NANETS (North American Neuroendocrine Tumor Society) is one of the biggest NET conferences, bringing together NET Specialists from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field of Neuroendocrine Neoplasms (Tumors and Carcinomas). This is fairly complex stuff but much of it will be familiar to many. I’ve filtered out several outputs from the conference which I think are both relevant and topical to patients. The list is below allowing you to easily peruse and read further via linkages if you need to read more. Remember, some of these are extracts so do not contain all the details of the research or study – although some of the linkages will take you to in-depth information if that’s your bag. Where applicable, I’ve also linked to some of my blog posts to add context and detail in patient speak. The list comprises articles which were published in medical news media and for which I received alerts. It does not comprise the entire schedule of NANETS 2017. I may add more to the list if other relevant and interesting articles are published downstream.
Please note: Some of the output from the conference is in ‘study form’ and has not yet been published as peer-reviewed data (important notice to readers).
NANETS to Bring All Specialties in the NETs Community Together for 10th Annual Symposium
Interview with Michael Soulen MD. Nice introduction.
PFS and OS After Salvage Peptide Receptor Radionuclide Therapy (PRRT) with 177-Lu[Dota⁰,Tyr³] octreotate in Patients with GastroEnteroPancreatic or Bronchial NeuroEndocrine Tumours (GEP-NETs) – The Rotterdam Cohort
On the day I was diagnosed, I hadn’t really thought about questions, the only one I actually remember asking was “how long do I have left to live” (I watch too many movies!). On the day of diagnosis and a period beyond, people tend to feel emotions of shock, denial, anger and sadness, before going on to accept their situation. Yes, I ‘googled‘ but not a great deal really – although some things I found did frighten me. I wish I had found this article way back then.
As things progressed in the weeks after ‘D-Day’, I started to work out the sort of things to ask but even then it was limited. I had been referred to an experienced NET team so I felt confident they would do whatever needed doing. In hindsight, I can now think of a quite a few questions I should have asked. That said, I suspect my team probably gave me the answers without having been asked the questions!
My blogging efforts have turned into a ‘Community’ of sorts. Consequently, I’m contacted daily from people finding me on the web. Many of these people are at the pre-diagnosis or initial phase. Many are undiagnosed. Most are looking for information and some sound like they are already at the ‘acceptance stage’; some are frightened about the future, some are angry because they think they are not being told important information and some also feel they have been messed about or ‘fobbed off’ by their doctors. Of course I’m happy to help but only after reminding them that I’m just a wee Scottish guy with the same disease!
I have to say that some people arrive on my site without a diagnosis but often seem to be very well prepared – the power of the internet I suspect. The questions I mostly get involve finding experts and then what questions to ask them.
As an extra bonus to this post, I offer you a starting point for the best places I know for finding NET expertise:
One US center is now the first to achieve a European NETs Center of Excellence accreditation – read more hear about University of Iowa Holden Comprehensive Cancer Center – click here
NANETS have listed “NET Centers” here – NANETS NET Centers and Clinics
The NET Research Foundation as they also have a ‘Doctor Database’ section which differs slightly from CCF below.
Dr. Shereen Ezzat at Princess Margaret in Toronto (PMH)
Dr. McEwan, The Cross Clinic, Alberta?
Dr Kavan at Montreal Jewish General Hospital (Oncology)
Dr Buteau / Beauregard at Quebec Hotel Dieu (Radiation Oncology (PRRT, Ga68)
Dr Rivera at Montreal General Hospital (Endocrinology)
Dr Metrakos at the Montreal Royal Victoria Hospital (Surgeon) sees a lot of NET patients
On the French side Dr Andre Roy at the CHUM in Montreal (surgeon) also sees a lot of NET patients
Dr. Jamil Asselah also treats net patients. He is an oncologist….Quebec
Michael Sawyer at Cross Clinic in Alberta Edmonton.
Drs. Parkins, Card, and Paseka at the Tom Baker CC in Calgary.
London Ontario: Dr. David Laidley, Dr. Robert Reid in the Neuroendocrine Clinic at London Regional Cancer Program and Dr. Daryl Gray, Surgeon.
Russia – Clinical Oncology Research Institute, N. N. Blokhin RCRC RAMS, Address: 24, Kashirskoye sh., Moscow, 115478, RF. NET specialist Alla Markovich
In my Group – ask other patients: Click here to join.
Neuroendocrine Cancer – 10 questions to ask your specialist
Many people ask me what sort of questions to ask and because NETs is such a diverse bunch of diseases, that leads to me ask them a series of questions to ascertain what they might consider asking. I’m not surprised to find some are unable to answer my questions and so those then become some of their questions to ask!
Also, questions don’t end at the diagnosis phase, they continue and in fact, some of the answers to the questions below, may bring up new questions in your mind. Some of these questions can be asked time and time again in the event of issues downstream.
If you’re currently confused about the essential facts of your condition, you’re not alone. In a recent study, almost half of cancer patients did not know basic stuff such as grade and stage of cancer, and after their initial treatment, whether they were free of disease or in remission.
For those entering or are recently just beyond the diagnostic phase, you may find certain questions cannot yet be answered without further test results etc. However, if the answer is not yet known for whatever reason, at least you have it on your list for follow up appointments. Consequently, I’ve constructed this list of questions that should function as a generic set. There may also be ‘specific to country’ questions such as insurance cover in addition to this suggested list. Of course, some of you may not want the answer to so certain questions. That’s perfectly understandable, so don’t ask!
1. Where is my primary tumour and what type of NET is it?
This is a fundamental question and it’s likely many will already have some inkling about location and perhaps a type. The difference between NETs and other types of cancer is the primary can be found wherever there are Neuroendocrine cells rather than a specific part of the anatomy in terms of naming the type of cancer, i.e. a NET of the pancreas is not Pancreatic Cancer.
The type of NET is key as it will drive a lot of other stuff including treatment. Location and type of NET are not always aligned, for example, you may have a NET in your Pancreas but there are several types of Pancreatic NET (or pNET) and these may depend on identification of a particular hormone (see syndrome below). Many NETs are non-functional (there is no oversecreting hormone).
For some the primary will not yet be found (i.e. cancer of unknown primary or CUP). There may also be multiple primaries.
2. What is the grade and differentiation of my tumour(s)?
Another fundamental question as this defines the aggressiveness of the disease and is absolutely key in determining overall treatment plans. Treatment plans for poorly differentiated can be very different from well differentiated. Read more here – Grading and here – Benign or Malignant
3. What is the stage of my disease?
Fundamental to understanding the nature of your disease. Stage confirms the extent of your disease, i.e. how far has it spread. Again this will drive treatment plans and long-term outlooks. Scans are really important in determining the Stage of your cancer – check out my scans post here. Read more here on Staging
4. Do I have a NET Syndrome?
Many NET patients will have been experiencing symptoms prior to diagnosis, perhaps for some time. It’s possible these symptoms form part of what is known as a ‘Syndrome’ and there are several associated with NETs. Syndromes are mostly caused by the effects of over-secretion of hormones from the tumours, a hallmark of Neuroendocrine disease. Carcinoid Syndrome is the most common but there are many more depending on the primary location. Read more here – NET Syndromes.
5. What is my treatment plan, and what are the factors that will influence my eventual treatment? When will I start treatment
This is a very complex area and will depend on many factors. Thus why your specialist may not have the answers to hand. Decisions on treatment are normally made by some form of Multi-disciplinary Team (MDT). Many people diagnosed with cancer expect to be whisked away to an operating theatre or chemotherapy treatment. However, for many this is not what actually happens. Depending on what testing has been done up to the actual diagnosis, it’s possible that even more testing needs to be done. Additionally, for those with an accompanying syndrome, this will most likely need to be brought until control before certain treatments can be administered; and even then, there may be checks to make sure the treatment will be suitable. Sometimes it’s a case of ‘Hurry up and wait’. My first treatment was 6 weeks after diagnosis and that was designed to control my syndrome ready for surgery which was undertaken 14 weeks after diagnosis. It’s also possible you will be placed on a ‘watch and wait’ regime, at least to begin with.
6. Can you comment on the potential for my type of NET to be related to any familial or genetic aspects of cancer?
A small percentage of NETs are hereditary/genetic in nature. This is mostly associated with those who have Multiple Endocrine Neoplasms (MEN) syndromes and a few other less common types of NET including Pheochomocytoma / Paraganglioma(Pheo/Para) and Medullary Thyroid Carcinoma (MTC) (the familial version of MTC is often referred to as FMTC). However, please note this does not mean that all those diagnosed with pancreatic, parathyroid, pituitary, Pheo/Para and MTC tumours, will have any hereditary or genetic conditions, many will simply be sporadic tumors.
7. Will you be able to get rid of all my disease?
This is a really difficult question for any specialist, even a Neuroendocrine expert. All published articles on NETs will say they are a heterogeneous collection of diseases (i.e. consisting of dissimilar entities) which makes this question (and others) difficult. I have read articles written by the world’s foremost NET experts and they all have the word ‘curative’ mentioned in various places. So I guess in particular scenarios with certain NETs, and if the disease is caught early enough, that possibility exists. However, for many, the disease could be incurable, particularly where there is distant metastasis. But, the disease has many treatment options for most types and for many it is possible to live as if it were a chronic condition. I call it ‘incurable but treatable’. Read more here – Incurable vs Terminal
8. What Surveillance will I be placed under?
Again, this is very individual in NETs and is mainly dependent on type of NET, grade and stage and how the patients reacts to treatment. This may not be known until you have undergone your initial treatment. For example, surveillance scans can be any period from 3 months to 3 years depending on tumour type(location) and stage/grade. Marker testing tends to average around 6 monthly but could be more or less frequently depending on what’s going on. Read more here – click here
9. Will I receive support and specialist advice after my treatment?
Let’s not be afraid of the word ‘Palliative’, it does not always mean ‘end of life’ care. Another example is nutrition. Many people with NETs, the condition in combination with the side effects of treatment may necessitate an alteration of diet and this is a very individual area. I would also emphasise that dietitians not well versed in NETs might not offer the optimum advice. Read more – My Nutrition Series.
10. How will treatment affect my daily life?
This is a question that many people miss but it’s becoming more important as we all live longer with cancer Again, this may not be possible to answer immediately but perhaps this question could be reserved once you know which treatment(s) you will be receiving. All treatment comes with side effects and can last for some time or even present with late effects after some years. The ‘consequences’ of cancer treatment need to be factored in earlier so that the necessary knowledge and support can be put in place. See also Unmet Needs for NET Patients
I suspect others will have suggestions for this list so feel free to submit these to me. I quite often refresh my posts over time.
Cabozantinib is an oral drug which works by blocking the growth of new blood vessels that feed a tumour. In addition to blocking the formation of new blood cells in tumours, Cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other “anti-angiogenic” drugs. It is a type of drug called a growth blocker. Cabozantinib has been studied or is already in research studies as a possible treatment for various types of cancer, including prostate cancer, ovarian cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer. During my research, I found that it has a connection to Medullary Thyroid Cancer (MTC) which is a type of Neuroendocrine Cancer, frequently associated with Multiple Endocrine Neoplasia (MEN). Cabozantinib, under the brand name of ‘Cometriq’ was approved by the FDA in 2012 for use in MTC. Read more about Cometriq here. It’s also been approved by the FDA for advanced renal cell carcinoma (RCC) (branded as Cabometyx). I also discovered that there is an exclusive licensing Agreement with the manufacturers (Elelixis) and Ipsen (of Lanreotide fame) to commercialize and develop Cabozantinib in regions outside the United States, Canada and Japan
Growth blockers are a type of biological therapy and include tyrosine kinase inhibitors, proteasome inhibitors, mTOR inhibitors, PI3K inhibitors, histone deacetylase inhibitors and hedgehog pathway blockers. Cabozantinib is a tyrosine kinase inhibitor (TKI). They block chemical messengers (enzymes) called tyrosine kinases. Tyrosine kinases help to send growth signals in cells so blocking them stop the cell growing and dividing. Some TKIs can block more than one tyrosine kinase and these are known as multi-TKIs.
So Capozantinib is a tyrosine kinase inhibitor and is therefore a biological therapy and growth blocker just like Everolimus (Afinitor) and Sunitinib (Sutent) – some texts describe thelattero two as chemotherapy but this is just not accurate.
Very technical process but in the simplest of terms, Cabozantinib is designed to disrupt the actions of VEGF (a growth factor) and MET (a growth factor receptor) which promote spread of cancerous cells through the growth of new blood vessels. Whilst we are on this subject, please note Everolimus (Afinitor) is an mTOR inhibitor and Sunitinib (Sutent) is a tyrosine kinase inhibitor. Many people think these drugs are a type of chemo – that is incorrect, these are targeted biological therapies. See more on this by clicking here.
What is the current trial status of Capozantinib?
A Phase III trial is now recruiting entitled “Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery”.
The trial has 172 locations across the US (see link below). The primary study (final data) is scheduled Jan 1st 2021.
A funded piece of research by the NET Research Foundation – check it out here – looks like they are trying to figure out what patients might benefit from Cabozantinib using biomarker data to predict response.
BOSTON — Cabozantinib (Cabometyx) may benefit patients with malignant pheochromocytomas and paragangliomas, according to results of a phase II trial presented here.
Patients receiving cabozantinib (Cometriq) treatment experienced notable tumor shrinkage in the lymph nodes, liver, and lung metastases, according to Camilo Jimenez, MD, of the MD Anderson Cancer Center in Houston, and colleagues.
Additionally, progression-free survival significantly increased after treated to 12.1 months (range 0.9-28) compared with just 3.2 months prior to treatment, they reported at the American Association of Clinical Endocrinologists (AACE) annual meeting.
Cabozantinib treatment was also tied to an improvement in blood pressure and performance status, as well as remission of diabetes among these patients.
“Malignant pheochromocytomas and paragangliomas are frequently characterized by an excessive secretion of catecholamines. [Patients] have a large tumor burden and they have a decreased overall survival,” explained Jimenez. “Tumors are frequently very vascular and frequently associated with bone metastases. In fact, up to 20% of patients who have malignancy of pheochromocytomas and paragangliomas may have predominant bone metastases.”
He added that “an interesting aspect of this tumor is that C-MET receptor mutation have been found in occasional patients with malignant pheochromocytomas and paragangliomas.”
Cabozantinib is an anti-angiogenic tyrosine kinase inhibitor, which also targets RET, MET, and AXL. It is approved for metastatic medullary thyroid cancer, and was more recently approved for first-line treatment of advanced renal cell carcinoma.
“MET pathway is also involved in the development of bone metastases. In fact, cabozantinib is a very effective medications for patients who have bone metastases in the context of cancer of different origins,” Jimenez said.
In order to be eligible for the trial, patients with confirmed pheochromocytoma or paraganglioma had to be ineligible for curative surgery, have ≥3 months life expectancy, no risk for perforation or fistula, and adequate organ functioning. Prior to cabozantinib initiation, patients could not receive chemotherapy or biologic agents within 6 weeks, radiation within 4 weeks, or MIBG within 6 months.
Following histological confirmation of disease progression >1 year according to RECIST 1.1, the trial included 14 patients with measurable disease and eight patients with predominant/exclusive bone metastases. Fifteen patients subsequently enrolled into the trial, six of whom had germline mutations of the SDHB gene.
All participants were all started at an initial daily dose of 60 mg of cabozantinib, which was subsequently reduced down to between 40 to 20 mg due to toxicity in 13 patients based on tolerance.
The majority of these patients with measurable disease experienced some level of disease response. Six patients reported a partial response, defined as over a 30% reduction, while three patients achieved moderate response, marked by a 15%-30% reduction. Five of the patients with predominant bone metastases reported disease stabilization, according to results of an FDG-PET scan. One patient experienced disease progression while on treatment.
Overall, cabozantinib was generally well-tolerated without any grade 4 or 5 treatment-related adverse events reported. Some of the most common adverse events reported included grade mild dysgeusia, hand and foot syndrome, mucositis, fatigue, weight loss, and hypertension, according to the authors.
Primary Source – American Association of Clinical Endocrinologists meeting – AACE 2018; Abstract 142. attended my Medscape writers
I generated this blog article to add value rather than just post the outputs for your own perusal. I hope you find it useful.
Please note that taking part in a clinical trial is a big decision and must be considered carefully in conjunction with your specialists if necessary. This article is not suggesting this trial is right for you. Please check the inclusion and exclusion criteria in the trials document carefully. (Pheo/Para patients see other clinical trial link above)
OPINION – nothing in here should be taken as advice from the author.
On paper, surgery remains the only potentially ‘curative‘ option for Neuroendocrine Tumours (NETs) but there are stage, grade and anatomical constraints to that opinion. Many people get ‘twitchy’ about any inference of the ‘C word’ (cure) but our most eminent NET specialists use the term frequently including in the major treatment guidelines.
I use the word ‘curative’ with some reservations because for many who are diagnosed at an advanced stage, surgery will not cure but will debulk or cytoreduce as much tumour as possible in order to palliate symptoms and improve quality of life. This is a big deal because NETs is one of a small number of cancers where debulking surgery can often provide a survival advantage for metastatic cases. One of the reasons it’s a big deal is because with more aggressive cancers at an advanced stage, surgery just might not be offered. It follows that surgery is most likely adding to the fairly decent NETs survival statistics, including for those with metastatic disease at diagnosis. More on this below.
That’s a fairly simplistic explanation on behalf of surgery. However, as we all know, nothing in Neuroendocrine Cancer is simple. There are always a number of factors involved and every decision can in some way be on an individual basis. There are guidelines for treatment of most types of NETs but ……. they are just that – guidelines. NET Centres and NET Specialists are encouraged to use these guidelines, for example, a European Centre of Excellence has ENETS Guidelines. There is a North American equivalent set published by NANETS and NCCN have a decent complementary set. The UK and Ireland guys (UKINETS) also published a set although many UK centres are ENETS accredited.
Whether to cut or not to cut (or watch and wait then cut if necessary) and the sequencing of treatments is a really difficult issue for NET specialists. I quite liked watching these two video clips and they cover this issue quite nicely including some interesting abdominal challenges in surgery from known NET Specialists – these short video sessions are highly recommended:
a. Risk Stratification and Management of NETs – click here
Surgery can sometimes be a tough call (……to cut or not to cut?)
It is an area where I have some sympathy for physicians and surgeons who sometimes have tough decisions to make. Surgery is risky, particularly where people are presenting in a weak condition, perhaps with very advanced disease, secondary illness and comorbidities. I also suspect age is a factor (I was surprised to find myself considered ‘young’ at 55). Physicians and surgeons need to weigh up these risks and the consequences of the surgery against a ‘watch and wait’ or alternative non-surgical approach. This would normally be discussed via a ‘Tumor Board’ or Multi-Disciplinary Team (MDT) meeting. However, and although imaging helps, the situation is not really 100% clear until the surgeon ‘gets inside’. Remember, all physicians and surgeons are bound by the ‘Hippocratic oath’ of “Do no harm“. Sometimes with NETs, it’s a tough call not only before they go inside but whilst they’re inside.
Surgery should be a carefully considered treatment (…..think before cutting?)
I read many stories from many different parts of the world and I also hear them from people who contact me privately on a daily basis. Some of them are perplexed why they are not receiving surgery and some are not entirely happy with the surgery they received. Many are perplexed by different advice from different doctors. I find it very difficult to respond to many. My most frequent answer is “ask your doctor” but I’m normally pretty helpful with the sorts of questions to ask.
One thing which tends to surprise people is speed – or lack of it! With lower grade NETs, the extent of the tumour (stage), its metastases, histological grade and secretory profile should be determined as far as possible before planning treatment. I like to remind people that in 2010, it took from 26 July to 9 Nov before my body saw a scalpel. With Grade 1/2 well differentiated NETs, you can often get away with that gap. Sometimes when you are diagnosed with NET, it’s a case of ‘hurry up and wait’.
Back to the guidelines, of course most people will probably fit reasonably well into the relevant guidelines flow chart. A very generic example here (not for active use please, your area may have an alternative based on availability of treatments etc):
If you search long and hard, you will find articles about whether to “cut or not to cut”. Not just a dilemma for NETs but also for many cancer types. During my research, I found there’s some overlap between this conundrum and the issue of “overdiagnosis”. By “overdiagnosis”, I mean the unnecessary declaration and treatment of something which would probably not harm a person whilst they live. This is a bit of a modern phenomena as diagnostic tools and screening programmes become more sophisticated and more sensitive …..something to consider with Ga68 PET scans as they are more widely used. If you search for ‘overdiagnosis’ you will see many articles, in particular (and as an example), with many Thyroid diagnoses. In another example, I read an article about Rectal cancerwhere the author suggested a ‘wait and see’ approach might be better for most. Worth adding at this point that many autopsies show up NETs in areas such as the appendix (…..more often than you think) – check out my article “Benign vs Malignant” and The Invisible NET Patient Population. When I attended ENETS 2017 and 2018, I heard many ‘experts’ talk about conservative approaches. However, I also heard many talk about aggressive approaches. Another term I see a lot is “one surgeon’s inoperable is another’s operable”.
Timing of Surgery (……to cut now, to cut later?)
Following on from the scenario above, timing of surgery can be another factor in a ‘watch and wait’ situation. I guess this might be something in the back of the minds of more cautious doctors when faced with a rather indolent and very slow growing Neuroendocrine Tumour. For some this can be a sensible thing – ‘kicking butt’ in a surgical context is sometimes the wrong approach. The worry is that if they are not a NET specialist, they may not fully understand the vagaries of neuroendocrine tumor behaviour (i.e. they all have malignant potential – WHO 2010/2017). We’ve all heard the stories of people being told it’s not cancer, right? Please note my article Benign vs Malignant. However, you may be interested in this post from someone who is one of the most experienced NET surgeons on the planet. Dr Eric Liu talks quite candidly about the ‘timing’ of surgery suggesting a ‘watch and wait’ approach in certain scenarios.
Of course cutting now might actually be a pre-emptive measure. For example, if physicians can see a growth which is critically placed close to an important structure such as a blood vessel or the bile duct or bowel. Even if the disease cannot be cured, removing the tumour may prevent problems in the future by removing disease from key areas before the vital structure has been damaged or blocked. For example, my surgeon conducted a high risk operation on some desmoplasia (serotonin fibrosis) which had encircled my aorta and cava almost occluding the latter. There’s an excellent surgery pamphlet from NET Patient Foundation and I strongly recommend a read as it’s an experienced surgeon’s approach to surgery with NETs (actually written by my own surgeon Mr Neil Pearce!). Click here to read it.
One NET centre in USA has published very detailed surgical statistics indicating that surgical cytoreduction in NET patients has low morbidity and mortality rates and results in prolonged survival. Their conclusion went on to say “We believe that surgical cytoreduction should play a major role in the care of patients with NETs”. You can read the extract from this document by clicking here. Authors: Woltering et al.
Was Steve Jobsa smart guy who made a stupid decision when it came to his health? It might seem so, from the broad outlines of what he did in 2003 when a CT scan and other tests found a cancerous tumour in his pancreas. Doctors urged him to have an operation to remove the tumour, but Mr. Jobs put it off and instead tried a vegan diet, juices, herbs, acupuncture and other alternative remedies. Nine months later, the Neuroendocrine Tumour had grown. Only then did he agree to surgery, during which his doctors found the cancer had spread to his liver. The rest is summarised in my article Steve Jobs.
This is a difficult subject and no one size fits all. Treatment for NETs can be very individual including surgery. I guess you need to be comfortable with your team. I was lucky, in that I lived close to a NET Centre. I was referred to their surgical team once my staging and grading were complete and I was stabilised on somatostatin analogues (carcinoid syndrome under control). I realise it’s difficult for many but I always say to people who make contact, it’s best if you can be seen by a NET centre or an experienced NET specialist – at least be guided by one if not possible or practical. Personally, I think the surgeon’s experience in dealing with NETs is really important. But even experienced NET centres/specialists have to make tough calls.
You may benefit from my 10 Questions article which also has links to NET Specialists.
There’s a constant debate regarding the validity of the term ‘Carcinoid‘. I’ve posted about this a few times and as far as I know, the debate has been raging for some years.
You may have noticed that ‘Carcinoid’ is often used as a standalone word and tends not to be suffixed with the word ‘Cancer’ or ‘Tumour’ – unlike Bowel Cancer, Breast Cancer, Prostrate Cancer, Lung Cancer, Brain Tumour, etc. Nobody goes around saying “Breast” or “Bowel” do they? But they happily say “Carcinoid”. Unfortunately, the term ‘Carcinoid’ has become entrenched in both pathology and clinical literature over the past 100 years. The main problem with the word Carcinoid is that it means different things to different people. Some use the term almost exclusively to designate serotonin-producing tumours that arise from the enterochromaffin cells that can result in carcinoid syndrome i.e. most commonly in the appendix, small intestine, stomach, lung, rectum and uncommonly in other places. Some use it to (incorrectly) refer to all Neuroendocrine Tumours. The most worrying connotation of the use of the word ‘Carcinoid’ is the belief that they all have benign clinical and biological behaviour. That is dangerous thinking and has the potential to kill people. Fortunately, NET specialists are starting to move away from using the word – check out the quote below:
The following history of ‘Carcinoid’ is well documented: Siegfried Oberndorfer (1876-1944) became the first to adequately characterise the nature of Carcinoid tumours and refer to them as “benign carcinomas.” During his tenure at the Pathological Institute of the University of Munich, Oberndorfer noted in 1907 that the lesions were distinct clinical entities and named them “karzinoide” (“carcinoma-like“), emphasizing in particular their benign features. However, In 1929 he amended his classification to include the possibility that these small tumours could be malignant and also metastasise. (Author’s note – a name change would have been handy at this point).
100 years later
NANETS, UKINETS and ENETS seem to defer to the WHO classification nomenclature and it is here another term is introduced – Neuroendocrine Neoplasms (NENs). NANETs state that “all of the entities under discussion are neoplastic, and neoplasm is therefore a more accurate term than tumor, which means only a mass“. These organisations tend to use the term Neoplasm as a catch-all for all Neuroendocrine disease and then the term ‘tumor’ and ‘carcinoma’ applies to well and poorly differentiated respectively. It’s worth noting that since 2010, the WHO classification 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. Neuroendocrine Carcinoma is malignant by defintion. All of this has been reinforced in the 2017 publication. The term ‘Carcinoid’ is conspicuously missing from these texts.
To put it simply – the term ‘carcinoid’ is no longer credible
Due to its historical meaning, Carcinoid does not adequately convey the potential for malignant behaviour that accompanies many of these neoplasms as described above. The term Carcinoid decodes to ‘Carcinoma like’. Contextually “Carcinoid Cancer” decodes to “carcinoma like cancer” which is, of course, totally misleading and its use simply perpetuates the claim by some that it is ‘not a proper cancer’. If we only needed one reason to ditch the word ‘Carcinoid’, this would be it.
I mentioned confusion above and this has led to a hybrid effect of naming the condition. For example, there is a tendency by some (including medical establishments and patient organisations) to use the term ‘Carcinoid’ and ‘Neuroendocrine Tumors’ interchangeably which is patently incorrect. Neither is it helpful that many patients and organisations continue to refer to this disease as “Carcinoid Neuroendocrine Tumor”, “Neuroendocrine Carcinoid Tumor”, “Neuroendocrine Carcinoid Cancer”, “Carcinoid/Neuroendocrine”, “CNET”; and many other variations along these lines. Many seemingly credible organisations will say “Carcinoid and Neuroendocrine Tumors” not realising it’s a contradiction in terms. Continued use of the term in any phrase or standalone context is not doing our case for recognition any good – it’s bad enough that some seem to cling to outdated and invalid diagnostic clichés and icons from the 1980s. All of it needs to go.
I know I’m not alone in this thinking given the decrease of its use in the NET world, including NET Specialists (see lead graphic) and NET Specialist organisations (some have changed their names). There’s an interesting article written by a NET specialist where the term ‘carcinoid’ is described as “unfortunate”, “misleading”, “outmoded”, “archaic”, “confusing” and “misnomer”. Exactly! In the recent SEER NET study, a NET specialist reaffirmed this thinking by stating that “the belief these tumors did not metastasize, did not reach any great size, and appeared harmless, has since been proven false”. Continued use of the term ‘Carcinoid’ has the potential to regress this thinking. We must not let this happen.
So what terms should we be using?
People and organisations will be out of date with modern Neuroendocrine Neoplasms nomenclature and some will still want to continue with their own nomenclature (….. and because of the confusion, some will fall into both categories not realising they’re out of date). Here’s a classic example of the problem we face – the American Cancer Society(ACS) does not even list Neuroendocrine Tumor as a cancer type. Instead you can find “Gastrointestinal Carcinoid Tumors” and “Lung Carcinoid Tumor”. You’ll find Pancreatic NETs inside Pancreatic Cancer. Americans should harangue the ACS to get this right. I could go on with many similar observations on seemingly respectable sites. I intentionally used a US example as this country appears to be way behind in the changes to NET nomenclature, pretty surprising as they tend to be at the forefront of many other aspects in the world of NETs.
Personally, I think the acceptance of a common worldwide nomenclature should come from the World Health Organisation (WHO) classification for Neuroendocrine Neoplasms. They are divided into a number of chapters including ‘Endocrine Organs’, Digestive System, Lung Tumours….. and no doubt some others. Frustrating, but medical people tend to look at things in anatomical terms. Nonetheless, the agreed classification nomenclature for the whole group of Neuroendocrine Neoplasms can be found with some research and access to clinical publications. The correct nomenclature should then be flowed down in regional groupings, e.g. ENETS representing Europe, NANETS representing North America, etc. As I understand it, ENETS and UKINETS are already essentially aligned with WHO and NANETS appears to be. From these organisations, the use of the correct terminology should then rub off on patients, patient advocate organisations and general cancer sites. However, the biggest challenge will be with hospitals/medical centres, cancer registries and insurance companies whose medical record processing is run using reference data (think drop down selections and database structures). Easier said than done but ‘change’ always has to start somewhere. Technically it has started (albeit late) as the big NET medical organisations are already starting to reduce the use of outmoded words such as ‘carcinoid’.
I once argued that the term ‘carcinoid’ needed to be retained as it represented a histopathological grouping of a particular type of NET comprising mostly appendiceal, stomach (gastric), rectal, small intestine and lung NETs. However, reading through the ENETS 2016 guidance in conjunction with the most up to date WHO classification publications, I’ve changed my mind after noticing they no longer use the word ‘Carcinoid’ in relation to a tumor type. Rather, they use the latest WHO terms above and then use the anatomy to distinguish the different types of NET (like we already do for Pancreatic NET or pNET).
Perhaps patients can lead the way here ………
Rather than say:
‘Carcinoid’ or ‘Carcinoid Tumor’….. why not say Neuroendocrine Tumor or NET (adding your primary location if required – see below);
‘Carcinoid Cancer; ….. why not say Neuroendocrine Cancer;
‘Lung Carcinoid’ ….. why not say Lung NET (adding typical or atypical if required);
‘Small intestine Carcinoid’, why not say Small Intestine NET (or ‘SiNET which is becoming popular); p.s. I’m not a fan of ‘small bowel’ due to the potential for confusion with the widely used term ‘bowel cancer’);
‘Gastric Carcinoid’, why not say Gastric NET (adding your type if required);
‘Rectal Carcinoid’, why not say Rectal NET;
‘Appendiceal Carcinoid’, why not say Appendiceal NET;
…. and so on. And you can add your stage and grade/differentiation for a richer picture.
You can listen to a very well known NET Specialist say something similar in this videohere.
Worth noting that even ENETS and NANETS cannot agree on tumor type terminology – the latter uses Small Bowel NETs (SBNETs) whereas ENETS uses Small Intestine NENs (SiNENs). I did say it’s easier said than done.
As I said above, the term ‘Carcinoid’ has become entrenched in both pathology and clinical literature over the past 100 years so it will still appear in many texts and need to be searchable online to support medical and advocacy business. However, these are technical issues and I don’t therefore believe people need to use the terms to make them searchable online. I tag all my posts with ‘Carcinoid’ even if I don’t mention the word in my text. I have started only using the term for context when it is required and am currently reviewing all of my posts to ensure that is still the case.
Hang on…what about Carcinoid Syndrome
When someone wants to know which syndrome you have, you can’t just state (say) “small intestine syndrome” or “midgut syndrome”. ‘NET Syndrome’ doesn’t work either as there are several NET syndromes. This has led to the situation where people try to drop the word ‘carcinoid’ and just say “the syndrome” which is even more confusing! I accept this one is a difficult challenge but I don’t believe it’s insurmountable, just needs some willpower and agreement. I could come up with other terms in about 5 minutes.
What about Carcinoid Heart Disease
Personally I don’t see why this cannot be renamed to ‘Neuroendocrine Heart Disease’ or its technical name – ‘Hedinger syndrome’.
What about Carcinoid Crisis
World renowned NET specialists already make statements that these issues can apply to all types of NET; and it’s well-known that a similar crisis situation already applies to other types e.g. Pheochromocytomas.I cannot see why something along the lines of ‘Neuroendocrine Crisis’ or ‘NET Crisis’ would not be acceptable.
We as patients are unlikely to be able to force changes on the medical and insurance communities but we can be a ‘force for change’ by setting the example of using a correct and more apt terminology to describe our disease.
Thanks for listening
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