In this cross-sectional study evaluating 145,477 NEN cases in the US, age-adjusted incidence rates increased 5.2-fold between 1975 and 2021, with an annual percentage change of 3% between 2000 and 2020, and the 20-year limited duration prevalence projected in the US population on January 1, 2021, was 243 896. Survival for all NENs improved, including for patients with distant-stage gastrointestinal and pancreatic NENs. And even this figure is understated as they have excluded some Neuroendocrine Carcinomas from the list adding to the known registry issues which must still need some work. Worth noting that although the data was published in 2025, the period covered was completed in 2021, meaning another 4 years of diagnoses has since passed – it must be assumed the figures are now even higher.
Click here to read more
🧠 Important Nuance: Subtypes May Still Qualify
Despite the overall prevalence exceeding the US Orphan Disese threshold, many NET subtypes may still benefit from Orphan Drug Designation but this would need to be agreed by FDA and/or other agencies recognising these subtypes; and if the drug manufacturer wants a limited label. As at time of this article, it is not clear that will always be the case. But what remains clear is that the group of tumours known as Neuroendocrine Neoplasms cannot now be considered rare.
The above summary is based on prevalance (how many people living with the disease) but in terms of incidence (how many people diagnosed), this ASCO summary of Gastroenteropancreatic NET (GEPNET) covering the period 2001-2020.
A total of 277,230 individuals (50.5% female) were diagnosed with GEP-NETs over the study period. Of these tumors, 65.4% were in older patients (aged ≥ 55 years).
The most common tumor sites were the anorectum (21.9%), pancreas (16.8%), and stomach (9.9%).The most cases by state were reported in California (10.3%). The highest incidence per 100,000 population by state was in Louisiana (5.44). The highest incidence per 100,000 population by region was in the Northeast (4.31).
Overall, the incidence of GEP-NETs increased during the study period (AAPC = 3.8%), with increases seen in most organs. The greatest increases were observed in the appendix (AAPC = 12.9%), pancreas (8.8%), duodenum (5.0%), jejunum (4.9%), esophagus (4.7%), biliary tract (3.8%), stomach (3.4%), ileum (2.8%), and anorectum (1.2%). Stable trends in AAPC were observed for the cecum, liver, and gallbladder, with a decrease observed in the colon (−1.0 %).
The increase in incidence was higher in female patients vs male patients (AAPC = 3.8% vs 3.6%) and in younger vs older adults (AAPC = 5.2% vs 2.7%). Many GEP-NETs (55.4%) were diagnosed as early-stage tumors; a greater increase in incidence was observed in patients with early-stage tumors (AAPC = 5.2%, 95% confidence interval [CI] = 4.5%–5.8%, P < .001) than in late-stage tumors (AAPC = 3.4% 95% CI = 3.1%–3.7%, P < .001).
The investigators concluded: “This study found an overall rising incidence of GEP-NETs across most organs—notably in the appendix, pancreas, and small intestine—[which was] more pronounced in females and younger adults and with early-stage tumors. The colon showed a decreasing incidence trend, whereas the cecum, liver, and gallbladder displayed stable trends.”
And even this figure is understated as they have excluded some Neuroendocrine Carcinomas from the list adding to the known registry issues which must still need some work.
Click here or on the graphic below to read more
I don’t like to gloat, but this post is heading for its 8th birthday. UK and Australian figures recently confirmed that Neuroendocrine Cancer is the 10th and 7th most common cancer type. Several NET specialists in USA have been more vocal (see some graphic quotes below) than the cancer organisations (including the ones who represent us) and disappointingly “carcinoid” use is still rife in that part of the world. Let’s hope they will now get on with moving to the new paradigm I’ve been suggesting for a long time. Read more in the “Meanwhile in USA” section.
Although initially considered rare tumours up until 10 years ago, the most recent data indicates the incidence of Neuroendocrine Neoplasms (NENs) has increased exponentially over the last 4 decades and they are as common as Myeloma, Testicular Cancer, and Hodgkin’s Lymphoma. In terms of prevalence, NENs represent the second most common gastrointestinal malignancy after colorectal cancer. Consequently, many experts are now claiming NENs are not rare (see below).
A recent study published in Dec 2020 indicates that Rectal NETs may be vastly understated having been included in the databases for Colorectal Cancer and hidden from NET figures. Read more here.
A recent study published on 5 Dec 2018 reports that even if you isolate Small Intestine NETs in the USA population, the incidence rate is 9/100,000. Contrast this against the US incidence rate as at 2012 of 7/100,000 for all NETs. The rare threshold in Europe is 5/100,000 and below. They’re not common (in incidence rate terms which means the numbers diagnosed each year) but they are certainly no longer rare, a more accurate description would be ‘uncommon’.
However, on 7th January 2019, an internationally known NET Specialist described NETs as very common but he was talking in terms of the prevalence (how many people are living with the disease)
In fact, the graph of the SEER database figures for NETs in both 2004 and 2012 indicates the rate of incidence increase is faster than any other cancer on the planet, particularly attributed to lung, small intestine, and rectal NETs. The World Health Organisation’s revised classification of Neuroendocrine Neoplasms in 2010, abandoned the division between benign and malignant NET as all NETs have malignant potential and should be graded accordingly. The 2004 SEER data compiled did not take into account what might have been considered to be benign NETs.
However, the most recent USA study up to 2012 has confirmed the incidence beyond 2004 has continued to rise (and rise, and rise, and rise) and this is covered below in the section entitled “Meanwhile in USA”. One of the principal authors of both database studies has now gone public and said NETs are no longer rare.
Worth noting that many data studies preclude a type of Neuroendocrine Carcinoma called Small Cell Lung Cancer (SCLC) which is said to account for 15-20% of all Lung Cancers. This would significantly increase published data figures detailing the incidence and prevalence of Neuroendocrine Neoplasms.
Before I continue, it’s important to understand the difference between incidence and prevalence. In the crudest of terms, incidence is the number of new cases of a disease being diagnosed (normally aligned to a specific quota of the population per year, generally 100,000). Prevalence normally indicates an amount of people living at any one time with a disease. It’s also important to note that different nations or groups of nations classify ‘rare’ in different ways – not really helpful when looking at worldwide statistics.
So why the increase? I suspect the reasons include (but are not limited to), more awareness (population and medical staff), better detection techniques and probably more accurate reporting systems, at least in USA, Norway, Canada and now in the UK i.e. a mixture of underdiagnoses and misreporting. The Canadian study is important as it also noted the proportion of metastases at presentation decreased from 29% to 13%. This is the first study that suggests an increased incidence of NETs may be due to an increased (and earlier?) detection. This has the knock on effect of increasing prevalence as most NET Cancer patients will normally live for longer periods. Add to this the plethora of better treatments available today, you have a highly prevalent cancer. Most of that is good news.
However, their true incidence may be higher owing to the lack of diagnosis until after death. For example, in USA, a respected NET specialist stated that the autopsy find for (excuse the outdated terminology) ‘carcinoid‘ is 4 times the recorded diagnosis rate. In Australia, one study claimed that 0.05% of all autopsies found a Pheochromocytoma or Paraganglioma. A very interesting slideshow from a well respected NET expert claimed there are 200,000 undiagnosed NET patients in USA. Slide below: You may also wish to check out my article “The Invisible NET Patient Population” where this is explored further.
In the largest study of its kind up to that point, well-known Neuroendocrine Cancer expert James C. Yao researched the Surveillance, Epidemiology and End Results (SEER) database. His team studied 35,825 cases of Neuroendocrine Cancers in the United States covering data between 1973 and 2004. The report concluded that in 2004 there were 5.25 new cases of NETs per 100,000 people, compared with 1.09 per 100,000 in 1973 [1]. This is in contrast to the overall incidence of malignancies, which has remained relatively constant since 1992 (see the yellow line on the graph). The study also pointed out that due to increased survival durations over time, NETs are more prevalent than previously reported. If you analyse the NET data for 1994 (10 years before the end of the study period), you will see an incidence rate of approx 3.25/100,000. In 2004, the incidence rate had risen to 5.25/100,000. Although not an exact science, it does suggest the potential incidence rate at 2014 (10 years after the study period) might possibly have climbed well beyond 6/100,000 and even further if the same rate of increase displayed by the study had continued (spoiler alert – it actually came out as 7/100,000 see below under ‘Meanwhile in USA’). This study also confirmed a prevalence of 103,000 NET patients as at 2004. As this is regarded as the most accurate NET statistic ever produced, it is interesting to note that was at a time when the prognostics for NET were not as good as they are today indicating there must be a very significant increase if extrapolated to the current time. Moreover, this was prior to the WHO 2010 reclassification of NETs so more diagnoses will be counted today that were not counted in 2004. See below to see the significance of this figure (see section ‘Do the math’).
The 2004 data was an astonishing set of statistics – particularly as they were based on 12 year old data. However, there is now new data up to 2012 that overtakes the above-mentioned groundbreaking study and confirmed the incidence is now even higher. See section entitled “Meanwhile in USA …….”
Some will claim that some of the individual types of Neuroendocrine Neoplasm are rare, so the disease is rare. That’s clutching at straws really, there’s rare types of breast, prostate, bowel and lung cancer but those diseases are hardly rare. On that subject let’s talk about something no one really seems to want to talk about – Small Cell Lung Cancer (SCLC) which is a type of Neuroendocrine Carcinoma. On its own this type is not rare (around 10-15% of all cancers of the lung). On its own, it would be the most common type of NEN.
A new study in 2022 confirms that Neuroendocrine Neoplasia (NEN), a term which encompasses all Neuroendocrine Carcinomas and Neuroendocrine Tumours, is a “formerly rare cancer“. It also goes on to say “NEN can now no longer be defined as a rare cancer”.
Even these figures are understated because it does not include Lung Neuroendocrine Carcinomas (i.e. SCLC and LCNEC) and Merkel Cell Carcinoma.
This follows an earlier piece of work from Public Health England (PHE) which indicates the incidence of NETs has risen to almost 9/100,000 (i.e. not rare) using the latest International Classification of Diseases for Oncology (ICD-O) methodology. Even that figure is understated because it does not include Lung Neuroendocrine Carcinomas (i.e. SCLC and LCNEC). Note that SCLC (classified as a Neuroendocrine Carcinoma) is the most common type of all Neuroendocrine Cancers.
That means a new diagnosis every 90 minutes hours. You can see a summary of the report by clicking on the graphic below.
A slide from the recent UKINETS 2017 conference indicating an agreement from UK and Ireland NET Specialists.
Did you know Neuroendocrine Cancer is the 7th most common in Australia? And that someone will be diagnosed in Australia with Neuroendocrine cancer every one or two hours?
Read this article here: Little known, complex cancer on the rise | 7NEWS
Australian doctors are on board with the math rather than the myth.
This article appeared in the June 2019 Edition of ePathWay which is an online magazine produced by the Royal College of Pathologists of Australasia (http://www.rcpa.edu.au/Library/Publications/ePathway). In Issue #092 in June 2019 published by the Royal College of Australasia, an interview with top pathologist Professor Anthony Gill said that NETs are uncommon but not rare.
And in 2022, Australia declared that NETs were the 7th most common cancer in that country. Read more here
Norway has a strong record in getting accurate registry data and now claims to have the most up-to-date Neuroendocrine Neoplasm (NEN) registry in the world. It follows that the Norway figures may well be what everyone else is experiencing but their cancer registries fail to output it properly.
In a new study published on 17 March 2023, From 1993 to 2021 altogether 10,288 NETs and 13,982 (1.756 outside the lungs) NECs were diagnosed. The incidence of NETs increased from 3.72 to 9.97 per 100,000 per year, corresponding to a 268% increase. The prevalence (people alive with the condition) for NENs increased 666% during the study period, NETs increased from 10.77 to 99.37 per 100.000 (927%). For NECs the increase was from 7.4 to 21.56 per 100,000 (291%) – you would expect NEC to be lower of course. (Ronny Allan comment – in addition to better cancer registry management, the huge prevalence increase may be reflecting earlier diagnoses, more specialist centres and better treatments).
, . Incidence and prevalence of neuroendocrine neoplasms in Norway 1993–2021. J Neuroendocrinol. 2023;e13264. doi:10.1111/jne.13264
Abstract
“The incidence of neuroendocrine neoplasms (NENs) has increased over the last decades. The prevalence of NENs has to a lesser extent been previously reported. We wanted to study the trends in incidence and prevalence of NEN in Norway from 1993 to 2021 through the Cancer Registry of Norway. This registry, which covers the whole population, has been found to be 99% complete. The neoplasms were classified as neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). From 1993 to 2021 altogether 10.288 NETs and 13,982 (1.756 outside the lungs) NECs were diagnosed. The incidence of NETs increased from 3.72 to 9.97 per 100,000 per year, corresponding to a 268% increase, p < .001. The largest increase in incidence for NETs was found for pancreas (338%), lung (330%) and small intestine (303%). For NECs there was no change in the incidence, from 9.74 to 9.95 per 100,000 per year, p = .4, but there was an increase in the incidence of NECs originating from the skin (Merkel cell carcinoma) (287%), p < .001, and the GI tract (200%), p = .03. There were no changes in stage distribution at diagnosis for NETs and NECs. The prevalence for NENs increased 666% during the study period, NETs increased from 10.77 to 99.37 per 100.000 (927%), p < .001. For NECs the increase was from 7.4 to 21.56 per 100.000 (291%), p < .001. GI-NECs increased the most from 0.005 to 0.94 (1880%), p = .002. In conclusion, there was a substantial increase in incidence and prevalence of neuroendocrine neoplasms in Norway from 1993 to 2021. This is the first study to report complete prevalence of NENs for a whole nation.”
————————————————
The previous update on Norway’s excellent work was presented at ENETS in 2019 – see below:
If we take Norway’s figures, the true NEN incidence rate is almost 3 times the figures most people quote. Interestingly, as pointed out by Dr Thor, the prevalence of small intestine NETs is almost 10 x the incidence rate and almost 17 times the incidence rate for appendiceal NETs.
CNETs have highlighted an article published in the magazine ‘Cancer’, February 15, 2015, showing that the incidence of Neuroendocrine Tumours has markedly increased in Canada over the course of 15 years (1994-2009). The results showed that the incidence of Neuroendocrine Tumours has increased from 2.48 to 5.86 per 100,000 per year. [3] [4]
In this cross-sectional study evaluating 145,477 NEN cases in the US, age-adjusted incidence rates increased 5.2-fold between 1975 and 2021, with an annual percentage change of 3% between 2000 and 2020, and the 20-year limited duration prevalence projected in the US population on January 1, 2021, was 243 896. Survival for all NENs improved, including for patients with distant-stage gastrointestinal and pancreatic NENs.And even this figure is understated as they have excluded some Neuroendocrine Carcinomas from the list adding to the known registry issues which must still need some work. Worth noting that although the data was published in 2025, the period covered was completed in 2021, meaning another 4 years of diagnoses has since passed – it must be assumed the figures are now even higher.
Dasari A, Wallace K, Halperin DM, et al. Epidemiology of Neuroendocrine Neoplasms in the US. JAMA Netw Open. 2025;8(6):e2515798. doi:10.1001/jamanetworkopen.2025.15798
Click here to read more
🧠 Important Nuance: Subtypes Still Qualify
Despite the overall prevalence exceeding the US Orphan Disese threshold, many NET subtypes can still benefit from Orphan Drug Designation. But it remains clear that the group of tumours known as Neuroendocrine Neoplasms cannot now be considered rare.
Analysis from The ASCO Post covering just GEPNETs
The above summary is based on prevalance (how many people living with the disease) but in terms of incidence (how many people diagnosed), this ASCO summary limited to Gastroenteropancreatic NET (GEPNET) covers the period 2001-2020.
UPDATE AS AT 21 JAN 2023 – a leading US cancer organisation accepts that NETs are not rare
I don’t necessarily agree with some of the words used but this is huge progress for USA. What I found most interesting is the claim that calling it rare when it’s not is potentially linked to a lack of research. “As a result of perceived disease rarity and nonmalignant clinical course, NENs have not been subjected to rigorous clinical research, as compared with other similar tumor types”. Read more by clicking here.
Original section of the article continues:
The latest evidence of its rise is contained in the largest ever study ever conducted. It is based on data up to 2012 so it’s worth noting that in 2022, this data is now 10 years old (8 years for the project prevalence figure), so even these figures may still be conservative. The document, which was published in 2017 can be found here: Click here. A short summary follows:
In this population-based study that included 64 971 patients with neuroendocrine tumors, age-adjusted incidence rates increased 6.4-fold between 1973 and 2012, mostly for early-stage tumors. Survival for all neuroendocrine tumors has improved, especially for distant-stage gastrointestinal and pancreatic neuroendocrine tumors.
Of the 64 971 cases of NETs, 34 233 (52.7%) were women. The age-adjusted incidence rate increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000). This increase occurred across all sites, stages, and grades. In the SEER 18 registry grouping (2000-2012), the highest incidence rates were 1.49 per 100 000 in the lung, 3.56 per 100 000 in gastroenteropancreatic sites, and 0.84 per 100 000 in NETs with an unknown primary site. The estimated 20-year limited-duration prevalence of NETs in the United States on January 1, 2014, was 171 321
Conclusion: The incidence and prevalence of NETs have continued to rise in the United States, owing to the increased diagnosis of early-stage disease and possibly stage migration. The survival of patients with NETs has improved, and this improvement has been greater for those with distant gastrointestinal NETs and, in particular, distant pancreatic NETs.
Combine with a revised annual incidence rate of 23,000 and the very well-known fact that NETs are a highly prevalent disease, it must be mathematically impossible for the figure not to be above the USA rare threshold of 200,000 in 2017. As you can see from the graph below, the incidence rate for NETs continues to outstrip the incidence rate for all malignant neoplasms (another word for tumour). Amazingly, the report authors even state “…….. it is likely that we have underestimated their true incidence and prevalence”.
A recent study published on 5 Dec 2018 reports that even if you isolate Small Intestine NETs in the USA population, the incidence rate is 9/100,000. Contrast this with the US incidence rate as of 2012 of 7/100,000 for all NETs (10 years ago as of 2022). They’re not common (in incidence rate terms which means the numbers diagnosed each year) but they are certainly no longer rare, a more accurate description would be ‘uncommon’.
In a study covering the period 2010-2015, the diagnosis rate has doubled. Perhaps influenced by improvements in awareness and diagnostics, it’s still an astonishing increase in a short space and an indication that the true incidence rate has been underestimated and under-reported for some time. Read more here.
I suspect on their own, these types of Neuroendocrine Tumours are rare based on the numbers but things are changing. Check out this short video clip from the Pheo/Para Alliance. Let’s do some maths: Based on the US population of 320,000,000, that’s 106,666.
A few more facts about Pheochromocytoma/Paraganglioma:
It would appear many Rectal NETs are being hidden within colorectal cancer statistics – check out the numbers in here – click.
This is what happens when we classify Neuroendocrine Cancer properly – Recent increase in cancer cases observed among adolescents and young adults (AYAs) in USA may be explained — at least in part — by the reclassification of appendiceal neuroendocrine tumours (NETs) according to research published in the Journal of the National Cancer Institute. Check “Meanwhile in USA” above to see the effect of that on US appendixe NET statistics.
This is important information supporting cancer ethology (the cause, set of causes, or manner of causation of a disease or condition). click here.
Neuroendocrine Cancer is not only the fastest growing cancer in incidence terms but as a group of cancers, given the mounting epidemiological evidence, it can no longer be rare as a grouping of cancers. Neuroendocrine disease IS NOT RARE.
For example, if you roughly extrapolate the US SEER data graph above to 2017 and recalculate the prevalence rate based on 23 000 per year from the 2014 figure of 171 321. Unfortunately, some people will have passed, but it’s well documented as a highly prevalent cancer and therefore more people live. The prevalence of neuroendocrine tumors in USA was higher than the combined estimated prevalence of esophageal cancer (n = 36,857), gastric adenocarcinoma (n = 79,843) and pancreatic adenocarcinoma (n = 49,620) in 2013. In fact, one of the conclusions of the 2012 SEER report is that we are living longer with NETs. This is in line with many other cancers due to improved diagnostic and treatment regimes. Cleary more work still needs doing.
The heading of this section is my name for those who have not yet been diagnosed with NETs but are walking around having been either misdiagnosed, diagnosed with another cancer in the same part of the anatomy, living and putting up with the symptoms whilst the tumours grow. Read my Invisible NET Patient Population article here. To add to this part of the underdiagnoses of NETs is this most amazing piece of research published in 2018 – Pan-cancer molecular classes transcending tumor lineage across 32 cancer types, multiple data platforms, and over 10,000 cases. It was published in the American Association of Cancer Research (AACR) journal ‘Clinical Cancer Research and authored by Chad Creighton et al. D. This was a pan cancer piece of research which indicated that Neuroendocrine disease may be more prevalent than anyone had ever thought. There’s a summary article here which I suggest you read fully. The rather explosive extract is as follows:
Whilst reporting has been improved, it is most likely still not 100% accurate. Therefore, even the figures above may be understated due to an incorrect cause of death reporting and incorrect diagnosis/recording of the wrong cancers (e.g. pNETs recorded as Pancreatic Cancer, Lung NETs recorded as Lung Cancer, etc). This is certainly still happening in UK and I suspect in most other countries. Add to that the regular reports of Neuroendocrine Tumours being found during autopsies and you have the potential for an even further unrecorded increase had these been found prior to death. In fact, according to SEER 2012, the true incidence and prevalence is most likely underestimated. In fact here is a statement straight from the horse’s mouth:
The issue is also complicated by the method used in USA for naming a disease ‘rare’. Rather than use incidence rates, the USA uses the number of people living with the disease at any one time (i.e. essentially the prevalence). This is currently 200,000 as a threshold – anything below that is considered rare. It seems mathematically impossible for NETs to be less than 200,000 given the data provided above.
When I first started researching NETs back in 2010, the US figure (which varies from source to source) was around 125-150,000. Why are people quoting figures less than this in 2017 when the 2014 figure has now been confirmed above? There also seems to be a selective omission of the new US incidence rate of 7/100,000.
You will also see that Dana Farber is estimating more than 200,000 people are as yet undiagnosed. Even if that were 50% accurate, it would put the current prevalence figure in US over 300,000.
Are we shouting loud enough about this? I don’t think so. ‘Rare’ is very frequently used within the NET community almost to the point of being a status symbol. Based on these figures, this looks like an outdated approach along with its associated icons. The evidence above is so compelling that saying the group of cancers officially called Neuroendocrine Neoplasms is rare is starting to sound like fake news.
“A neoplasm on the rise. More prevalent than you may think. Incidence increased dramatically during past 3 decades” (Novartis)
“it’s less rare than we used to think. It’s more malignant than we previously thought” (Dr Richard Warner)
“…..it is one of the most rapidly increasing cancers in the U.S. There has been a 500-percent increase in the last 30 years” (Dr Edward Wolin)
“Estimated more than 200,000 undiagnosed cases in the US” (Dana Farber)
“I actually think NETs are not a rare cancer” (Dr James Yao)
“NETS will no longer be rare” (UKINETS 2017 one of the opening slides)
“NETs are no longer rare” (Dr Andrew Hendifar)
“…..when you think of prevalence, NETs are actually quite common” (Dr Jonathan Strosberg)
“One study showed that the number of people diagnosed has risen 50% over the last decade and unfortunately, I worry that is an underestimate” (Dr Eric Liu)
“Neuroendocrine Cancer – NETs are not rare, just less common. We need a new paradigm” (Ronny Allan since 2015)
“NETs are uncommon but not rare” (Professor Anthony Gill)
You may also wish to check out my article “The Invisible NET Patient Population” where this is explored further.
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.
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Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
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