Ronny Allan – Living with Neuroendocrine Cancer

All you need to know about Peptide Receptor Radionuclide Therapy (PRRT)

Updated 23rd April 2024

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Updated 23rd April 2024

 Short PRRT Primer

What is Peptide Receptor Radionuclide Therapy (PRRT)?

What is PRRT?  PRRT stands for Peptide Receptor Radionuclide Therapy, an FDA-approved therapy used for systemic treatment of neuroendocrine tumors.

Peptide refers to the small molecule for this therapy. The Peptide used (e.g. DOTATATE or DOTATOC or DOTANOC) is very similar to Somatostatin, a hormone which binds to receptors found on neuroendocrine tumors.
Receptor refers to a specific target on neuroendocrine tumor cells that the peptide attaches to. After the peptide joins with a Receptor, it becomes attached and enters the targeted tumor cell.
Radionuclide refers to radioactive atom that is attached to the peptide. As the peptide enters the cell, it brings the Radionuclide into the tumor cell. The radionuclide (e.g. lutetium-177), then decays and emits radiation within the tumor cell.
Therapy refers to the idea that we are using this combination of Peptides, Receptors, and Radionuclides to Treat these targeted tumor cells, improve

For those who are still not sure what it’s all about. This is a non-surgical treatment which is normally administered intravenously. It’s based on the use of somatostatin receptors to attract a ‘radiopeptide’. The radiopeptide is a combination of a somatostatin analogue and a radioactive material. As we already know, somatostatin analogues (i.e. Lanreotide/Octreotide) are a NET cell targeting drug using somatostatin receptors, so when combined with radioactivity, it binds with the NET cells and delivers a high dose of targeted radiation to the cancer while preserving healthy tissue in an attempt to reduce or kill tumours. In general, patients tend to receive up to 4 sessions spaced apart by at least 2 months. PRRT will not work on all NETs and not everyone will be suited to this treatment. In general, for this treatment to be more successful, you must have somatostatin receptors in your tumours. Success rates are not 100% – it should not be considered a cure or ‘magic bullet’. However, the results are said to be pretty good in comparison to other therapies. The NETTER-1 trial data which has led to formal approval in Europe, USA and other areas, can be found here.

You may also see it described as “Radioligand Therapy” which means a particle which consists of a therapeutic radioactive isotope (radio) and the cell-targeting compound (ligand). 

Who can get LU177 Lutathera?

This is a controversial point, and you need to start with the wording of the various regional/national approvals:

As examples:

Europe (EU 27/28 countries plus Norway, Liechtenstein and Iceland) – The European Medicines Agency (EMA) approval wording is as follows:

“….. the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults”.

USA – The FDA approval wording is as follows:

“….. the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors, in adults”.  On 23rd April 2024, pediatric patients aged 12 and above are now included.  See pediatric section below. 

These approvals remain controversial because the term GEP-NETs technically excludes lung tumours. That’s not to say tumours outside the GEP-NET area cannot get access, it just makes it more difficult to access due to the approvals. The US approval has a much wider scope given the introduction of a Grade 3 well differentiated NET in the latest classification systems. Access criteria in different countries/healthcare locations may be adapted for specific scenarios to suit limited availability and costs.

There can be authorised use of Lu177 Lutathera and other PRRT variants outside of the normal approvals system, so it might be possible to get access to non GEP-NET tumour types.  However, even within GEP-NETs, patient selection is not straightforward.  Read more in this guidance document from NANETS/SNMMI.  There’s also an interesting Italian study into patient selection and also how to monitor the benefits of this therapy during and after treatment completion – click here.  

What about Grade 3 (High Grade) Neoplasms?

The main treatment for Grade 3 is chemotherapy, particularly poorly differentiated types. PRRT tends to work better with efficient somatostatin receptors (i.e. somatostatin receptor-positive tumours). The European approval wording only covers Grades 1 and 2. The US FDA approval indicates “somatostatin receptor-positive tumors”. It’s also worth noting that with Grade 3, working somatostatin receptors are more likely to exist in Grade 3 well differentiated NETs, particularly in the lower Ki-67 readings (less than 55%). However, there’s an interesting study from Australia which might be useful to read – check out the abstract here (note the full version is not available free).

2019 Updated data for Grade 3 Neuroendocrine Neoplasms:

“Compared to studies evaluating the efficacy of chemotherapy for NEN patients with a Ki-67 index less than or equal to 55 percent, PRRT has a longer overall survival rate–22 months versus 14 months,” the researchers pointed out. “These results suggest that PRRT, rather than chemotherapy, may be a superior first-line therapeutic option in selected patients with a high level of SSTR expression and a Ki-67 index of less than or equal to 55%.” Read more here. This supports the new thinking behind the revised classification of high-grade tumours published in 2017 – read more here

Another European study stated “This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3”.

Click here to read.

Merkel Cell Carcinoma. Although not indicated for this type of Neuroendocrine Neoplasm, there is evidence to suggest that this skin Neuroendocrine Carcinoma does express somatostatin receptors. Read more here.

Case Rep Oncol 2019;12:98–103 Merkel Cell Carcinoma https://doi.org/10.1159/000496335

Now read the clinical trial section below

What about Lung NETs?

The  term “GEPNETs” does not cover thoracic (Lung/Thymus) meaning that  Lung NETs are technically not approved for Lutathera.  The problem is the somatostatin receptors are not always as efficient as they are with GEPNETs.  This study abstract from Moffatt Cancer Center explains it better than I can (click on the blue link to read).

Somatostatin Receptor Expression in Lung Neuroendocrine Tumors: An Analysis of DOTATATE PET Scans

Taymeyah Al-ToubahJaime Montilla-SolerGhassan El-HaddadMintallah Haider and Jonathan Strosberg

Clinical Trial: Lu-177 DOTATOC (PRRT) in adult subjects with Somatostatin receptor (SSTR) positive Pulmonary, Pheochromocytoma, Paraganglioma, Unknown primary, and Thymic Neuroendocrine Tumors (the PUTNET trial)

What about Pheochromoctyoma/Paraganglioma?

23rd April 2024 – see breaking news re Pediatric Patients in the Pediatric Section below.

This article discusses the efficacy of PRRT in Pheo/para – click here.

There are actually trials for Pheochromocytoma/Paraganglioma (Pheo/Para). It is known that Pheo/Para can have somatostatin receptor tumours.

1. Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs. The objective of this trial is to learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return. – read more by clicking here

2. Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs.  The objective of this trial is to assess the safety and tolerability. You can read about the trial here.

3. PUTNET trial.  See the box above. (….tumours not covered by GEPNETs”)

What about pediatric patients?

Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs. The objective of this trial is to learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return.

The multicenter trial sponsored by Advanced Accelerator Applications will study the safety and dosage of Lutathera (Lutetium [177Lu] oxodotreotide/dotatate) in patients between 12 to 17 years of age with somatostatin receptor-positive GET-NETs and PPGLs (pheo/para). 

read more by clicking here

BREAKING NEWS ON 23RD APRIL 2024

The Food and Drug Administration approved lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications USA, Inc., a Novartis company) for pediatric patients 12 years and older with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.  This also incudes Pheochromoctyoma and Paraganglioma. This represents the first FDA approval of a radioactive drug, or radiopharmaceutical, for pediatric patients 12 years of age and older with SSTR-positive GEP-NETs.

Read the FDA approval by clicking here 

What about Carcinoid Syndrome?

Technically, for many people surgery including debulking surgery and/or somatostatin analogues, will help control carcinoid syndrome.  However, for some people, breakthrough symptoms till occur

A new study from NET experts in Netherlands, suggests that PRRT with 177Lu-DOTATATE for symptomatic control of refractory Carcinoid Syndrome (i.e. not adequately controlled by somatostatin analogues) is a viable, safe and effective option for patients with stable and recently diagnosed advanced midgut NENs.  The study also showed reductions in 5HIAA and I suspect this might be useful to those with very severe effects of carcinoid syndrome with highly elevated 5HIAA.  

Read more here

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for symptomatic control of refractory carcinoid syndrome. Wouter T. Zandee, MD, PhD; Tessa Brabander, MD, PhD; Anela Blaževid, MD; Noémie S. Minczeles, MD; Richard A. Feelders, MD, PhD; Wouter W. de Herder, MD, PhD; Johannes Hofland, MD, PhD. © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society

July 2021 – New Section – Side Effects of PRRT (Lutathera)

Like many anti-cancer drugs there are side effects.  Within the approval system, these are carefully documented – for example, see the Lutathera manufacturer’s website – click as appropriate US Patients, European Patients.  I suspect there won’t be much difference in other geographical areas.

In 2021, the output from two small studies was published by the Society of Nuclear Medicine and Molecular Imaging. and Mayo Clinic.  Both studies indicated there was a small risk PRRT can lead to bowel obstruction in patients with mesenteric or peritoneal disease, likely by inducing inflammation. IMHO, more studies, bigger studies are needed, as there could have been a higher than average of peeps with mesenteric problems over the period data was collected.

Strosberg JR, Al-Toubah T, Pellè E, Smith J, Haider M, Hutchinson T, Fleming JB, El-Haddad G. Risk of Bowel Obstruction in Patients with Mesenteric or Peritoneal Disease Receiving Peptide Receptor Radionuclide Therapy. J Nucl Med. 2021 Jan;62(1):69-72. doi: 10.2967/jnumed.120.242875. Epub 2020 May 22. PMID: 32444368. “Risk of Bowel Obstruction in Patients with Mesenteric or Peritoneal Disease Receiving Peptide Receptor Radionuclide Therapy – PubMed” 

The Moffat report – click here

The second report requires a login.

What is Alpha PRRT?  

Said to be the next generation, it uses alpha-emitter tech rather than the currently approved beta-emitter tech.

Click here to read more or click the picture below.

Are there any Guidelines for PRRT?

Until a few years ago, most PRRT was done via clinical trials and early access programs. However, while national guidelines on how PRRT should be delivered do exist, a generic set of formal guidelines has been developed collaboratively by the North American Neuroendocrine Tumor Society (NANETS) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Read these here for further information about Lu-177 PRRT including these topics:

  1. BACKGROUND
  2. TREATMENT OVERVIEW
  3. PATIENT SCREENING
  4. SOMATOSTATIN ANALOG THERAPY
  5. TREATMENT LOCATION
  6. ROOM PREPARATION
  7. PATIENT PREPARATION
  8. AMINO ACID SOLUTIONS
  9. ANTIEMETIC MEDICATIONS
  10. RADIOPHARMACEUTICAL ADMINISTRATION
  11. DOSAGE MODIFICATIONS FOR ADVERSE REACTIONS
  12. PATIENT MONITORING AND POTENTIAL REACTIONS
  13. RADIATION SAFETY
  14. DOSIMETRY AND POSTTREATMENT IMAGING
  15. TOXICITY
  16. FOLLOW-UP

One of the most FAQs in my patient group is the guidelines for contact following PRRT treatment.  People also ask about pets but I have never seen animals mentioned in any guideline document.  

The following extract from above is based on USA (but despite that, patients in US hospitals appear to be given a wide range of information.

Note: the above guidelines may differ from country to country and even within countries due to local regulations in force.

Always consult your specialist or treatment centre for the guidelines which apply to your treatment.  Do not trust what you are told in patient groups, it could be wrong/unnecessary/not enough. 

 

Somatostatin Analogues

Interest point. The above guidelines suggest stopping and starting periods for somatostatin analogues when being treated with PRRT.  However, while these guidelines remain in place, a new study in Nov 2021 indicates that small intestine NETs may benefit from an injection of somatostatin analogues at the beginning of each cycle. The conclusion is here:

“SSTR recycling is faster in small-intestinal NETs than in liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.”

Read the study here.  Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT | EJNMMI Research | Full Text (springeropen.com)

Can I have PRRT more than the regulated 4 times?  (retreatment or salvage PRRT)

This is complex and will rely on individual healthcare arrangements in place plus in insurance-based systems, willingness of insurance companies to cover costs. However, there is a recently released study covering some data from what is known as “Salvage PRRT“. Salvage PRRT, defined as a re-challenge with one or more 177Lu-DOTATATE therapy cycles after 4 initial PRRT cycles with initial response. Read more here. I have one lady on my social media sites who has had almost a dozen cycles.

There’s another study coming out of NANETS symposium 2020, where the term “re-treatment” is introduced based on the addition of 2 further cycles (total 6) which concluded that retreatment with Lutathera-based PRRT provided an encouraging median PFS in a relatively refractory setting among patients with advanced NETs and it wasn’t really associated with a worsened safety profile compared with initial PRRT. 

This study published in 2024 suggests retreatment of PRRT is generally safe.  Click here to read. 

Theranostics

Understanding the terminology is half the battle in understanding the latest developments. I’ve included somatostatin receptor PET (SSTR PET) e.g. Ga-68 PET scans within this section as the term ‘Theranostics‘ is becoming a commonly used theme. Theranostics is a joining of the words diagnostics and therapy.

LUTATHERA is the radionuclide ‘mix’ for use in Peptide Radio Therapy Treatment (PRRT). You may also see this drug called ‘Lutetium’ or ‘Lu-177 dotatate’, or just ‘Lu-177’ on its own. Yttrium 90 (Y-90) is a radionuclide also used in PRRT.

NETSPOT (USA) or SOMAKIT TOC (Europe) is not PRRT but it is the commercial name for the radiopeptide used in Gallium 68 (Ga-68) PET diagnostic scans.

Together they form a ‘theranostic pair’. Theranostics is apt as together (NETSPOT / SOMAKIT TOC and Lutathera), both target NETs expressing the same somatostatin receptor, with Lutathera intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version.

Moreover, thanks to the theranostic approach that nuclear medicine allows, Novartis/AAA’s NETSPOT/SomaKit TOC products will be able to determine when Lutathera is the appropriate treatment.

Read more about Theranostics by clicking here.

What’s next for NETs and PRRT including Clinical Trials?

Some trials are featured in the “What about …..” sections above. 

Read the latest news on the NETTER-2 trial here. This is designed to look at the benefits of using PRRT on Grade 2 and Grade 3 patients as a first-line treatment. However, also read this

Other associated PRRT trials are in the pipeline or underway or complete, some based on Lutathera LU177 and others based on new radionuclides:

See this great summary from NET Research Foundation of what might be next plus basic facts about PRRT – click here

The future of PRRT delivered by Dr Richard Baum who is the most experienced PRRT doctor on the planet.  click here

Interest point – Trial of an antagonist PRRT usng 161Tb-dota-lm3 radioligand

This is an interesting trial and has been described as “beta plus” given the advantages over the current beta PRRT system. Click here or on the picture below.

Generic PRRT?

As at 12 Jan 2024, nothing approved but it is in the pipeline.

Read more here or click on the picture below.

Click on the picture to read more

Where can I get PRRT?

Where can I get PRRT?

Regional Updates

The aim of this section is to update on a regional basis in order to inform an international community of followers and readers.  This information changes all the time

Background

I wanted a place to review what is happening globally given my following. In many countries, however, I’m dependent on feedback from patients in those countries. Please note this is not intended to be a 100% complete breakdown on everything about PRRT or PRRT centres – it’s a summary. It should be clear from below but please bear that in mind when reading.

This section of this article will cover each region, indicating where PRRT can be obtained (as far as I know). It is not designed to indicate whether this is through public or private facilities (this will depend to too many factors beyond the reach of this article). Please note this is not intended to be a 100% complete breakdown on every single PRRT centre – it’s a summary. This actually should be clear from below but please bear that in mind when reading.

United Kingdom

On 29 August 2018. National Institute for Health Care Excellence (NICE) England has formally published that Lutetium (177Lu) oxodotreotide, within its marketing authorisation, is an option for treating unresectable or metastatic, progressive, well-differentiated (grade 1 or grade 2), somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (NETs) in adults. Click here to read the approval. Currently available in the following NHS locations:

  • London – at least 4 locations – Royal Free, Guys and St Thomas, University College (UCH), King’s College
  • Liverpool – The Royal
  • Manchester – The Christie
  • Sheffield – Weston Park
  • Bristol – Bristol Oncology Centre
  • Newcastle – Freeman Hospital
  • Coventry – University Hospital
  • Glasgow
  • The Royal Surrey St Lukes Guildford
  • University Hospital Southampton
  • Medway Maritime Hospital, Gillingham, Kent
  • Oxford, Churchill Hospital
  • Leicester

On 9 July 2018. The Scottish Medicines Consortium (NICE equivalent) approved lutetium 177Lu (Lutathera) for patients in NHS Scotland. Good news for Scotland once their hospitals have the capability to deliver. Scottish patients would then not need to travel to England for the NHS Scotland-funded treatment. Read more here.

It is funded in Wales and Northern Ireland but is currently administered in England with inter-NHS budget transfers.

Canada

On 7th Feb 2019, Health Canada approved Lutathera™ (lutetium (177Lu) oxodotreotide) for the treatment of unresectable (not removable by surgery) or metastatic, well-differentiated, somatostatin receptor-positive (expressing the somatostatin receptor) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults with progressive disease. The treatment was previously available on a trial basis. Read more here.

Site updates to follow but the following trial locations may be up and running first:

  • Juravinski Hamilton
  • LHSC London
  • PMCC Toronto
  • Sunnybrooke Toronto
  • Cross Cancer Institute, Edmonton

USA

PRRT was approved in USA on 26 Jan 2018. The approval is for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Click here.

The LUTATHERA US website contains a map search which can be found at this link.

Europe (excluding UK which is listed above)

The European Medicines Agency (EMA) “market authorisation” received a positive indication on 20th July followed by EC approval on 29 Sep 2017. The positive indication reads “Lutathera is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP NETs) in adults”. Of Course, the decision to fund the drug will be with national approval organisations. Whilst I’m sure there are many more, these well-known centres have been making PRRT available for some years (but please note there are others):

Denmark – ‘Rigshospitalet’ since 2009. They have treated around 250 patients- and given 800 treatments.

Finland – Helsinki: Docrates Cancer Center

France – Hopital Beaujon AP-HP, Clichy (next to Paris)

Germany:

Italy – Milan, European Institute of Oncology

Netherlands – the combined NET centres of the UMCU Utrecht and AVL Amsterdam have an ENET certification and they both do PRRT.

UMCU – Utrecht
https://www.umcutrecht.nl/nl/Ziekenhuis/Ziekte/PRRT-behandeling-bij-NET-kanker
(only available in dutch)

AVL – Amsterdam
https://www.avl.nl/behandelingen/peptide-receptor-radionuclide-therapie-prrt/
(only available in dutch)

Rotterdam Treatment Centreclick here

Poland – Poland, Maria Skłodowska-Curie Institute of Oncology, regional branch in Gliwice

SerbiaClinical Center Kragujevac, Centre of Nuclear Medicine
Slovenia – Ljubljana, University medical Centre Ljubljana

Sweden – Department of Endocrine Oncology Uppsala University Hospital – click here

Switzerland – University Hospital Basel, Radiology & Nuclear Medicine Clinicclick here. The University of Zurich also has excellent facilities – click here (call first to see if they accept patients not treated in Zurich)

I’d be interested to hear from countries in Europe with their full list of centres or a link to it.

Australia

Australia seems to be ahead of the game or that is what I sense when I read output from there. There’s a good section on the Australian effort – click here.

New Zealand

EDIT.  Due to COVID, an interim arrangement was put in place in Auckland. However, in July 2021, it was confirmed this was to become a permanent arrangement.  Read more here.

Original info.  These guys have had to fight to get some progress on the provision of PRRT. Currently, New Zealanders have to go to Melbourne Australia for treatment – almost 50 New Zealanders with NETs are currently raising tens of thousands of dollars to pay for treatment in Australia because the life-prolonging treatment isn’t available locally. But this could change in 2018. Unicorn Foundation New Zealand announced that Pharmac, the New Zealand government agency that decides which pharmaceuticals, have said that PRRT will be funded for patients with medium priority for the treatment of unresectable or metastatic, well-differentiated NETs (irrespective of primary site) that express somatostatin receptors.

Africa

South Africa:

India

I have been contacted by CNETS India to add this to the list.

PRRT is now available in more than 10 cities in India including Delhi, Mumbai, Chennai, Chandigarh, Lucknow, Pune, Vellore, Vishakapatnam, Ahmedabad, Baroda, Kolkata, Jaipur. Both Lu177 and Actinium 225 / alpha PRRT is available in Delhi and a few other centres. Kind regards Dr Sugandha Dureja.

From patients I’m told the waiting list is long but the cost is much lower than in other countries,

Middle East, Asia, Far East (less India) 

Azerbaijan – Nuclear Medicine Centre in Baku, Lu-177-DOTATATE and Ас-225-DOTATATE. Click here.

Turkey
– Istanbul, Dr.Levent Kabasakal.

IsraelHadassah Medical Center, Jerusalem – click to read

Lebanon – The American Hospital of Beirut – Dr Ali Shamseddine “We have started using Lu-177 here in Lebanon. So far, we have treated 3 patients, with good response. The operational cost is much less than in Europe”.

Kuwait – Kuwait Cancer Control Center (KCCC) – read article here.

Malaysia Sunway medical Centre, Beacon hospital

Pakistan – check out this article – click here

Singapore – Singapore General Hospital and National University Hospital.

Hong Kong – Queen Elizabeth Hospital and Hong Kong Sanatorium & Hospital.

PhilippinesSt. Luke’s Medical Center, Global City, Taguig, Metro Manila.

South America

Brazil – Hospital SÍRIO LIBANÊS, SÃO PAULO

ChileInstituto Oncológico Fundación Arturo López Pérez, Santiago

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

General Clinical Trials Disclaimer

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 in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact.  If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 

 
 
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