Clinical Trial: Intra-arterial Lu177 (PRRT) for Neuroendocrine Cancer liver metastases (LUTIA)


PRRT INTRA ARTERIAL

 

The treatment of liver metastasis is a common approach following a metastatic diagnosis or discovery of liver metastasis downstream via re-staging. In addition to surgery, there are several liver directed therapies available via embolization techniques. This comes in several flavours:

1. Bland liver embolization – a minimally invasive technique which simply blocks the blood supply to the liver tumours in an attempt to reduce or kill those tumours. Sometimes called Hepatic Arterial Embolization or HAE.

2. Chemotherapy liver embolization – as above but adds in some cytotoxic chemo to the mix. Sometimes called Trans Arterial Chemo Embolization or TACE.

3. Radioembolization is a minimally invasive procedure that combines embolization and radiation therapy to treat liver cancer. Tiny glass or resin beads filled with the radioactive isotope yttrium Y-90 are placed inside the blood vessels that feed a tumour. Often known as Sirtex or SIR-Spheres.

Of course systemic treatment is body-wide and so includes the liver as a target. Systemic treatment includes (but is not limited to) Lu177 (PRRT), Chemotherapy, Targeted Therapies such as Everolimus (Afinitor) and Sunitinib (Sutent). Also included are somatostatin analogues such as Lanreotide and Octreotide.

Sometimes systemic treatment is not fully effective on all metastases and although PRRT response rates are good, often patients still live with the burden of remnant liver tumours once therapy is finished.

Doctors in the Netherlands are looking at a trial using Lu177 (PRRT) as a liver directed therapy. The trial is based at 3 sites in the Netherlands and is titled: Intra-arterial Lutetium-177-dotatate for Treatment of Patients With Neuro-endocrine Tumor Liver Metastases (LUTIA). You can read more about the trial by clicking here.

I will keep this article open for any updates.

Thanks for reading

Ronny

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Clinical Trial SPARTALIZUMAB – Immunotherapy for Neuroendocrine Neoplasms (PDR001)

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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.  It’s brand name is SPARTLIZUMAB.

How PDR001 works

PDR001 is a type of immunotherapy, meaning that it acts by activating the body’s own immune system to recognize and fight cancer cells. Normally, an immune system cell called T-cells recognizes and kills infected or abnormal cells, including those that are cancerous. To prevent T-cells from accidentally damaging healthy and essential tissues, however several immune system checkpoints exist to inhibit, or block, them from going about this work. One example is the programmed cell death 1 (PD-1) pathway. Healthy cells produce and display a protein called programmed cell death ligand-1 or ligand-2 (PD-L1 or PD-L2) on their surface. These proteins bind to and activate a receptor called PD-1 that is produced by T-cells. When activated, PD-1 sends a message to the T-cells that prevents them from attacking that particular cell. Cancer cells can hijack this system by producing PD-L1 or PD-L2, effectively hiding from T-cells and evade destruction.
PDR001 is an antibody, a protein designed to interact with and block a specific target. It acts by binding to PD-1, blocking it from interacting with both PD-L1 and PD-L2. This binding blocks the PD-1-mediated inactivation of the T-cells, so that they are able to recognize and target cancer cells. This should result in a reduction in tumor growth and size.

PDR001 in clinical trials

PDR001 has been investigated in multiple completed and ongoing clinical trials, both alone and in combination with a wide range of other agents.

Novartis presented results from an ongoing first-in-human Phase 1/2 clinical trial (NCT02404441) of PDR001 at the American Society of Clinical Oncology (ASCO) meeting in 2016. Preliminary trial results suggested that the drug is well-tolerated and safe, with a similar profile to other anti-PD-1 drugs currently being developed. The trial is still recruiting patients with various types of advanced cancer at 43 sites across North America, Europe, and Asia; more information is available by clicking on its identification number.

Novartis then initiated several dozen other Phase 1, 2 and 3 trials, all registered on clinicaltrials.gov, to continue investigating the safety and anti-tumor activity of PDR001 in a wide range of cancer types, and in combination with other investigational and approved therapies. For example, a Phase 3 trial (NCT02967692) is comparing the safety and efficacy of PDR001 to a placebo, in combination with Tafinlar (dabrafenib) and Mekinist (trametinib), as a treatment for advanced melanoma.

What about Neuroendocrine?

A phase 2, multi-center study assessed the efficacy and safety of PDR001 in patients with non-functional well and poorly-differentiated Neuroendocrine Neoplasms.  According to the clinical trial document, the types of NENs covered are:

  • Well-differentiated Non-functional NET of Thoracic Origin
  • Well-differentiated Non-functional NET of Gastrointestinal Origin
  • Well-differentiated Non-functional NET of Pancreatic Origin
  • Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma

The clinical trial indicates the trial is active but not recruiting but it would look like they have all the patients needed and are currently analysing the trial data so far awaiting the next phase perhaps.  In fact I have discovered two pieces of evidence from the trial sponsors:

pdr001 results conclusion
Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293

In another analysis of the results:  “Patients with well-differentiated advanced NETs were eligible if they had progressed on prior therapy, including everolimus, while the GEP-NEC patients were eligible if they had progressed on one line of chemotherapy. All patients in the trial received spartalizumab via a 30-minute infusion once every 4 weeks until disease progression or unacceptable toxicity.

In the full well-differentiated cohort, there were 7 partial responses (7%), and 55% had stable disease, while 31% had progressive disease. The confirmed objective response rate was 7%, and the disease control rate was 63%. In the GEP-NEC cohort, the objective response rate was 5%, and the disease control rate was 19%.

The thoracic NETs patients fared best with spartalizumab, with limited responses seen in the pancreatic and GI NETs groups; responses seemed to be associated with PD-L1 expression. In the thoracic NETs cohort, two of five PD-L1–positive patients had a partial response. PD-L1 positivity was more common in the GEP-NEC cohort; among 14 PD-L1–positive patients in that group, the partial response rate was 43%.

The most common adverse events regardless of cause included abdominal and back pain, anemia, dyspnea, and hypertension.

Kjell Öberg, MD, PhD, of Uppsala University in Sweden, discussed the study for ESMO. “We have hope,” he said. “We see that maybe there are some tumor types that might respond to immunotherapy.” In general, NETs are considered an “immunological desert.” There is usually very low infiltration of immune cells in these tumors, and there are a low number of genetic mutation events.”

You can also listen to two very well known NET experts (Simron Singh and Jonathan Strosberg) talk about this trial and the drug ……. “the highest response rate was seen in atypical lung neuroendocrine tumors. It was approximately 20%, but in most cases was not durable”.  See the remainder of the discussion by clicking here.

You can read more about immunotherapy trials for Neuroendocrine Neoplasms by clicking here. This article includes some advice in interpreting the ‘hype’ that can surround immunotherapy which is still a developing approach to treating cancer.

Thanks for reading

Ronny

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Q-Sphera™ – Next Generation Somatostatin Analogue delivery system?

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From my article about the somatostatin analogues and their drug delivery systems pipeline, there has been a very interesting development in a product called Q-Sphera (was previously known as Q-Octreotide).  In a press release today, 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.  Only a guess from me, but I suspect it’s either Novartis or Ipsen.

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.

Thanks for reading

Ronny

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64Cu-DOTATATE – a potential expansion of the Somatostatin Receptor PET Imaging for Neuroendocrine Cancer?


Edit 10 Jan 2019: RadioMedix and Curium Announce FDA Fast Track Designation For 64Cu-Dotatate.  Read more by clicking here.

Curium and RadioMedix Inc. announce an exclusive agreement to develop and commercialize 64Cu-Dotatate, an investigational positron emission tomography (PET) diagnostic agent for patients with Neuroendocrine Tumors (NETs). RadioMedix is currently engaged in Phase III clinical trials of the agent and expects to file a New Drug Application with the Food and Drug Administration in 2019. This partnership builds on the initial development work conducted by RadioMedix and will benefit from Curium’s regulatory, manufacturing, distribution, and commercial expertise. The radionuclide is not new, it’s been in use for some time, mainly in Denmark.

64Cu is a PET isotope that can be produced at a central location in quantities to meet the commercial needs of hospitals and imaging centers without the supply limitations of nuclear generator-based PET isotopes,” said Ebrahim Delpassand, MD, CEO of RadioMedix. “Once approved, 64Cu-Dotatate will be available to patients in medical centers with PET capability across the country. This will address the shortage or lack of availability of somatostatin analogue PET agents that we are currently experiencing in many parts of the U.S.”

Ga68 PET Shortages explained

This statement is in relation to the current shortage of Ga68 PET radionuclide. For those not aware, the Society of Nuclear Medicine and Molecular Imaging (SNMMI) has written a letter to the FDA about ongoing shortages of generators that produce gallium-68 (Ga-68), a radioisotope used regularly in medical imaging. The letter—available here.

The letter explains that Ga-68 is currently used to produce NETSPOT from Advanced Accelerator Applications (a Novartis company), which was approved in June 2016 to help treat neuroendocrine tumors (NETs) in adult and pediatric patients using PET. NETSPOT, however, is only approved using specific generators. And those generators are only approved for either 400 uses or one year, whichever comes first. This has led to shortages throughout the United States.

SNMMI notes some possible remedies for this shortage. For instance, “a temporary exemption to the 400-elution limit would have a major impact on NETSPOT capacity for patients,” according to the letter. In addition, using a wider variety of generators to produce NETSPOT or using cyclotron-produced gallium chloride are two other methods that could improve production in a relatively short amount of time. “Further discussion with the manufacturers is necessary,” the authors added.

Read more about Ga68 PET and its use in Neuroendocrine Cancer – click here. Worth also noting that RadioMedix is also involved in a number of NET related initiatives including:

1. Trials for a new type of PRRT called ‘Targeted Alpha-emitter Therapy (TAT) – I’ve written about this previously. Read my article here.
2. An exclusive distributor for the TM Isotopen Technologien München AG (ITM) PRRT product currently in trial. I wrote about this here.

How does 64Cu-Dotatate compare with Ga68 PET and Octreotide Scans?

To learn more about previous studies on 64Cu-Dotatate, here’s 2 articles published in the Journal of Nuclear Medicine which are a head to head comparison of 64Cu-Dotatate with Ga68 Dotatoc and with 111 Indium Octreotide (Octreoscan).

Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors – http://jnm.snmjournals.org/content/58/3/451.full

PET/CT (left) and PET (right) scans of patient with intestinal NET and multiple metastases. More lesions are seen in intestinal region with 64Cu-DOTATATE than with 68Ga-DOTATOC.

Conclusion: 64Cu-DOTATATE has advantages over 68Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64Cu-DOTATATE and 68Ga-DOTATOC in this cohort, significantly more lesions were detected by 64Cu-DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64Cu-DOTATATE favorable and easy to use in the clinical setting.

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients –http://jnm.snmjournals.org/content/56/6/847.full

Multiple small liver metastases (>10), peritoneal solitary tumor mass, and 3 lymph node metastases shown on 64Cu-DOTATATE PET/CT in patient with pancreatic NET. No foci were detected by 111In-DTPA-OC SPECT (Precedence scanner). All findings on PET were confirmed to be true-positive. (A) 111In-DTPA-OC planar images. (B) 64Cu-DOTATATE maximum-intensity-projection image with arrows pointing at liver and lymph node metastases. Insert is fused PET/CT of peritoneal solitary tumor mass. (C) Axial CT and SPECT of liver. (D) Axial CT and PET of liver revealing several small liver metastases.

Conclusion: With these results, we demonstrate that 64Cu-DOTATATE is far superior to 111In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of 64Cu-DOTATATE as a replacement for 111In-DTPA-OC.

Summary

The shortage of Ga68 PET radionuclide caused by limitations of the generators in use is unfortunate. Reading the SNMMI letter, I think progress can be made downstream. However, the introduction of a new scanning agent could be useful as long as the trials prove its safety and efficiently and is comparable to current tools. There is no news of any plans to extend this potential new radionuclide outside the US but I suspect that would change following an FDA approval.

If you can see it, you can detect it!

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included

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Neuroendocrine Cancer: Ga68 PET Scan – a game changer?

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This slide from a recent NET Research Foundation conference confirms the power of more detailed scanning – it does look like a game changer

When I was offered my very first Ga68 PET/CT at a 6 monthly surveillance meeting in May 2018, I was both excited and apprehensive. Let me explain below why I had a mix of emotions.

I was diagnosed in 2010 with metastatic NETs clearly showing on CT scan, the staging was confirmed via an Octreotide Scan which in addition pointed out two further deposits above the diaphragm (one of which has since been dealt with). In addition to routine surveillance via CT scan, I had two further Octreotide Scans in 2011 and 2013 following 3 surgeries, these confirmed the surveillance CT findings of remnant disease. The third scan in 2013 highlighted an additional lesion in my thyroid (still under a watch and wait regime, biopsy inconclusive but read on….).

To date, my 6 monthly CT scans seem to have been adequate surveillance cover and all my tumour and hormone markers remain normal. I’m reasonably fit and well for a 62-year-old.

Then I ventured into the unknown

this is not actually my scan!

I wrote a comprehensive post about the Ga68 PET entitled “…. Into the unknown” – so named because that is how I felt at the time. It’s well-known that the Ga68 is a far superior nuclear scan to the elderly Octreotide type, showing much greater detail with the advantage of providing better predictions of PRRT success if required downstream. It has been a game changer for many and if you look below and inside my article, you will see statistics indicating just how it can ‘change the game’ in somatostatin receptor positive Neuroendocrine Cancer diagnostics and treatment.

The excitement of the Ga68 PET

I was going to get the latest ‘tech’ and thought it could be useful confirmation of what I already knew. I also felt lucky to get one, they are limited in UK and there has to be a clinical need to get access. I was excited because it might just rubber stamp the stability I’ve enjoyed for the past 5 or so years since my last surgery in 2012.

The apprehension of the Ga68 PET

I also felt apprehensive because of the ‘unknown’ factor with cancer, i.e. what is there lurking in my body that no-one knows about, and which might never harm me but this scan will light it up demanding attention. I was also apprehensive in case this more detailed scan found something potentially dangerous. As we know, NETs are mostly slow-growing but always sneaky. Of course, any new tumours found may not actually be new, they were just not seen until the Ga68 PET was able to uncover them.  How annoying!

Was Ga68 PET a game changer for me?

Yes, I believe so.  I’m now in the ‘bone met club’ and although that single metastasis has probably been there for some time, it’s not a ‘label‘ I was keen to add to my portfolio. It’s brought more light onto my thyroid issue and continues to indicate some issues above the diaphragm including what looks like a new issue around my left pectoral and lights up an existing issue in the clavicle lymph nodes (first pointed out via Octreotide scan in 2010).

It also formed part of an investigation into progression of my retroperitoneal fibrosis (initially diagnosed 2010 but potential growth spotted on recent surveillance CT). I may now need surgery to prevent kidney/bladder issues and/or radiation therapy to tackle the root cause (the latter is ruled out for now – Nov 2018)

It would appear I’m no longer a boring stable patient

The Ga68 PET Scan confirmed:

Bone Metastases. Report indicates “intense focal uptake“. It always amazes me that people can be thankful for having an extra tumour.  I’m thankful I only have a single bone metastasis (right rib number 11). I had read so many stories of those who got their first Ga68 PET and came back with multiple bone metastases. I’ll accept one and add to my NET CV. I have no symptoms of this bone metastasis and it will now be monitored going forward. I’m annoyed that I don’t know how long it’s been there though!

Confirmation and better understanding of the following:

  1. Thyroid lesion There is some uptake showing. A 2014 Biopsy of this lesion was inconclusive and actual 2018 Ga68 PET report infers physiological uptake. I’m already diagnosed hypothyroidism, possibly connected.  (Edit – on ultrasound in Jan 2019, looks slightly smaller than previous check).
  2. Left Supraclavicular Fossa (SCF) Nodes lighting up “intense uptake“.  I’ve had an exploratory biopsy of the SCF nodes, 5 nodes removed negative. Nothing is ‘pathologically enlarged’ in this area. Monitored every 6 months on CT, annually on ultrasound.  I had 9 nodes removed from the left axillary in 2012, 5 tested positive for NETs and this area did not light up. This whole area on the left above the diaphragm continues to be controversial. My surgeon once said I had an unusual disposition of tumours.  (Edit: Nothing sinister or worryingly enlarged showing on Jan 2019 ultrasound – measuring 6mm).
  3. Report also highlights left subpectoral lymph nodes which is new.  The subpectoral area is very interesting as from my quick research, they are closer to the left axillary (armpit) nodes than they are to the SCF nodesI’m hoping to get an ultrasound of these in January at my annual thyroid clinic (Edit: nothing sinister showing on ultrasound in Jan 2019).
  4. My known liver metastases lit up (remnant from liver surgery 2011) – not marked as intense though. The figure of 3 seems to figure highly throughout my surveillance scans although the PET report said “multiple” and predominately right-sided which fits.
  5. Retroperitoneal area. This has been a problem area for me since diagnosis and some lymph nodes are identified (intense word not used). This area has been highlighted on my 3 octreotide scans to date and was first highlighted in my diagnosis trigger scan due to fibrosis (desmoplasia) which was surrounding the aorta and inferior venous cava, some pretty important blood vessels. I wrote an article on the issue very recently – you can read by clicking here. So this scan confirms there are potentially active lymph nodes in this area, perhaps contributing to further growth of the fibrosis threatening important vessels – read below.

Retroperitoneal Fibrosis (Desmoplasia)

I have learned so much about desmoplasia in the last week that I now fully understand why I had to have radical surgery to try to remove as much of the fibrosis as possible from the aortic area. You can read more about this in my article.  Desmoplasia via fibrosis is still very much of an unknown and mystery condition in NETs.

I now know that my fibrosis is classed as clinically significant and according to the Uppsala study of over 800 patients inside my article, I’m in 5% of those affected in this way (2% if you calculate it using just the retroperitoneal area).

It appears this problem has come back with new fibrosis or growth of existing fibrosis threatening to impinge on blood vessels related to the kidneys and also my ureters (kidney to bladder urine flow).

I didn’t expect this particular problem – it was a bit of a shock. This is not a straightforward surgery.  My hormone markers have been normal for 7 years and this just emphasises the importance of scans in surveillance. 

Conventional Imaging is still important though

There’s still quite a lot of hype surrounding the Ga68 PET scan and I get this.  However, it does not replace conventional imaging (CI) such as CT and MRI scans which still have their place in routine surveillance and also in diagnostics where they are normally at least the trigger for ‘something is wrong’. For the vast majority, a CT/MRI scan will find tumours and be able to measure reductions and progress in regular surveillance regimes. There are actually recommended usages for the Ga68 PET scan here.  For example, it is not recommended for routine surveillance in place of CI.

In fact, the retroperitoneal fibrosis has appeared on every CT scan since diagnosis but the changes were highlighted on my most recent standalone CT and it triggered the Ga68 PET (although my new Oncologist did say I was due a revised nuclear scan).  It’s not a ‘functional’ issue (although it is caused by functional tumours). In fact the fibrosis is not mentioned on the Ga68 PET because it is not lighting up – but the lymph nodes surrounding it are mentioned and they are under suspicious as being active.

Read a summary of all conventional scans and nuclear scans by clicking here.

Next Steps

I’ve since has meetings with my Oncologist and Surgeon and a treatment plan is underway. My surgeon explained it all in his wonderfully articulate and brilliant surgical mind. Fortunately it’s not really urgent but pre-emptive treatment will be required at some point as the consequences of kidney/bladder function are quite severe. It’s also possible that PRRT will be considered as a way to treat the tumours responsible for new and renewed growth of the fibrosis.  I will keep my blog updated as things progress.

Summary

My game has changed, that’s for sure. I’m now entering a new phase and I’m waiting on details of my revised surveillance regime. However, at least my medical team and I now know what WE are dealing with and the risks vs benefits are currently being assessed. I’m heavily involved in that.

If you can see it, you can detect it. If you can detect it, you can monitor or treat it.

Neuroendocrine Cancer: Fibrosis – an unsolved mystery?


Background

It has long been observed that certain Neuroendocrine Tumours (NETs) are often associated with their ability to secrete hormones and these substances are thought to be responsible for the collection of symptoms which include (but not limited to) diarrhea, flushing and wheezing.  One of the lesser known aspects of this disease is the development of fibrosis, both local and distant. These fibrotic complications may lead to considerable morbidity. They can also result in incidental diagnoses of NETs after causing abdominal obstructions.

The most well known form of fibrosis is ‘Hedinger Syndrome’ (so-called Carcinoid Heart Disease) tightly associated with midgut NETs and will not be covered further. However, mesenteric fibrosis is actually more common and also associated with midgut NETs.  There are other less common locations involved including retroperitoneal fibrosis, pleural and pulmonary fibrosis and skin fibrosis.

According to a paper (abstract linked below) by Professor Martyn Caplin (et al) regarding mesenteric fibrosis, “it often has a characteristic appearance of a mesenteric mass with linear soft tissue opacities radiating outward in a “wheel spoke” pattern associated with distortion of the surrounding tissues” (see graphic below).

The mesentery and retroperitoneum areas

The mesentery and retroperitoneum are complex to describe but think of the mesentery as something holding the small intestine together with all its folds and the retroperitoneum describes the part of the abdomen that is generally closer to your backbone than to your belly button, i.e. behind the intestines.

Often labelled ‘Desmoplasia’, it is easily spotted on CT and MRI scans and is one of the unusual features of NETs vs other types of cancer.  Some examples are below:

Desmoplastic-reaction-The-characteristic-desmoplastic-reaction-comprises-a-mesenteric
Desmoplastic reaction. The characteristic desmoplastic reaction comprises a mesenteric mass (black asterisks) with linear soft tissue opacities radiating outwards in a ‘spoke-wheel’ or stellate pattern (black arrows) and associated indrawing of the surrounding tissues . Distortion and retraction of the adjacent soft tissues results in kinking of the small bowel and can cause partial or complete bowel obstruction. The mesenteric mass is often associated with coarse calcification (black arrowhead).  
Metastatic-carcinoid-tumor-to-the-root-of-the-mesentery-arrow-causing-typical
Metastatic Neuroendocrine Tumor to the root of the mesentery (arrow) causing typical circumferential desmoplastic

Axial CT image of a patient with a metastatic neuroendocrine tumor that demonstrates retroperitoneal thickening and fibrosis (arrow).

Small intestinal neuroendocrine tumor with characteristic serosal fibrosis causing kinking of the bowel wall (hematoxylin-eosin, original magnification 3 1; scanned slide) Grin, Andrea & Streutker, Cathy. (2015). Neuroendocrine Tumors of the Luminal Gastrointestinal Tract. Archives of pathology & laboratory medicine. 139. 750-756. 10.5858/arpa.2014-0130-RA.

What causes it, what problems does it cause and how can it be treated?

As with Hedinger Syndrome, which mostly causes right-sided fibrosis in the heart, mesenteric and retroperitoneal fibrosis (and others) is thought to be caused by the excess secretion of serotonin (5-HT) from NETs. I say ‘thought’ but no-one really knows for sure.  There’s a few quite recent studies on the subject which I’ll provide abstracts here.

Uppsala Hospital Sweden. In one study entitled “Clinical signs of fibrosis in small intestinal neuroendocrine tumours” first published in November 2016 by Uppsala Hospital Sweden, it said that it was caused by serotonin and other cytokines released from tumour cells and which may induce fibrosis, leading to carcinoid heart disease and abdominal fibrotic reactions. A cohort study of patients with SI NETs diagnosed between 1985 and 2015 was carried out – a total of 824 patients. Clinically significant abdominal signs and symptoms of fibrosis occurred in 36 patients. Of these, 20 had critically symptomatic central mesenteric fibrosis causing obstruction of mesenteric vessels, and 16 had retroperitoneal fibrosis causing obstructive uropathy with hydronephrosis (the swelling of a kidney due to a build-up of urine).  Extensive fibrosis causing mesenteric vessel obstruction and/or obstructive uropathy was more often associated with symptomatic and advanced disease encompassing lymph node metastases in the mesenteric root, para‐aortic lymph node metastases, as well as liver metastases and peritoneal carcinomatosis. Palliative intervention in terms of superior mesenteric vein stenting or resection of central mesenteric metastases and/or percutaneous nephrostomy and J stent treatment was beneficial in the majority of the patients. They concluded by saying that extensive abdominal fibrosis associated with clinically significant symptoms of intestinal ischaemia and/or obstructive uropathy was linked to advanced disease in patients with SI NETs. Prompt recognition and minimally invasive intervention was effective in disease palliation.

Royal Free Hospital. In another fairly recent paper entitled “Neuroendocrine tumors and fibrosis: An unsolved mystery?”, published by Professor Martyn Caplin of the Royal Free (and others), where this issue is discussed alongside the role of serotonin, growth factors, and other peptides in the development of NET related fibrotic reactions.  They also suggested serotonin as the main culprit in both CHD fibrosis and in mesenteric/retroperitoneum and expressed many of the factors above.  This study suggested that up to 50% of SI NET patients may be involved but looking at both reports together indicates that the first study above only isolated clinically significant cases whereas Royal Free looked for signs in all cases.

Another recent paper (also a paid subscription) from Royal Free (Caplin et al) indicated that the severity of mesenteric desmoplasia did not seem to demonstrate a statistically significant effect on overall survival or long-term outcome (taken from a study of 147 patients at Royal Free London). Sounds like good news but there are clearly consequences that could arise from the issue.

I do not have access to all the texts above, only the abstracts which I’ve linked above (all only available from paid subscriptions).

One older publication authored by known UK NET expert endocrinologist, covered some of the above issues but added that fibrosis in the pleural/pulmonary areas and the skin could also be associated.   For ease of reference, the following extracts are cited to Fibrosis and carcinoid syndrome: from causation to future therapy Maralyn Druce, Andrea Rockall and Ashley B. Grossman Druce M. et al. Nat. Rev. Endocrinol. 5, 276–283 (2009); doi:10.1038/nrendo.2009.51

Mesenteric fibrosis and carcinoid syndrome.  Intestinal fibrosis in a series of 37 patients with jejunoileal carcinoid tumors, 8 of 12 patients with bowel obstructions had evidence of fibrosis or kinking of the bowel.6 among 36 patients with carcinoid syndrome who were seen at Yale university, 15 either had fibrosis at the time of surgery, or developed it subsequently. In a surgical series of 121 patients with midgut carcinoid tumors, 75 required laparotomy, due to abdominal pain; of these patients, 59 were noted to have marked mesenteric fibrosis at the time of surgery. Spread of the primary tumor into the mesentery and peritoneum can result in a marked fibrotic reaction. This fibrosis can mat together multiple loops of bowel and result in kinking, ischemia, volvulus and obstruction.

Retroperitoneal fibrosis. True retroperitoneal fibrosis is a rare clinical entity, in which inflammation results in fibrosis throughout the retroperitoneum. In two-thirds of patients this condition is idiopathic. The majority of cases that are not idiopathic are associated with drugs, such as antihypertensive agents and methysergide. Although retroperitoneal fibrosis is not commonly seen in the context of carcinoid syndrome and has not been reported in any recent, major review, several cases have been reported in literature. 

Pleural and Pulmonary Fibrosis. In a review of 50 patients with carcinoid tumors who presented to a single unit over 9 years and were examined using CT, 14 patients had pleural thickening, and in 9 of these cases no other attributable cause was established. All 14 patients had developed this pleural thickening within 2 years of being diagnosed as having carcinoid syndrome, and 7 of the 9 patients also had fibrosis elsewhere, for example, in the heart valves, skin or mesentery. Carcinoid syndrome has rarely been described as a cause of alveolar fibrosis, but fibrosis elsewhere in the lung occurs more frequently. in a series of 25 patients known to have peripheral carcinoid tumors of the lung, 19 displayed hyperplasia of neuroendocrine cells elsewhere in the lung, and 8 patients (25%) had lesions of obliterative bronchiolitis, including 2 with asymptomatic obstruction of airflow. These data suggest that bronchiolar fibrosis is not uncommon, although it is usually subclinical.

Skin fibrosis. Dermal fibrosis may be primary or secondary to peripheral vasospasm, which occurs in response to vasoconstrictor substances that are secreted by the tumor. Carcinoid syndrome associated with scleroderma has been reported: in one series, its prevalence was 2 cases in 25 individuals. This complication of carcinoid syndrome is usually a late feature and may be attenuated by the use of cyproheptadine hydrochloride, parachlor phenylalanine and prednisolone, which suggests a causative role for tryptophan metabolism and 5-HT”

What happened to me?

Since I was diagnosed in 2010, I’ve always known I’ve had a fibrosis issue in the retroperitoneal area, as it was actually identified on my very first CT Scan, which triggered my diagnosis.  Here’s how the radiologist described it – “There is a rind of abnormal tissue surrounding the aorta extending distally from below the renal vessels. This measures up to 15mm in thickness”.  He went on to describe that “almost certainly malignant”.  The second and third scans would go on to describe as “retroperitoneal fibrosis” and “a plaque like substance”.  Interestingly the fibrosis itself does not appear to ‘light up’ on nuclear scans indicating it was not cancerous (see below).

I really didn’t know what to make of this issue at diagnosis, although I did know the aorta was pretty important!  Fortunately I had a surgeon who had operated on many NET patients and has seen this issue before.  After my first surgery, he described it as a “dense fibrotic retroperitoneal reaction encircling his aorta and cava (inferior vena cava (IVC))”. My surgeon was known for difficult and extreme surgery, so as part of the removal of my primary, he also spent 3 hours dissecting out the retroperitoneal fibrosis surrounding these important blood vessels and managed 270 degree clearance. The remnant still shows on CT scans. Some of the removed tissue was tested and found to be benign, showing only florid inflammation and fibrosis (thankfully).  That said, the abstract papers above has led me to believe that my retroperitoneal fibrosis is clinically significant.

Routine surveillance in 2018 has picked up that retroperitoneal fibrosis is potentially impinging on important vessels in this area, particularly the left ureter but including some blood vessels. A follow up Ga68 PET confirms active lymph nodes in the retroperitoneal area that might be contributing to continued or new fibrosis growth.

In order to further assess risk to my kidneys, I had a different nuclear can known as a Renal MAG3. This scan looks at the blood supply, function and flow of urine from the kidneys. The output will inform my MDT and surgical team looking at treatment options to counter the risk of damage and the timing of potential surgery to correct the issue. I’m happy to report that the MAG3 scan confirmed there are no blockages to my kidneys or bladder. It did confirm my right kidney is doing 60% of the work, the suspected left one is covering the remaining 40% effort.  Apparently it’s pretty normal that it isn’t exactly 50/50.  Surgery is now on the back burner (phew!).  The kidney function will be monitored closely going forward.

Summary

These issues need to be identified early on in diagnostics, preventative treatment considered and then monitored going forward.  Potential complications may include (but not be limited to) bowel and blood vessel obstructions.  Retroperitoneal fibrosis also needs to be monitored as potential complications may include (but not be limited to) obstructive uropathy.

For those worried about this issue, please note that when you look at the statistics from Uppsala, only 4.5% of cases are classed as clinically significant and with the retroperitoneal area, the figure reduces to 2%.

Neuroendocrine Cancer is normally slow growing BUT …..

Thanks for reading

177Lu-DOTA-EB-TATE – Long-lasting radionuclide therapy for advanced neuroendocrine tumors proves effective

For your information only. In the News.

Since PRRT was formally approved last year in USA and Europe (and other places), it’s triggered a whole mini-industry in PRRT variants or enhancements. An interesting study from China, a country starting to become very active in the NET world. I guess they have been active for some time given that I’ve seen their NET experts presenting at the last 2 years of ENETS in Barcelona.  In this particular study, there is linkages to the Laboratory of Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, Maryland in USA.

This is news of a first-in-human study presented at the 2018 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) which demonstrated the benefits and safety of a new, long-lasting type of radionuclide therapy (PRRT) for patients with advanced, metastatic neuroendocrine tumors (NETs) – 177Lu-DOTA-EB-TATE. 

How is this different from the current PRRT standard – Lutathera?

“Lu-DOTA-EB-TATE is a “three-in-one” therapeutic compound, with an octreotate peptide to find the tumor, an ‘Evans blue motif’, which uses endogenous albumin as a reversible carrier to effectively extend the half-life in the blood and substantially increase targeted accumulation and retention within the tumor, and a therapeutic radionuclide to kill the tumor cells, to finally provide effective treatment of NETs,”  …….. explains Shawn(Xiaoyuan) Chen, PhD, senior investigator, of National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health , Bethesda, Maryland.

Lutathera-177 (177Lu)-DOTATATE (trade name Lutathera), a peptide receptor radionuclide tharapy (PRRT) with radiolabeled somatostatin analogues (peptides), was recently approved by the USA FDA and the EMA for the treatment of somatostatin receptor positive NETs. It is the therapeutic part of a nuclear medicine theranostic pairing. Gallium-68 (68Ga)-DOTATATE is the diagnostic agent used in  PET/CT scans that first locates and marks the lesions for follow-up with targeted PRRT delivery directly to the tumor cells which express high levels of somatostatin receptors (SSTRs). Because the PRRT binds to receptors expressed by the tumor cells, healthy cells are unharmed. However, the peptide quickly clears from the blood through the kidneys limiting the accumulation of radioactivity within tumors and making additional treatment cycles necessary to provide the therapeutic dose.

177Lu-DOTA-EB-TATE.  This first-in-human, first-in-class, Phase I trial (ID: NCT03308682) investigated the safety and dosimetry of a novel long-lasting radiolabeled somatostatin analogue that adds an albumin-binding Evans blue (EB, an azo dye) derivative to 177Lu-DOTATATE. Albumin, the most abundant plasma protein in human blood, is a natural transport protein and has a long circulatory half-life.  This is an open-label, non-controlled, non-randomized study.

For the study, conducted in collaboration with researchers at the U.S. National Institute of Biomedical Imaging and Bioengineering, 8 patients (6 men and 2 women ranging in age from 27 to 61 years old) with advanced metastatic neuroendocrine tumors were recruited from Peking Union Medical College Hospital and the Chinese Academy of Medical Sciences in Beijing, China.

Each patient underwent whole-body 68Ga-DOTATATE PET/CT. Five of the patients then accepted intravenous injection with a single dose of 0.35-0.70 GBq of 177Lu-DOTA-EB-TATE within one week, and were monitored at 2, 24, 72, 120 and 168 hours after 177Lu-DOTA-EB-TATE administration with serial whole-body planar and single photon emission computed tomography (SPECT)/CT images acquired. The other 3 patients accepted a dose of 0.28-0.41 GBq of 177Lu-DOTATATE and were monitored at 1, 3, 4, 24 and 72 hours with the same imaging procedures. Complete physical examinations, including vital signs, blood count, biochemistry, and immunology analyses were performed immediately before and 1, 3, and 7 days, as well as 3 months, after treatment.

Administration of 177Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms reported throughout the procedure and follow-up. The total effective dose equivalent and effective dose were 0.2048 ± 0.1605 and 0.0804 ± 0.0500 mSv/MBq for 177Lu-DOTA-EB-TATE and 0.1735 ± 0.0722 and 0.0693 ± 0.0317 mSv/MBq for 177Lu-DOTATATE. The liver, kidneys, bone marrow and total body received slightly higher doses (mGy/MBq) with 177Lu-DOTA-EB-TATE than with 177Lu-DOTATATE, while the spleen received lower doses with 177Lu-DOTA-EB-TATE. Blood clearance of 177Lu-DOTA-EB-TATE was also slower. Most importantly, 177Lu-DOTA-EB-TATE lasted in the tumors more than 4 times longer than 177Lu-DOTATATE.

Jingjing Zhang and Zhaohui Zhu of Peking Union Medical College Hospital point out, “By introducing an albumin binding moiety, this long-lasting radiolabeled somatostatin analogue has remarkably enhanced uptake and retention in SSTR-positive tumors, which is important to increase the therapeutic efficacy in patients. With proper selection of patients with advanced metastatic neuroendocrine tumors, 177Lu-DOTA-EB-TATE has great potential to be a highly effective treatment, while providing a safe dose with less frequency of administration than is possible with 177Lu-DOTATATE.”

FIGURE: SPECT/CT of a 45-year-old male patient with advanced NETs and multiple liver metastases – persistently retained in the tumors after 168 hours

Scans were done at 2, 24, 72, 120 and 168 hours after the administration of 177Lu-DOTA-EB-TATE. The radiopharmaceutical cleared from the blood pool over time and persistently retained in the tumors (arrows). Credit: J Zhang et al., Peking Union Medical College Hospital, Beijing, China; X Chen et al., Laboratory of Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, MD

Sources:

Abstract 118: “Safety, Pharmacokinetics and Dosimetry of a Long-lasting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors: A Phase 1 First-in-human Study,” Jingjing Zhang, MD,PhD, Yuejuan Cheng, MD,Hao Wang, MD, Jie Zang, PhD, Fang Li, MD, Chunmei Bai, MD, and Zhaohui Zhu, MD, Peking Union Medical College Hospital; Gang Niu, MD, Orit Jacobson, PhD4, and Xiaoyuan Chen, PhD, U.S. National Institutes of Health, Bethesda, MD. SNMMI’s 65th Annual Meeting, June 23-26, Philadelphia.  Link to SNMMI Abstract

Other articles in this series:

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Sapanisertib – a drug on trial for Neuroendocrine Tumors (NET) with a pancreatic primary


Researchers are testing the drug Sapanisertib to see if it can halt the progression of pancreatic NETs (pNETs) which cannot be surgically removed, have not responded to other treatment, and have spread to other parts of the body.

What is Sapanisertib?

Sapanisertib is one of a group of targeted therapy drugs that interferes with tumor progression by inhibiting an enzyme known as mTOR which a tumor cell needs for growth.  In fact this is the same technique used in Afinitor (Everolimus), already approved for NETs.

It is also being tested in a number of different advanced cancers, including bladder, kidney, breast, liver, and certain types of lung cancers, among others.

The Clinical Trial

The primary goal of the phase II study is to evaluate how well pNET tumors respond to Sapanisertib. To qualify for this trial patients must have advanced pNET that cannot be surgically removed, and which have not responded to previous treatment with similar drugs. All participants will receive Sapanisertib, and will be checked periodically to see if their tumors are responding to the drug.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided at this link which provides more details about the Sapanisertib pNET trial – click here and check the inclusion and exclusion criteria; and other data.  There are 354 study locations across the USA.

Thanks for reading

Ronny

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Update – Oncolytic Virus Trials for Neuroendocrine Cancer

I’ve posted extensively about this subject on Facebook early last year, focused on the ongoing Neuroendocrine Cancer trial in Uppsala Sweden. I wanted to incorporate this information into a single article ready for future news, whilst at the same time updating you on further developments in the field of Oncolytic Viruses for Neuroendocrine Cancer.

What exactly are Oncolytic Viruses?

Oncolytic Viruses infects and breaks down cancer cells but not normal cells. Oncolytic viruses can occur naturally or can be made in the laboratory by changing other viruses. Certain oncolytic viruses are being studied in the treatment of cancer. Some scientists say they are another type of immunotherapy whilst others say it’s too early to classify as such. The good news is that Neuroendocrine Cancer seems to figure in this work with two of these viruses apparently working on mice to date. Listed below are two active projects involving NETs, one directly and one indirectly.

The Uppsala Trial – AdVince

15871660_793548617450098_750736690369970047_n
The Oncolytic Virus AdVince is removed from the freezer ready for the Neuroendocrine Cancer Trial

There has been no real update on what is happening since I posted last year. Hopefully, positive thinking indicates no news is good news. If anyone has anything more than what I’ve written or linked to in this article, please let me know. I’ll briefly described what’s happening and then you can link to my Facebook article if you need more background.

The trial is called AdVince after Vince Hamilton who funded it. Unfortunately he died before he saw any output but his forward thinking and benevolence lives on and might hopefully help NET patients in the longer term. It’s quite a small trial and is being conducted in Uppsala University Sweden, a famous European NET Centre of Excellence and where many people from across the world attend to take advantage of PRRT availability and experience and is home to famous NET specialist Kjell Öberg, MD, PhD, a professor of endocrine oncology.

A Swedish man (Jan-Erik Jannsson) was the first to get the virus to their cancer (NETs) using a genetically modified virus.

Unfortunately, I was given the news from a source close to the trial that Jan died last year of pneumonia.  I have no evidence to suggest his death is in anyway connected to the trial but I’m told he was an ill man prior to the trial commencing.  I have therefore dedicated this post to him.  RIP Jan.

Jan

The initial data presented by the trial indicated that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET.  The last I heard from the trial is that they are trying to recruit a further 12 patients to Phase IIa (the trial document allows for up to 36). 

Read more background on my Facebook post here: Click here

The trial document on Clinical Trials Website: Click here

Then read this status update from the trial sponsors released in March 2018

Pexa-Vec Oncolytic Virus Trials

This is an oncolytic viral therapy currently in phase III and phase Ib/II clinical trials for use against primary liver (Hepatocellular Carcinoma) and Colorectal cancers, respectively. Pexa-Vec is a weakened (or attenuated) virus that is based on a vaccine used in the eradication of smallpox. The modified virus is injected directly into the cancer tumour, to grow inside these rapidly growing cancer cells and hopefully kill them.

According to the Colorectal Clinical Trial, the aim of the study is to evaluate whether the anti-tumor immunity induced by Pexa-Vec oncolytic viral therapy can be enhanced by immune checkpoint inhibition i.e. they are testing it in conjunction with Immunotherapy drugs (Durvalumab, and a combination of Durvalumab and Tremelimumab).

The Hepatocellular Carcinoma trial (Phocus) is at Phase III where the sponsors are evaluating Pexa-Vec to determine if it can slow the progression of advanced liver cancer and improve quality of life.

The work is a collaboration forged between University of California San Francisco (UCSF) vascular researcher Donald McDonald, MD, PhD, and researchers at San Francisco-based biotech SillaJen Biotherapeutics Inc. (formerly Jennerex Biotherapeutics, Inc.), a subsidiary of SillaJen, Inc., headquartered in Korea.

A tumor with green patches of vaccinia virus infection surrounded by red blood vessels. Image by Donald McDonald Lab

So what’s the Neuroendocrine Connection with Pexa-Vec?

As part of the research, McDonald’s lab injected it intravenously into mice genetically modified to develop pancreatic neuroendocrine cancer. They found that the virus failed to infect healthy organs or make the animals ill, but succeeded in infecting blood vessels within tumors. These initial infections caused the vessels to leak and expose the tumor cells to the virus. In these experiments, the virus managed to infect and destroy only a small proportion of tumor cells directly, the researchers found, but within five days of the initial infection, the rest of the tumor began to be killed by a powerful immune reaction.

“At first small spots of the tumor were infected, but then most of the tumor started to die,” McDonald said. “We were able to show that while only about five percent of cells were infected by the virus, the number of cells that were killed was more than ten times higher. As far as I know, no one has ever done this kind of analysis.”

McDonald’s team wondered whether they could improve the efficacy of the virus by adding in a second drug called Sutent (sunitinib) that blocks blood vessel growth and alters immune function. The combination worked, with significantly greater tumor killing than with the virus alone. When the researchers examined the tumors, they discovered that the second drug acted by making the immune system hyper-alert to tumor proteins released by the viral infection, rather than through effects on tumor blood vessels.

Summary

Clearly it’s still early days in the Oncolytic Virus field with minimum breakthrough in terms of success on humans. In terms of the Neuroendocrine connection, it is exciting that two programmes are showing results (albeit in mice). We wait to hear from Uppsala on how the human test of AdVince is coming along. My agents are scanning the internet every day looking for any comment.
If you want to learn more about Oncolytic Viruses in general – there’s a great summary here.

Thanks for reading

Ronny

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Clinical Trial: Advanced Oncology Formula enterade® – a breakthrough for NET Patients?


enterade

Diarrhea is a huge subject for NET patients, whether it’s caused by the tumor itself (i.e. a syndrome), due to treatment, knock on effects of treatment, or some other reason, it can dramatically limit qualify of life.  Working out the root cause can be problematic even for medical teams. I wrote about these issues before in my article Neuroendocrine Cancer – the diarrhea jigsaw. So when I saw the data from a trial of something called enterade®, I was immediately drawn to investigate.  I don’t normally write articles on over the counter commercial products but this one is an exception given that it has been classed as a medical food since 2012 and is also used to rehydrate patients undergoing radiotherapy and chemotherapy for cancer (so not just for NETs).

What is enterade® ?

It’s a drink currently produced in 8oz bottles.  It’s a first-in-class, glucose-free medical food i.e. it is intended to be used under the supervision of a healthcare provider.  The solution comprises five critical amino acids – Valine, Aspartic Acid, Serine, Threonine, Tyrosine and electrolytes – potassium and sodium.

What does it do?

It’s designed to help manage debilitating gastrointestinal (GI) side effects. With no sugar to exacerbate the GI tract, enterade® supports the small bowel’s ability to absorb fluids, nutrients, and electrolytes and leads to improved digestive function. By helping to restore normal GI function, enterade® reduces diarrhea and dehydration, leading to a significant improvement in the patient’s overall quality of life and a healthier GI tract.

Is there evidence that it works?

Since May 2017, it’s been trialled by University of Kentucky Markey Cancer Center (MCC) for potential use by NET patients – trial coordinators include the well-known NET specialist Dr Lowell Anthony.  The results so far are very interesting.  The recent  conference reported revised data as follows:

  • 33 of 41 patients (80%) reported subjective improvement in diarrheal symptoms.
  • 51% (21/41) reported more than 50% reduction in diarrhea frequency.
  • click here or on the poster below to see the trial poster data output.
asco poster enterade as a graphic
click to read full screen

As you will see from the poster, there were a wide range of patient types including (but not limited to) small intestinal NETs, bronchial NETs, NETs of unknown primary, gastric NETS, pancreatic NETs and one high grade neuroendocrine carcinoma of the prostate.

A follow on Phase 2 trial is now recruiting  with the following detail available:

1. Up to 30 patients will be recruited.

2. The trial is coordinated by Markey Cancer Centre, Kentucky.

3.  There will be two cohorts, those with carcinoid syndrome and those without.

4.  The trial will run from December 2018 to August 2020.

  • Click here to see the trial information – important to note the inclusion and exclusion criteria.
  • Read the trial start announcement by clicking here.
  • Please also note there’s a plan for a follow on trial covering more locations.  I will update further when known.

Can I buy Enterade now?  

The product is available in North America on Amazon.com,  www.enterade.com and 1-855-enterade.  However, the parent company (Entrinsic Health) recently announced a partnership with global company  Nestlé Health Science to provides worldwide commercial license and supply agreement for enterade®. The announcement is linked here:

NORWOOD, Mass., November 15, 2018 – Entrinsic Health Solutions (EHS), an innovative health sciences company, today announced that they have entered into a partnership with Nestlé Health Science (NHSc), a global innovative leader pioneering premium-quality, science-based nutritional health solutions. The partnership gives NHSc the exclusive rights to market EHS’s enterade® product.

Disclaimer

Please note this is not a recommendation to go out and buy the product.  It is actually described as a ‘medical food’ and is formulated to be consumed or administered under the supervision of a physician.

Further reading:

1. Enterade FAQ – click here

2. A breakthrough for NET Patients. click here.

3. Recent output from ASCO 2018 – click here. (contact data update for 2018)

4. If you are interested in more information about how enterade® works, check out this short video

Disclaimer

Please note this is not a recommendation to go out and buy the product.  It is actually described as a ‘medical food’ and is formulated to be consumed or administered under the supervision of a physician.

Thanks for reading

Ronny

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Neuroendocrine Cancer and Pancreatic Enzyme Replacement Therapy (PERT) – the Digested Version (Nutrition Series Article 5)

 

PERT

After 7 years of avoiding pancreatic enzyme replacement therapy (PERT), I finally asked for some on a trial basis.  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.  Plus my key vitamin levels (B12 and D) are in range.  However, I’ve been struggling with a lot of bloating issues in the last couple of months, 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.

Background

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:

  • protease which breakdown proteins (e.g meat, fish, seafood, dairy, nuts, etc)
  • 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 (it is with Creon).  The entire mix of enzymes may be given a name, in my case it’s ‘Pancreatin’. 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.

  1. 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.”

Supplementary Questions:

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”.

  1. 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.”

Supplementary Questions

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.”

  1. 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.”

Supplementary Questions

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”

  1. 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.”

Supplementary Questions:

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.

  1. 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.

Supplementary Questions:

5a. I take a probiotic also, when is best time to take this, before, during or after food?

“Timing doesn’t matter”

  1. 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.”

  1. 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.”

  1. 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). Details to follow.

Supplementary Questions:

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.”

  1. 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.”

Supplementary Questions:

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.

  1. 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.”

  1. 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”

Supplementary Questions:

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”

  1. 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.”

Summary

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,  No 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.

You may also enjoy these articles:

“Nutrition Article 1 – Vitamin/Mineral Risks”click here.

“Nutrition Article 2 – GI Malabsorption”click here.

“Nutrition Article 3 – SIBO/Probiotics”click here

“Nutrition Article 4 – Food for Thought – amines etc”click here

Post publishing edit:  “I feel like I now take food with my medicine” 🙂

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!


 

NET Cancer Blog – Top 6 posts of 2017

Top 6 posts

These are my top performing posts for 2017 – comprising one eighth of my entire hits for the year.  My blog hits for 2017 almost reached a quarter of a million, double that of 2016 which was double that of 2015.  A chunk of these figures can be attributed to most of these articles.  Please share to maintain the momentum.

Top 6 posts for 2017 (Click on each article title to read) Short Description Hits in 2017
The Human Anatomy of Neuroendocrine Cancer Making the point that Neuroendocrine Cancer is not confined to a particular part of the body 9,906
Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis All about syndromes 7,546
Neuroendocrine Neoplasms – Grade and Stage (incorporating WHO 2017 changes) The very latest information (particularly about grading) 7,027
Neuroendocrine Cancer – no treats, just tricks A very powerful awareness message.  It was only published 2 months ago and is already the 10th most read post in over 220 since this site was set up. 6,083
Steve Jobs – the most famous Neuroendocrine Cancer Ambassador we NEVER had Love him or hate him, he generates external hits on my site – you could say he is now helping with Neuroendocrine Cancer awareness.  It also debunks the Pancreatic Cancer myth 6,046
Ignore this post about Neuroendocrine Cancer Another very powerful awareness message – it is also the most tweeted post about NETs on twitter 4,812

Thanks for reading

You may also enjoy my article “10 Questions to ask your Doctor” – click here.

Most Viewed Posts – click here

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included


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Update: Management of Neuroendocrine Tumors

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.

Screenshot 2017-12-12 16.34.54

Great update and worth the 30 minutes it takes to watch – you can view it CLICK HERE.

 

 

All graphics courtesy of www.oncologytube.com

Thanks for reading

Ronny

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Expanding PRRT – Trial of 177Lu-Edotreotide (Solucin®) – COMPETE Phase 3 Clinical Trial

ITM_header_products_endolucinbeta
graphic courtesy of ITM AG

In the News.

On the heels of the approval of PRRT in USA and whilst we all wait on positive national announcements of PRRT approval in UK and elsewhere, here’s news of a new PRRT compound undergoing a phase 3 clinical trial.  Isotopen Technologien München AG (ITM), a specialized radiopharmaceutical company, today announced the enrolment of the first patient recruited in Europe for the COMPETE phase III clinical trial at the University Hospital Marburg, Germany. The CEO of ITM said “This marks the starting point of COMPETE in Europe, whereby we expect a rapid increase in the number of recruits.”  I actually met these guys at ENETS 2018 – sounds great.

What is the COMPETE trial?

COMPETE is led as an international pivotal multi-center phase III clinical trial evaluating the efficacy and safety of (no-carrier-added) n.c.a.177Lu-Edotreotide (Solucin®) and the trial is comparing it to Everolimus (Afinitor). The trial runs until Dec 2020. The enrolment requires patients with inoperable, progressive, somatostatin-receptor positive neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET). The primary endpoint is progression-free survival (PFS). The study will be conducted predominantly in Europe, North America, South Africa and Australia (ITM is waiting on FDA clearance to include North American locations in the trial). The first patient to be enrolled and treated was in Australia.  The clinical trial document (see references below) indicates its for non-functional GI tumours but for non-functional and functional pNETs. The list of locations can also be found in the clinical trial document. The usual inclusion/exclusion rules apply but the most notable would appear to be an exclusion for those with prior exposure to any PRRT or mTor inhibitor such as Everolimus (Afinitor).

What is 177Lu-Edotreotide (Solucin®) ?

The compound under investigation, Solucin®, is known as a Targeted Radionuclide Therapy (TRT) agent, which consists of the targeting molecule Edotreotide, an octreotide-derived somatostatin analogue and ITM´s EndolucinBeta® (no-carrier-added Lutetium-177). EndolucinBeta® is a synthetic, low-energy beta-emitting isotope of Lutetium, a recently EMA approved pharmaceutical precursor. The radiopharmaceutical Solucin® is administered as an intravenous infusion, specifically targeting and destroying the tumor cells with ionizing radiation. Solucin® received an Orphan Designation (EMA/OD/196/13) for the treatment of GEP-NET, based on early clinical experience, which has demonstrated a substantial clinical benefit with increased PFS and quality of life.

From ITM’s website … “Edotreotide contains DOTA which functions as a chelator for radioisotopes and TOC, a synthetic Somatostatin receptor ligand” (chelator and ligand are just fancy names for ‘bonding’ or ‘binding’). “The compound Edotreotide binds with high affinity Somatostatin receptors and retains both its receptor binding properties and its physiological function when labeled with 177Lu. Somatostatin receptors are predominantly overexpressed by neuroendocrine tumors. 177Lu-Edotreotide, upon binding to Somastotatin receptors in vivo is internalized and retained by tumor cells.” 

“Compared to 90Y-Edotreotide, 177Lu-Edotreotide Targeted Radionuclide Therapy in NET was found to be less haematotoxic and associated with a longer median overall survival. That was highly significant for patients with low tumor uptake as well as for patients with extra hepatic and solitary metastases. In a retrospective Phase II trial 177Lu-Edotreotide showed a low uptake/dose delivered to normal organs and very high tumor-to-kidney ratio.”

Other Spin offs from ITM

Interestingly the company is also working on a ‘theranostic pair’ for imaging and treating bone metastases – see graphic below.  It does not say whether this includes NET bone metastases but I don’t see why not given the connection with Solucin. However, please note this is some years away from fruition.

graphic courtesy of ITM AG

 

References:

1.  ITM News Release – click here

2. ITM Website – click here

3. Clinical Trials Document – click here

4. FDA authorises trial to go ahead in USA – click here

5. Useful video about the trial – click here

compete US trial locations

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Living with Neuroendocrine Cancer – the 7 Year Itch

7 year itch

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:

Round up of NANETS 2017 – Let’s talk about NETs #NANETS2017

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.

https://goo.gl/tMT6KS
Location of Neuroendocrine Tumors in the Small Bowel Does Not Affect Survival

 

https://goo.gl/zf9k9j
Diagnosing and Treating NET-Related Diarrhea

 

Incorporated into my Diarrhea article – https://goo.gl/PwsXmX
Emerging Therapies, Biologic Discoveries, and Improved QoL on Horizon for NETs

 

https://goo.gl/p4cCyd
Retrospective Database Analysis Studies Somatostatin Analog Usage in NETs

 

https://goo.gl/KWM4p7
Regional Lymph Node Involvement and Outcomes in Appendiceal Neuroendocrine Tumors: A SEER Database Analysis. https://goo.gl/vfF4DA
Personalizing Therapy With PRRT and Improving Imaging With SSTR-PET Brings Novel Options to NETs Landscape

(new term SSTR-PET generically meaning any PET scan using somatostatin receptors), e.g. Ga68 etc.

https://goo.gl/s8sked
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 https://goo.gl/yZ56YZ
Molecular Classification of Neuroendocrine Tumors: Clinical Experience with the 92-gene Assay in >24,000 Cases https://goo.gl/aqgfRf
Neuroendocrine Tumors: A Patient Survey

“Regarding their biggest challenges, patients reported fatigue as their biggest challenge followed by diarrhea, sleep disturbances, and pain.”

https://goo.gl/qEeNRM
Phase III Trial Needed to Confirm Clinical Benefit of Cabozantinib in NETs

 

Incorporated into my Cabozantinib article – https://goo.gl/mR2yFT
QOL Improvements in NETTER-1 Phase III Trial in Patients with Progressive Midgut Neuroendocrine Tumors. (I think this is well-known but no harm in repeating it!) https://goo.gl/UmKsFi

 

The full link to all poster abstracts for NANETS 2017 can be found here

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Can NETs be cured?

cure quote

OPINION:

“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.

Summary

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.

cure quote

Weight – the NET Effect

Weight – The NET Effect

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. 

Hypothyroidism is another potential issue. 

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.

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.

Summary

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.

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.

weight online chat
Click the Link to see the online event output

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included

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The shock effect never wears off

The Hidden NET patient voices

Patient stories are key to any awareness campaign.  Nothing like a human being standing up and letting you know about their experience.  Many are positive examples of how they are overcoming their trials and tribulations, others tell stories of a struggle. They all have different styles, some are the ‘kick ass’ type stories, some are just thankful, some are reflective – all of them are perfectly acceptable. I normally like to place myself somewhere in the middle with phrases like “I’m still here“, although I can veer left and right when the mood takes me!

Because of my social media footprint, I get a lot of private messages from people across the globe. Many are from people who have no wish to go public and that’s fine. Many are from people who value my opinion and that’s humbling. On forums, you can get 50 answers (all well meaning ones), with me you normally only get one (even if it’s a “I don’t know”).  Most are fairly easy to answer, just a link to something or asking for one of my articles they can’t seem to find.  Some are a bit trickier but I get there in the end.  Some are pretty worrying and really difficult to answer.  And nearly all of them amplify something we already know ……. despite some tremendous medical advances, there’s still a lot of unmet needs for Neuroendocrine Cancer patients, in particular access to NET specialists, access to the best and latest proven treatments and follow-up support for those affected by their experience (physical and mental). I’m talking in a global sense including countries perceived to be advanced in medical terms.

Take ‘A’ for example.  This patient has a classic well differentiated Small Intestinal NET (Si NET) with lymph node metastasis.  That resulted in fairly complex abdominal surgery that many of us will have had (including myself). For the past year, this patient has struggled with no follow on support, no dietary advice and has been left alone. This patient told me he is actually receiving his follow on advice from my blog site. This patient is also struggling on the emotional side because people say he looks rather well and have commented that he must have been wrongly diagnosed but at least is now “cured“.

Example ‘B’ is similar.  This patient has had surgery (the surgeon got everything apparently ….) but has been declared non-syndromic on the basis there is no diarrhea.  However, there is flushing, joint paint, general abdominal issues, weight loss, headaches, fatigue, dehydration and chronic constipation.  It took this patient 6 months to find out about a local NET advocate organisation and 10 months to find out there was access to a dietitian.

Example ‘C’ is worrying.  In this example I was contacted and asked about surveillance intervals as it was noticed I was having regular scans. What I found was someone who had a metastatic midgut NET and not had any surveillance for 3 years (including tumour/hormone marker checks and Echocardiograms).  This is despite an advanced healthcare system and oodles of availability. This patient is now seeing a NET specialist.

Example ‘D’ is horrendous.  This patient was treated as a bowel cancer case when they had a low-grade classic Si NET …… surgery and then classic bowel adenocarcinoma chemo. Now, it might be that was the only treatment modality available in this patient’s country but it’s a worrying example of the extent of the unmet needs for NET patients in the country concerned.

I could go on with many other examples and I might expand this post downstream.

One thing is very clear to me, we need a new paradigm in international advocacy and we need to start focusing more on these support issues.  As the number of people living with cancer rises, the requirement for post diagnostic support also rises.  Even those who are ‘stable’ need support.  One thing is for sure, the shock effect of what people tell me never wears off because I know there are more shocking stories still to hear.

Thanks for reading

Ronny

I’m also active on Facebook.  Like for even more news. And check out my latest Facebook page here.

Disclaimer

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

WEGO Awards

patients included

 

Cancer Isn’t All About Me

As featured by Cure Magazine
It’s about others too

Since my diagnosis of incurable and metastatic neuroendocrine cancer in 2010, it’s really all been about me. I didn’t see the trauma coming, and my family has supported me throughout every single step. I really don’t want to be the focus of attention as that mantle was normally evenly distributed. However, there’s nothing like a cancer diagnosis to put you into the spotlight.

Facing an uncertain future with regular scans, injections, treatment, pills, examinations and blood tests has made me the center of attention, whether I like it or not. The focus is on me because these things are necessary to keep me alive for as long as possible and also because I live with the consequences of cancer and its treatment which provides further challenges. A good quality of life is not only a motivator for change, good planning and constant surveillance, but it’s also hard work and has an additional impact on the whole family. It means all activities including work, holidays, days out, social activities and, even the simple act of eating, might all need to be organized around me due to the vagaries of my condition. It will never stop, it will never end and it will always be about me!

This has gone on for seven years and counting. “Cancerversaries” are on the calendar alongside birthdays and wedding anniversaries. Tumor marker tests and scans are reviewed twice yearly so the relentless attention continues, often peaking at these test milestones and worrying moments in between. The detailed analysis of unusual pain or other disturbances are documented. The attention is on me.

Then, my wife finds a lump. The local doctor investigates and refers her for a mammogram. The mammogram check leads to an ultrasound which then leads to a biopsy of some fibrous tissue. We have a two-week wait before the all clear is given but the worry doesn’t immediately dissipate as another check was scheduled for three months (done, no issues).  The following check 6 months after on 7 Aug 2018 is also no change.   Hang on a minute … this is not about me!

I’m starting to realize it shouldn’t be all about me and it needn’t be all about me. It’s about other people, too. There is nothing in the rule book that allows cancer to be limited to a single family member. Cancer doesn’t really care how many in your household already have the disease – anyone is a target. It’s bad enough having one cancer patient in the house without another cropping up. One thing is for sure, when it comes to a cancer diagnosis in the family, I really want it to be all about me.

Thanks for reading

Ronny

 

Postscript:  Very excited to share my first article published in CURE magazine. This is a real story about recent events involving my own family. As a long-term cancer patient, it can seem like it’s always about ‘me’ and then something happens which changes that perception. It’s actually about others too, and always has been. If you want to talk about something similar in your life, please share with others in your comments below or  message me. 

This is the beginning of a new phase in my activities and another opportunity to spread awareness of Neuroendocrine Cancer to new audiences, something I promised I would do.  I hope you will support my first contribution to an exciting organisation brand.

It would be great if you would take the time to read the article directly on the Cure site here, and any likes, comments and sharing would be appreciated. 

The article can be found here

caricture

You may also enjoy my second Cure Magazine article “Poker Face or Cancer Card”

NETwork with Ronny © – Community Newsletter SEPTEMBER 2017

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is September 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).

NET News

The following news items may be of interest:

 
  • The European Commission (EC) approved Lu-177 Lutathera (PRRT) on 28 Sep.  This is the first time the drug has ever been approved, despite being in use for  over 10 years.  In USA, the FDA gave a date of 28 Jan 2018 for its decision to approve or not.  Read more here.
 
  • The European Commission approved the use of XERMELO (telotristat ethyl) for use in Carcinoid Syndrome diarrhea not adequately controlled by somatostatin analogues. Read more here.
 
  • The US FDA approved an add-on indication for Lanreotide (Somatuline) for treatment of carcinoid syndrome, adding when used, it reduces the frequency of short-acting somatostatin analogue rescue therapy (….. ergo Octreotide).  Read more here.
 
  • GA-68 PET (NETSPOT) continues to roll out across the USA, see CCFs latest list by clicking here.

 

 
  • The WEGO Health Finalists were announced on 25 Sep and I’m through to the finals in all 3 awards which you nominated me for. Many thanks for the support!  I posted this info here.

Blog Site?  

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, includes updated blogs. You can actually sign up to receive my blog articles direct to your inbox when published – subscribe here.

 
 
 
  • The Invisible NET Patient Population.  Centred on the issue of a cohort of as yet undiagnosed people with NETs; or have been labelled with another cancer; or have been told their cancer is benign and therefor not recorded.
 
  • The WEGO Health Finalists were announced on 25 Sep and I’m through to the finals in all 3 awards which you nominated me for. Many thanks for the support!  I posted this info here.

 Other Activity

September was a slower month in ‘new’ blogging terms mainly due to personal activities (holiday) and the consequences of being ‘contactable’ by a large internet footprint! Striking a balance remains difficult, I’m keen to support and advocate but as a patient, I also need my own time.  I’m currently seeing a trend of low ‘new’ blog months, mainly due to external projects and a continuous stream of offline messages from patients (more on this later) – my strategy is constantly under review.  However, despite a low month for brand new blogs, I still managed to break through 20,000 views for the 4th month in a row…….. Thank you all so much for the support.

Please join my 2017 awareness campaign event here (select ‘Going’)

I continue to receive a steady flow of private contacts, mainly from patients seeking information.  I don’t have an issue with private contact but please note my disclaimer.  Please also note that I cannot accept telephone calls on a one to one basis.  Also, the number of non-patients contacting me for other reasons (mainly to help with something) continues to grow and this is producing some great publicity and awareness.

Awareness Activity in September 2017

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.

  • Article features.  I was featured in a well shared and positive article entitled A revolution in the treatment of Neuroendocrine Tumors. A very positive look at the new treatments coming through. I didn’t agree with some of the content but ‘hey ho’ I cannot control what others write.  You can check out the article by clicking here.
  • Twitter.
    • I took part in a patient chat on twitter where I was able to contribute to some general cancer questions.  It was attended by many patient advocates representing many different conditions. The taking part in these activities is time-consuming and hard work but it does allow me to grow as a general patient advocate and to occasionally mention “Neuroendocrine Cancer” spreads awareness to new audiences.  A summary of the conversation can be found here.
    • 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 and are made aware of NETs in the process).  In Sept, I tweeted 109 times on my personal account which lead to almost 75,000 views.  I was mentioned 78 times by other tweeters and gained 68 new followers.  My tweet “Ignore this post” remains the most tweeted article about NETs ever posted on twitter.  Check it out – click here.

  • Daily Newsletter from my twitter feed (Nuzzel).  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 – you don’t need to have a twitter account to read, just sign up with an email.  Currently 336 subscribers – up 12% on last month.

  • WEGO. I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  The recent awards will continue to showcase my work which has the effect of spreading Neuroendocrine Cancer awareness to NEW audiences in addition to enriching my experience as a Patient Leader.  WEGO is a fantastic organisation!

  • Macmillan Cancer Support.  I’m proud to be a ‘Voice’ and ‘Community Champion’ on the Macmillan Cancer Support Forum.  In addition I help ‘outliers’ from the NET community there. There are only 27 champions for a site supporting hundreds of thousand patients – it’s a community of communities.  I’ll be reporting more on this in the coming weeks.  This is the biggest cancer support organisation in the UK and I’m intent on developing relationships with various departments in this fantastic organisation.  On August 30th, one of my blogs made their “top picks” generating some NET awareness – check out Living with Cancer – 6 tips for conquering fear They have recently agreed to feature NETs on 10 Nov 17.
that’s me in the centre
  • Cure Magazine.  I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.  Cure Magazine has a readership of 1 million.  Click here to read more.

Speaking Engagements

  • On 5th October, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting (moved from July due to forecast low attendance)  Things are starting to happen in this area and I already know their NET Specialist Dr Mo Khan who is working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.

Writing and other types of Engagement (external) – watch this space as I’m working on quite a few projects concurrently.  I’m currently in a pool of patients who may be featured in a UK national, fingers crossed.

Social Media and Stats

Blog Milestone.  In September, I’m very close to 380,000 views! Thank you all so much Keep sharing! On track for 400,000 by end of the October.

Facebook Milestone.  I would love to achieve 6000 followers by the end of 2017 but this will be a challenge.  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.

Also check out my sister Facebook sites here (click on ‘Like’)

These are fallback  sites to counter the Facebook algorithm whereby you may not see all my posts on the main site:

Ronny Allan’s Community

Neuroendocrine Cancer Awareness and Networking

Instagram

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

Community Statistics (the measurement of my efforts on your behalf)

Figures

  • Facebook 5220.  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).
  • Twitter4153 / 3195 Follow me here @RonnyAllan1 / @NETCancerBlog
  • Total Blog Views: 379,320
  • Blog with most views: 12761 – The Human Anatomy of Neuroendocrine Cancer 
  • Most blog views in one day:  2043 on 15 January 2017.  Why the spike? ….. The Human Anatomy of Neuroendocrine Cancer” 
  • Most blog views in one week: 7538 in July 2017.
  • Most blog views in one month: 24142 in July 2017.  Why the spike? … these blogs here:
Home page / Archives More stats 2,482
Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis More stats 1,418
Steve Jobs – the most famous Neuroendocrine Cancer Ambassador we NEVER had More stats 1,326
Diagnosed with Neuroendocrine Cancer? 10 questions to ask your doctor More stats 1,253
Neuroendocrine Cancer – Incurable vs. Terminal More stats 1,212
Neuroendocrine Neoplasms – Grade and Stage (incorporating WHO 2017 changes) More stats 985
I’m still here More stats 869
Neuroendocrine Cancer Nutrition Blog 2 – Gastrointestinal Malabsorption More stats 846
Living with Neuroendocrine Cancer – Home Page More stats 824
Ignore this post about Neuroendocrine Cancer More stats 763
The Human Anatomy of Neuroendocrine Cancer More stats 759

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and they also keep me humble.  The sharing gives me a bigger platform.  A bigger platform generates more awareness.

 

Thanks for your great support in September.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

community_titled_transparent_2013-10-22

NETwork with Ronny © – Community Newsletter AUGUST 2017

background scene from my Instagram account – to see more check out the newsletter. Photo credit to Nick Lucas

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is August 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).

NET News

The following news items may be of interest:

  • PRRT takes a step forward to being formally approved in USA. FDA acknowledges receipt of revised application for approval.  Click here.
  • However, in UK, there is a threat that PRRT won’t be approved despite a positive recommendation by the scientific committee of the European Medicines Agency (EMA).  Advanced Accelerator Applications (AAA), the manufacturers of Lu-177 Lutathera for use on PRRT, has had to respond to the UK’s drug approver NICE’s negative recommendation.  Read more here.
  • GA-68 PET (NETSPOT) is still rolling out across the USA, see CCFs latest list by clicking here.
  • Ipsen launches the Brazilian version of ‘Living with NETs’ website.  Click here.  (See the English language version – click here).

What’s happening on my Blog Site?  

A quiet month.  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, includes updated blogs.

  • The Invisible NET Patient Population.  My latest published blog and received some great viewing figures (and this continues).  Controversial for some but backed up by facts.
  • NETs – not as rare as you think. An older post with some tweaks.  Again, controversial for some but backed up by facts.
  • Carcinoid vs Neuroendocrine – One of my most controversial posts – this is an older post which previously had an element of sitting on the fence. I jumped off the fence following some further research and period of reflection.  I was happy with some of the positive comments I subsequently received on this post.
  • Steve Jobs.  An updated version with some new research timelines added.  This post continues to receive hits daily even when I’m not sharing.  Most of the hits are from people searching and find my article online, an indication of the interest Steve Jobs still has today.  And many of the hits are NEW audiences.
  • NETwork with Ronny © – Community Newsletter JULY 2017.  My July 2017 newsletter ICYMI.
  • Your favourite posts.  All posts with viewing figures above 2000.

Misc Blog Stuff

  • There’s a lot of chatter about use of the word ‘fight’ in cancer parlance but many people are misrepresenting the word’s multiple meanings as per the most eminent English language dictionaries.  As for me, I’m ‘sticking to my guns’ on the subject.
  • I got some great comments on my monthly Lanreotide ‘butt dart’ post.  Feel free to add questions.  I may know some of the answers and cannot promise answers from Ipsen due to their regulatory arrangements but I will try!  Check out the discussion here …… ‘click here’.
  • My notification about the Ipsen HomeZone (or equivalent services within your own country) got an interesting response.  Since then many others have taken advantage by contacting Ipsen or their specialist asking about the service.  This has also led to feedback about the similar schemes from Novartis for Octreotide.  I’m happy that my post has provided publicity to services which help patients.  Read my post At Home with Lanreotide by clicking here.

Other Activity

August was a slower month in ‘new’ blogging terms mainly due to personal activities and the consequences of having a large internet footprint! Striking a balance is becoming more difficult.  I’m seeing a trend of low ‘new’ blog months, mainly due to external projects and a continuous stream of offline messages from patients (more on this later).  Also, I’ve been suffering with minor right hip pain but now seeing improvements working with a physiotherapist.  However, despite a low month for brand new blogs, I still managed to make the second highest monthly views ever……..Thank you all so much for the support.

Please join my 2017 awareness campaign event here (select ‘Going’)

I continue to receive a steady flow of private contacts, mainly from patients seeking information.  I don’t have an issue with private contact but please note my disclaimer.  Please also note that I cannot accept telephone calls on a one to one basis.  However …..the number of non-patients contacting me for other reasons (mainly to help with something) continues to grow and this is producing some great publicity and awareness.

By the time you read this update, the nominations and endorsements for the 2017 WEGO Health Awards will be closed.  If you remember last year, I made it to the final in two categories of Blog and Community, and then won the latter.  I should find out if I made the finals by the middle of September. Fingers crossed!  Many thanks to those who took the time and trouble to vote for me.

 

Awareness Activity in August 2017

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.

  • Article features.  I was featured in a well shared and positive article entitled A revolution in the treatment of Neuroendocrine Tumors. A very positive look at the new treatments coming through. I didn’t agree with some of the content but ‘hey ho’ I cannot control what others write.  You can check out the article by clicking here.
  • Twitter. 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 and are made aware of NETs in the process).  In Aug, I tweeted 130 times on my personal account which lead to almost 90,000 views.  I was mentioned 94 times by other tweeters and gained 64 new followers.  My tweet “Ignore this post” remains the most tweeted article about NETs ever posted on twitter.  Check it out – click here.
  • Daily Newsletter from my twitter feed (Nuzzel).  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 – you don’t need to have a twitter account to read, just sign up with an email.  Currently 294 subscribers – up 10% on last month.  Will you be number 300?
  • WEGO. I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  The recent awards will continue to showcase my work which has the effect of spreading Neuroendocrine Cancer awareness to NEW audiences.
  • Macmillan Cancer Support.  I’m proud to be a ‘Community Champion’ on the Macmillan Cancer Support Forum helping ‘outliers’ from the NET community there. There are only 27 champions for a site supporting hundreds of thousand patients.  I’ll be reporting more on this in the coming weeks.  This is the biggest cancer support organisation in the UK and I’m intent on developing relationships with various departments in this fantastic organisation.  On August 30th, one of my blogs made their “top picks” generating some NET awareness – check out Living with Cancer – 6 tips for conquering fear
  • Cure Magazine.  I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.  Cure Magazine has a readership of 1 million.  Click here to read more.

Speaking Engagements

  • On 5th October, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting (moved from July due to forecast low attendance)  Things are starting to happen in this area and I already know Dr Mo Khan who is a NET specialist working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.

Writing and other types of Engagement (external) – watch this space as I’m working on quite a few projects concurrently

Remember …….

Social Media and Stats

Blog Milestone.  In August, I tipped a 360,000 views! Thank you all so much Keep sharing! On track for 400000 by end of the October.

Facebook Milestone.  I would love to achieve 6000 followers by the end of 2017 but this will be a challenge.  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.

Also check out my sister Facebook sites here (click on ‘Like’).

Ronny Allan’s Community

Neuroendocrine Cancer Awareness and Networking

Instagram

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

Community Statistics (the measurement of my efforts on your behalf)

Figures

  • Facebook 5143.  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).
  • Twitter4091 / 3160 Follow me here @RonnyAllan1 / @NETCancerBlog
  • Total Blog Views: 360875
  • Blog with most views: 12568The Human Anatomy of Neuroendocrine Cancer 
  • Most blog views in one day:  2043 on 15 January 2017.  Why the spike? ….. The Human Anatomy of Neuroendocrine Cancer” 
  • Most blog views in one week: 7538 in July 2017.
  • Most blog views in one month: 24142 in July 2017.  Why the spike? … these blogs here:
Home page / Archives More stats 2,482
Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis More stats 1,418
Steve Jobs – the most famous Neuroendocrine Cancer Ambassador we NEVER had More stats 1,326
Diagnosed with Neuroendocrine Cancer? 10 questions to ask your doctor More stats 1,253
Neuroendocrine Cancer – Incurable vs. Terminal More stats 1,212
Neuroendocrine Neoplasms – Grade and Stage (incorporating WHO 2017 changes) More stats 985
I’m still here More stats 869
Neuroendocrine Cancer Nutrition Blog 2 – Gastrointestinal Malabsorption More stats 846
Living with Neuroendocrine Cancer – Home Page More stats 824
Ignore this post about Neuroendocrine Cancer More stats 763
The Human Anatomy of Neuroendocrine Cancer More stats 759

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and they also keep me humble.  The sharing gives me a bigger platform.  A bigger platform generates more awareness.

Thanks for your great support in August.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

community_titled_transparent_2013-10-22

Lanreotide for Lung NETs – SPINET Clinical Trial

Somatuline (Lanreotide)

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.

 

thanks for reading

NETwork with Ronny © – Community Newsletter JULY 2017

 

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is July 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).  July 26th was the ‘Cancerversary‘ of my diagnosis – I’m still here after 7 years and I’m apparently a veritable newbie!  There’s some great comments on my ‘I’m Still Here’ post – check them out … ‘click here’

NET News

The following news items may be of interest:

  • Telotristat Ethyl (Xermelo) takes a step forward to being approved in Europe. Click here.
  • PRRT takes a step forward to being approved in USA.  Click here.
  • Ipsen launches the German version of ‘Living with NETs’ website.  Click here.

What’s happening on my Blog Site?  

As per above, a quiet month.  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, includes updated blogs.

There’s a lot of chatter about use of the word ‘fight’ in cancer parlance but most people are misrepresenting the word’s multiple meanings as per the most eminent English language dictionaries.  As for me, I’m ‘sticking to my guns’ on the subject.

I got some great comments on my monthly Lanreotide ‘butt dart’ post.  Feel free to add questions.  I may know some of the answers and cannot promise answers from Ipsen due to their regulatory arrangements but I will try!  Check out the discussion here …… ‘click here’

NET Cancer Blog Activity

July was a slower month in ‘new’ blogging terms mainly due to holiday.  I’m seeing a trend of low ‘new’ blog months, mainly due to external projects and a continuous stream of offline messages from patients.  Also, I’m still suffering with minor pain which has decided to move to my right hip (hopefully localising where the real problem is).  Physiotherapist appointment is next week.  However, despite a low month for brand new blogs, I managed to totally smash my monthly blog view record (after smashing it last month too!)  ……..Thank you all so much for the support.

I continue to receive a steady flow of private contacts, mainly from patients seeking information.  I don’t have an issue with private contact but please note my disclaimer.  Please also note that I cannot accept telephone calls on a one to one basis.  The number of non-patients contacting me for other reasons (mainly to help with something) continues to grow and this is producing some great publicity and awareness.

I’ve been nominated for the 2017 WEGO Health Awards in three categories so far, Blog, Patient Leader Hero and Lifetime Achievement.  If you remember last year, I made it to the final in two categories of Blog and Community and won the latter.  A vote for me is a vote for Neuroendocrine Cancer awareness. VOTE HERE PLEASE

Click on ‘Endorse Ronny Allan’.  It defaults to ‘Blog’ but the other two are there via the drop down menu.  Thanks, I cannot get to the finals without the votes.

Awareness Activity in July 2017

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 and are made aware of NETs in the process). 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.  Currently 269 subscribers – up 12% on last month.
  • I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  Other irons are in the fire but unable to bring you firm news just yet.
  • I’m proud to be 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.  This is the biggest cancer support organisation in the UK.
  • I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.  Click here to read more.

Speaking Engagements

  • On 12 July, I delivered a ‘patient view’ presentation to Ipsen (UK) which was well received.
  • On 5th October, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting (moved from July due to forecast low attendance)  Things are starting to happen in this area and I already know Dr Mo Khan who is a NET specialist working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.
Me with some very nice Ipsen people! 12 July 2017 in London

Writing and other types of Engagement (external) – watch this space as I’m working on quite a few projects concurrently

Remember …….

Social Media and Stats

Blog Milestone.  In July, I tipped a THIRD OF A MILLION views! Thank you all so much Keep sharing! On track for 400000 by end of the year.

Facebook Milestone.  I met my target of 5000 followers a few months before my self inposed deadline date.  I’m very grateful!  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.

Instagram

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

Medicine

Figures

  • Facebook 5007.  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’)
  • Twitter4000 / 3095 Follow me here @RonnyAllan1 / @NETCancerBlog
  • Total Blog Views: 337313
  • Blog with most views: 12323The Human Anatomy of Neuroendocrine Cancer 
  • Most blog views in one day:  2043 on 15 January 2017.  Why the spike? ….. The Human Anatomy of Neuroendocrine Cancer” 
  • Most blog views in one week: 7538 in July 2017.
  • Most blog views in one month: 20498 in July 2017.  Why the spike? … these blogs here:
Home page / Archives More stats 2,482
Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis More stats 1,418
Steve Jobs – the most famous Neuroendocrine Cancer Ambassador we NEVER had More stats 1,326
Diagnosed with Neuroendocrine Cancer? 10 questions to ask your doctor More stats 1,253
Neuroendocrine Cancer – Incurable vs. Terminal More stats 1,212
Neuroendocrine Neoplasms – Grade and Stage (incorporating WHO 2017 changes) More stats 985
I’m still here More stats 869
Neuroendocrine Cancer Nutrition Blog 2 – Gastrointestinal Malabsorption More stats 846
Living with Neuroendocrine Cancer – Home Page More stats 824
Ignore this post about Neuroendocrine Cancer More stats 763
The Human Anatomy of Neuroendocrine Cancer More stats 759

 

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and the sharing gives me a bigger platform.  A bigger platform generates more awareness.

Thanks for your great support in July.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

community_titled_transparent_2013-10-22

At home with Lanreotide

 

The Somatuline ‘reservoir’ forming in the deep subcutaneous tissue

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.

side view of Lanreotide with needle cap off but with plunge protector still on

Boom!

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

Cake with Needle
Celebrating 100 Lanreotide injections

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
Somatuline Depot.
• 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
plans.
• 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
eligible.

Click here for more details.

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.

20190114_123409
Received, ready for next injection

 

 

So far so good.

You may also appreciated my other blog posts on Somatostatin Analogues and Lanreotide (Somatuline):

Lanreotide – it’s calling the shots

Lanreotide vs Octreotide

PoNETry – An Ode to Lanreotide

A video showing how Lanreotide works

Lanreotide trial for Lung NETs (SPINET)

Somatostatin Analogues and Delivery Methods in the Pipeline

Thanks for reading

Ronny

I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients includedThis is a Patients Included Site

Please Share this post for Neuroendocrine Cancer awareness and to help another patient

 

NETwork with Ronny © – Community Newsletter JUNE 2017

 

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is June 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).

NET News

The following news items may be of interest:

  • NETs in the UK National News.  Great publicity.  Featuring NET Patient Foundation.  Click here.
  • Personalised PRRT is highlighted.  Click here.
  • Everolimus and Sunitinib. In England, NICE approves Everolimus (Afinitor) and Sunitinib (Sutent). Read more by clicking here.
  • Videos from LACNETS.  I’ve not watched them all yet due to holiday but they are always great!  Click here.
  • PRRT.  News of a PRRT trial being set up for Inoperable Pheochromocytoma/ Paraganglioma. Not yet recruiting but read more here.
  • Immunotherapy.  Merkel Cell Carcinoma is already benefiting from an FDA approved drug with another pending.  Check out this link.
  • Awareness.  Giovanni from LACNETS generates awareness in her local area – I have no doubt that awareness saves lives.  Read here.
  • Lanreotide.  Ipsen announces approval in Japan for treating NETs.   Click here.

NET Cancer Blog Activity

June was a slower month in ‘new’ blogging terms mainly due to holiday but even during this holiday, I’m being invited to external projects and a continuing flow of private messages. I’m still suffering with back pain but patiently waiting to see a physiotherapist. However, despite a low month for brand new blogs, I still managed for the first time to break through the monthly blog view figure of 20000.  ……..Thank you all so much, a lot of this was down to your support for some scheduled posts whilst I was on holiday ♥

I continue to receive a steady flow of private contacts, mainly from patients seeking information.  I don’t have an issue with private contact but please note my disclaimer.  Please also note that I cannot accept telephone calls on a one to one basis.  The number of non-patients contacting me for other reasons (mainly to help with something) continues to grow and this is producing some great publicity and awareness.

I’ve been nominated for the 2017 WEGO Health Awards in three categories so far, Blog, Patient Leader Hero and Lifetime Achievement.  If you remember last year, I made it to the final in two categories of Blog and Community and won the latter.   The nominations period ends on 7th July and I’ll let you know how you can vote for me. A vote for me is a vote for Neuroendocrine Cancer awareness.

BREAKING NEWS (…ish).  I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.   You can see my profile here: http://www.curetoday.com/community/contributors

 

New (or significantly updated) 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:

Awareness Activity in June 2017

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 and are made aware of NETs in the process). 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.  Currently 239 subscribers – up 25% on last month.
  • I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  Other irons are in the fire but unable to bring you firm news just yet.
  • I’m proud to be 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.  This is the biggest cancer support organisation in the UK.
  • I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.  Click here to read more.

Speaking Engagements

  • On 7 July, I’ve been invited to speak for 10 minutes at the PLANETS patient conference in Southampton.  This is special for me as it’s where my major treatments took place and some of my medical team will be there.
  • On 5th October, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting (moved from July due to forecast low attendance)  Things are starting to happen in this area and I already know Dr Mo Khan who is a NET specialist working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.

Writing and other types of Engagement (external)

On 12 July, I’ve been invited to speak to Ipsen (UK). Still setting up this short notice meeting, details to follow in a separate post.  Additionally, I was interviewed by a health reporter and separately by a health consultant. I’m not at liberty to provide details yet but if anything is published in the public domain, I will of course publish it on my social media channels.

Remember …….

Social Media and Stats

Blog Milestone.  In June, I tipped over 310000 views! Thank you all so much Keep sharing! On track for 400000 by end of the year.

Facebook Milestone.  I’m aiming for 5000 followers 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.

Instagram

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

Figures

Where did June 2017 Blog views come from? – Top 10 countries:  Germany on the up (wunderbar). And thanks to USA!

 

For interest. the 10 Ten Facebook followers by Country – Germany still sneaking up (wunderbar wieder).  Interestingly Canada always reads more than Australia despite fewer followers.

 

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and the sharing gives me a bigger platform.  A bigger platform generates more awareness.

Thanks for your great support in June.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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Immunotherapy: Studies with 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).

Be cautious with 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 those considering a trial, I think it’s worth spending some time reading this article from Cancer.NET – Doctor Approved Patient Information from the American Society of Clinical Oncology – “What You Need to Know About Immunotherapy Side Effects“.

For Neuroendocrine Neoplasms, only Neuroendocrine Carcinoma of the skin (Merkel Cell Carcinoma) 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.

Worth also noting that NANETS 2018 reported limited use of Keytruda (see below) as a single agent to treat high grade Neuroendocrine Neoplasms.

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:

  • Hodgkin lymphoma in adults and children. It is used in patients whose disease is refractory (does not respond to treatment) or has relapsed after at least three other types of treatment.
  • Melanoma that cannot be removed by surgery or that has metastasized (spread to other parts of the body).
  • Non-small cell lung cancer that has metastasized. It is used:
    • With pemetrexed and carboplatin as first-line treatment in patients with nonsquamous disease.
    • As first-line treatment in patients whose cancer has the PD-L1 protein and does not have a mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene.
    • In patients whose cancer has the PD-L1 protein and got worse during or after treatment with platinum chemotherapy. Patients whose cancer has EGFR or ALK gene mutations should receive Pembrolizumab only if their disease got worse after treatment with an FDA-approved therapy for these mutations.
    • in combination with Pemetrexed and Platinum as first-line treatment of patients with metastatic, non-squamous non-small cell lung cancer.
  • Squamous cell carcinoma of the head and neck that has metastasized or recurred (come back) in patients whose disease got worse during or after treatment with platinum chemotherapy.
  • Urothelial carcinoma (a type of bladder cancer) that is locally advanced or has metastasized. It is used in patients who cannot be treated with cisplatin or whose disease got worse during or after platinum chemotherapy.
  • Microsatellite instability-high (MSI-H) cancer that is metastatic and cannot be removed by surgery. It is used in adults and children for:

    MSI-H cancer has certain genetic mutations and may not respond to some types of treatment.

  • The most recent approval in May 2017 MSI-H disease is a very interesting development as it’s the US FDA’s very first approval on a tissue/site agnostic basis. You can read about this approval here. Cancers of the breast, prostate, thyroid, bladder, colon, rectum and endometrium are just some of the cancers that have been found to have these biomarkers and would be new possible targets for Keytruda. There’s a great article which explains this approval in an easy way – click here to read.

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. More Information.

I found the following trials for high-grade NEC:

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.

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.

PDR001 (Spartalizamab) – click here.

Study of Pembrolizumab in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28) – NCT03054806

From Gastrointestinal Tumor symposium 2019.  “Disappointing results for single agent pembrolizumab in Well Differentiated NET. Response Rate 3.7%. Not a viable option.

Study for the Evaluation of Pembrorolizumab (MK-3475) in Patients with Rare Tumors (Experimental: Paraganglioma-Pheochromocytoma Group)

This study is recruiting at MD Andersen Houston Texas. Read more 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.

Criteria:

  • 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.

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

Disclaimer

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Most Popular Posts

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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