I campaign hard for Neuroendocrine Cancer awareness including continually pointing out that a Neuroendocrine Cancer with a pancreatic primary is NOT Pancreatic Cancer as is often quoted in the press. The two main reasons I take up these campaigns are as follows:
1. They are totally different cancers despite an anatomical relationship. Although they share some similar presentation, they have different signs, different treatments and vastly different prognostic outcomes. What that means is that anyone who is looking for useful information on either needs to be very careful on interpretation, they could end up with very bad advice and in some situations, become more concerned than they should be (particularly with the prognostics). See more below.
2. These two different cancer types have different awareness organisations, patient support groups and patient leaders/advocates. In most cases, vastly different awareness messages. Both of these organisations and advocates need all the help they can get, they need all the resources and funding they can get.
Both Pancreatic Cancer and Neuroendocrine Cancer are diseases that need maximum publicity, both types of cancer have their own unique situations, thus why the awareness messages can be so vastly different. It’s really important, therefore, that publicity surrounding famous patients be attributed to the correct cancer type in order that the advocate organisations and supporters can gain maximum benefit to forward their causes. Unfortunately, thanks to doctors and media, this very often doesn’t work out in favour of Neuroendocrine Cancer due to the Human Anatomy of Neuroendocrine Cancer (this problem actually goes beyond the pancreas).
Where the press and doctors regularly get it wrong
Two famous people in particular, one in 2011 and the other this year, are regularly reported in the press as having died of Pancreatic Cancer.
Steve Jobs. One of the most famous technical innovators of his time and creator of the most valuable company in the world. He had a Neuroendocrine Cancer with a pancreatic primary. Read his story here.
Aretha Franklin. One of the most famous soul singers of her time. She had a Neuroendocrine Cancer with a pancreatic primary. Read her story here.
For me, one of the two main differences are the cell type. When people talk about Pancreatic Cancer, they really mean something known as “Pancreatic Adenocarcinoma”. It starts in the exocrine cells, which produce enzymes to support digestion. Neuroendocrine Tumors start in the endocrine cells which produce hormones.
For me, the other big difference is prognostics. Unfortunately, it is statistically proven that most people with Pancreatic Adenocarcinoma will die, whereas most people with Neuroendocrine Tumors with a pancreatic primary will live.
For a more detailed comparison, see this excellent article from NET Research Foundation.
Pancreatic Cancer – Why I support their campaigns
Personally speaking, as a healthcare advocate online, I do support many cancer awareness campaigns, I think this is important to get similar help coming the other way (this frequently works for me). However, I very much suspect, other than Neuroendocrine Cancer, my biggest support area online is for Pancreatic Cancer and other “less survivable” cancers. I’m drawn by their excellent campaigns where they focus on key messages of prognostics for what is essentially a silent disease (in many ways the same issue with Neuroendocrine Cancer) and they make these more compelling by focusing on people rather than gimmicks. The prognostics can be upsetting reading as they are quite shocking figures which have not changed much in the past 40 years, a key sign that more must be done for this awful disease. I frequently share this symptom graphic below because it might save a life and I ask that you do too.
Often though, the patients with a Neuroendocrine Cancer (pancreatic primary) are drawn to getting support from Pancreatic Cancer organisations. I suspect this is a combination of their own perceptions, their doctor’s language in describing their cancer type, and even something as simple as it was the first place they found help and support and they stick with that organisation. You may also be interested in my article “I wish I had another cancer” – click here.
Cancer is a growth industry …literally! More people are being diagnosed than ever before. Fortunately, more people are surviving than ever before. This is against a backdrop of better awareness, better screening in the big population cancers, and to a certain extent better diagnostic tools, all of which is leading to earlier diagnosis.
So how does this affect Neuroendocrine Cancer?
According to the latest SEER database figures for Neuroendocrine Cancer, one reason for the 7 fold increase in incidence rates since the 1970s is all of those things above including better diagnostics. This has led to a revised set of epidemiological information in many countries that have made the effort to accurately update their cancer registries and there are consistent reports of incidence rates way beyond the recognised rare thresholds. Another piece of good news is that the increase in NET incidence is also due to earlier diagnosis. To sum that up – NETs is also a growth industry.
Combined with more awareness and education (including the important pathologists), more NETs than ever are being found, and many found earlier. However, it’s not party time yet because there remains far too many misdiagnoses due to the low population of the disease and the difficulty in diagnosing it. I want to focus on scanning (thus the title of the article). Whilst there are really important factors involved in a diagnosis, such as tumor and hormone markers, and biopsies (tissue is the issue), a scan is very frequently what triggers many deeper investigations to unearth a NET, i.e. if you can see it, you can normally detect it (whatever the ‘it’ is). And I include the widespread availability and increasing advances in endoscopy/ultrasounds/cameras which have also been instrumental in picking up many Gastrointestinal NETs.
The Gallium 68 PET Scan
There’s a lot of excitement about the Gallium 68 PET Scan since it was approved by the US FDA. It’s not new though and has been in use in several countries for some time. It’s a ‘nuclear scan’ and can often form part of what is known as a ‘Theranostic Pair’ (i.e. in conjunction with a therapy – read more here).
What does it do?
It comprises two main components – a PET scanning machine, and the use of a diagnostic imaging agent which is injected into the person undergoing the scan. Most machines have an inbuilt CT which forms part of the scan. The agent is a somatostatin analogue labeled radionuclide (Gallium 68) and basically the PET will then be used to see where the peptide/radionuclide mix ‘loiters’ (i.e. where there are concentrations of somatostatin receptors (SSTR) normally indicating ‘focal intense abnormality‘ of the type that is regularly found with NETs.
Imaging Agents. There are different agent variants, namely, DOTATATE, DOTATOC and DOTANOC. In USA, you may sometimes see this referred as NETSPOT which is more of a commercial label for the agent (NETSPOT is a DOTATATE). Ga68 PET or SSTR PET are common descriptors for the entire process regardless of the compound. Clearly the scan works best for those with ‘somatostatin receptor positive’ tumours.
These newer agents have several benefits over the elderly In111-pentetreotide (Octreotide scan), including improved detection sensitivity, improved patient convenience due to the 2-3 hour length of the study (compared to 2 or 3 days with Octreoscan), decreased radiation dose, decreased biliary excretion due to earlier imaging after radiotracer administration, and the ability to quantify uptake. The quantification of the uptake can help decide whether a patient is suitable for radionuclide therapy such as PRRT. Eventually, all Octreotide scans should be replaced with SSTR PET but it will take some time (and money).
To confirm the advantages of SSTR PET over Octreotide scans, a study comprising 1,561 patients reported a change in tumour management occurred in over a third of patients after SSTR PET/CT even when performed after an Octreotide scan. Worth pointing out that SSTR PET is replacing the ageing Octreotide scan and not conventional imaging (CI). You can see the recommended scenarios for use of SSTR PET in this article published by the Journal of Nuclear Medicine. The slide below is interesting, although it was a small study. However, you can see the treatment changes as a result of a Ga68 PET are quite striking.
Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors
I see many people complaining because the cannot get access to a Ga68 PET which is available through their healthcare system or local hospital. Many of these issues are insurance based. Worth pointing out that there are actually recommended usages for the Ga68 PET scan here. For example, it is not recommended for routine surveillance in place of Conventional Imaging (CI).
Any pitfalls with Ga68 PET Scan?
When you look at the study data above, it looks like an excellent addition to the diagnostic and surveillance toolkit for NETs. However, one of the challenges with modern scanning equipment and techniques is the ability to correctly interpret the results – in my opinion, this is almost as important as the efficiency of the machines and radionuclides. This requirement has been acknowledged in many articles and I particularly like this technical paper from a very experienced nuclear medicine physician Professor Michael Hofman from the Centre for Cancer Imaging at the Peter MacCallum Cancer in Melbourne. I had a chat with Professor Hofman who added that this is a very sensitive scan, so often picks up “new” disease, which isn’t really new, just never identifiable on standard imaging. However, there’s an excellent section on pitfalls in interpretation and I’m quoting an abstract below.
“Although GaTate PET/CT is a highly sensitive and specific technique for NETs, the attending physician or radiologist must be aware of various physiologic and other pathologic processes in which cellular expression of SSTR can result in interpretative error. Most of these processes demonstrate low-intensity and/or nonfocal uptake, in contrast with the focal intense abnormality encountered in NETs. Causes of interpretative pitfalls include prominent pancreatic uncinate process activity, inflammation, osteoblastic activity (degenerative bone disease, fracture, vertebral hemangioma), splenunculi or splenosis, and benign meningioma.”
“The highest-intensity physiologic uptake of GaTate is seen in the spleen, followed by the adrenal glands, kidneys, and pituitary gland”
It follows that failure to interpret nuclear scans alongside the patient’s clinical history can sometimes result in two big issues for patients:
1. Unnecessary worry when ‘something’ shows up which is actually a false positive.
2. Something which leads to irreversible treatment when it is was not required.
Just imagine something which is 40 times better than current PET scan technology? That’s what the scientists are working on now. Here’s an example called “EXPLORER“. You can update yourself here. The issue of interpretation will be even more difficult when the new generation of scans appear. There’s an excellent article from Cancer Research UK talking about the modern phenomenon called ‘overdiagnosis’ – readhere
Lanreotide and Octreotide and timing the scan?
From the same technical document referred above, here’s an extract (updated to include Lanreotide). “Uptake at physiologic and pathologic sites may change in patients who undergo concomitant short- or long-acting somatostatin analog therapy, which competes with the radiotracer for bioavailability. We generally discontinue short-acting octreotide for 12–24 hours and perform imaging in the week before the next dose of long-acting Octreotide/*Lanreotide, which is typically administered monthly“. It’s actually the same text as found in the manufacturer’s drug leaflet (click here). More evidence behind the reason for this restriction is found here (please refer to the comments on Ga68 PET – the article also covers the issue of PRRT which is very interesting as a separate subject to the scan timings).
*added by the author for completeness.
Having my first Ga68 PET Scan after 8 years of living with NETs?
When I was offered my very first Ga68 PET/CT at my recent 6 monthly surveillance meeting, I was both excited and apprehensive. I was diagnosed in 2010 and my staging was confirmed via an Octreotide Scan pointing out two further deposits (one of which has since been dealt with). I’ve had two further Octreotide Scans in 2011 and 2013 following 3 surgeries. The third scan in 2013 highlighted my thyroid lesion – still under a watch and wait regime. So far, my 6 monthly CT scans seemed to be adequate surveillance cover and my markers remain normal.
I’m apprehensive because of the ‘unknown’ factor with cancer – what is there lurking in my body that no-one knows about and which might never harm me.
I’m excited because it might just confirm that there is nothing new to worry about.
However, I’m both excited (morbidly) and apprehensive because the scan might find something potentially dangerous. As we know, NETs are mostly slow growing but always sneaky. That said, at least I will know and my medical team will know and be able to assess the risk and decide on a course of action.
Doing the Scan
On 5th June 2018, I attended a very experienced Ga68 PET establishment called Guys Cancer Centre in London. I arrived and was immediately taken under the wing of the nuclear medicine guys who asked me fairly in depth questions about my clinical background. They then inserted a cannula ready for the injection of the radiolabelled tracer. I was then installed in the ‘hot room’ where they injected the radionuclide tracer through the cannula and then I had to remain in the hot room for 1 hour to let the tracer circulate. After 1 hour, I was taken to the PET scanner and it took around 30-35 minutes. Following that I was allowed to leave for home. It was an extremely easy experience and a significant improvement on doing the 3 day Octreotide scan.
OPINION. When you’re diagnosed, you go through a whole host of emotions. It’s not just the initial shock, the disbelief, the anxiety and morbid worry produced by the words “you have cancer”, it’s other stuff such as anger and denial. With the latter, the denial normally wears off as you finally accept the predicament.
In hindsight, the anger is interesting because there can be a mixture of thoughts including “why me“, “what could I have done to head this off“; and would you believe I was even angry that my diagnosis was going to affect my performance at work and even my personal credibility. We all react differently but in general terms our experiences can be categorised into 3 main areas: initial reaction, distress and then adjustment.
Initially, I was frustrated I didn’t know what had caused my cancer, perhaps my thinking was that I could warn others. Those feelings soon wore off as I discovered that no-one really knows why people succumb to certain cancers.
If you don’t know what caused your NET, you’re not alone. According to several studies in the past 10 years, around 40% of cancers are preventable indicating that up to 60% might just be plain bad luck. Clearly this figure varies between cancer types with the biggest culprits being Lung and Skin cancer with too much exposure to tobacco and ultraviolet light respectively. However, the reports also pointed out that people can and will still get these cancers without significant exposure to the commonly preventable causes. The latest study is interesting because it raises the issue that some cancers may be totally unavoidable as they are caused by random errors associated with DNA replication. This study remains controversial because it undermines government prevention strategies. There’s a balanced article from Cancer Research UK which is a useful read (interesting quote … “Even if, as this study suggests, most individual cancer mutations are due to random chance, the researchers admit that the cancers they cause may still be preventable”).
I carried out some research and discovered the only currently known causes of NETs are heredity/genetic in nature and this only affects a small proportion of all NETs. As for the remainder, will we ever know? Perhaps one day but in my opinion, not anytime soon. One interesting find is a studyfunded by NET Research Foundation which is designed to discover the molecular causes of a Small Intestine NET (SiNET). In addition, they will investigate potential environmental causes, including epigenomic and infectious causes.
I often think about what actually caused my NET but I no longer worry about what the answer might be. I’m the first to admit I could have led a healthier life (like many others) but that may not have had any impact or involvement in my cancer diagnosis. There doesn’t seem to be any point worrying because the clock cannot be turned back …..even if I knew, I would still have metastatic NETs. However, if the cause of my cancer was connected to a heredity condition, clearly this would be important to know. That’s only my own opinion though.