is a listed symptom. I just been diagnosed with hypothyroidism this year but I was not gaining weight!
The NETs Jigsaw
Like anything in NETs, things can get complex. So it is entirely possible that weight loss or weight gain is directly caused by NETs, can be caused by side effects/secondary effects of treatment, and it’s also possible that it could be something unrelated to NETs (Dr Liu “Even NET patients get regular illnesses“). I guess some people might have a good idea of the reason for theirs – my initial weight loss was without doubt caused by the cancer and the post diagnostic issues caused by the consequences of the cancer.
I guess that weight loss or weight gain can be a worry. I also suspect that people might be happy to lose or gain weight if they were under/over weight before diagnosis (every cloud etc). However, if you are progressively losing weight, I encourage you to seek advice soonest or ask to see a dietician (preferably one who understands NETs).
Edit: I changed my blood thinner in May 2017 and lost 2kg (4 pounds) after 6 months.
Edit: I started Creon at the beginning of 2018 (read about this here) and almost immediately put on 2kg (4 pounds) to offset the 2kg loss from 6 months prior. However, no real change after 3 months of Creon (March 2018).
Edit: I was recently diagnosed with Hypothyroidism, one of the symptoms can be weight gain. Clearly that has not applied to me. Hyperthyroidism is the opposite condition where weight loss is a symptom.
Edit: Due to a bad chest infection in June 2018 and due to the consequences of the effects of that illness and most likely the treatments undergone, I have dropped three quarters of a stone (~10lbs). My lightest weight for over 30 years. To me that is a significant loss of weight in such a short space of time. Currently trying to put it back on again – I need the weight!
Edit: 4 Sep 2018. After the 10lbs (~4.5kg) loss following the chest infection, people who see me regularly have noticed the visible difference. I’m still struggling to get back beyond 10st after 2 months. I’m monitoring this really closely.
Edit: 28 Nov 2018. I’m back at 10st after increasing my dosage of Creon.
Edit: 10 Jan 2019. I’m back at 10st 3lbs, my approximate weight before the chest infection. It’s taken 7 months and the recent acceleration coincides with Creon dose increase.
Edit 7th Feb 2019. Changed from Creon to Nutrizym.
Edit: 17 Mar 2019. It appears my trouser waist size is back to 32″. Is the use of Pancreatic Enzymes making me eat more, or getting more nutrients through, or making me eat food which makes me put on weight?
For those wishing to see the output from an online discussion with Tara Whyand on the subject of ‘Weight’ issues for NET patients – please see this link inside my closed Facebook group.
Patient stories are key to any awareness campaign. Nothing like a human being standing up and letting you know about their experience. Many are positive examples of how they are overcoming their trials and tribulations, others tell stories of a struggle. They all have different styles, some are the ‘kick ass’ type stories, some are just thankful, some are reflective – all of them are perfectly acceptable. I normally like to place myself somewhere in the middle with phrases like “I’m still here“, although I can veer left and right when the mood takes me!
Because of my social media footprint, I get a lot of private messages from people across the globe. Many are from people who have no wish to go public and that’s fine. Many are from people who value my opinion and that’s humbling. On forums, you can get 50 answers (all well meaning ones), with me you normally only get one (even if it’s a “I don’t know”). Most are fairly easy to answer, just a link to something or asking for one of my articles they can’t seem to find. Some are a bit trickier but I get there in the end. Some are pretty worrying and really difficult to answer. And nearly all of them amplify something we already know ……. despite some tremendous medical advances, there’s still a lot of unmet needs for Neuroendocrine Cancer patients, in particular access to NET specialists, access to the best and latest proven treatments and follow-up support for those affected by their experience (physical and mental). I’m talking in a global sense including countries perceived to be advanced in medical terms.
Take Patient A for example. This patient has a classic well differentiated Small Intestinal NET (Si NET) with lymph node metastasis. That resulted in fairly complex abdominal surgery that many of us will have had (including myself). For the past year, this patient has struggled with no follow on support, no dietary advice and has been left alone. This patient told me he is actually receiving his follow on advice from my blog site. This patient is also struggling on the emotional side because people say he looks rather well and have commented that he must have been wrongly diagnosed but at least is now “cured“.
Patient ‘B’ is similar. This patient has had surgery (the surgeon got everything apparently ….) but has been declared non-syndromic on the basis there is no diarrhea. However, there is flushing, joint paint, general abdominal issues, weight loss, headaches, fatigue, dehydration and chronic constipation. It took this patient 6 months to find out about a local NET advocate organisation and 10 months to find out there was access to a dietitian.
Patient ‘C’ is worrying. In this example I was contacted and asked about surveillance intervals as it was noticed I was having regular scans. What I found was someone who had a metastatic midgut NET and not had any surveillance for 3 years (including tumour/hormone marker checks and Echocardiograms). This is despite an advanced healthcare system and oodles of availability. This patient is now seeing a NET specialist.
Patient ‘D’ had a horrendous experience. This patient was treated as a bowel cancer case when they had a low-grade classic Si NET …… surgery and then classic bowel adenocarcinoma chemo. Now, it might be that was the only treatment modality available in this patient’s country but it’s a worrying example of the extent of the unmet needs for NET patients in the country concerned.
Patient E is so shocking, I wrote an entire article about this case. Click hereto read it.
Patient F has a similar story to patient E. Click hereto read it.
I could go on with many other examples and I might expand this post downstream.
One thing is very clear to me, we need a new paradigm in international advocacy and we need to start focusing more on these support issues. As the number of people living with cancer rises, the requirement for post diagnostic support also rises. Even those who are ‘stable’ need support. One thing is for sure, the shock effect of what people tell me never wears off because I know there are more shocking stories still to hear.
In my article ‘Ever wonder what caused your NET’, I concluded that currently, the only known scientifically explained causes for NETs were hereditary/genetic in nature. This is mostly associated with those who have MEN syndromes (yes, they are a syndrome not a type of tumour) and a few other less common types of NET including Pheochomocytoma/Paraganglioma (Pheo/Para) and Medullary Thyroid Carcinoma (MTC) (the familial version of MTC is often referred to as FMTC). However, please note this does not mean that all those diagnosed with pancreatic, parathyroid, pituarity, Pheo/Para and MTC tumours, will have any hereditary or genetic conditions, many will simply be sporadic tumors.
In recent years, it has become increasingly apparent that a number of Neuroendocrine tumours arise as a result of germline genetic mutations and are inherited in an autosomal dominant pattern. The number of genes implicated is increasing.
Apparently, 5-10% of Gastroenteropancreatic NETs (GEP NETs) are estimated to have a hereditary background. Hereditary syndromes associated with these include Multiple Endocrine Neoplasia (MEN), Von Hippel Lindau (VHL), Neurofibromatosis Type 1 (NF1), Tuberous Sclerosis (TS) and others. People who have a genetic condition may present with the tumors (perhaps along with an associated functional hormone syndrome) and so the genetic condition if there is one, may not be known at this point.
How will I know if I am affected?
Some people do worry about this, often because of what they find on the internet including inside patient forums. I suspect some people already know via family connections and as an example (there are many), I guess if you have 2 tumors found in (say) parathyroid and pancreas, it should at least raise a suspicion for MEN1 and be investigated.
Many people say how do I know, how do I check and this is obviously a delicate subject. Of course, your first port of call should be your NET specialist if you suspect or know of any connection.
Thus why I was interested in a paper published in Springer Link – titled “When should genetic testing be performed in patients with neuroendocrine tumours.” When reading, you’ll find it’s actually much more than that! Check it out here:
When should genetic testing be performed in patients with neuroendocrine tumours?
In this review, the authors examined the features which may lead a clinician to suspect that a patient may have an inherited cause of a NET and they outlined which underlying conditions should be suspected. They also discussed what type of screening may be appropriate in a variety of situations. If there is a way to identify which patients are likely to have a germline mutation, this would enable clinicians to counsel patients adequately about their future disease risk, and allows for earlier detection of at-risk patients through family screening. There’s a couple of minor errors in the text but I’ve contacted the authors who also agreed they should have included the pituitary.
The authors focused on presentations of NETs of the gastrointestinal system, chromaffin cell tumours (Pheochromocytoma and Paraganglioma) and Medullary Thyroid Carcinoma. Pituitary tumors (normally associated with MEN1), were not considered in scope for the review. Interesting thought, the review includes news of a move by endocrinologists to reclassify ‘Pituitary Adenomas’ as Pituitary NETs (PitNETs). Read the abstract here. This would appear to be in line with a gradual shift from the benign nomenclature associated with certain NETs to the ‘malignant’ potential of these type of tumors. The abbreviation is also in line with others, e.g. pNET, SiNET, etc. A useful reminder that we must stop using the term ‘Carcinoid‘ as this is regressing this extremely useful initiative to highlight the malignant potential of all NETs.
There also appears to be some linkage to the study looking at the possibility of familial Small Intestine NETs (SiNETs). You can read more about a US registered trial here (with apologies for use of the now defunct term ‘Carcinoid‘).
This is a complex subject and the text above is very basic. If you wish to dig further, the quoted reference is a good read. Just to emphasise, it’s aim is to provide advice about when to recommend genetic testing for NETs, and in doing so provides some useful reference information. Please also note they are finding new genetic links all the time so there could be some omissions of recently discovered genes but the article remains good enough as a primer on the subject. It’s broken down into 4 distinct tumor groupings:
Since my diagnosis of incurable and metastatic neuroendocrine cancer in 2010, it’s really all been about me. I didn’t see the trauma coming, and my family has supported me throughout every single step. I really don’t want to be the focus of attention as that mantle was normally evenly distributed. However, there’s nothing like a cancer diagnosis to put you into the spotlight.
Facing an uncertain future with regular scans, injections, treatment, pills, examinations and blood tests has made me the center of attention, whether I like it or not. The focus is on me because these things are necessary to keep me alive for as long as possible and also because I live with the consequences of cancer and its treatment which provides further challenges. A good quality of life is not only a motivator for change, good planning and constant surveillance, but it’s also hard work and has an additional impact on the whole family. It means all activities including work, holidays, days out, social activities and, even the simple act of eating, might all need to be organized around me due to the vagaries of my condition. It will never stop, it will never end and it will always be about me!
This has gone on since 2010. “Cancerversaries” are on the calendar alongside birthdays and wedding anniversaries. Tumor marker tests and scans are reviewed twice yearly so the relentless attention continues, often peaking at these test milestones and worrying moments in between. The detailed analysis of unusual pain or other disturbances are documented. The attention is on me.
Then, a couple of years ago, my wife finds a lump. The local doctor investigates and refers her for a mammogram. The mammogram check leads to an ultrasound which then leads to a biopsy of some fibrous tissue. We have a two-week wait before the all clear is given but the worry doesn’t immediately dissipate as another check was scheduled for three months (done, no issues). The following check 6 months after on 7 Aug 2018 is also no change. Hang on … this is not about me!
I suddenly realised it shouldn’t be all about me, it’s about other people too. It always has been, I just got wrapped up in my own issues. There is nothing in the rule book that allows cancer or other illnesses to be limited to a single family member. Cancer doesn’t really care how many in your household already have the disease – anyone is a target. It’s bad enough having one cancer patient in the house without another cropping up. One thing is for sure, when it comes to a cancer diagnosis in the family, I really want it to be all about me.
Postscript: Very excited to share my first article published in CURE magazine. This is a real story about recent events involving my own family. As a long-term cancer patient, it can seem like it’s always about ‘me’ and then something happens which changes that perception. It’s actually about others too, and always has been. If you want to talk about something similar in your life, please share with others in your comments below or message me.
This is the beginning of a new phase in my activities and another opportunity to spread awareness of Neuroendocrine Cancer to new audiences, something I promised I would do. I hope you will support my first contribution to an exciting organisation brand.
It would be great if you would take the time to read the article directly on the Cure site here, and any likes, comments and sharing would be appreciated.
Before I was diagnosed with cancer, my health was in reasonable condition. I had minor irritants that seemed to come back now and then, nothing that was going to kill me. So I just put up with most of it and time was frequently a good healer. Occasionally, I would use medicine to speed up the healing or ask a doctor for advice. Even leading up to my diagnosis, this was my strategy despite some strange things going on. Luckily for me, the ‘system’ picked up something suspicious and I am where I am today. It’s amazing to think a cancer can grow inside you for years causing a lot of damage but without a grand announcement.
Following diagnosis, I got quite a lot of attention in the first 2 or 3 years as I went through various surgical and other types of treatment, and I eventually earned the accolade of ‘stable’. Not cured, not in remission, not totally free of disease, just ‘stable‘. I guess I’m one of millions of people who now have a condition to live with for the rest of their life.
I may be stable but I still need support and surveillance!
But I haven’t really been left alone, I have meetings with my specialists every 6 months plus routine surveillance testing. I have my GP (PCP) on tap via same day appointments. Thankfully, my tumours are slow growers and the biochemistry results that check their growth and function have been normal for some years now. I also have my specialists’ telephone numbers in the event of an emergency. The other great thing is that I’m lucky to have a direct line to a specialist Neuroendocrine Cancer Nurse for routine stuff. So I can sit back and relax, right? ……… Sounds good but not really the whole story.
I’m in tune with my body
I can honestly say I’ve never been more in tune with my body – there’s nothing like a cancer diagnosis to force you into a change of attitude. Not just about how you look after your body but learning how to read the signs and assess risk. However, the difficult area with this disease is that many of the side effects of treatment can mimic the symptoms of a recurrence or further spread and vice versa. And sometimes there can be no rhyme or rhythm (or logic) when patients experience these things. I once wrote about the “Neuroendocrine Cancer Jigsaw” where patients had pieces called Signs, Symptoms, Side Effects, Secondary Illnesses, Syndromes, Comorbidities and Coincidences. I also include the proverbial ‘missing piece’ as part of the jigsaw! However, I do think the ‘missing piece’ can sometimes be a metaphor for an instantly contactable NET expert or even some experience and education by the patient or a trusted advocate.
Sorting out the symptoms
The comorbidity and coincidence pieces were belated add-ons to the list because sometimes it not all about the cancer – even cancer patients get regular diseases and ailments. The difficulty is working out if there is a connection or not. Take my 2017 issue of back/hip/leg pain for example. I analysed all the timings in my diary (…top tip, keep a diary), there were no common connections to any particular occurrence or activity for all occurrences of the pain. I got some pain killers and decided to tough it out. After 14 days, I got fed up and saw my GP (PCP). I also ran it past my NET Specialist Nurse for assurance. After 22 days, I was still doing pain killers, waiting on a physiotherapy appointment; and doing back exercises at home. Why is my back pain suddenly a lot worse? My Calcium and Vitamin D are checked regularly and everything is in range. I’ve been receiving somatostatin analogues for over 6 years, so that might be a factor. I also reminded myself I’m no longer 21 (so did my NET Nurse!). Three months later, after seeing a physiotherapist, things improved. However, I would be lying if it didn’t cross my mind that the problem could be bone metastasis. I studied the symptoms of bone metastasis and concluded that I have none of those other than the pain. I analysed my recent scan which said there were “no bony lesions”. I also registered the fact that my biochemistry results are rather good and have been for 6 years.
And then there were the 3 episodes of constipation where the possibility of a bowel obstruction floated around in my thoughts. However, time was once again a healer (along with some quick advice from my specialist NET Nurse!).
A couple of years ago, I thought I felt a lump on my right clavicle by the sternum. However, an MRI later dismissed it as nothing. Due to a piece of metal in my body, to be honest I was more scared about the MRI than the potential lump!
I always remember a great quote from Dr Eric Liu “Even NET Patients get regular illnesses“. He’s right. But it’s also right that people living with a long-term cancer can live in perpetual fear of a worsening state of health or a recurrence of the cancer. For the incidents I highlighted above, the fear that these things were related to cancer growth or recurrence did go through my mind.
Fear can actually be a side effect of cancer
I think all those living with cancer need to be alert and be proactive via education and communication with their medical team and GP (PCP). However, stopping yourself thinking that anything wrong with your body is somehow connected to the cancer, perhaps needs a different approach, particularly if you have a higher than average risk for recurrence. Fear of cancer relapse or recurrence, is said to be associated with poor quality of life, greater distress, lack of planning for the future, and greater healthcare utilisation. However, if you do suffer from this type of fear, you’re not alone. A recent study stated that 50 percent of all cancer survivors have moderate to high, or clinically significant, fear of cancer relapse, which could persist over the whole trajectory of their illness. Younger patients might have a bigger challenge on their hands as their future is uncertain. Patients with young children have an additional concern, that’s another fear area and a very difficult and tough one. And those on the older side who initially thought they might not see grandchildren, or see them growing into adults, that is something I personally found tough.
Psychological problems – another unmet need? Probably.
Conquering fear is difficult and no one size fits all. However, in the most general terms I would suggest the following 8 tips:
Accept your diagnosis – you have cancer, it has the potential to change your life, you most likely need to make adjustments. But this is not to say you also accept that improvements cannot be made and things will not get better …. because they can. This is particularly important for those with incurable cancers needing treatment for the foreseeable future. I accepted my situation very early on and I think that has been helpful in the long-term. Prognostic detail is a worrying thought and a difficult one. However, no-one really knows for sure. After 8 years with an incurable metastatic cancer, I’m still here and continue to be heartened by comments such as these here (click here).
Accept that your road will probably not be straight and smooth. There will be bumps and bends and you will need to deal with them as and when they arise. Don’t try to second guess what the bumps and bends might be and then worry in case they happen. No-one really knows for sure and they might not happen.
Identify your triggers – what is it that is triggering your thoughts? For me it’s more physical things like the lump, constipation and back pain. Other triggers for some might simply be an anniversary of a diagnosis or a treatment etc (or both), or an upcoming treatment. Think about how you can get past these obstacles. For example, on ‘cancerversaries’, plan to be doing something that’ll take your mind of it. For physical things including upcoming treatment, it’s all about what I said above, education, risk management and communication with your medical team ….. put yourself in control. I also have great sympathy for younger patients and those with young dependent children. I can’t put myself in their shoes and all I can suggest is that these tips are still relevant in some way.
Talk about it. Family, friends, other patients, your medical team. I don’t have any issues talking about it – writing posts in my blog is also really therapeutic for me (even this one!) and I hope others appreciate it too. Patient forums can be frighteningly good but …. be careful, many can also be good at frightening and stressful.
Social Media and the Internet. Although talking about your cancer can be a stress reliever, clearly social media can actually be fraught with danger. As I said above, patient forums can be frighteningly good but also good at frightening. You can extend this issue to the entire internet, which is full of false claims of internet cures spreading false hope, out of date prognostic data causing unnecessary fear and anxiety. Pick your social media and internet sites carefully, fake news, incorrect healthcare news, and bad advice is very easy to find.
Focus on Wellness. This is a huge area and it’s pretty much up to you to resolve. Yes, some willpower is involved and it includes both physical and mental wellness. For me I try to do exercise when I can (mostly walking) and I try to make sure I get 8 hours sleep (this is a fairly recent tactic which is really helping with fatigue). With diet, I try to avoid anything that greatly exacerbates the side effects of my treatment. Travelling, family and visiting places with fantastic views is most definitely a tonic for me (and that normally means exercise to get there). Anything that makes you relaxed!
Be patient. Fear of your condition taking a downwards movement will probably never completely go away but perhaps as I said above, time is a healer. It took me over 3 years to become more relaxed about my own future.
If all the above doesn’t work, perhaps professional counselling is required? There are specialists who work with cancer patients to help them accept that fear of recurrence/relapse is a normal part of the cancer experience. They can help you develop strategies to cope with your fears and move forward with your life.
If you think your psychological issues are unmanageable, I strongly encourage you to talk with your doctor or a counsellor. In fact, you may appreciate this excellent videofrom NET Patient Foundation presented by Kym Winter, a qualified Psychotherapist and Counsellor – click here.
I also liked this videoby Dr Michael Burke, a Psychiatric Oncologist – click here
Remember …….. “Googling your symptoms when you’re ill can sometimes be the most efficient way to convince yourself you’re dying”. Anon
ASCO (American Society of Clinical Oncology) is one of the biggest cancer conferences in the world normally bringing together more than 30,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field. As Neuroendorine Tumors is on a roll in terms of new treatments and continued research, we appear to be well represented with over 20 ‘extracts’ submitted for review and display. This is fairly complex stuff but much of it will be familiar to many. I’ve filtered and extracted all the Neuroendocrine stuff into one list providing you with an easy to peruse table of contents, complete with relevant linkages if you need to read more. For many the extract title and conclusion will be sufficiently educational or at least prompt you to click the link to investigate further. Remember, these are extracts so do not contain all the details of the research or study. However, some are linked to bigger trials and linkages are shown where relevant. I’ve also linked to some of my blog posts to add context and detail.
I’m hoping to capture any presentations or other output from the meeting which appears to be relevant and this will follow after the meeting. I will also be actively tweeting any output from the live event (for many cancers, not just NETs).
There’s something for everyone here – I hope it’s useful.
Conclusions: Objective response to PRRT defines a subset of patients with markedly improved PFS. SUVave 21.6 defines a threshold below which patients have a poor response to PRRT. This threshold should be taken forward into prospective study.
Check out my recent blog discussing ‘Theranostic pairing” – click here
Conclusions: The duration of SSA use was positively associated with QoL benefit among CS patients. This may be explained by long-term effectiveness of SSAs or selection bias favoring patients with more indolent disease. Future studies will be needed to distinguish between these possibilities.
Conclusions: The incidence of weight gain was dose-related on TE and was greater than that on pbo. It was possibly related to a reduction in diarrhea severity, and it may be a relevant aspect of TE efficacy among patients with functioning metastatic NETs. Clinical trial information: NCT01677910
Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.
Conclusions: CAPTEM shows activity in neuroendocrine tumor of unknown primary. Currently FDA approved treatment options for grade I and grade II GI NETs includes somatostatin analogs and everolimus. Both of which are cytostatic and of limited use in case of visceral crisis or bulky disease where disease shrinkage is required. CAPTEM should be considered for grade II NETS of unknown primary.
Conclusions: This is the first multi-center study in Mexico. Which reflects the clinical characteristics of the NET_GET. The results differ in their epidemiology from that reported in other countries. However, the clinical and therapeutic results are very similar.
Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496
Conclusions: CLARINET OLE suggests sustained antitumor effects with LAN 120 mg in enteropancreatic NETs irrespective of tumor origin, and suggests benefits with LAN as early treatment. Clinical trial information: NCT00842348
Conclusions: Pts showed improvement in CS symptoms of flushing and diarrhea and reduction in 5HIAA levels with LAN treatment, indicating efficacy of LAN regardless of prior OCT use. Transition from OCT to LAN was well tolerated among prior OCT pts in ELECT. Clinical trial information: NCT00774930
Conclusions: These findings highlight the utility of molecular classification to identify distinct NET tumor types/subtypes to improve diagnostic precision and treatment decision-making. In addition, significant differences in the distribution of molecular diagnoses of NET subtype by age and gender were identified.
Conclusions: In this poor prognosis G3 NET cohort of whom 77% had received prior chemotherapy, a median OS of 18 months from start of PRRT is encouraging and warrants further study. PRRT is a promising treatment option for patients with G3 NET with high somatostatin-receptor expression selected by SSRI.
Conclusions: Occurrence of documented carcinoid crisis was low in this high-risk population. However, a significant proportion of patients developed hemodynamic instability, suggesting that carcinoid crisis is a spectrum diagnosis and may be clinically under-recognized. Use of octreotide was not associated with risk of carcinoid crisis or hemodynamic instability; however, this analysis was limited by our modest sample size at a single institution. There remains a need to establish an objective definition of carcinoid crisis and to inform standardization of periprocedural use of octreotide for at-risk patients.
Conclusions: By assessing patients with GI NET from two independent US claim databases, this study suggested that patients diagnosed with CS were 2-3 times more likely to be diagnosed with liver disorder, enlargement of lymph nodes, or abdominal mass, than those without CS during the one year prior to CS diagnosis. Future studies using patient medical charts are warranted to validate and interpret the findings. These findings, when validated, may aid physicians to diagnose CS patients earlier.
Conclusions: Radiological progression within 12 months of completion of PRRT is associated with a worse outcome in terms of OS. Patients with greater liver involvement and highest CgA levels are more likely to progress within 12 months of treatment completion. Earlier treatment with PRRT in patients with radiological progression not meeting RECIST criteria may need to be considered. There may be a greater survival benefit if PRRT is given prior to the development of large volume disease.
Conclusions: To the best of our knowledge, this is the first population-based study to examine potentially relevant pre-existing symptoms, resource utilization and healthcare costs before NET diagnosis. NET patients were more likely to have certain conditions and incurred higher resource utilizations and costs in the year preceding diagnosis of NET.
Conclusions: This population-based study showed that elderly NET pts have significantly different prevalence of co-morbidities compared to non-cancer controls. The impact of these conditions on survival and therapeutic decisions is being evaluated.
Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.
Role of 92 gene cancer classifier assay in neuroendocrine tumor of unknown primary. | 2017 ASCO Annual Meeting Abstracts
Conclusions: Tissue type ID was able to identify a primary site in NETs of unknown primary in majority (94.7%) of cases. The result had direct implication in management of patients with regards to FDA approved treatment options in 13/38 patients (pNETs, merkel cell and pheochromocytoma).
Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NET. The NETest accurately measures the effectiveness of treatment.
Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.
Check out my blog post on Gradingwhich has incorporated latest thinking in revised grade 3 classification
Seung Tae Kim
Theranostic trial of well differentiated neuroendocrine tumors (NETs) with somatostatin antagonists 68Ga-OPS202 and 177Lu-OPS201.
Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 68Ga-OPS202/177Lu-OPS201 as a theranostic combination for imaging and therapy. Additional studies are planned to determine an optimal therapeutic dose and schedule. Clinical trial information: NCT02609737
Conclusions: SREs in NEN patients with BM were not uncommon, especially in patients with grade 3 NEN and osteolytic metastases. Application of ART did not significantly alter median OS or TTSRE, no subgroup with a benefit of ART could be identified. The use of ART in NEN should be questioned and evaluated prospectively.
Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach and this highly targeted patient therapy may significantly improve treatment of tumors that over express somatostatin receptor.
What is Peptide Receptor Radionuclide Therapy (PRRT)?
For those who are still not sure what it’s all about. This is a non-surgical treatment which is normally administered intravenously. It’s based on the use of somatostatin receptors to attract a ‘radiopeptide’. The radiopeptide is a combination of a somatostatin analogue and a radioactive material. As we already know, somatostatin analogues (i.e. Lanreotide/Octreotide) are a NET cell targeting drug, so when combined with radioactivity, it binds with the NET cells and delivers a high dose of targeted radiation to the cancer while preserving healthy tissue. In general, patients tend to receive up to 4 sessions spaced apart by at least 2 months.
PRRT will not work on all NETs and not everyone will suited to this treatment. In general, for this treatment to be more successful, you must have somatostatin receptors in your tumors. Success rates are not 100% – it should not be considered a cure or ‘magic bullet’. However, the results are said to be pretty good. The NETTER-1 trial data which has led to formal approval in Europe, USA and other areas, can be found here.
LATEST ON EXPANDED NETTER-1 TRIAL DATA. “Novartis has announced presentation of a new analysis of Lutathera (lutetium Lu 177 dotatate) NETTER-1 data at the 2018 European Society for Medical Oncology (ESMO) congress examining the impact of Lutathera treatment on patients with low, medium or high liver tumor burden. The data show that Lutathera treatment results in significant improvement in progression free survival (PFS) regardless of the extent of baseline liver tumor burden (LTB), elevated alkaline phosphatase (ALP) liver enzyme or presence of large (>30mm diameter) lesion in patients with progressive midgut neuroendocrine tumors (NETs) compared to octreotide LAR alone.”
Read the latest news on the NETTER-2 trial here. This is designed to look at the benefits of using PRRT on Grade 2 and Grade 3 patients as a first line treatment.
Understanding the terminology is half the battle in understanding the latest developments. I’ve included Ga-68 PET scans within this section (or in more general terms Somatostatin Receptor PET (SSTR PET)) as the term ‘Theranostics‘ is becoming a commonly used theme. Theranostics is a joining of the words diagnostics and therapy.
LUTATHERA is the radionuclide ‘mix’ for use in Peptide Radio Therapy Treatment (PRRT). You may also see this drug called ‘Lutetium’ or ‘Lu-177 dotatate’, or just ‘Lu-177’ on its own. Yttrium 90 (Y-90) is a radionuclide also used in PRRT.
NETSPOT (USA) or SOMAKIT TOC (Europe) is not PRRT but it is the commercial names for the radiopeptide used in Gallium 68 (Ga-68) PET diagnostic scans.
Together they form a ‘theranostic pair’. Theranostics is apt as together (NETSPOT / SOMAKIT TOC and Lutathera), both target NETs expressing the same somatostatin receptor, with Lutathera intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version.
Moreover, thanks to the theranostic approach that nuclear medicine allows, Novartis/AAA’s NETSPOT/SomaKit TOC products will be able to determine when Lutathera is the appropriate treatment.
Of course, this therapy has been in use in Europe and some other places for some time but to be honest, they have been on a limited scale and never formally approved by national drug agencies. Despite its extensive use, the EU approval in 2017 was actually the very first approval of PRRT anywhere in the world. For example, in UK, it was used for some time for those in need but was removed from routine availability through a ‘slush fund’ formally known as the Cancer Drugs Fund – to cut a long story short, the funding source was cut off, although there are still ways of obtaining the treatment pending formal acceptance by the NHS (certain criteria apply).
In the meantime, I constantly see stories of patients travelling to Switzerland, Germany, Netherlands, Sweden, Great Britain and others; mostly at their own cost. However, it does indicate one thing, there is a huge unmet need in that many patients do not have access to the best treatments in their own country. I see this daily through many private messages.
What about Grade 3 (High Grade) Neoplasms?
The main treatment for Grade 3 is chemotherapy, particularly poorly differentiated. PRRT tends to work better with efficient somatostatin receptors (i.e. somatostatin receptor-positive tumors). The European approval wording only covers Grades 1 and 2. The US FDA approval indicates “somatostatin receptor-positive tumors”. It’s also worth noting that with Grade 3, working somatostatin receptors are more likely to exist in Grade 3 well differentiated NETs, particularly in the lower Ki-67 readings (less than 55%). However, there’s an interesting study from Australia which might be useful to read – check out the abstracthere (note the full version is not available free).
2019 Updated data for Grade 3 Neuroendocrine Neoplasms:
“Compared to studies evaluating the efficacy of chemotherapy for NEN patients with a Ki-67 index less than or equal to 55 percent, PRRT has a longer overall survival rate–22 months versus 14 months,” the researchers pointed out. “These results suggest that PRRT, rather than chemotherapy, may be a superior first-line therapeutic option in selected patients with a high level of SSTR expression and a Ki-67 index of less than or equal to 55%.” Read more here.
Merkel Cell Carcinoma. Although not indicated for this type of Neuroendocrine Neoplasm, there is evidence to suggest that this skin Neuroendocrine Carcinoma does express somatostatin receptors. Read more here.
What about Pheochromoctyoma/Paraganglioma?
This article discusses the efficacy of PRRT in Pheo/para – click here. There’s actually still a trial for Pheochromocytoma/Paraganglioma (Pheo/Para). It is known that Pheo/Para can have somatostatin receptor tumors so a useful trial. The aim of the trial is to assess the safety and tolerability. You can read about the trial here.
Where can I get PRRT?
The aim of this section is to update on a regional basis in order to inform an international community of followers and readers.
I wanted a place to review what is happening globally given my following. In many countries, however, I’m dependent on feedback from patients in those countries. Please note this is not intended to be a 100% complete breakdown on everything about PRRT or PRRT centres – it’s a summary. It should be clear from below but please bear that in mind when reading.
This section of this article will cover each region, indicating where PRRT can be obtained (as far as I know). It is not designed to indicate whether this is through public or private facilities (this will depend to too many factors beyond the reach of this article). Please note this is not intended to be a 100% complete breakdown on every single PRRT centre – it’s a summary. This actually should be clear from below but please bear that in mind when reading.
On 29 August 2018. National Institute for Health Care Excellence (NICE) England has formally published that Lutetium (177Lu) oxodotreotide, within its marketing authorisation, is an option for treating unresectable or metastatic, progressive, well-differentiated (grade 1 or grade 2), somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (NETs) in adults. CLICK HERE to read the approval. Currently available in the following NHS locations:
London – at least 2 locations – Royal Free, Guys and St Thomas
Liverpool – The Royal
Manchester – The Christie
Sheffield – Weston Park
Bristol – Bristol Oncology Centre
Newcastle – Freeman Hospital
Coventry – University Hospital
Anecdotal mention of Leicester but waiting to hear confirmation.
On 9 July 2018. The Scottish Medicines Consortium (NICE equivalent) has approved lutetium 177Lu (Lutathera) for patients in NHS Scotland. Good news for Scotland once their hospitals have the capability to deliver. Scottish patients would then not need to travel to England for the NHS Scotland funded treatment. Read more here.
It is funded in Wales and Northern Ireland but is currently administered in England with inter NHS budget transfers.
On 7th Feb 2019, Health Canada approved Lutathera™ (lutetium (177Lu) oxodotreotide) for the treatment of unresectable (not removable by surgery) or metastatic, well-differentiated, somatostatin receptor-positive (expressing the somatostatin receptor) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults with progressive disease. The treatment was previously available on a trial basis. Read more here.
Site update to follow but the following trial locations may be up and running first:
Cross Cancer Institute, Edmonton
PRRT was approved in USA on 26 Jan 2018.The approval is for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. CLICK HERE.
The extended access program (trial) is no longer offered but these locations should be ahead of the game in terms of provision, notwithstanding insurance and provision of sufficient nuclear material.
In the meantime, known USA sites offering routine “live site” insurance based PRRT treatment are as follows – please note information has been gleaned from US patients due to no other consolidated source of this information being readily available. It’s possible some patients got mixed up between trial locations and live locations so let me know of any omissions or additions/corrections – thanks in advance.
DRAFT – NOT YET COMPLETE – (as at 16 May 2019)
Due in Service?
Dr Boris Naraev
UCSF Medical Center Mission Bay San Francisco
California – Antioch
Kaiser Permanente Antioch Medical Center
Cedars Sinai Medical Center LA
Stanford Medical Center
Kaiser Permanente Los Angeles Medical Center
Hoag Hospital Newport Beach
Kaiser Santa Clara Medical Center
City of Hope LA
Yale New Haven Medical Center
Salner, Andrew, MD
Rocky Mountain Cancer Center Denver
Dr Eric Liu
University of Colorado UC Health Denver
University of Miami
Winter Park, Florida Radiation Oncology Orlando
David Diamond MD
CCTA Newnan, Atlanta
Queen’s Medical Center
Dr. Marc Coel
Mountain States Tumor Institute at St. Luke’s Hospital, Boise
Eastern Idaho Regional Medical Center, Idaho Falls, Idaho
Rush University Chicago
The University of Chicago Medicine
Xavier M. Keutgen, MD
Loyola University Medical Center Maywood
Indiana University Health
University of Iowa
Dr T O’Dorisio
University of Kansas Medical Center Fairway
University of Kentucky, Markey Cancer Center
John Hopkins Baltimore
Dana Farber Boston
Massachusetts General Hospital
Detroit – Karmanos Cancer Center
Dr. Thor Halfdanarson
University of Minnesota Health
Sara Canon Cancer Center Kansas City
Siteman Cancer Center St. Louis/Barnes Jewish Hospital St. Louis
Dr Samuel Mehr
Nebraska Cancer Specialists Omaha
Dr Samuel Mehr
Lenox Hill NYC
Stony Brook University Cancer Center Long Island
Nurse Navigator, Patty Zirpoli, RN
Roswell Park Buffalo
The James, Columbus
Oregon Health & Science University (OHSU)
Fox Chase Philadelphia
Dr Paul Engstrom
Rhode Island Hospital Providence
Dr Paul Engstrom
Sanford in Sioux Falls
MD Anderson Houston
Excel Diagnostics Houston
CHI St Lukes Houston
BAMC San Antonio(VA) Houston
Huntsman Cancer Institute, Salt Lake City
University of Vermont Medical Center
Jay Kikut, MD, Director of Nuclear Medicine and PET
Carilion Clinic Roanoke
Virginia Mason Seattle
Dr. Hagen Kennecke
VMedStar Georgetown University Hospital
VMU Cancer Institute Morgantown
Shalu Pahuja, M.D
UW Health Madison, Carbone Cancer Center
Noelle K. LoConte, MD Specialty: Medical Oncology Primary Location: UW Carbone Cancer Center (608) 265-1700 (800) 323-8942
Europe (excluding UK which is listed above)
The European Medicines Agency (EMA) “market authorisation” received a positive indication on 20th July followed by EC approval on 29 Sep 2017. The positive indication reads “Lutathera is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP NETs) in adults”. Of Course, the decision to fund the drug will be with national approval organisations. Whilst I’m sure there are many more, these well-known centres have been making PRRT available for some years (but please note there are others):
Denmark – ‘Rigshospitalet’ since 2009. They have treated around 250 patients- and given 800 treatments.Netherlands – Rotterdam Treatment Centre – click here
Slovenia –Ljubljana, University medical Centre Ljubljana
Sweden – Department of Endocrine Oncology Uppsala University Hospital – click here
Switzerland – University Hospital Basel, Radiology & Nuclear Medicine Clinic – click here
I’d be interested to hear from countries in Europe with their full list of centres or a link to it.
Australia seems to be ahead of the game or that is what I sense when I read output from there. There’s a good section on the Australian effort – click here.
These guys have had to fight to get some progress on the provision of PRRT. Currently New Zealanders have to go to Melbourne Australia for treatment – almost 50 New Zealanders with NETs are currently raising tens of thousands of dollars to pay for treatment in Australia because the life-prolonging treatment isn’t available locally. But this could change in 2018. Unicorn Foundation New Zealand announced that Pharmac, the New Zealand government agency that decides which pharmaceuticals, have said that PRRT will be funded for patients with medium priority for the treatment of unresectable or metastatic, well-differentiated NETs (irrespective of primary site) that express somatostatin receptors.
Lebanon – The American Hospital of Beirut – Dr Ali Shamseddine “We have started using Lu-177 here in Lebanon. So far, we have treated 3 patients, with good response. The operational cost is much less than in Europe”.
India – Mahatma Gandhi Cancer Hospital, Visakhapatnam. Recently started radionuclide therapy. Although only currently available privately, some patients have been sponsored by the companies that they work for. Point of contact is Dr. K. Raghava Kashyap. I’ve been assured by CNETS India that many locations have PRRT capability – contact them direct please. Also – TATA Memorial Hospital Mumbai (waiting time is long, but cost is low: $200) and there are private clinics in Pune (cost is $1500) and Bengaluru (cost is around $6000). (Info from Russian patient group).
Kuwait – Kuwait Cancer Control Center (KCCC) – read article here.
On the day I was diagnosed, I hadn’t really thought about questions, the only one I actually remember asking was “how long do I have left to live” (I watch too many movies!). On the day of diagnosis and a period beyond, people tend to feel emotions of shock, denial, anger and sadness, before going on to accept their situation. Yes, I ‘googled‘ but not a great deal really – although some things I found did frighten me. I wish I had found this article way back then.
As things progressed in the weeks after ‘D-Day’, I started to work out the sort of things to ask but even then it was limited. I had been referred to an experienced NET team so I felt confident they would do whatever needed doing. In hindsight, I can now think of a quite a few questions I should have asked. That said, I suspect my team probably gave me the answers without having been asked the questions!
My blogging efforts have turned into a ‘Community’ of sorts. Consequently, I’m contacted daily from people finding me on the web. Many of these people are at the pre-diagnosis or initial phase. Many are undiagnosed. Most are looking for information and some sound like they are already at the ‘acceptance stage’; some are frightened about the future, some are angry because they think they are not being told important information and some also feel they have been messed about or ‘fobbed off’ by their doctors. Of course I’m happy to help but only after reminding them that I’m just a wee Scottish guy with the same disease!
I have to say that some people arrive on my site without a diagnosis but often seem to be very well prepared – the power of the internet I suspect. The questions I mostly get involve finding experts and then what questions to ask them.
As an extra bonus to this post, I offer you a starting point for the best places I know for finding NET expertise:
One US center is now the first to achieve a European NETs Center of Excellence accreditation – read more hear about University of Iowa Holden Comprehensive Cancer Center – click here
NANETS have listed “NET Centers” here – NANETS NET Centers and Clinics
The NET Research Foundation as they also have a ‘Doctor Database’ section which differs slightly from CCF below.
Dr. Shereen Ezzat at Princess Margaret in Toronto (PMH)
Dr. McEwan, The Cross Clinic, Alberta?
Dr Kavan at Montreal Jewish General Hospital (Oncology)
Dr Buteau / Beauregard at Quebec Hotel Dieu (Radiation Oncology (PRRT, Ga68)
Dr Rivera at Montreal General Hospital (Endocrinology)
Dr Metrakos at the Montreal Royal Victoria Hospital (Surgeon) sees a lot of NET patients
On the French side Dr Andre Roy at the CHUM in Montreal (surgeon) also sees a lot of NET patients
Dr. Jamil Asselah also treats net patients. He is an oncologist….Quebec
Michael Sawyer at Cross Clinic in Alberta Edmonton.
Drs. Parkins, Card, and Paseka at the Tom Baker CC in Calgary.
London Ontario: Dr. David Laidley, Dr. Robert Reid in the Neuroendocrine Clinic at London Regional Cancer Program and Dr. Daryl Gray, Surgeon.
Russia – Clinical Oncology Research Institute, N. N. Blokhin RCRC RAMS, Address: 24, Kashirskoye sh., Moscow, 115478, RF. NET specialist Alla Markovich
In my Group – ask other patients: Click here to join.
Neuroendocrine Cancer – 10 questions to ask your specialist
Many people ask me what sort of questions to ask and because NETs is such a diverse bunch of diseases, that leads to me ask them a series of questions to ascertain what they might consider asking. I’m not surprised to find some are unable to answer my questions and so those then become some of their questions to ask!
Also, questions don’t end at the diagnosis phase, they continue and in fact, some of the answers to the questions below, may bring up new questions in your mind. Some of these questions can be asked time and time again in the event of issues downstream.
If you’re currently confused about the essential facts of your condition, you’re not alone. In a recent study, almost half of cancer patients did not know basic stuff such as grade and stage of cancer, and after their initial treatment, whether they were free of disease or in remission.
For those entering or are recently just beyond the diagnostic phase, you may find certain questions cannot yet be answered without further test results etc. However, if the answer is not yet known for whatever reason, at least you have it on your list for follow up appointments. Consequently, I’ve constructed this list of questions that should function as a generic set. There may also be ‘specific to country’ questions such as insurance cover in addition to this suggested list. Of course, some of you may not want the answer to so certain questions. That’s perfectly understandable, so don’t ask!
1. Where is my primary tumour and what type of NET is it?
This is a fundamental question and it’s likely many will already have some inkling about location and perhaps a type. The difference between NETs and other types of cancer is the primary can be found wherever there are Neuroendocrine cells rather than a specific part of the anatomy in terms of naming the type of cancer, i.e. a NET of the pancreas is not Pancreatic Cancer.
The type of NET is key as it will drive a lot of other stuff including treatment. Location and type of NET are not always aligned, for example, you may have a NET in your Pancreas but there are several types of Pancreatic NET (or pNET) and these may depend on identification of a particular hormone (see syndrome below). Many NETs are non-functional (there is no oversecreting hormone).
For some the primary will not yet be found (i.e. cancer of unknown primary or CUP). There may also be multiple primaries.
2. What is the grade and differentiation of my tumour(s)?
Another fundamental question as this defines the aggressiveness of the disease and is absolutely key in determining overall treatment plans. Treatment plans for poorly differentiated can be very different from well differentiated. Read more here – Grading and here – Benign or Malignant
3. What is the stage of my disease?
Fundamental to understanding the nature of your disease. Stage confirms the extent of your disease, i.e. how far has it spread. Again this will drive treatment plans and long-term outlooks. Scans are really important in determining the Stage of your cancer – check out my scans post here. Read more here on Staging
4. Do I have a NET Syndrome?
Many NET patients will have been experiencing symptoms prior to diagnosis, perhaps for some time. It’s possible these symptoms form part of what is known as a ‘Syndrome’ and there are several associated with NETs. Syndromes are mostly caused by the effects of over-secretion of hormones from the tumours, a hallmark of Neuroendocrine disease. Carcinoid Syndrome is the most common but there are many more depending on the primary location. Read more here – NET Syndromes.
5. What is my treatment plan, and what are the factors that will influence my eventual treatment? When will I start treatment
This is a very complex area and will depend on many factors. Thus why your specialist may not have the answers to hand. Decisions on treatment are normally made by some form of Multi-disciplinary Team (MDT). Many people diagnosed with cancer expect to be whisked away to an operating theatre or chemotherapy treatment. However, for many this is not what actually happens. Depending on what testing has been done up to the actual diagnosis, it’s possible that even more testing needs to be done. Additionally, for those with an accompanying syndrome, this will most likely need to be brought until control before certain treatments can be administered; and even then, there may be checks to make sure the treatment will be suitable. Sometimes it’s a case of ‘Hurry up and wait’. My first treatment was 6 weeks after diagnosis and that was designed to control my syndrome ready for surgery which was undertaken 14 weeks after diagnosis. It’s also possible you will be placed on a ‘watch and wait’ regime, at least to begin with.
6. Can you comment on the potential for my type of NET to be related to any familial or genetic aspects of cancer?
A small percentage of NETs are hereditary/genetic in nature. This is mostly associated with those who have Multiple Endocrine Neoplasms (MEN) syndromes and a few other less common types of NET including Pheochomocytoma / Paraganglioma(Pheo/Para) and Medullary Thyroid Carcinoma (MTC) (the familial version of MTC is often referred to as FMTC). However, please note this does not mean that all those diagnosed with pancreatic, parathyroid, pituitary, Pheo/Para and MTC tumours, will have any hereditary or genetic conditions, many will simply be sporadic tumors.
7. Will you be able to get rid of all my disease?
This is a really difficult question for any specialist, even a Neuroendocrine expert. All published articles on NETs will say they are a heterogeneous collection of diseases (i.e. consisting of dissimilar entities) which makes this question (and others) difficult. I have read articles written by the world’s foremost NET experts and they all have the word ‘curative’ mentioned in various places. So I guess in particular scenarios with certain NETs, and if the disease is caught early enough, that possibility exists. However, for many, the disease could be incurable, particularly where there is distant metastasis. But, the disease has many treatment options for most types and for many it is possible to live as if it were a chronic condition. I call it ‘incurable but treatable’. Read more here – Incurable vs Terminal
8. What Surveillance will I be placed under?
Again, this is very individual in NETs and is mainly dependent on type of NET, grade and stage and how the patients reacts to treatment. This may not be known until you have undergone your initial treatment. For example, surveillance scans can be any period from 3 months to 3 years depending on tumour type(location) and stage/grade. Marker testing tends to average around 6 monthly but could be more or less frequently depending on what’s going on. Read more here – click here
9. Will I receive support and specialist advice after my treatment?
Let’s not be afraid of the word ‘Palliative’, it does not always mean ‘end of life’ care. Another example is nutrition. Many people with NETs, the condition in combination with the side effects of treatment may necessitate an alteration of diet and this is a very individual area. I would also emphasise that dietitians not well versed in NETs might not offer the optimum advice. Read more – My Nutrition Series.
10. How will treatment affect my daily life?
This is a question that many people miss but it’s becoming more important as we all live longer with cancer Again, this may not be possible to answer immediately but perhaps this question could be reserved once you know which treatment(s) you will be receiving. All treatment comes with side effects and can last for some time or even present with late effects after some years. The ‘consequences’ of cancer treatment need to be factored in earlier so that the necessary knowledge and support can be put in place. See also Unmet Needs for NET Patients
I suspect others will have suggestions for this list so feel free to submit these to me. I quite often refresh my posts over time.
There’s a lot of inaccurate and out of date information out there. Some is just a lack of understanding, often with a combination of patient forum myth spreading. Some can only be described as propaganda.
Myth 1: All Neuroendocrine Tumours are benign
Not true. By any scientific definition, the word ‘tumour’ means ‘an abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumours may be benign (not cancerous), or malignant (cancerous)’. Sure, some NETs will be benign. However, The World Health Organisation (WHO) 2010 classification for digestive system is based on the concept that all NETs have malignant potential, and has therefore abandoned the division into benign and malignant NETs and tumours of uncertain malignant potential. This has been reinforced in the 2017 update to include clarification for other endocrine organ types of NET including Pheochromocytoma. Read more here. The word ‘Carcinoid’ is inextricably linked with this issue – read here why we need to stop using the term to help fight the benign myth.
Myth 2: Neuroendocrine Tumours is a terminal condition
Not true. By any definition of the word terminal in a medical diagnostic context, most NET patients have a good prognostic outlook, even those with metastatic and incurable variants of the disease. Read more here.
Myth 3: Carcinoid is another word for Neuroendocrine Tumours
Not true. Carcinoid is a very old term and was phased out years ago. Carcinoid is not mentioned in the latest WHO Classification schemes for Neuroendocrine Neoplasms (a term covering Neuroendocrine Tumours and Neuroendocrine Carcinoma). Unfortunately, the problem is exacerbated by organisations and individuals who still use the word. Also, those who use the following terms:
“Carcinoid and Neuroendocrine”,
“Neuroendocrine and Carcinoid”,
“Carcinoid NETs” or “CNET”
These are all contextually incorrect and misleading terms (not to mention the bad grammar). ENETS, NANETS and NCCN publications are gradually phasing the word out except in relation to Carcinoid Syndrome (and even then there could be easy solutions for this). Read more here and here.
Myth 4: All NET patients get ‘carcinoid syndrome’
Not true. Firstly, many NET cancers are non-functional; and secondly, carcinoid syndrome is only one of a number of “NET Syndromes” associated with the various types of NET. However, the issue is further confused by those who use the word ‘Carcinoid‘ to incorrectly refer to all NETs and use Carcinoid Syndrome to refer to all NET Syndromes. Read more here.
Not true. Steve Jobs had a Neuroendocrine Tumour of the Pancreas. Ditto for a few other famous names. Read more here.
Myth 7: I’m not getting chemotherapy, I must be doing OK?
Not true. For some cancers or some sub-types of cancers, although it remains an option, chemotherapy is not particularly effective, e.g. some types of Neuroendocrine Cancer (NETs). In general, well differentiated NETs do not normally show a high degree of sensitivity to chemotherapy, although some primary locations fare better than others. However, many of the treatments for NET Cancer are somewhat harsh, have long-term consequences, and have no visible effects. NET patients are often said to “look well” but that doesn’t mean they are not struggling behind the scenes or under the surface. Read more here. P.S. Afinitor (Everolimus), Sutent (Sunitinib) are not chemo – Read more here.
Myth 8: All diarrhea is caused by carcinoid syndrome
Not true. It could be one of the other syndromes or tumor types or a side effect of your treatment. Check out this post.
Myth 9: Neuroendocrine Tumours is a ‘good cancer’
Not true. Simply, no cancer is good. Some are statistically worse than others in prognostic terms, that’s true…… but living with NETs is very often not a walk in the park. However, no one cancer is better to get than any other – they’re all bad. Read more here.
Myth 10: Every NET Patient was misdiagnosed for years
Not true. Many NET Patients are correctly diagnosed early on in their investigation and in a reasonable time. This myth is perpetuated because of two things: firstly, on forums, the ratio of long-term misdiagnosis is high creating a false perception; and secondly, the method of capturing patient surveys is not extensive enough – again creating a false perception. In fact, the latest and largest database analysis from US indicates earlier diagnosis is improving, with more and more NETs being picked up at an early stage. Read more here.
Myth 11: Somatostatin Analogues are a type of Chemotherapy
Not true. Somatostatin Analogues (e.g. Octreotide and Lanreotide) are not chemotherapy, they are hormone inhibiting drugs. They are more biotherapy. As the drugs latch onto somatostatin receptors, they are more targeted than systemic. For the record, Everolimus (Afinitor) and Sunitinib (Sutent) are not chemotherapy either. Read more here.
Myth 12: Stuart Scott (ESPN) and Audrey Hepburn had Neuroendocrine Cancer.
Not true. This is a common misunderstanding within the community. They both had Pseudomyxoma Peritonei (PMP). Read more about PMP here.
Myth 13: I’ve been diagnosed with Neuroendocrine Tumours – my life is over
Not true. Many patients live a very long time and lead fairly normal lives with the right treatment and support. It’s difficult but I try not to use ‘I can’t’ too much. Read more here.
Myth 14: There are only a handful of Neuroendocrine specialists in the world
Not true. There are many specialists in many countries. Get links to specialists by clicking here
Myth 15: The Ga68 PET scan is replacing the CT and MRI scan in routine surveillance for all NET Patients
Not true. It is actually replacing the Octreotide Scan for particular purposes, or will eventually. Read more by clicking here.
Myth 16: All NET Patients are Zebras
Not true. They are in fact human beings and we should treat them as such. Please don’t call me a zebra, I and many others don’t appreciate it. Please don’t use the term on my social media sites, the comment or post will be removed. Sorry but I refuse to perpetuate this outdated dogma. Read why here:
Myth 17: Multiple Endocrine Neoplasia (MEN) is a type of Neuroendocrine Tumour
Not true. Multiple Endocrine Neoplasia are syndromes and inherited disorders not tumours. You can actually have MEN and not have any tumours. However, these disorders can put people at more risk of developing Neuroendocrine or Endocrine Tumours. Read morehere
Myth 18: Palliative Care means end of life or hospice care
Not true. Palliative care is specialized medical care that focuses on providing patients relief from pain and other symptoms of a serious illness. A multidisciplinary care team aims to improve quality of life for people who have serious or life-threatening illnesses, no matter the diagnosis or stage of disease. Read more here
Myth 19: Serotonin is found in foods
Not true. Serotonin is manufactured in the body. Read more here
Myth 20: NETs cannot be cured
Not true. If caught early enough, some NETs can be treated with curative intent (totally resected with margins) with little or no further follow up. It says this in ENETS and NANETS publications which are authored by our top specialists. If we can’t believe them, who can we believe? Read more here.
Myth 21: Pancreatic Enzyme Replacement Therapy (Creon etc) is only for pancreatic patients
Not true. It’s for any patient who is exhibiting exocrine pancreatic insufficiency. Read more here.
Myth 22: High Grade NETs are Carcinomas
Not entirely true. Grade 3 (high grade) comprises well differentiated tumours and poorly differentiated tumours. Only poorly differentiated tumour are carcinomas. Read more here.
More to follow no doubt
For general cancer myths and the dangers of fake health news, please see my ARTICLE HERE
Thanks for reading
Hey Guys, I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan
OPINION. Date of Article March 2017. In the last 24 months, there seems to have been announcement after announcement of new and/or upgraded/enhanced diagnostics and treatment types for Neuroendocrine Cancer. Increased availability of radionuclide scans, increased availability of radionuclide therapies, combination therapies, increased availability of somatostatin analogues, biological therapies, enhanced surgical and minimally invasive techniques, new oral drugs for carcinoid syndrome, more trials including immunotherapy. Admittedly, some of the announcements are just expansions of existing therapies having been approved in new regions. Compared to some other cancers, even those which hit the headlines often, we appear to be doing not too badly. However, the pressure needs to stay on, all patients, regardless of where they live, need access to the best diagnostics and treatments for them; and at the requisite time. This alone is one very big unmet need in a whole range of countries still lacking.
The ‘War on Cancer’ forgot about Neuroendocrine
The ‘war on cancer’ has been around for the last 50 years, it’s still being waged. There are now more ‘fronts’ and it’s taking longer than thought to find the ‘cure’. Despite this 50 year war, it seems like there’s only been a war on Neuroendocrine Cancer for the last 10 of those years. I guess they were focused on the big cancers and/or the seemingly impossible ‘universal cure’. Prior to that, for NETs, there is only evidence of some skirmishes, more like guerrilla warfare. Now we have a developed nuclear capability! I believe the turning point was the SEER database work carried out by Dr James Yao in 2004 who confirmed the incidence had grown by 400% in 3 decades, i.e. confirming it was no longer rare. The rise of both incidence and prevalence was then amplified in the follow on ‘2012’ study (Desari et al) which confirmed a 640% increase in 40 years.
Let’s not forget about the consequences of cancer
It is true that half of people diagnosed with cancer now survive for at least ten years. Many live for years with cancer, on ‘watch and wait’ or going through various treatments and tests; their future remaining uncertain. For this group, and even for those whose treatment has successfully removed or shrunk their tumour, the struggle with the consequences and late effects of cancer and its treatment can last for years. Many Neuroendocrine Cancer patients fit into this category.
There’s a lot of work going on within all cancer communities to address the unmet needs of cancer patients who are now living with cancer rather than dying of it. Clearly we need this type of support in the NET world. The issue has been discussed at ENETS for the last two years and I was pleased to have asked the very first question about this particular unmet need, emphasising we need more support for those living with Neuroendocrine Cancer, including research into their common issues. I’ve yet to see any concrete output from the two year’s worth of campaigning.
Unmet Needs for NETs
So, there’s a lot of treatments for many types of Neuroendocrine Cancer out there, just not everyone has access to them – therefore an unmet need at the international level. Others are earlier diagnosis, access to multi-disciplinary teams (MDT), ability to access quality information at diagnosis and beyond including clinical trials, funding, accurate national registries to improve statistics and more treatments fot some of the less common types. One area where I feel there is a huge unmet need is in the area of patient support following diagnosis. Although some countries are more advanced than others in this area, even in the so-called advanced countries, there are huge gaps in provision of long-term support for those living with Neuroendocrine Cancer. For example, physicians need to focus more on:
Late diagnosis. People will be dealing from the effects of late diagnosis which has resulted in metastatic disease – and some people will have been fighting misdiagnosed illnesses for years. That takes its toll.
Consequences of Surgery. People will have had surgery which in many cases is life changing – various bits of the gut (gastrointestinal tract) are now missing, lungs are now missing – many other locationswill have been excised or partly excised. These bits of our anatomy were there for a purpose and QoL takes a hit when they are chopped out.
Inoperable Tumours and Syndromes. People will be dealing with remnant and/or inoperable tumours which may or may not be producing an associated NET syndrome (some of the symptoms can be rather debilitating in the worst cases)
Consequences of Non-surgical Treatment. Additionally, people will be dealing with the side effects of multi-modal non surgical treatments, such as somatostatin analogue hormone therapy (Octreotide/Lanreotide), chemotherapy, biological therapy (mTOR inhibitors) (i.e. Everolimus (Afinitor)), biological therapy (protein kinase inhibitors (i.e. Sunitinib (Sutent)), radionuclide therapy (i.e. PRRT). Whilst it’s great there are a wide range of therapies, they all come with side effects.
Secondary Illnesses and Comorbidities. Some people will have gained secondary illnesses in part due to the original cancer or treatment – e.g. somatostatin analogue hormone therapy can have a side effect of increasing blood sugar to diabetic levels. There are many other examples.
Finances. NET Cancer can be an expensive cancer to treat and this is exacerbated by the length of time the treatment lasts. A highly prevalent cancer, treatment is for life. It follows that NET Cancer is an ‘expensive’ cancer to have. Whilst most people have access to free public services or private insurance, many people will still end up out-of-pocket due to their cancer.
Emotional Aspects. Many NET patients are kept under surveillance for the remainder of their lives. With that comes the constant worry that the cancer progresses, tumours get bigger, new tumours show up, treatments are denied (i.e. PRRT in the UK). It’s no surprise that anxiety and depression can affect many patients in these situations. To some extent, there can be a knock-on effect to close family members and carers where applicable.
As I said in my question to the panel, even if you found a cure for NETs tomorrow, it will not replace the bits of my GI tract excised as part of my treatment. For many people, even ‘beating’ cancer might not feel much like a ‘win’. It’s a two-way street though – we need to work with our doctors, trying to change lifestyles to cope better with some of these issues. This is why it’s really important to complete patient surveys. However, my point is this: more research into some of these issues (e.g. nutrition, optimum drug dosage, secondary effects) and earlier patient support to help understand and act on these issues, would be good starters. I think some centres are doing elements of this type of support but we need a guideline generating in national and international groupings so that that others can be persuaded to formally introduce it.
“Adding life to years is as important as adding years to life”
Thanks for listening
I’m also active on Facebook. Like my page for even more news. Please also support my other site – click here and ‘Like’
Before I was diagnosed, I had my share of illnesses. Fortunately, many of them were the routine stuff that most people tend to get from time to time, and most did not stop me getting on with whatever needed doing. I served in the military from age 16 until 45 – a long time! On only two occasions during that 29-year period, did I involuntary visit a hospital: aged 16 having been knocked out at boxing (you should have seen the other guy!) and aged 39 after falling off a vehicle (in my defense it was really dark). Illness wasn’t really something I thought much about and for minor things, I would just “soldier on.” So, from an early age, I truly believed a “poker face” was necessary for “street cred” but I guess that was ingrained in the military mindset.
Even out of the military environment, old habits die hard as I adopted the same attitude. The “mission” comes first and my health second. A few “civilians” once suggested I go home after coughing, sniffing and sneezing my way through a day in the office. I responded in the only way I knew by saying I would only be leaving the office early on a stretcher having lost consciousness. To get them off my back, I made sure there was no hint of banter or joviality in the statement. This tactic didn’t really work and they laughed at something they perceived as a joke. However, little did they know, I was deadly serious. Little did I know, my gung-ho attitude and poker face were to become seriously deadly.
In 2010, along came cancer. For a couple of years before diagnosis, I had not been sufficiently focused on my health and soldiered on, ignoring what I now know to be key symptoms of neuroendocrine cancer. Even leading up to diagnosis, I was dismissive, refusing to acknowledge this was a threat. Other people get cancer, but not me! I even landed in the hospital via the ER as I refused to slow down after a biopsy. Still in denial, I thought I could beat cancer not knowing that cancer knew with 100 percent certainty that it could beat me. I went on to have surgery and other treatments, but apart from that, I basically marched on as it nothing had happened. However, as the effects of cancer and the consequences of the treatment started to bite, I accelerated my learning on how the disease might affect me in the future. This knowledge has enabled me to manage risk and make better assessment/decisions about seeking help. But it took a while, and gradually over a period of three years, I shifted the focus from work to health.
It’s not been easy to learn how to live with my incurable disease since diagnosis. Finding a balance between how I want to live and how to stay alive has been difficult. My “stiff upper lip” combined with an appetite for work didn’t really help in the end. In 2013 (three years after diagnosis), I finally found the time to work on the reasons for fatigue and many other symptoms. I made some really good improvements to my quality of life. I still have issues, but my cards are no longer close to my chest – they’re now more frequently on the table, particularly when speaking to doctors and close family. My poker face is still there for special occasions, just more relaxed!
“It’s the cancer,” can sometimes be the most convenient excuse to not do stuff. I can play the “cancer card” as well as the next person, and it will trump all others! I also understand that motivation can be difficult with a chronic illness. However, I don’t want to fall into the trap of doing nothing all the time. That’s not a good outcome. Consequently, I try not to use the metaphorical cancer card too much. In fact, I sometimes even say “I can” when I actually feel like playing the cancer card. I’m nearly always glad I did.
5 years ago today, I had a bunch of lymph nodes removed. Two separate areas were resected, only one was showing growth but both were showing up as hotspots on an Octreoscan. I had known since shortly after diagnosis in 2010 that ‘hotspots’ were showing in my left ‘axillary’ lymph nodes (armpit) and my left ‘supraclavicular fossa’ (SCF) lymph nodes (clavicle area). Some 10 months previously, I had a major liver resectionand 5 months prior to the liver resection, I had a small intestinal primary removedincluding work on some associated complications. There had always been a plan to optimise cytoreduction of my distant metastases, it was just a matter of timing. I still can’t get my head round why metastases from a small intestinal NET managed to get to this area but not others!
Distant nodal metastasis treatment
A total of 9 nodes were removed from my left armpit (a very common operation for breast cancer patients). The surgeon had inspected the area and found some were palpable and my normally stable Chromogranin Amarker was showing a small spike out of range. During the same operation under general anaesthetic, an ultrasound directed SCF nodal ‘exploration’ was carried out. When biopsied, 5 of the 9 resected axillary nodes were tested positive (Ki-67 <5) but the 5 SCF nodes removed were tested negative. The subsequent Octreoscan still lit up in the left SCF area but the lights on the left axillary area were ‘extinguished’. There is no pathological enlargement or pain in the left SCF area – so this is just monitored.
Apart from a very faint scar in the left SCF area, there does not appear to be any side effects from this exploratory surgery. The left axillary area cut is well hidden by hair growth but I do sense a lack of feeling in the area. Additionally, I have a very mild case of lymphedema in my left hand which occasionally looks slightly swollen – the consequences of cancerand its treatment. Fluid build-up, or post-operative seroma, can be a side effect of a lymphadenectomy. In fact, within a month of the operation, I had to have circa 160mls of fluid removed on 4 occasions from my armpit. It was uncomfortable and painful, resulting in additional time off work. The surgeon used a fine needle aspiration to draw out the fluid, a painless procedure. It eventually cleared up and everything was back to normal. The specialist said my left arm would be slightly more susceptible to infections and suggested to avoid using my left arm for blood draws and other invasive procedures and injuries.
Other close calls (“to cut or not to cut”)
I have a 19mm thyroid lesion which was pointed out to me in 2013. This has been biopsied with inconclusive results. Although the thyroid is an endocrine gland, it looks like a non-NET problem so far. Thyroid nodules are in fact very common and statistically, 50-70% of all 50-70 year olds will have at least one nodule present (i.e. if you are in your 50s, there is a 50% chance you will have one nodule and so on). The vast majority will never bother a person while they live. I attend an annual Endocrine MDT where this is monitored in close coordination with the NET MDT. It’s actually managed by the same surgeon who carried out the nodal work above.
I have a 3mm lung nodule, discovered in 2011. Apparently, lung nodules are a pretty common incidental finding with 1 per 500 X-rays and 1 per 100 CT scans finding them. This is monitored and hasn’t changed since noted.
OK – we’ve gone through diagnosis, we’ve gone through treatment and now we need to live with the consequences of cancer and it’s treatment. Not a day goes by when I don’t feel some twinge or some minor pain and I think ‘what was that?‘. Fortunately, many things can just be day-to-day niggles. It’s the cancer …. easy to say, sometimes not easy to prove.
However, for Neuroendocrine Tumour (NET) patients who have had surgery, anything that seems like a bowel obstruction is quite a scary thought (I suspect this is also an issue for other cancer types). In fact, even before diagnosis, a bowel obstruction rears its head as it can be how the condition is diagnosed in the first place, i.e. pain leads to more pain and that can sometimes result in a visit to the ER/A&E which can very often lead to a scan and an incidental diagnosis of NETs (and I suspect some other cancers).
I guess this isn’t just a threat for those who’ve had intestinal NETs but others in the vicinity of the intestines could also have this issue – the abdominal cavity is full of organs all very closely packed together! Both the small intestine and the large intestine can become blocked and if it can’t be unblocked by non-surgical means, it can become a bit of a drama for the patient. Blockages can be full or partial so it can often be a tough call for the medical team due to the effects of the patient’s existing surgery including but not limited to previous surgical scarring (adhesions), mesentery or retroperitoneal fibrosis complications (read about that by clicking here). Clearing the blockage by non-surgical means is the optimum solution. The presentational symptoms and scans can give immediate clues. Although there are slightly different symptoms for large and small intestine (bowel) obstructions, the key symptoms of a blockage would appear to be:
Feeling bloated and full
Severe abdominal pain
Vomiting large amounts
Looking at some authoritative sites, the logical (and fairly obvious) decision steps seem to be:
Is there an obstruction or is the problem something else?
If an obstruction, where exactly is it?
What is causing the obstruction?
Are there any complications such as adhesions, twisted loops or hernias
In 2016, I had 3 bouts of constipation and I confess that a potential blockage did cross my mind on all 3 occasions. However, I was comforted by the fact that I had no nausea and/or vomiting which I suspect is one of the key symptoms indicating a blockage rather than just a sluggish system. Fortunately, on all 3 occasions, the matter settled following a few days of right-sided pain (RLQ). One occasion required lactulose but all three required patience sprinkled with a pinch of endurance! I have to say the lactulose experience was not a good one – fatigue, brain fog and general malaise …..but much better than surgery. If you have issues with ‘fear’ living with cancer, check out my 7 tips article by clicking here.
I’m once again making some adjustments to try to find the magic spot between stool frequency and bulk….. it’s really difficult and not an exact science. I’m suspecting diverticular disease might be playing some part as I was diagnosed with a mild version in 2008 spotted during a colonoscopy(a common problem when you’re over 50). Although that tends to be a left-sided problem, I remain conscious that my ‘new plumbing’ may not be the best representation of a conventional layout!
NET Patient Foundation are really good at producing cards and there’s one for this too! Here’s the back of it here:
A fairly common disposition of metastatic Neuroendocrine Tumours (NETs) is a primary with associated local/regional secondary’s (e.g. lymph nodes, mesentery and others) with liver metastases. Technically speaking, the liver is distant. However, many metastatic patients have additional and odd appearances in even more distant places, including (but not limited to) the extremities and the head & neck. In certain NETs, these might be an additional primary (e.g. in the case of Multiple Endocrine Neoplasia (MEN); or they could even be a totally different cancer. The worry with NETs is that the ‘little suckers‘ can sometimes make these surprise appearances given that neuroendocrine cells are everywhere.
Cancer doesn’t just spread through the blood steam, it can also spread through the lymphatic system. This is a system of thin tubes (vessels) and lymph nodes that run throughout the body in the same way