In my article listing the somatostatin analogues and their drug delivery systems pipeline (click here), there has been a very interesting development in a product called Q-Sphera (was previously known as Q-Octreotide). In a press release, it was announced that an unnamed ‘pharma giant’ has signed a deal with Midatech Pharma Plc that will see it evaluate the latter’s Q-Sphera drug delivery platform. Later in Feb 2019, the pharma was identified as China Medical System Holdings Limited (based out of Hong Kong). Adding to the excitement behind this development, it was announced in Mar 2019 that the Spanish Government had conditionally approved a €6.6m loan that will be used to help commercialise this flagship drug.
Midatech’s Q-Sphera™ is an advanced microencapsulation and polymer-depot sustained release (SR) drug delivery platform produced using a novel and disruptive printing based process, with numerous and distinct advantages over conventional reactor based technologies. From a manufacturing perspective Q-Sphera™ is a precise, scalable, efficient, and environmentally friendly microparticle platform. From a clinical perspective Q-Sphera™ ensures monodispersed microparticles that release active drug compounds into the body in a superior linear tightly controlled and predictable manner over an extended period of time from 1 – 6 months. An injection lasting 6 months sounds very exciting but I have no more detail on the feasibility or likelihood of such a change in frequency with Octreotide or Lanreotide but the press release does mention the possibility, i.e. “Q-Sphera allows drug compounds to be released into the body in a “highly controlled manner” over a prolonged period of time; potentially from a few days to up to six months.”
What’s the main differences?
The current trials are based on the use of Sandostatin LAR (Octreotide) using the Q-Sphera delivery system (previously known as Q-Octreotide). The key aspects of usability are reconstitution and needle size but there is also an inference that less frequent injections could be possible. A comparison of the trial output is as follows:
Reconstitution: For Sandostatin LAR (SLAR)™ the procedure to prepare the product for injection is a complex 30 step error prone process, taking up to 40 minutes and, once reconstituted, the product has to be given immediately to prevent solidifying and wastage of the injection. For MTD201™ Q-Octreotide the preparation process is a simple 5 – 7 minute procedure, after which the product is stable up to 2 hours. For the nurse preparing and giving the injection, the short and flexible process of MTD201™ has clear advantages over the all consuming SLAR process™.
Needle size: For SLAR, a large 19G needle is prescribed for the injection to prevent blockage, and often an even large 18G needle is required for successful injection. For MTD201 Q-Octreotide the precision microencapsulation technology means that a much smaller 21G needle can be used, and there are no blockages. Other Q-Sphera products use even finer needles as small as 27G. The importance of this is evident from the first-in-human phase I data where MTD201 had lower injection pain – 8% for MTD201 versus 25% for SLAR™, and much lower injection site
tenderness – 8% for MTD201 versus 83% for SLAR.
This is an exciting development and I will keep this article live with further information as I receive it.
There’s a Brit saying known as “on your bike” (sometimes colloquially called “on yer bike“). It basically means “go away and stop bothering me” but there are other definitions including some ‘Anglo-Saxon’ versions (I won’t repeat those here!)
When I moved to my current home nearly 7 years ago, the removals lorry unloaded our rather dusty bikes (pedal cycles) and stuffed them in the garage where they mostly remained until this year. A couple of months ago, I dusted them off, repaired punctures etc, and basically started putting them to better use. In fact, Chris got a new one out of the deal! I’m reasonably fit (considering) but finding it so easy to opt for the sofa and there’s always something worth watching on TV, or something to do on my computer. My personal trainer (Chris ♥) tends to provide some motivation, so it felt good that the recent bike idea came from me rather than from her.
However, some of the personal motivation came from a recent ‘brush’ with potential diabetic problems. My blood glucose test has been spiking in the last 12-18 months and an HbA1c in May (a better guide) put me just inside pre-diabetic range. This prompted me to look more carefully at diet and exercise. I need to do this without losing too much weight though, I’m still struggling to put the weight back I that I lost from the June chest infection.
I have so say I’m enjoying my new exercise and have had some nice bike rides in the local forests. I’ve since had a new HbA1c test which is back in normal range so I guess something is making it spike. Lanreotide is my first guess – you can read more about Diabetes and NETs by clicking here.
I’m working with my doctors on the issue.
In the meantime, I’m getting on my bike and so can Neuroendocrine Cancer!
My chest infection is now settled, as too is the excitement and apprehension behind my first ever Ga68 PET – the outcome of that is still a work in progress. Earlier this year, my thyroid ‘lesion’ on watch and wait was given a ‘damping down’ with the prescription of a thyroid hormone supplement but I await a re-ignition of that small bush fire downstream.
Bubbling behind the scenes and clamoring for attention is the spiking of my blood glucose test results and I was very recently declared ‘at risk’ for diabetes One of my followers entitled a post in my group with “The hits keep coming” in reference to encountering yet another problem in the journey with Neuroendocrine Cancer. I now know how she feels, this issue is a bit of a ‘left fielder’. However, having analysed the situation and spoken to several doctors, I can now put pen to paper.
Neuroendocrine Cancer is not a household name (…… I’m working on that) but diabetes certainly is. The World Health Organisation reports that the number of adults living with diabetes has almost quadrupled since 1980 to 422 million adults. In USA, estimates from CDC stated around 10 million people diagnosed with diabetes with a further 84 million in pre-diabetes state (at risk). In UK around 3.7 million people have diabetes with about 4 times that amount ‘at risk’. It’s a growth industry (…….. but so is NETs – in the last 40 years, the incidence of NETs is rising at a faster rate than diabetes, a disease which some writers have described as an epidemic).
With those numbers, it follows that many NET patients will be diabetic before diagnosis, some will succumb to diabetes whether they have NETs or not, and some may have an increased risk of succumbing due to their treatment. Some may even be pushed into diabetes as a direct result of their NET type or treatment. It’s important to understand diabetes in order to understand why certain types of NET and certain treatments could have an involvement.
For understanding of this article, it’s worth noting the pancreas has two main functions: an exocrine function that helps in digestion and an endocrine function that regulates blood sugar. I have talked about the exocrine function in relationship to Neuroendocrine Cancer at length – check out this article on Pancreatic Enzyme Replacement Therapy. In this article, I now want to cover the issues with the endocrine function and blood sugar. First a short primer on diabetes – it is necessarily brief for the purposes of this article.
TypeS OF DIABETES
Type 1 and Type 2 Diabetes are fairly well-known. There’s actually more than two types, but these are the most common. Type 2 is the most prevalent with around 90% of diabetes cases. When you’ve got Type 1 diabetes, you can’t make any insulin at all. If you’ve got Type 2 diabetes, the insulin you make either can’t work effectively, or you can’t produce enough of it. Additional types may come up in the subsequent discussion.
What is the problem?
What all types of diabetes have in common is that they cause people to have too much glucose (sugar) in their blood. But we all need some glucose. It’s what gives us our energy. We get glucose when our bodies break down the carbohydrates that we eat or drink. And that glucose is released into our blood. We also need a hormone called insulin. It’s made by our pancreas, and it’s insulin that allows the glucose in our blood to enter our cells and fuel our bodies.
If you don’t have diabetes, your pancreas senses when glucose has entered your bloodstream and releases the right amount of insulin, so the glucose can get into your cells. But if you have diabetes, this system doesn’t work properly. Diabetes is associated by being overweight but there isn’t a 100% correlation with that. However, when an individual becomes overweight, there is an increase in free fatty acids in the blood stream which may contribute to reduced insulin sensitivity in the tissues, leading to increased glucose levels in blood.
Symptoms and diagnosis of Diabetes
Different people develop different symptoms. In diabetes, because glucose can’t get into your cells, it begins to build up in your blood. And too much glucose in your blood causes a lot of different problems. To begin with it leads to diabetes symptoms, like having to wee a lot (particularly at night), being incredibly thirsty, and feeling very tired. You may also lose weight, get infections like thrush or suffer from blurred vision and slow healing wounds.
I see these symptoms mentioned very frequently and normally people are trying to associate them with NETs and/or the treatment for NETs.
Diabetes diagnosis is normally triggered diagnosed based on blood tests such as fasting Blood Glucose (snapshot) and/or Glycated Hemoglobin (A1C) or HbA1C.
Over a long period of time, high glucose levels in your blood can seriously damage your heart, your eyes, your feet and your kidneys. These are known as the complications of diabetes.
But with the right treatment and care, people can live a healthy life. And there’s much less risk that someone will experience these complications.
What are the direct connections with Diabetes and NETs?
It’s not surprising that diabetes is mostly associated with Neuroendocrine Tumors of the Pancreas but there are other areas of risk for other types of NETs including to those who are existing diabetics – see below.
The main types of surgery for Neuroendocrine Tumors of the Pancreas are Distal Pancreatectomy (tail), Sub-total pancreatectomy (central/tail), Classic Whipple (pancreaticoduodenectomy – head and/or neck of pancreas), Total pancreatectomy (remove the entire pancreas) or an Enucleation (scooping out the tumour with having to remove too much surrounding tissue). From the PERT article link above (exocrine function), you can see why some people need this treatment to offset issues of reduced production of pancreatic enzymes. The same issue can develop with a reduced endocrine function leading to the development of diabetes.
The different types of functional pancreatic NETs often called syndromes in their own right due to their secretory role. One might think that Insulinomas are connected to diabetes issues but this hormonal syndrome is actually associated with low blood sugar (hypoglycemia), although low blood sugar can turn out to be a complication of diabetes treatment.
A NET syndrome known as Glucagonoma (a type of functional pancreatic NET) is associated with high blood glucose levels. About 5-10% of pancreatic neuroendocrine tumors are Glucagonomas, tumors that produce an inappropriate abundance of the hormone glucagon. Glucagon balances the effects of insulin by regulating the amount of sugar in your blood. If you have too much glucagon, your cells don’t store sugar and instead sugar stays in your bloodstream. Glucagonoma therefore leads to diabetes-like symptoms (amongst other symptoms). In fact Glucagonoma is sometimes called the 4D syndrome – consists of diabetes, dermatitis, deep venous thrombosis (DVT), and depression.
Another functional pancreatic NET known as Somatostatinoma is prone to developing insulin resistance. Somatostatinomas produce excessive amounts of somatostatin which interferes with the insulin/glucagon function and could therefore lead to diabetes.
Diabetes caused by cancer or cancer treatment
Worth noting that this type of diabetes is sometimes known as ‘Pancreatogenic diabetes’ and this is actually classified by the American Diabetes Association and by the World Health Organization as type 3c diabetes mellitus (T3cDM) and refers to diabetes due to impairment in pancreatic endocrine function due to acute cancer and cancer treatment (and several other conditions). The texts tend to point to cancers (and other conditions) of the pancreas rather than system wide. Prevalence data on T3cDM are scarce because of insufficient research in this area and challenges with accurate diabetes classification in clinical practice. (Authors note: Slightly confusing as many text say that type 3 diabetes is proposed for insulin resistance in the brain (diabetes associated with Alzheimer’s disease). There’s another term for a complete removal of the entire pancreas – Pancreoprivic Diabetes
Other treatment risks
Somatostatin Analogues (e.g. Octreotide and Lanreotide) are common drugs used to control NET Syndromes and are also said to have an anti-tumor effect. They are known to inhibit several hormones including glucagon and insulin and consequently may interfere with blood glucose levels. The leaflets for both drugs clearly state this side effect with a warning that diabetics who have been prescribed the drug, should inform their doctors so that dosages can be adjusted if necessary. The side effects lists also indicates high and low blood glucose symptoms indicating it can cause both low and high blood glucose (hypoglycemia and hyperglycemia). For those who are pre-diabetic or close to pre-diabetic status, there is a possibility that the drug may push blood tests into diabetic ranges. Afinitor (Everolimus). The patient information for Afinitor (Everolimus) clearly states “Increased blood sugar and fat (cholesterol and triglycerides) levels in blood: Your health care provider should do blood tests to check your fasting blood sugar, cholesterol and triglyceride levels in the blood before you start treatment with AFINITOR and during treatment with AFINITOR” Sutent (Sunitinib). The patient information for Sutent (Sinitinib) clearly states that low blood sugar (hypoglycemia) is a potential side effect. It also advises that low blood sugar with SUTENT may be worse in patients who have diabetes and take anti-diabetic medicines. Your healthcare provider should check your blood sugar levels regularly during treatment with SUTENT and may need to adjust the dose of your anti-diabetic medicines.
In rare cases, certain NETs may produce too much Adrenocorticotropic hormone (ACTH), a substance that causes the adrenal glands to make too much cortisol and other hormones. This is often associated with Cushing’s syndrome. Cortisol increases our blood pressure and blood glucose levels with can lead to diabetes as a result of untreated Cushing’s syndrome.
I think it’s sensible for all NET patients, particularly those with involvement as per above and who are showing the signs of hypoglycemia and hyperglycemia, to be checked regularly for blood glucose and if necessary HbA1c. Many patient information leaflets for the common NET treatments also indicate this is necessary. Always tell your prescribing doctors if you are a diabetic or about any history of low or high blood glucose before treatment for NETs.
My brush with Diabetes (as at Jan 2019)
My blood glucose levels started to climb slightly in 2016 but HbA1c remained normal. However, an HbA1c test in early 2018 put me into pre-diabetic range (44 mmoL/moL). I explained some of the above article to my GP who is corresponding with a diabetes expert at secondary care – the expert suggested that I need to be monitored carefully as weight loss is not necessarily the best response. I have kept my NET team up to date.
At the time of updating, two separate and sequential HbA1c tests (3 month interval) came back normal at 36 mmoL/moL. I’m pragmatic enough to know that I do not need to lose weight as one of the aims of reducing my blood glucose and HbA1c levels (something emphasised by the above mentioned diabetes specialist).
I even got on my bike to do a little bit more exercise just in case!
At this point, I cannot yet say if this is the beginning of progressive Type II diabetes or if my medication is causing these spikes in my blood glucose and HbA1c. Judging by 2 x normal HbA1c, looks like the somatostatin analogue (Lanreotide in my case) may caused a spike to a pre-diabetes score. I will keep you posted.
Summary – if you are noticing these symptoms, get your blood sugar checked (with acknowledgement to Dr Pantalone from Cleveland Clinic)
1. You’re making more trips to the bathroom
Having to go to the bathroom more than normal, particularly at night, is a sign that your blood sugar might be out of whack.
Dr. Pantalone says one of his patients came in for a diagnosis after a family member noticed that he was using the bathroom during each commercial break when they watched TV.
2. You’re getting frequent urinary or yeast infections
When your blood sugar is high and your kidneys can’t filter it well enough, sugar ends up in the urine. More sugar in a warm, moist environment can cause urinary tract and yeast infections, especially in women.
3. You’re losing weight without trying
If you have diabetes, your body isn’t able to use glucose (sugar) as effectively for its energy. Instead, your body will start burning fat stores, and you may experience unexpected weight loss.
4. Your vision is getting worse
High sugar levels can distort the lenses in your eyes, worsening your vision. Changes in your eyeglass prescription or vision are sometimes a sign of diabetes.
5. You’re feeling fatigued or exhausted
Several underlying causes of fatigue may relate to diabetes/high sugar levels, including dehydration (from frequent urination, which can disrupt sleep) and kidney damage.
This feeling of exhaustion is often persistent and can interfere with your daily activities, says Dr Pantalone.
6. You’re noticing skin discoloration
Something that Dr. Pantalone often sees in patients before a diabetes diagnosis is dark skin in the neck folds and over the knuckles. Insulin resistance can cause this condition, known as acanthosis nigricans.
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
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.
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?
“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.
There’s been a lot of action in the area of what is termed Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP-NETs). It can therefore sometimes appear that Lung NETs are the poor relation. There are certainly some unmet needs in this area of the anatomy including a lack of research. Thus far, no prospective trials specifically for patients with lung NETs appear to have been reported.
However, there has been some recent movement. Last year, the use of Afinitor (Everolimus) was approved for progressive, non-functional NET of GI or Lung origin.
SPINET Trial for Lung NETs
In late 2016, I tipped you off about an Ipsen sponsored trial for Lung NETs involving Lanreotide (Somatuline). SPINET is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of Lanreotide plus “Best Supportive Care” (BSC) versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical lung NETs. The aim of the SPINET study is to evaluate the safety and antitumor efficacy of Lanreotide 120 mg in patients with advanced lung NETs. I suspect that many Lung NET patients are already receiving somatostatin analogues (Octreotide/Lanreotide) but prescribed only for syndrome/symptom control.
SPINET is now recruiting in many locations (see below).
The countries involved in the SPINET trial are as follows (in case my post goes out of date – see the latest update to the trials document here). Please also check the inclusion and exclusion criteria.
USA, Austria, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, UK.
In addition to the trial document linked above, you can read more about the SPINET trial here with commentary from a well-known NET Specialist – Dr Diane Reidy-Lagunes, who is the principal investigator for the trial.
How do I get on the trial?
You may be interested in this organisation – Trialbee. They are a company helping Ipsen to raise awareness of the SPINET trial using a cloud based platform to connect patients, investigators and sponsors (I’ve authenticated their participation with Ipsen). There is no fee for using their services. There’s a useful questionnaire which can help you decide if this trial is for you – here.
Please note, if you are concerned about participating in clinical trials, you should always consult your specialist for advice.
If you are a patient advocate or an advocate organisation, please share with your communities in order that Lung NET patients are at least made aware of the trial.
I think after 105 injections (as at 26th November 2018), I think it’s safe to say I’m now ‘at home’ with Lanreotide (Somatuline Autogel – Somatuline Depot elsewhere).
I was fortunate enough to actually have the injection ‘at home’ via an insurance policy for the first 4 of the years of my treatment. That was really handy because it was informal, chatty, and I had excellent ‘continuity of service’ with the same nurse administering 80-85% of those 54 injections. I only had 3 other nurses over that period covering my local nurse’s holiday etc.
When I retired from work, I then had to travel to my local hospital and take my turn amongst the ‘great unwashed’. Don’t get me wrong, I have the greatest respect for the UK NHS. However, it’s also true to say my monthly ‘butt dart’ suddenly became more of a conveyor belt feeling, less chatty but in the main, the continuity effect I enjoyed previously was thrown right out of the window. I had some superb injections but I also had some ‘not so superb’ ones. There was very little continuity as my 33 hospital administered injections were carried out by 17 different nurses.
If I had to list 6 common discussions between NET patients, issues with their injections of somatostatin analogues would almost definitely be on the list. Common administration problems with Lanreotide include untrained administrators, fridge problems, incorrect injection site, pinching instead of stretching, plunge speed, painful injections and many others. All of these issues can be linked to training and continuity. One thing NET patients like is an expert injection by the same person if at all possible. It’s also true to say that these issues can cause some anxiety amongst patients leading up to and during the procedure.
I was therefore delighted to be signed up this week for a service in UK called HOMEZONE+ whereby a trained nurse will come to my house and administer my injection. Although it’s been available for some time, this element of the service has not been particularly well publicised. The drug will arrive a few days prior and be stored in my fridge ready for the injection day. For those worried about transport, the drug arrives by courier in a refrigerated vehicle. The service is provided by a third-party via NHS, at no cost to the NHS or the patient, as it is a service funded by Ipsen Ltd.
Now …… I got wind of this service 6 months prior to starting but it took me sometime to discover what it was all about, despite a lot of ‘digging’. I had previously heard of other elements of this service whereby the drug is delivered directly to patient’s house for self injection, injection by a trained carer or for injection at a third-party site such a local GP (PCP). However, the service I’ve signed up for is none of those, this is a service where a trained nurse will come to my house and administer the injection. Happy days. Royal Bournemouth Hospital is actively promoting the scheme to patients being administered with Lanreotide.
But ….. It was also suggested to me that not all hospitals are making the service available. If this of interest to other UK patients, I suggest you initially make contact with your specialist nurse or doctor and enquire (….. and if it was me, I would ask why not if they’re not making it available!). I’ve probably documented all I know but happy to chat more with UK patients about the scheme – you can message me here: Message Ronny Allan
What about outside UK?
I researched to see if other countries have something similar for Somatuline (Lanreotide) – please note not all patients will be eligible so you need to check first:
1. The Netherlands. I attended ENETS Barcelona and sat in on a presentation from a Nurse in The Netherlands who described a similar scheme. The presentation was entitled Home Injection Service for Somatostatin Analogues so may also include Octreotide. Contact is Wanda Geilvoet at the Erasmus Medical Centre in Rotterdam.
2. USA. Ipsen US appears to have a similar scheme through their Ipsen Cares program. It’s called “Home Health Administration (HHA)”. This is available for patients who are unable to receive their Somatuline Depot injections at the doctor’s office. Eligible patients can have a nurse visit their home to administer their injections. There is no cost to the patient for this option. HHA must be requested by the doctor and the patient must be enrolled in IPSEN CARES. The Nurse HHA Program is an additional offering of
IPSEN CARES available via a doctor for all eligible patients prescribed
• A physician must prescribe Somatuline Depot to be administered by Nurse
Home Health Administration for the patient.
• The program is available to most patients covered by commercial insurance
• Patients may not participate if prescriptions are eligible to be paid in part or
full by any state or federally funded programs, including, but not limited to
Medicare or Medicaid, VA, DOD, or TRICARE.
• Residents of Massachusetts, Michigan, Minnesota, and Rhode Island are not
3. Canada. There is not enough detail on the Ipsen Canada site to say there is a scheme but worth asking. Click here
4. Australia. There seems to be a programme called ‘Assist’. Click here for more details.
5. Republic of Ireland. They have the same service as UK, also called HomeZone. They will send a trained nurse out to your home monthly to do the injection for you free of charge. To arrange, the number is 01 4291820
I will add other locations as and when I find out.
Let’s share data!
I’m sure there must be more countries involved so please let me know. In fact, would UK patients let me know if you are on the ‘Homezone’ scheme where a nurse comes to your house and administers the drug, and via which hospital was this arranged. I’ll update the blog so we can all find out about it.
How’s it going so far?
On 26th November 2018, I had my 18th ‘HomeZone+ nurse administered injection and a permanent nurse allocated to my area. It’s a first class service from the main UK provider – Healthcare at Home (HAH) (I’m told Lloyds Pharmacy do certain areas). I’m told which day it will arrive and I receive two text messages with timings, the second one is a more precise time allowing me to get on with my life. The Nurse then makes an appointment to come and administer the injection. This works excellently too. The Nurse calls me with some notice in order to get the injection out of the fridge ready for administration. The injection is given very efficiently and my next appointment is made ready for 28 days time. I also found out that sharps box provision and collection is available through the programme, another bonus.
So far so good.
You may also appreciated my other blog posts on Somatostatin Analogues and Lanreotide (Somatuline):
“A combination of two common immunotherapy drugs shrinks rare, aggressive neuroendocrine tumors, according to new research results presented at the American Association for Cancer Research Annual Meeting 2019, held March 29-April 3 in Atlanta“. See below under section: – Nivolumab (Opdiva) and Ipilimumab (Yervoy) in Treating Patients With High Grade Neuroendocrine Carcinoma
Immunotherapy for Neuroendocrine Neoplasms
There’s a lot of Immunotherapy stuff out there! However, I also wanted to break it down and perhaps see if I can pick up the what, when, why, where and how in regards to Neuroendocrine Cancer. It’s really difficult, not least because the picture is not clear and there is no general roadmap printed, let alone one for Neuroendocrine disease. Immunotherapy for NETs was discussed at ENETS 2017 in Barcelona. The presentation that sticks out was one given by Dr Matthew Kulke, a well-known NET Specialist in Boston. My reaction to the presentation was one of ‘expectation management’ and caution i.e. it’s too soon to know if we will get any success and when we will get it. He also hinted that it’s more likely that any success will first be seen in poorly differentiated high-grade Neuroendocrine Carcinoma (NEC). Dr Jonathan Strosberg also said similar in a post here. In fact, from below you will see that grade 3 poorly differentiated is where the bulk of trial activity is (…..but read on, there is some action around plain old well differentiated NETs). You will also see that there are disappointing results so far with single agent Keytruda.
Retain hope but just be cautious with some of the hype surrounding Immunotherapy
Immunotherapy is exciting, but we also need to be aware of the risks of taking the brakes off the immune system. We have seen and heard more and more stories about people with grim cancer diagnoses who became cancer-free after treatment with immunotherapy. This offers hope to those with cancer, but we need to be cautious when discussing immunotherapy. This treatment method is still new, and the cancer community is still learning about how it affects the body. An unfettered immune system may end up attacking healthy, functioning parts of a person’s body, causing unpredictable side effects that may be life-threatening EVEN if not treated early.
For Neuroendocrine Neoplasms, only Neuroendocrine Carcinoma of the skin (Merkel Cell Carcinoma) and Small Cell Lung Cancer (SCLC) has an approved drug (see below). Anything else is currently an experimental scenario (clinical trial). Before launching into what is out for with an interest in NET and NEC, it’s worth pointing out that Immunotherapy is not for everyone, does not work for everyone, and has side effects for everyone.
Let’s start with Pembrolizumab (Keytruda)?
‘Pembrolizumab’ is more famously known as ‘Keytruda‘. This drug crops up everywhere and it has connections to many different cancers. Before I talk about this trial called PLANET, it’s very useful to take a quick look at the history of Keytruda which was only really made famous after former US President Jimmy Carter was treated with it for metastatic melanoma. There was a lot of media hype surrounding what made his treatment successful as he was also given radiation for his brain tumours and his large liver tumour was removed by surgery. However, putting the hype and conjecture to one side, Keytruda’s CV is pretty impressive. Pembrolizumab (Keytruda) is currently approved to treat certain scenarios in Hodgkin lymphoma, Melanoma, Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck, Urothelial carcinoma, Microsatellite instability-high (MSI-H) related cancers (a very interesting development as it’s the US FDA’s very first approval on a tissue/site agnostic basis).
However, despite this excelent record, it’s worth also noting that NANETS 2018 reported limited use of Keytruda (see below) as a single agent to treat high grade Neuroendocrine Neoplasms.
Other approvals are anticipated.
So what about Neuroendocrine Neoplasms?
FDA granted accelerated approval to Avelumab (BAVENCIO) for the treatment of patients 12 years and older with metastatic Merkel cell carcinoma (MCC). MCC is a Neuroendocrine Carcinoma of the skin. Avelumab is a programmed death-ligand 1 (PD-L1) blocking human IgG1 lambda monoclonal antibody. This is the first FDA-approved product to treat this type of cancer – CLICK HERE for more information.
In Aug 2018, the FDA granted Nivolumab (OPDIVO) accelerated approval for third-line treatment of metastatic small cell lung cancer (a type of Neuroendocrine Carcinoma. Read more – click here.
In Dec 2018, US FDA approves pembrolizumab for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Click here.
On March 18, 2019, the FDA approved Atezolizumab (TECENTRIQ) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Click here.
This trial is interesting. Nivolumab (Opdiva) and Ipilimumab (Yervoy) in Treating Patients With High Grade Neuroendocrine Carcinoma It’s a multiple cancer setup and includes several of the less common NET/NEC types including ‘Lung Carcinoid’, ‘Anal NEC’, ‘Gastic NEC’, ‘Pancreatic NEC’ ‘Esophageal NEC. Interesting because this is the drug combo that NEC patient Danielle Tindle has moved onto after Keytruda didn’t really work in the medium to long-term (see the Danielle Tindle story below). Looking at the list in the trial document, I’m thinking they might mean high-grade Lung Neuroendocrine rather than ‘carcinoid’. I could be wrong. It’s currently recruiting.
Update from 2019 AACR Annual Meeting.
The immune checkpoint inhibitor combination of nivolumab (Opdivo) and ipilimumab (Yervoy) induced a greater than 40% response rate and was well tolerated in patients with high-grade neuroendocrine carcinoma, according to findings from the phase II DART trial presented at the 2019 AACR Annual Meeting.
“DART is the first NCI-funded rare tumor immunotherapy basket study which we think is unique in its design scale,” lead author Sandip Patel MD, an associate professor of medicine at the University of California San Diego School of Medicine, said in a press briefing at the meeting. “We’re studying over 37 rare tumor types [using the] combination of ipilimumab plus nivolumab. The neuroendocrine cohort, the nonpancreatic cohort, had promising signs of benefit—[particularly] in patients with high-grade neuroendocrine carcinoma—independent to primary site,” added Patel.
I also have some evidence of the use of Pembrolizumab (Keytruda) by an Australian high-grade thymus patient – I posted something here (Danielle Tindle)
PDR001 (Spartalizamab) – see below.
UPDATE from NANETS 2018. “A preliminary trial of checkpoint blockade for neuroendocrine tumors (NETs) produced little evidence of activity, according to data reported here. Only one of 21 patients with high-grade NETs responded to treatment with pembrolizumab (Keytruda). Three others had stable disease. The trial had an objective response threshold of 5% as the definition of clinically interesting, as reported at the North American Neuroendocrine Tumor Society annual symposium. “Pembrolizumab, though generally well tolerated, showed limited activity as a single agent in high-grade neuroendocrine neoplasms (NENs) in this study,” Arvind Dasari, MD, of MD Anderson Cancer Center in Houston, and colleagues concluded.” More info.
Update from Gastrointestinal Tumor symposium 2019. “Disappointing results for single agent pembrolizumab (Keytruda) in well differentiated NET. Response Rate 3.7%. Not a viable option. Listen to Dr Jonathan Strosberg describe the poor results. Click here.
This is an interesting trial sponsored by Novartis (of Octreotide fame). PDR001 (anti-PD-1) is an investigational immunotherapy being developed by Novartis to treat both solid tumors and lymphomas (cancers of the blood). It is currently being trialled on many cancers including Neuroendocrine Neoplasms both well and poorly differentiated. Click here:Clinical Trial SPARTALIZUMAB – Immunotherapy for Neuroendocrine Neoplasms (PDR001)
NET Research Foundation
Please also see the wonderful work done by NET Research Foundation who are using their funds to explore the use of Immunotherapy in NETs – check out their update by clicking here.
But what about just plain old well differentiated low or moderate grade NETs?
I found the following:
Pembrolizumab (Keytruda) in combination with Lanreotide
According to the trial documentation, it’s for patients with non-resectable, recurrent, or metastatic well or moderately (sic) differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). i.e. most of us. It is recruiting. You can read about the PLANET trial by clicking here. Make sure you fully check the inclusion and exclusion criteria. Please note the incorrect reference to ‘moderately differentiated’ – this is no longer used in the grading classification for Neuroendocrine Neoplasms.
Study of Pembrolizumab in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28) – NCT03054806 and another called ‘A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors’ (KEYNOTE 158) NCT02628067
From Gastrointestinal Tumor symposium 2019. “Disappointing results for single agent pembrolizumab in Well Differentiated NET. Response Rate 3.7%. Not a viable option. Listen to Dr Jonathan Strosberg describe the poor results. Click here.
Study for the Evaluation of Pembrorolizumab (MK-3475) in Patients with Rare Tumors (Experimental: Paraganglioma-Pheochromocytoma Group)
It is not known if this part of the trial is affected by the results above in Keynote-28. This study is recruiting at MD Andersen Houston Texas. Read more here.
PDR001 (Spartalizamab) -a Novartis drug – read about this trial click here.
Atezolizumab and Bevacizumab in Solid Tumors
In 2016, US FDA approved Atezolizumab (TECENTRIQ) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). Bevacizumab (also known as AVISTAN) is a well known drug already used to treat many cancers. Avastin is not actually Immunotherapy but is a tumor-starving (anti-angiogenic) therapy, i.e. its purpose is to prevent the growth of new blood vessels …. ergo this is a combo treatment using an Immunotherapy drug and an anti-angiogenic drug.
Well differentiated Neuroendocrine tumors, Grade 1 or grade 2 according to reviewing pathologist
Progressive disease over the preceding 12 months
Any number of prior therapies
Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrolment.
According to the trial documenation, there are two ‘baskets’ of types: Pancreatic NET (pNET) and “extrapancreatic” (i.e. beyond or not in the pancreas) including typical or atypical Lung NETs. Merkel Cell Carcinoma (a type of Neuroendocrine Carcinoma of the skin) is also included in the trial. You can read about this trial by clicking here. Make sure you fully check the inclusion and exclusion criteria. Again, within the trial documentation, please note the incorrect reference to ‘moderately differentiated’ – this is no longer used in the grading classification for Neuroendocrine Neoplasms.
By the way, what exactly does Immunotherapy do?
For those still wondering what cancer immunotherapy actually is, this is the most basic description I could find!
Immunotherapy – Hype or Hope?
I mentioned above that there was a lot of hype surrounding Keytruda and other immunotherapy treatments. You may therefore enjoy this CNN article about the hype and hope aspect, it was given considerable sharing at ASCO17 – read the article by clicking here
If you’re on an Immunotherapy trial not listed here, please let me now so I can update the post. Thanks in advance.
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 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.”
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, are more likely to exist in Grade 3 well differentiated NETs, particularly in the lower Ki-67 readings. 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).
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?
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
Anecdotal mention of Leicester and Newcastle 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:
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
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
26 Apr 2018
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
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.
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)
There’s a lot of inaccurate and out of date information out there. Some of it is propaganda but most is a combination of misunderstanding and patient forum myth spreading …….
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 and please don’t use the term on my social media sites, I refuse to perpetuate this outdated dogma.
Myth 17: Multiple Endocrine Neoplasia (MEN) is a type of Neuroendocrine Tumour
Not true. Multiple Endocrine Neoplasia are syndromes and inherited disorders. You can 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 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.
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
Welcome to my fifth ‘community’ newsletter, the monthly summary of NET news, views and ICYMI (in case you missed it!).
The highlight of the month was my attendance at the first ever Joint Patient-Physician symposium at ENETS Barcelona. I remain thankful to INCA for the honour of attending and for the experience that came with it. It was also great to finally meet other NET advocates face to face for the first time. Some of them have been great supporters since the inception of my blog and community.
March was a slower month in blogging terms due to a number of external projects and a continuing flow of private messages. I don’t have an issue with private contact but please note my disclaimer. My winter cold extended into March including during the ENETS/INCA symposium and although I had no voice, I still managed a question to the panel.
Despite a low number of blogs, I still managed to accumulate the second biggest monthly blog views ever. Thank you all so much ♥
New Blogs Published
Due to the vagaries of Facebook inner workings, some of these may not have even shown on your Facebook timeline. So, ICYMI …….here’s a summary with links:
New Audiences for NET Cancer. From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community.
I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. Click this link and sign up if you think this is something you’d be interested in receiving. I almost doubled the amount of subscribers in March! Currently 168.
I’m making new friends in the interventional radiologist community and am waiting on a video featuring a NET Patient (will bring you details in due course) and I’m learning more about these technologies from reading their tweets – I had no idea how many different jobs these guys do! I’m also seeing an increase from the Pathology community.
I’m proud to have been asked to become a ‘Community Champion’ on the Macmillan Cancer Support Forum helping outliers from the NET community there. I’ll be reporting more on this in the coming weeks.
Patients Included.A new campaign for 2017. I was excited to have been invited to the first ever joint Patient-Physician symposium at the annual ENETS conference in Barcelona 8 – 11 March. I have really good information which will feed into my blogs, either as updates or new blogs. This new blog is a result of attending this symposium but it’s from an existing campaign run along the ‘Consequences’ campaign run by Macmillan Cancer Support for all cancers. In the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life
Blog Milestone. In March, I tipped over the quarter of a million views! Thank you all so much ♥ Keep sharing!
Facebook Milestone. I’m aiming for 5000 by year-end and this is on track. The Facebook page is now my biggest outlet for awareness and education so please please please recommend this page to anyone you think would be interested. The picture of the invite button shown here is an example from a windows computer, it may differ on other platforms.
I’m expanding into Instagram to see how that goes. I’ve amassed over 200 followers to date. Initially, I’ll just be posting pictures of things that inspire me, mostly scenic photos of places I’ve been or want to go! You can follow me here: Click here to go to my Instagram page
Facebook – 4350. This is a key outlet for my blog – please encourage others to like my page(if you’d like to know how to use your Facebook to invite others to my page – let me know, I can provide you with a step by step approach). Please also join my 2017 awareness campaign event here (select ‘Going’)
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
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Welcome to my fourth ‘community’ newsletter, the monthly summary of NET news, views and ICYMI (in case you missed it!).
February was a slower month in blogging terms due to a major increase in contact from people privately asking for advice and others asking me to support external projects. I don’t have an issue with private contact but please note my disclaimer. I also had a winter cold for a few days, so I relaxed a bit. Only a short month but I managed to accumulate the second biggest monthly blog views ever (January 2017 will be difficult to beat). Thank you all so much ♥
January’s success also led to increased Facebook followers and I broke through the 4000 milestone with a plan to reach 5000 by the end of the year or before. If I grew at January’s rate, it could easily be 6000 but that’s probably wishful thinking!
The month ended with a bang! The long-awaited FDA approval of ‘XERMELO’ (Telotristat Ethyl) was announced yesterday. Check out my blog which has all the links you need in one area.Click here to read
New Blogs Published
Due to the vagaries of Facebook inner workings, some of these may not have even shown on your Facebook timeline. So, ICYMI …….here’s a summary with links:
New Audiences for NET Cancer. From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community.
I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. Click this link and sign up if you think this is something you’d be interested in receiving. I reached 100 email subscribers today!
I’m making new friends in the interventional radiologist community having been invited to join their twitter chat. That turned out to be profitable as I won $40 of Starbucks e-gifts for being a quick tweeter! I now have some new friends who are producing a video featuring a NET Patient (will bring you details in due course) and I’m learning more about these technologies from reading their tweets – I had no idea how many different jobs these guys do!
I’m proud to have been asked to become a ‘Community Champion’ on the Macmillan Cancer Support Forum. I’ll be reporting more on this in the coming weeks.
Patients Included.A new campaign for 2017. I’m very excited to have been invited to the first ever joint Patient-Physician symposium at the annual ENETS conference in Barcelona 8 – 11 March. I’m being sponsored by the International Neuroendocrine Cancer Alliance (INCA). I’ll be tweeting and posting stuff live from the conference, look out for this.
Blog Milestone. Accelerated viewing figures should put me into a quarter of a million blog views by the end of this month! Thank you all so much ♥ Keep sharing!
Facebook Milestone. My Facebook page is now my biggest outlet for awareness and education so please please please recommend this page to anyone you think would be interested. The picture of the invite button shown here is an example from a windows computer, it may differ on other platforms.
I’m expanding into Instagram to see how that goes. Initially I’ll just be posting pictures of things that inspire me, mostly scenic photos of places I’ve been or want to go! You can follow me here: Click here to go to my Instagram page
Facebook – 4213. This is a key outlet for my blog – please encourage others to like my page(if you’d like to know how to use your Facebook to invite others to my page – let me know, I can provide you with a step by step approach). Please also join my 2017 awareness campaign event here (select ‘Going’)
I recently wrote a blog called Neuroendocrine Cancer – Exciting Times Ahead! I wrote that on a day I was feeling particularly positive and at the time, I wanted to share that positivity with you. I genuinely believe there’s a lot of great things happening. Don’t get me wrong, there’s a lot still to be done, particularly in the area of diagnosis and quality of life after being diagnosed. However, this is a really great message from a well-known NET expert.
In an interview with OncLive, Jonathan R. Strosberg, MD, associate professor at the H. Lee Moffitt Cancer Center in Florida, discussed his presentation on NETs at a recent 2016 Symposium, and shed light on the progress that has been made in this treatment landscape.
OncLive: Please highlight some of the main points from your presentation.
Strosberg: The question I was asked to address is whether we’re making progress in the management of NETs, and I think the answer is unequivocally yes. Prior to 2009, there were no positive published phase III trials.
Since then, there have been 8 trials, 7 of which have reached their primary endpoints. So it’s been a decade of significant improvement. And even though none of these studies were powered to look at overall survival as an endpoint, we’re certainly seeing evidence of improvement in outcomes.
OncLive: What are some of the pivotal agents that you feel have impacted the paradigm in the past several years?
Strosberg: The first group is the somatostatin analogs. We use them to control hormonal symptoms like carcinoid syndrome, but with the CLARINET study, we now know that they substantially inhibit tumor growth.
The next significant drug we use in this disease is everolimus (Afinitor), an oral mTOR inhibitor, which is now approved in several indications based on positive phase III studies. The first was in pancreatic NETs and subsequently, based on the RADIANT-4 trial, it was also approved in lung and gastrointestinal NETs. So that was an important advance.
The next important category of treatment is radiolabeled somatostatin analogs, otherwise known as peptide receptor radiotherapy. The one that’s been tested in a phase III trial is lutetium dotatate, also known as Lutathera. It was tested in patients with progressive midgut NETs and showed a very substantial 79% improvement in progression-free survival, and a very strong trend toward improvement in overall survival, which we hope will be confirmed upon final analysis.
OncLive: Are we getting better at diagnosing and managing the treatment of NETs?
Strosberg: Certainly. I think pathologists are better at making the diagnosis of a NET, rather than just calling a cancer pancreatic cancer or colorectal cancer. They’re recognizing the neuroendocrine aspects of the disease, and doing the appropriate immunohistochemical staining.
We also have better diagnostic tools. We used to rely primarily on octreoscan, and in many cases we still do, but there is a new diagnostic scan called Gallium-68 dotatate scan, also known as Netspot, which has substantially improved sensitivity and specificity. It’s not yet widely available, but it is FDA approved and hopefully will enable better diagnosis as well as staging in the coming years.
And, with the increase in number of phase III studies, we’re developing evidence-based guidelines, which will hopefully lead to more standardization, although knowing how to sequence these new drugs is still quite challenging.
OncLive: With sequencing, what are the main questions that we’re still trying to answer?
Strosberg: If we take, for example, NETs of the midgut, beyond first-line somatostatin analogs, physicians and patients often face decisions regarding where to proceed next, and for some patients with liver-dominant disease, liver-directed therapies are still an option.
For others, everolimus is a systemic option, and then hopefully lutetium dotatate will be an option based on approval of the drug, which is currently pending. Knowing how to choose among those 3 options is going to be a challenge, and I think there will be debates. Hopefully, clinical trials that compare one agent to another can help doctors make that choice. It’s even more complicated for pancreatic NETs. Beyond somatostatin analogs, we have about 5 choices—we have everolimus, sunitinib (Sutent), cytotoxic chemotherapy, liver-directed therapy, and peptide receptor radiotherapy. It’s even more challenging in that area.
OncLive: Are there any other ongoing clinical trials with some of these agents that you’re particularly excited about?
Strosberg: There’s a trial that is slated to take place in Europe which will compare lutetium dotatate with everolimus in advanced pancreatic NETs, and I think that’s going to be a very important trial that will help us get some information on both sequencing of these drugs, as well as the efficacy of Lutathera in the pancreatic NET population, based on well-run prospective clinical trials. I’m particularly looking forward to that trial.
OncLive: Looking to the future, what are some of the immediate challenges you hope to tackle with NETs?
Strosberg: One area of particular need is poorly differentiated neuroendocrine carcinomas. That’s a field that’s traditionally been understudied. There have been very few prospective clinical trials looking at this particular population, and we’re hoping that will change in the near future. There are a number of trials taking place looking at immunotherapy drugs. If these agents work anywhere in the neuroendocrine sphere, they are more likely to work in poorly differentiated or high-grade tumors, in my opinion, given the mutational profile of these cancers. So that’s something I’m particularly looking forward to being able to offer these patients something other than the cisplatin/etoposide combination that goes back decades, and is of short-lasting duration.
See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-24/expert-discusses-recent-progress-in-net-management#sthash.ypkilX2A.dpuf
Thanks for reading
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Welcome to my third ‘community’ newsletter, the monthly summary of NET news, views and ICYMI (in case you missed it!).
January was a month for breaking records. I recorded the biggest ever amount of views in any one day, any one week and now any one month and it will probably be a long time before they’re broken again! This was mainly due to the fantastic support you showed for one particular blog post The Anatomy Of Neuroendocrine Cancer. Thank you all so much ♥
January was also a month for making new friends after being invited to speak to an audience of 30 pharma managers at Ipsen’s Germany HQ near Karlsruhe. I was made very welcome by the Ipsen staff and I think it’s great they want to hear the patient voice. Bad weather was coming in fast and I only just escaped in time from Frankfurt Airport, suffering a 2 hour delay while the plane was ‘de-iced’. Nonetheless, I really enjoyed a flying visit to a country where I had lived for 12 years in the 70s/80s. See my Facebook post about this visit: https://goo.gl/hyJ0Si
New Blogs Published
A busy month for new blogs. Due to the vagaries of Facebook inner workings, some of these may not have even shown on your timeline. So, ICYMI …….here’s a summary with links:
New Audiences for NET Cancer. From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community. Two new openings in Dec to report:
Ipsen isn’t really a new audience but the individual employees at their German HQ are now more aware of life with Neuroendocrine Cancer. See my Facebook post about this visit: https://goo.gl/hyJ0Si
I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. You can sign up for this newsletter here as I won’t be posting it every day. Click this link and sign up if you think this is something you’d be interested in receiving.
I’m making new friends in the interventional radiologist community having been invited to join their twitter chat. Many of us will know an Interventional Radiologist (some are known as Interventional Oncologists) following treatment (e.g. a liver embolization). I’m hoping to soon have access to some great videos about their work with NETs.
I’m proud to have been asked to become a ‘Community Champion’ on the Macmillan Cancer Support Forum. I’ll be reporting on this in the coming weeks.
Patients Included.A new campaign for 2017 and I’ll shortly be bringing you news of an opportunity in Mar 2017. We want to be included right?
Blog Milestone. My blog tipped over 220,000 views in Jan and I’m half way from the 1 Jan position to reaching a quarter of a million. Thanks – keep sharing!
Facebook Milestone. My Facebook page is now my biggest outlet for awareness and education so please please please recommend this page to anyone you think would be interested. The picture of the invite button shown here is an example from a windows computer, it may differ on other platforms.
Facebook – 3985. This is a key outlet for my blog – please encourage others to like my page(if you’d like to know how to use your Facebook to invite others to my page – let me know, I can provide you with a step by step approach). Please also join my 2017 awareness campaign event here (select ‘Going’)
Welcome to my second ‘community’ newsletter, the monthly summary of NET news in Dec 2016, views and ICYMI (in case you missed it!).
December was a particularly special month. For the previous 3 months, I had been busily working behind the scenes and on my various social media presences to put on a good show for the 2016 WEGO Health Activist Awards. This paid off and I won the Best in Show ‘Community’ category in addition to being shortlisted as one of 5 finalists in the blog category. The community award was special because it means we all won the award as a part of this ‘Community’. I’ve picked up a whole new bunch of friends outside the NET world bringing much-needed exposure to NET Cancer. I had a quiet week resting before I resumed normal activity and then a sprint finish at the end of the month took me over the magic 10,000 blog hits figure (and even more on Facebook). Stick with me because I really need your help and support and anyone else you know who can assist. The WEGO awards brought a significant increase in twitter followers.
A quiet month in terms of numbers of blogs. Due to the vagaries of Facebook inner workings, some of these may not have even shown on your timeline. So, ICYMI …….here’s a summary with links:
First in a series of ‘spotlight on ……’ posts – this one on Pheochromocytomas and Paragangliomas. Read here.
I shared an inspiration message with you – one that I received from an old friend. Read ‘Keep your light burning’ which had a great response.
Confused about the difference between Lanreotide and Octreotide? This blog will help – it got a really good response and you can read it here. I also received lots of questions about the individual drugs which was great and shows the importance of this subject to patients out there.
Other News in Dec
New Audiences for NET Cancer. From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community. Two new openings in Dec to report:
The exposure during the build up to the 2016 WEGO Health Activist Awardswhere I made the final in two categories continued into Dec culminating in the award win (you can listen to the announcement live here). I also featured in a radio show just before the announcement and you can listen to it here (start at 40.30).
I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. You can sign up for this newsletter here as I wont be posting it every day. Click this link and sign up if you think this is something you’d be interested in receiving.
Blog Milestone. My blog tipped over 200,000 views in Dec and it’s already accelerating toward a quarter of a million. Thanks – keep sharing!
Facebook Milestone. My Facebook page was 2 years old in Dec 🙂 Please recommend this page to anyone you think would be interested.
Facebook – 3726. This is a key outlet for my blog – please encourage others to like my page(if you’d like to know how to use your Facebook to invite others to my page – let me know, I can provide you with a step by step approach)Please also join my 2017 awareness campaign event here (select ‘Going’)
Somatostatin Analogues are the ‘workhorse’ treatments for those living with NETs, particularly where certain syndromes are involved. So not just for classic NETs with Carcinoid Syndrome but also for treating insulinoma, gastrinoma, glucagonoma and VIPoma (all types of pNETs) and others. They are most effective if the NETs express somatostatin receptors. They also have an anti-tumour effect but more of a slowing down of growth rather than a killing or reduction of tumour size – but there are always outliers where such effects are displayed.
Somatostatin is actually a naturally occurring hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. However, it can only handle the normal release of hormones. When NET syndromes occur, the naturally occurring somatostatin is unable to cope. The word ‘analogue’ in the simplest of terms, means ‘manufactured’ and a somatostatin analogue is made to be able to cope with the excess secretion (in most cases).
Although there is hidden complexity, the concept of the drug is fairly simple. It can inhibit insulin, glucagon, serotonin, VIP, it can slow down bowel motility and increase absorption of fluid from the gut. It also has an inhibitory effect on growth hormone release from the pituitary gland (thus why it’s also used to treat a condition called Acromegaly). You can see why it’s a good treatment for those with NET syndromes, i.e. who suffer from the excess secretions of hormones from their NETs. Clearly there can be side effects as it also inhibits digestive enzymes which can contribute to, or exacerbate, gastro-intestinal malabsorption.
Please note somatostatin analogues are not chemo. There are two major types in use:
Octreotide – or its brand name Sandostatin. It is suffixed by LAR for the ‘long acting release’ version.
Lanreotide – brand name Somatuline (suffixed by ‘Depot’ in North America, ‘Autogel’ elsewhere)
So what’s the difference between the two?
A frequently asked question. Here’s a quick summary:
They are made by two different companies. Novartis manufactures Octreotide and Ipsen manufactures Lanreotide. Octreotide has been around for much longer.
The long-acting versions are made and absorbed very differently. Octreotide has a complex polymer and must be injected in the muscle to absorb properly. Lanreotide instead uses has a novel nanotube structure and is water based (click here to see a video of how this works). It is injected deep-subcutaneously and is therefore easier to absorb and is not greatly impacted if accidentally injected into muscle.
Their delivery systems are mainly via injections but are fundamentally different as you can see from the blog graphic which shows the differences between the long acting release versions. Octreotide long acting requires a pre-mix, whilst Lanreotide comes pre-filled.
The long-acting versions are 60, 90 and 120 mg for Lanreotide and 10, 20 and 30 mg for Octreotide.
Octreotide also has a daily version which is administered subcutaneously.
Octreotide has something called a ‘rescue shot’ which is essentially a top up to tackle breakthrough symptoms. It is a subcutaneous injection.
You can also ‘pump’ Octreotide using a switched on/off continuous infusion subcutaneously.
Other than for lab/trial use, to the best of my knowledge, there is no daily injection, rescue shot or ‘pump’ for Lanreotide that is indicated for patient use.
Whilst both have anti-tumour effects, there are differences in US FDA approval: Octreotide (Sandostatin) is approved for symptom control (not anti-tumor) whereas Lanreotide (Somatuline) is approved for tumour control. However, the US FDA recently added a supplemental approval for syndrome control on the basis that it is proven to reduce the need for short acting somatostatin analogues use – read more here. This supplementary approval followed the ELECT trial – results here.
Always refer to the patient information leaflet as it is not safe to assume that all healthcare professionals are familiar with the administration. Common issues include (but are not limited to): drug temperature requirements, injection site, pinching vs stretching skin, speed of injection.
Please note a new syringe for Lanreotide will be available in June 2019. Further information will be communicated to healthcare professionals in advance of this, to enable them to inform their patients, whom have been prescribed Lanreotide. In addition, the patient information leaflet included in the packet will have clear instructions for use. There will be a prominent yellow box located on the outer carton of the medicine, alerting healthcare professionals and patients that a new syringe is contained inside. Please note that the medicine is still the same and the formulation and storage conditions have not changed.
Here are some interesting videos showing and explaining their administration:
Administering a Somatuline Depot (Lanreotide) injection:
Administering a Sandostatin LAR (Octreotide) injection:
This link also provides guidance on the “new formulation” Octreotide. Click here.
My own experience only includes daily injections of Octreotide (Sep-Nov 2010) and Lanreotide (Dec 2010 onwards). I’ve also had continuous infusion of Octreotide in preparation for surgical or invasive procedures over the period 2010-2012 (i.e. crisis prevention). You can read about my Lanreotide experience by clicking here. If you are interested in what might be coming downstream, please see my blog entitled ‘Somatostatin Analogues and Delivery Systems in the Pipeline’.
Injection site granulomas (lumps)
The issue of ‘granulomas‘ or ‘injection site granulomas’ seems to figure in both drugs. Gluteal injection site granulomas are a very common finding on CT and plain radiographs. They occur as a result of subcutaneous (i.e. intra-lipomatous) rather than intramuscular injection of drugs, which cause localised fat necrosis, scar formation and dystrophic calcification. But no-one seems to know why they occur with somatostatin analogues.
Personally, I find that they are more conspicuous if the injection is done slightly too high which was my initial experience and they took months to fade. I opted to stand up for the first two injections and I attribute this decision for a slightly too high injection site. I now lie down which is actually recommended for the smaller and thinner patient. Although the lumps have reduced in size, I have not seen a new lump for some time indicating location might have been the cause. They sometimes show up on scans. This is not a new problem and has been highlighted for the last 10 years in academic papers. This particular paper is useful and the conclusion confirms this is not something that should worry patients too much. Read more here
Somatostatin Analogues and raised blood sugar levels
It is well documented that both Octreotide and Lanreotide can elevate blood glucose (sugar) levels. Read more in my article Diabetes – the NET Effect.
We’ve all heard the age-old question about the chicken and the egg? Scientists claimed to have ‘cracked’ the riddle of whether the chicken or the egg came first. The answer, they say, is the chicken. Researchers found that the formation of egg shells relies on a protein found only in a chicken’s ovaries. Therefore, an egg can exist only if it has been inside a chicken. There you have it!
On a similar subject, I’m often confused when someone says they have been diagnosed with ‘Carcinoid Syndrome’and not one of associated ‘Neuroendocrine Tumours’. So which comes first? I guess it’s the way you look at it. In terms of presentation, the syndrome might look like it comes first, particularly in cases of metastatic/advanced disease or other complex scenarios. Alternatively, a tumour may be found in an asymptomatic patient, quite often incidentally. However, on the basis that the widely accepted definition of Neuroendocrine Tumours would indicate that a syndrome is secondary to tumour growth, then the tumour must be the chicken.
I sometimes wonder what patients are told by their physicians….. or perhaps by their insurance companies (more on the latter below). That said, I did see some anecdotal evidence about one person who was diagnosed with Carcinoid Syndrome despite the lack of any evidence of tumours or their markers. This might just be a case of providing a clinical diagnosis in order to justify somatostatin analogue treatment but it does seem unusual given that scientifically speaking, Carcinoid Syndrome can only be caused by a particular type of NET.
I have a little bit of experience with this confusion and it still annoys me today. Shortly after my diagnosis, I had to fill out an online form for my health insurance. The drop down menu did not have an entry for Neuroendocrine ‘anything’ but I spotted Carcinoid only to find it was actually Carcinoid Syndrome. By this stage I had passed the first level of NET knowledge and was therefore suspicious of the insurance company list. I called them and they said it was a recognised condition and I should not worry. Whilst that statement might be correct, I did tell them it was not a cancer per se but an accompanying syndrome caused by the cancer. I added that I was concerned about my eligibility for cancer cover treatment and didn’t want to put an incorrect statement on the online form. However, they persisted and assured me it would be fine on that selection. On the basis it was really the only option I could select, I selected and submitted. I did get my cover sorted. However, it’s now clear to me that their database was totally out of date. A similar thing happened when I was prescribed Octreotide and then Lanreotide, the only ‘treatment type’ they could find on their database was ‘chemotherapy‘ – again their system was out of date. I’m told by someone in the know, that individual insurance companies are not responsible for this list, they all get it from a central place – I’d love to pay that central place a visit!
I quickly thought about all the other NET Syndromes for their ‘chicken and egg’ status! Pancreatic NET (pNET) Syndromes must all be ‘chicken’ given the tumour definition and the secretion of the offending hormones that cause these other syndromes e.g. Insulin, Gastrin, Glucagon, Pancreatic Polypeptide (PP), Vasoactive Intestinal Peptide (VIP) and Somatostatin, etc.
All of that said, the exception might be hereditary syndromes e.g. MEN (yes it is a syndrome, not a tumor type). MEN syndromes are genetic conditions. This means that the cancer risk and other features of MEN can be passed from generation to generation in a family. A mutation (alteration) in the various MEN genes gives a person an increased risk of developing endocrine/neuroendocrine tumors and other symptoms of MEN. It’s also possible that the tumors will be discovered first. It’s complex as you will see in my article entitled “Genetics and Neuroendocrine Tumors”.
I’m continually seeing certain drugs for treatment of Neuroendocrine Tumours (NETs) described as chemotherapy. I think there must be some confusion with more modern drugs which are more targeted and work in a different way to Chemotherapy.
I researched several sites and they all tend to provide a summary of chemotherapy which is worded like this: Chemotherapy means:
a treatment of cancer by using anti-cancer medicines called cytotoxic drugs. Cytotoxic medicines are poisonous (toxic) to cancer cells. They kill cancer cells or stop them from multiplying. Different cytotoxic medicines do this in different ways. However, they all tend to work by interfering with some aspect of how the cells divide and multiply. Two or more cytotoxic medicines are often used in a course of chemotherapy, each with a different way of working. This may give a better chance of success than using only one. There are many different cytotoxic medicines used in the treatment of cancer. In each case the one (or ones) chosen will depend on the type and stage of your cancer. Interestingly, there are several statements along the lines of ‘Cytotoxic medicines work best in cancers where the cancer cells are rapidly dividing and multiplying’, a key issue with lower grade NETs.
Well known chemotherapy treatments for NETs include (but are not limited to): Capecitabine (Xeloda), Temozolomide (Temodal), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) Cisplatin, Etoposide (Etopophos, Vepesid), Carboplatin, Streptozotocin (Zanosar). Some of these may be given as a combination treatment, e.g. CAPecitabine and TEMozolomide (CAPTEM).
In the past, any medication used to treat cancer was regarded as chemotherapy. However, over the last 20 years, new types of medication that work in a different way to chemotherapy have been introduced. Many of these new types of medication are known as targeted therapies. This is because they’re designed to target and disrupt one or more of the biological processes that cancerous cells use to grow and reproduce. They are classed as biological therapy. In contrast, chemotherapy medications are mostly systemic in nature and designed to have a poisonous effect on cancerous cells, thus the term ‘cytotoxic’.
The following well known NETs treatment are not really chemotherapy and describing them in this way is not only misleading but may actually cause alarm to other patients. Furthermore, if you check any authoritative NET Cancer specialist or advocate organisation; any general and authoritative cancer site or the manufacturer’s websites; you will not see the drugs below listed within the term chemotherapy.
Somatostatin Analogues e.g. Sandostatin (Octreotide), Somatuline (Lanreotide). Although these drugs have an anti-cancer effect for some, they are in fact hormone inhibitors and are therefore a hormone therapy.
Everolimus (Afinitor). This is a targeted biological therapy or more accurate a mammalian target of rapamycin (mTOR) inhibitor. It is a type of treatment called a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.
Sunitinib (Sutent). This is a targeted biological therapy or more accurate a protein (or tyrosine) kinase inhibitor. Protein kinase is a type of chemical messenger (an enzyme) that plays a part in the growth of cancer cells. Sunitinib blocks the protein kinase to stop the cancer growing. It can stop the growth of a tumour or shrink it down.
I can only speculate why some of the confusion exists but I do have some personal experience I can quote too. Firstly I believe it could be easier for some people to describe the new agents as ‘chemotherapy’ rather than explain things such as somatostatin analogues, ‘mammalian target of rapamycin (mTOR) inhibitors’, protein kinase inhibitor or angiogenesis inhibitors. Another reason could be that health insurance companies do not have the correct database structures in place on their IT systems and therefore need to ‘pigeon hole’ drugs into the closest category they can see. Often this is chemotherapy and this only adds to the confusion. In the days when I had health insurance, my Lanreotide injections were coded as chemotherapy on all my bills. I challenged it and this is how they explained the issue.
When you’ve been diagnosed with cancer at an incurable stage, certain words start to mean more. Take ‘palliative’ for example. Before I was diagnosed I had always associated the word ‘palliative’ with someone who had a terminal disease and this type of care was to make the final days/weeks as comfortable as possible. So it was a bit of a shock to find out in 2010 that my treatment was palliative in nature. However, I’m still not dead and I’m still receiving palliative care. Go figure! The answer is simple – the cancer story is changing. What was once feared as a death sentence is now an illness that many people survive. As survival rates increase, so too will the number of people living with the legacy of cancer and its treatment.
What is palliative care?
Some people with incurable cancer will continue to receive treatment to keep the cancer at bay and that treatment is by definition, palliative. In fact, palliative care can be given at any time during an illness. It’s not just for treatment of the cancer, it’s also to help with the effects of that treatment, i.e. the consequences of cancer. It also encompasses things such as emotional and other practical support.
In the most general terms and while it clearly can go into some detail and long lists, palliative care can be defined as follows:
Cancer and its treatment often cause side effects. Relieving a person’s symptoms and side effects is an important part of cancer care. This approach is called symptom management, supportive care, or palliative care. Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care.
I looked at a few sites and many of them confirm the above. However, there appears to be even more sites where it is still heavily associated and inextricably linked with end of life or hospice care where you may come into contact with the term palliative care specialist. Whilst it’s not wrong to make that association, more work needs to be done to cater for the growing numbers of ‘incurable but treatable’ who are not ‘terminal’ and still need this type of support, in some ways like you would with a chronic condition. I also sense a push in certain areas to emphasise the meaning of palliative care to include a much broader definition than is currently in most people’s minds. This needs much more publicity. I’m not saying that ‘palliative’ does not include ‘hospice care’ but I’m not intending to cover that aspect in this blog which is aimed as those with incurable but treatable cancers.
My palliative care experience
When I was diagnosed with metastatic Neuroendocrine Tumours (NETs) in 2010, I quickly accepted the fact that any treatment I would receive would not be curative. I also quickly accepted that if I didn’t have any treatment, I would probably die. The words used were ‘debulking’ and ‘cytoreductive’, more technical sounding but essentially meaning the same thing as palliative. Debulking means removing as much tumour as possible in order to increase the chance that perhaps other treatments can be of some help. Cytoreductive means the same thing but generally extends the ‘debulking’ activity to other modes of treatment (e.g. chemotherapy/radiotherapy).
NETs is one of a number of cancers for which ‘debulking’ and ‘cytoreductive’ therapies can in many cases confer some survival advantage. In fact if you read ENETS or NANETS guidance for advanced NETs, you will frequently see the statement that cytoreductive surgery should be considered if greater than 90% of metastatic tumour burden can be safely resected or ablated. NETs, particularly with distant metastases, can come with a ‘syndrome’ and some of the symptoms can be rather debilitating for many patients. These syndromes are a result of tumours secreting excess amounts of hormonesand the types vary from patient to patient and from NET type to NET type. It follows that if surgical debulking reduces the amount of tumours, then it should normally decrease the effects of the associated syndrome. In fact, one letter from a specialist did describe my surgery in symptom palliation terms. I can confirm this is about right as my hormone marker 5HIAA remained elevated after surgery to remove my primary and local tumours, but did not return to normal until after my liver surgery.
However, there are a number of other treatments that can be considered ‘palliative’ in a metastatic or advanced environment. Getting rid of tumours is always the optimum treatment for any cancer but just as surgical debulking can reduce the amount of cancer, other non-surgical modalities such as liver embolization or ablation can have the effect of reducing the symptoms of the cancer and therefore providing relief to the patient. Somatostatin Analogues (Octreotide/Lanreotide) are another good example of palliative care. Although they might have an anti-tumour effect for some, they mostly work by reducing or inhibiting the secretion of excess hormones which contribute to the various NET syndromes. ‘Symptom control’ is as defined above, palliative care.
I’m already looking forward to my next palliative care appointment.