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| Wiemar & Bad Berka, May 09 |
I have written about my results, and this "NOVEL THERAPY" and "NOVEL IMAGING", not available in North America!
Also, as noted in the past, I started this blog to post my JOURNEY&SHARE INFORMATION, for the readers searching for data in order to empower themselves, and if appropriate, discuss these new findings with their MD.
This is how I found some of my treatments- clinical trial and PRRT, through the internet, 1-1 discussions with others and prayer!
This blog is set around my story, experiences/"adventures" and the years I have spent studying this damn monster! ("keep your enemies close, your NET tumor, uninvited friends, closer") in order to live attempt to live a good quaility of life and stay alive.
I made this very important blog post relative to data on prrt therapies and treatments (including studies, videos, etc),
which I hope is of value to the blog reader.....
(ALSO REFER TO LINKS ON LEFT IN SECTIONS...there is a lot of data ON ALL SUBJECTS AND THERAPIES! AS IN THE DISEASE, PRRT THERAPY IS NOT FOR EVERYONE AND TIMING IS EVERYTHING!)
Overview
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| PRRT, administered via IV infusion in arm |
During my "stay live European Vacation" trip in May, 2009 Bad Berka trip, I made a concerted effort to document the therapy in detail.
I did this as potential help to the reader, IF YOU NEED IT, and also send emails during my trip connected BB with some very good USA Md's, which I visited prior during March/April 09. We had "talked" PRRT during my visits, but at the time they did not have a PRRT contact.
> THEY DO NOW AND ARE USING BAD BERKA WHEN APPROPRIATE!
The purpose was to "OUT" this "novel therapy" (its been around since 1999) and, the new imaging and treatment options. I have included a lot of research, and added my experience, to address some of the issues/questions I have heard prior on this-"it dangerous", "it is nephrotoxic", "it does not work", etc?
So, I went to save attempt to save my life, if possible, and I used this trip to publish PRRT data-- the good, bad and ugly!
During my trip to BB in May 2009, I captured the event thru pictures of the trip, center and equipment, and documented the therapy process and my results in detail. (http://www.renalcarcinoid.com/2009/05/may-26-day-after-my-own-little.html )
I documented my event daily, and "my day" in PRRT treatment.
This is meant to help you, whether you use this or not, agree with it or not (you will learn very little is agreed to in this diseae with everything!). But at least it is now "out there" , as well as in other blogs, such as Anthony Vizzari's blog and experience who went in the past:
( http://anthonyvizzari.blogspot.com/2010/02/live-from-bad-berka-its-prrt.html )
WHY THE INTEREST PRRT?
Good question! But its easy answer when you think about it.
PRRT is different- its un approved in the USA, it has no formal marketing, drug/marketing reps and or md's touting the drug/therapy, no major company sponsoring studies, conferences (except during some of carcinoid conferences, at times), and some very big competitors, which PRRT is up against! Finally, PRRT deals with radiation, which is a always "red light' with the FDA, especially without deep pocket companies financing/influencing it!
For comparison, take the newly used for carcinoid drug, which I took for 16 months, "AFFINITOR" (RAD001).
Although not currently approved for NET's, it is approved for other indications (and therefore Md's can give it to a patient), there are clinical trials going on in the USA for NETs to enroll in. Its a good drug and helps many people and has shown activity in NET tumors.
If you were to search for information on the drug on the Internet (the "official" web site is on my blog, left, btw), one will find many web sites, videos, video discussions, presented in Oncology conferences, with big booths sometimes staffed by respected Md's & giving out information; seminars, CME training on the Internet and conferences, with most sponsored by the manufacturer of the drug themselves. In addition, there are strong relationships by respected NA Md's, that have long relationships with the drug and company, who believe in, and generally very supportive for the therapy. Net, the entire "team and marketing arm" is in place.
There is much data and marketing literature available, perhaps advertisements, introducing us to the drug, and reps following up wiuth Md's regularly on "detail visits" to inform them of the latest news.
To be clear, it is the drug company's responsibility to educate people on their drug, and to their shareholders to market and sell it aggressively. This drug works on NET tumors and the system is set to teach and market it!
The bottom line, a patient has many opportunities to learn about these "FDA approved" (and almost approved), big phamra drugs and therapies, studied/approved in the USA, thru available resources, marketing and reps supporting their particular drug and/or therapy. The system works-- it educates Md's and others on the efficacy of the drug, options for its indications.
However, for PRRT, it is different and information is typically lacking in the same structure as other therapies....
My Opinion Only
The PRRT therapy does not have a large pharma company backing it. It has no central organizational structure, disseminating information and developing study data on the product, results, etc.
It's principally a European led therapy. It does not market itself well, if at all, nor does it not have the drug rep network structure to meet with the medical professionals on a going basis. It has not invested in the "final solution" for this therapy-- "randomized, double blind, multi center, clinical trials. (however, there is enough actual data to compensate for this, I BELIEVE).
In addition, the therapy competes against current therapies, making it more vulnerable to competitive practices. Unless one gets the information from one of the carcinoid sponsored conferences, where at times PRRT Md's and topic are presented, or informally, or thru the Internet, or perhaps their Md (but normally it's YOU THAT NEED TO BRING THIS TOPIC UP, in detail), the data is hard to come by!
Finally, I post because I believe in the therapy- IT WORKED FOR ME- and think it is NOT RIGHT to have this option for patients, readily available in most of Europe, Australia, soon in Singapore, BUT not in North America? HIV patients did not accept bureaucracy or "it can;t be done" in finding options and therapies and really pushed the system. The disease is now controlled....
I have experienced of surgeries, trials, drugs, I have read and have a deep understanding about this disease, and options. I know, THAT EVERYONE IS DIFFERNET, BUT THIS THERAPY IS EFFECTIVE. PERHAPS NOT FOR ALL, BUT EFFECTIVE FOR MANY, AND SHOULD BE MADE AVAILABLE or INFORMED OF THE OPTION.
meanwhile, I also continue to post data, on all therapies and options, for those interested enough to read and learn about them.
I did this as potential help to the reader, IF YOU NEED IT, and also send emails during my trip connected BB with some very good USA Md's, which I visited prior during March/April 09. We had "talked" PRRT during my visits, but at the time they did not have a PRRT contact.
> THEY DO NOW AND ARE USING BAD BERKA WHEN APPROPRIATE!
The purpose was to "OUT" this "novel therapy" (its been around since 1999) and, the new imaging and treatment options. I have included a lot of research, and added my experience, to address some of the issues/questions I have heard prior on this-"it dangerous", "it is nephrotoxic", "it does not work", etc?
So, I went to save attempt to save my life, if possible, and I used this trip to publish PRRT data-- the good, bad and ugly!
During my trip to BB in May 2009, I captured the event thru pictures of the trip, center and equipment, and documented the therapy process and my results in detail. (http://www.renalcarcinoid.com/2009/05/may-26-day-after-my-own-little.html )
I documented my event daily, and "my day" in PRRT treatment.
This is meant to help you, whether you use this or not, agree with it or not (you will learn very little is agreed to in this diseae with everything!). But at least it is now "out there" , as well as in other blogs, such as Anthony Vizzari's blog and experience who went in the past:
( http://anthonyvizzari.blogspot.com/2010/02/live-from-bad-berka-its-prrt.html )
WHY THE INTEREST PRRT?
Good question! But its easy answer when you think about it.
PRRT is different- its un approved in the USA, it has no formal marketing, drug/marketing reps and or md's touting the drug/therapy, no major company sponsoring studies, conferences (except during some of carcinoid conferences, at times), and some very big competitors, which PRRT is up against! Finally, PRRT deals with radiation, which is a always "red light' with the FDA, especially without deep pocket companies financing/influencing it!
For comparison, take the newly used for carcinoid drug, which I took for 16 months, "AFFINITOR" (RAD001).
Although not currently approved for NET's, it is approved for other indications (and therefore Md's can give it to a patient), there are clinical trials going on in the USA for NETs to enroll in. Its a good drug and helps many people and has shown activity in NET tumors.
If you were to search for information on the drug on the Internet (the "official" web site is on my blog, left, btw), one will find many web sites, videos, video discussions, presented in Oncology conferences, with big booths sometimes staffed by respected Md's & giving out information; seminars, CME training on the Internet and conferences, with most sponsored by the manufacturer of the drug themselves. In addition, there are strong relationships by respected NA Md's, that have long relationships with the drug and company, who believe in, and generally very supportive for the therapy. Net, the entire "team and marketing arm" is in place.
There is much data and marketing literature available, perhaps advertisements, introducing us to the drug, and reps following up wiuth Md's regularly on "detail visits" to inform them of the latest news.
To be clear, it is the drug company's responsibility to educate people on their drug, and to their shareholders to market and sell it aggressively. This drug works on NET tumors and the system is set to teach and market it!
The bottom line, a patient has many opportunities to learn about these "FDA approved" (and almost approved), big phamra drugs and therapies, studied/approved in the USA, thru available resources, marketing and reps supporting their particular drug and/or therapy. The system works-- it educates Md's and others on the efficacy of the drug, options for its indications.
However, for PRRT, it is different and information is typically lacking in the same structure as other therapies....
My Opinion Only
The PRRT therapy does not have a large pharma company backing it. It has no central organizational structure, disseminating information and developing study data on the product, results, etc.
It's principally a European led therapy. It does not market itself well, if at all, nor does it not have the drug rep network structure to meet with the medical professionals on a going basis. It has not invested in the "final solution" for this therapy-- "randomized, double blind, multi center, clinical trials. (however, there is enough actual data to compensate for this, I BELIEVE).
In addition, the therapy competes against current therapies, making it more vulnerable to competitive practices. Unless one gets the information from one of the carcinoid sponsored conferences, where at times PRRT Md's and topic are presented, or informally, or thru the Internet, or perhaps their Md (but normally it's YOU THAT NEED TO BRING THIS TOPIC UP, in detail), the data is hard to come by!
Finally, I post because I believe in the therapy- IT WORKED FOR ME- and think it is NOT RIGHT to have this option for patients, readily available in most of Europe, Australia, soon in Singapore, BUT not in North America? HIV patients did not accept bureaucracy or "it can;t be done" in finding options and therapies and really pushed the system. The disease is now controlled....
I have experienced of surgeries, trials, drugs, I have read and have a deep understanding about this disease, and options. I know, THAT EVERYONE IS DIFFERNET, BUT THIS THERAPY IS EFFECTIVE. PERHAPS NOT FOR ALL, BUT EFFECTIVE FOR MANY, AND SHOULD BE MADE AVAILABLE or INFORMED OF THE OPTION.
meanwhile, I also continue to post data, on all therapies and options, for those interested enough to read and learn about them.
Remember, I am not a medical doctor; however, I was not a medical doctor in March 2009, alone, in pain, tears and without an EFFECTIVE therapy/option that suited me at the time.
I saw a video on the Internet on Sunday night, relative to Carcinoid and PRRT & imaging options performed in Europe and presented by Dr Richard Baum. The conference and video was from the Asia Pacific CNETS center conference & the video has since been posted on YouTube by CFCFoundation. (sites on links on left)
I saw a video on the Internet on Sunday night, relative to Carcinoid and PRRT & imaging options performed in Europe and presented by Dr Richard Baum. The conference and video was from the Asia Pacific CNETS center conference & the video has since been posted on YouTube by CFCFoundation. (sites on links on left)
This started me on the path of research, many discussions with Md's, verification tests, and many prayers, which led me to decide and act on this therapy.
I captured my "European Vacation trip" notes throughout this blog.
However, for ease, I put a summary together w/links, the video link, and plus some of the pictures on this post, which gets one a "80 for 20" on my treatment journey, experience, video and study data relative to PRRT and PET ga 68.
The data meant a lot to me and I hope it's of help to you!
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What is PRRT?
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| BB Hospital, May 09 when I arrived! |
The link below, is a detailed study by the Bad Berka Hospital, (which I have on the links on the left side of the blog, but since I have so much data on the blog, I decided to re-post it here).
I initially posted the first study doc, on a prior blog post, way back in June 2009...(go find it!)
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| "Billy Idol" look in CT w/ Pazopanib, Jan 08 |
I have posted at length, in the beginning of my blog which started August, 2008, about these experiences
(BTW, the 2nd blog entry on 8/2009 outlines my clinical history).
Information.
My disease is called Renal Carcinoid (very rare but a NET tumor)(or Neuroendocrine Carcinoma, primary in the right kidney), with intermediate/Atypical grade tumor (I have aggressive disease and was given 5 years to live in 2004 by a well known carcinoid MD).
How do I know what type of tumor I have? Via a tumor staining...one way is thru the "ki index" staining (another is called High Power Field HPF). Mine is 10% primary tumor, & 20-30% lymph nodes.
The disease presented itself initially mets to a lymph node, 18 months later the primary was discovered but I then also had mets to the liver, retropreitonium, and more lymph nodes!
I write about me to tell you that you may be facing your own challenges, but there is hope and therapies! So don't give up and stay active!...
Hell, as I am still alive 9 years later, due in large part to the medical personal that have helped me during these years, and staying aggressive with my disease therapy!
Prior to PRRT
With my prior history, however, I received very little interest or questions via this blog on the things I was doing. In large part due to reasons above I believe...we have all "been there done that" with surgery, Sando, etc.
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| Patient and Professor Baum, May 2009 |
Initially it was from some of my "noid" friends, and then by blog strangers, who came across my web site, while searching for data to their own issues, for a very complex and varying disease.
So with this in mind, I started to post much more about this therapy.
How did I start the process of learning? I saw the PRRT video by Dr Baum (4-6 times), starting reading study data (links on the left side of blog) such as the article below.
This which outlines in detail, from a Nuclear Medicine point of view, how PRRT (and other therapies) are used for NET disease.
How did I start the process of learning? I saw the PRRT video by Dr Baum (4-6 times), starting reading study data (links on the left side of blog) such as the article below.
This which outlines in detail, from a Nuclear Medicine point of view, how PRRT (and other therapies) are used for NET disease.
Although the article is written by Bad Berka, it references study data from others centers-Basel, Rotterdam.
Remember, although I tend to write about BAD BERKA CLINIC in my blog primarily (I know more about them),
I also have studies, links and patient blogs on other centers in this blog, that perform cutting edge NET/Carcinoid therapy in Europe-
Uppsala, Sweden
Rotterdam, Netherlands
Basel, Switzerland.
I have written all the centers in the past for additional information, links, pictures, questions. I have received responses from Uppsala and Rotterdam.
I THANK THEM BOTH FOR TAKING THE TIME TO RESPOND!
Remember, although I tend to write about BAD BERKA CLINIC in my blog primarily (I know more about them),
I also have studies, links and patient blogs on other centers in this blog, that perform cutting edge NET/Carcinoid therapy in Europe-
Uppsala, Sweden
Rotterdam, Netherlands
Basel, Switzerland.
I have written all the centers in the past for additional information, links, pictures, questions. I have received responses from Uppsala and Rotterdam.
I THANK THEM BOTH FOR TAKING THE TIME TO RESPOND!
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| First PRRT May 2009, ghost figure is ME! |
.jpg) |
| April 2010, color due to tan booth! |
I will be posting much more detail on these centers at a later date.
However, I do have data NOW, both in the links on left (find it!) and prior blog entries. Plus, I can refer people to patients that have been to these sites that I communicate with, including Bad Berka, for additional data if needed!
However, I do have data NOW, both in the links on left (find it!) and prior blog entries. Plus, I can refer people to patients that have been to these sites that I communicate with, including Bad Berka, for additional data if needed!
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| prrt module |
PRRT Data and FAQ
I am re-posting the article entitled (given to me after my therapy in May 2009):
Changing role of somatostatin receptor targeted drugs in NET: Nuclear Medicine’s view
Viikas Prasad 1, S. Fetscher 2, and Richard P. Baum 1 Department of Nuclear Medicine, Center for PET/CT, Zentralklinik Bad Berka, Germany, 2 Department of Hematology and Oncology, Sana Kliniken Lübeck, Germany
Why you ask? Since the interest level for this therapy is so high, I thought it important to re post this report. Also, I now can add some of my comments, and KEY LEARNING'S from my perspective, based on what I, and others, have gone through with this therapy.
Finally, this study paper addresses some very important questions relative to PRRT therapy, which I get inquiries on regularly (FAQ):
What is PRRT and what are the different types?
Which PRRT is better and what are they used for?
When should I consider PRRT? How do I know if I qualify for PRRT and what tests are there for this?
What is the toxicity of PRRT? I understand it is toxic on kidneys and bone marrow, is that true? How do they prevent this in therapy?
How is therapy done and how long does it take (for this you have to go to the link above and below find the BLOG LINK for my therapy day! I documented it in exact detail what I went through the day of and days after therapy- and I suffered more than most after therapy relative to side effects (all transitory).- What are the inclusion and exclusion criteria for this therapy?
What results should I expect from the therapy (based on study data)?
How does PRRT compare to chemo or other therapies in toxicity?
Can I take Sando while undergoing PRRT or PET GA 68 imaging?
How do I contact the center or Bad Berka (search the post above for Bad Berka and links on left for other sites)? Also, I have BLOGS from others that I have have gone to other centers and linked their JOURNEY TO ROTTERDAM and BASEL (on left side of blog- find it!)
Net, net, this one BLOG entry should give one as much data, as you choose to read and prepare, to understand NET Carcinoid disease and some very important options available.
As many of you have also done, to further you knowledge, there are carcinoid/NET discussion boards where one can get additional information and contact others 1-1,for further information! I have also posted my email and also offer to communicate with anyone who may have a question, 1-1, just write me!
Finally, this is a lot of data, and I am not a medical doctor, and this disease varies so widely its impossible for a "one size fits all", even something close to it, so after you start to learn about this, and feel its appropriate, WORK WITH YOUR PHYSICIAN TO INQUIRE FURTHER, AS THEY ARE THE TEAM MEMBER TO BEST DECIDE WHAT IS BEST FOR YOU, AND CAN HELP YOU WITH A REFERRAL TO ONE OF THE CENTERS. HOWEVER, BECOME YOU OWN ADVOCATE THROUGH KNOWLEDGE.
BELOW IS THE LINK TO THE ARTICLE, AND FURTHER DOWN IS THE PRRT "cheat sheet", taken from the study, IN EASY TO READ LANGUAGE, FOR YOUR PERUSAL.
AFTER THAT IS ANOTHER STUDY ON PRRT. IF YOU READ THIS AND LEARN IT, SEE THE VIDEO AND MY LINKS OF MY JOURNEY, YOU WILL BE ON TYOU WAY TO UNDERSTADNING THIS BETTER!
AFTER THAT IS ANOTHER STUDY ON PRRT. IF YOU READ THIS AND LEARN IT, SEE THE VIDEO AND MY LINKS OF MY JOURNEY, YOU WILL BE ON TYOU WAY TO UNDERSTADNING THIS BETTER!
I HOPE THIS BLOG ENTRY HELPS YOU TO BETTER UNDERSTAND OTHER OPTIONS, AS IT HAS DONE FOR ME, BOTH WHEN I READ IT LAST YEAR, AND NOW MORE THAN EVER, AFTER ONE ADDITIONAL YEAR OF PRRT/NET SCHOOL?
Changing role of somatostatin receptor targeted drugs in NET: Nuclear Medicine’s view
Vikas Prasad 1, S. Fetscher 2, and Richard P. Baum 1 Department of Nuclear Medicine, Center for PET/CT, Zentralklinik Bad Berka, Germany, 2 Department ofHematology and Oncology, Sana Kliniken Lübeck, Germany
THIS IS A MUST READ ARTICLE FOR ANYONE WHO IS BATTLING THIS DISEASE, ENCOUNTERING CHALLENGES AND INTERESTED IN GA68/FGD IMAGING, & FINALLY PRRT TREATMENT.
I THINK IT IS ONE OF THE BEST WRITTEN ARTICLES I HAVE READ ON THIS TOPIC.
PRINT IT OUT AND READ IT A FEW TIMES, BRING IT TO YOUR MD IF THEY ARE UNFAMILIAR WITH THIS, AND YOU HAVE A GOOD WORKING RELATIONSHIP WITH THEM, AND NEED TO DISCUSS OTHER OPTIONS AS YOUR DISEASE IS PROGRESSING.
LEARNING and UNDERSTANDING ABOUT ALL TREATMENT OPTIONS, IS CRITICALLY IMPORTANT WITH THIS RARE DISEASE! (refer to Dr Fiske's input on what are "patient responsibility with this disease"?, its on the CFCF You Tube Video)
PRRT (AND THE 3 OPTIONS AND VARIATIONS ON CENTERS THAT ADMINSTER THIS) IS ONE THERAPY THAT SHOULD BE UNDERSTOOD!
ONE MORE TIME. WHY DO I WRITE SO MUCH ABOUT THIS OPTION?
GOOD QUESTION! SINCE PRRT IS NOT AVAILABLE IN THIS COUNTRY, IT MEANS THE NORMAL MEDICAL INDUSTRY/PHARMA LED AND SPONSORED KNOWLEDGE AND TEACHING SUPPORT STRUCTURE IS MISSING. I ALSO UNDERTOOK THIS THERAPY AT A VERY ADVANCED STAGE DUE TO LACK OF KNOWLEDGE. IF, I BELIEVE, I HAD UNDERTOOK THIS AFTER MY 2ND SURGERY, I MAY NOT BE IN THIS CONDITION TODAY (MANY REPORTS/STUDIES NOTE IT IS BETTER TO DO THIS THERAPY WITH LOW TUMOR BURDEN AND PERHAPS IN FRONT END OF DISEASE, AFTER SURGERY....TYPICALLY, WHAT HAPPENS IS NA PATIENTS UNDER GO THIS THERAPY IN A VERY ADVANCED STAGE (LIKE ME).
THEREFOR, IT IS HARD TO FIND INFORMATION AND MD'S THAT UNDERSTAND THIS OPTION, HENCE, ONE REASON WHY I POST SOME MUCH DATA ON THIS BLOG (AND OH YEA, IT ALSO SAVED MY LIFE FOR THE MOMENT! I BELIEVE IN IT AND FEEL SOME RESPONSIBILITY TO REPORT ON THIS..)
NOTE- I ALSO HAVE DATA ON ALL OTHER THERAPY OPTIONS ON THIS BLOG, IN PREVIOUS POSTS AND LINKS...FIND THEM AND STUDY THEM ALSO!
THERE ARE NA MD'S THAT UNDERSTAND THIS THERAPY IN THE USA, AND SOME OF THEM REFER PATIENTS TO EUROPE FOR THE TREATMENT (I INTRODUCED 2 TO DR BAUM WHEN I UNDERWENT THIS THERAPY AND KNEW THEY DID NOT HAVE A CONTACT. THEY NOW REFER PATIENTS ON A GOING BASIS!
ONE CAN FIND THEM ON THE DISCUSSION BOARDS, AND/OR WRITE ME FOR A LIST.
HOWEVER, THERE ARE THINGS YOU SHOULD FIND OUT FROM YOUR MD ABOUT THIS THERAPY (AND YOUR OVERALL THERAPY/TREATMENT PLAN):
1) HOW FAMILIAR ARE THEY WITH THIS THERAPY-PRRT?
2) HOW SUPPORTIVE ARE THEY FOR IT (REMEMBER, DO YOU HAVE ADVANCED DISEASE AND "LITE UP" ON OSCAN)? (NOTE- IF YOU GO TO 4 MD'S YOU MAY GET 4 OPINIONS ON A LOT OF THINGS...I CAN OUTLINE DIFFERENCES WITH SANDOSTATIN IN PREVIOUS WRITE UP'S, AND HAVE EXPERIENCED IT ALSO!)
3) WHERE DO THEY SEE THIS THERAPY, IF AT ALL, IN YOUR TREATMENT SEQUENCE, WITH YOUR DISEASE? (THE LATTER IS VERY IMPORTANT....
EG.,IF YOU HAVE SLOW GROWING, TYPICAL DISEASE, LOW TUMOR BULK, THE PLAN MAY DIFFERS THAN IF YOU HAVE AGGRESSIVE DISEASE, EVEN WITH LOW BURDEN BUT DISSEMINATED DISEASE...(ALL WITH SSTR2 RECEPTORS OF COURSE).
NET, THERE ARE A LOT OF FACTORS THAT NEED TO COME INTO PLAY FOR THIS AND ANY THERAPY OPTION..... THAT IS WHY ITS IMPORTANT TO UNDERSTAND PRRT, YOUR DISEASE CHARACTERISTICS, TO ENABLE YOU TO HELP YOUR MD TEAM IN DEVELOPING YOUR TREATMENT PLAN!
Below is my "cheat sheet" which I took from this report, RELATIVE TO
PRRT, with some of my comments added- (but please read the entire study link above as it refers to tables, scans and data, which I have not copied on the summary and
help in learning).
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PRRT OVERVIEW (prrt cheat sheet)
Overview
Based on the success achieved by SRS,somatostatin analogues were labeled with particle emitters such as 90Y, 177Lu, 111In and used for therapy. These three radionuclides differ significantly in their physical properties (when talking prrt, these are the three treatments).
>111In emits auger electron and conversion electrons which have a path length in tissue of only 0.02-10 and 200-500μm, respectively. Studies demonstrating the internalization of 111In DTPA-octreotide in tumor cells have clearly shown that the therapeutic effect of this radionuclide is due to the auger electrons and
not to the conversion electrons. The low tissue penetration path-length of auger electrons results in
reduced tissue toxicity, however, in our mind it is not sufficient for achieving a satisfactory therapeutic effect due to lack of a ‘cross fire’ effect whereby non SSTR positive cells could also receive lethal radiation damage.
The limitation in the therapeutic utility of 111In DTPA-octreotide led to tagging of SSTR analogues with beta particle emitting radionuclides (RADIATION) such as 90Y and 177Lu. Numerous studies have documented that the tumor shrinking capacity of 90Y and 177Lu labeled SSTR analogues is much higher than that achieved with 111In labeled SSTR agents. The most important physical properties of these three radionuclides are presented in Table 6 (38). Based upon a mathematical model for determining tumor curability in relation to tumor size (38), de Jong et al. (39,40) have demonstrated in a rat model that
- 90Y is more effective in killing bulky tumors, (11mm kill range)
- 177Lu is more effective in small tumors; (2mm kill range)
- Combination of both radionuclides resulted in better control of both, small and large tumors.
The clinical efficacy of different radiolabeled somatostatin analogues (the"payload carrier) varies from tumor to tumor because of their affinity to different SSTR subtypes. As can be seen from Table 4, unlabeled octreotide (‘cold’) has highest affinity for sstr2, binds with somewhat lower affinity to sstr3 and 5 and does not bind to sstr1 and sstr4. In contrast, 111In-Octreotide binds with lower affinity to sstr2, sstr3 and sstr5.
Since most of the metastatic tumors express sstr2, the decreased binding affinity of 111In-octreotide to all SSTR subtypes does not affect the scintigraphic results (41,42).
Several other studies have also documented that for PRRT it is primarily more important to have the
somatostatin analogue with the highest affinity for sstr2 (when you are scanned prior either Oscan or GA 68, they are looking to see if you are "hot" for this receptor PRIOR TO THERAPY!).
In fact we found that 90Y-DOTA-NOC, which has higher affinity for sstr3 and sstr5, is more toxic than 90Y-DOTA-TATE (DOTA-Octreotate), probably because of the higher uptake in normal tissues. Therefore DOTA-NOC is no longer used for PRRT at our centre.
Selection criteria for PRRT
Because of the potential for renal and hematologic toxicity associated with PRRT, it is important todefine patient subgroups that will most likely benefit from this specialized therapy. A recent
article, based upon the survey of phase I and phase II clinical trials conducted so far, provided the
following selection criteria for gastroenteropancreatic neuroendocrine tumors:
Inclusion criteria
1. Intense SSTR expression of the tumor/metastases (as demonstrated by SRS or SR-PET/CT, Figure 3) -via O-scan and or PETw/Ga68
(NOTE- IF YOU DO NOT HAVE "SSTR RECEPTORS", or "VERY WEAK UPTAKE" (look for this in your Oscan report- note for "FOCUS AREAS" in the report. You want to see "FOCUS 3 or 4" as measure of "UPTAKE").
IF YOU HAVE NO OR LOW SSTR EXPRESSION, PRRT MAY NOT BE AN EFFECTIVE THERAPY, AND YOU MAY NOT BE ACCEPTED FOR THIS THERAPY. BUT DONT WORRY, THERE ARE MANY MORE OPTIONS FOR YOU TO CONSIDER. THIS IS REVIEWED/DETERMINED PRIOR TO THERAPY BY YOUR MEDICAL DOCTOR.
2. Hemoglobin, WBC and platelet count should be ≥ 6 mmol/L, 4 x 109/L and 100 x 109/L, respectively.
3. Serum creatinine should ≤ 110 μmol/L or creatinine clearance ≥ 50 mL/min.
In view of the authors,wherever there is a possibility to determine the glomerular filtration rate (GFR) by using 99mTc-DTPA (or using plasma clearance methods), it is advisable to do so. In addition, the tubular extraction rate (TER) should be determined by dynamic renal scintigraphy using 99mTc-MAG3 before and serially after PRRT. (these tests are done in Bad Berka)
4. Karnofsky Index ≥ 50 (you will see this in you clinical report)
5. Average life expectancy should be > 6 months
Exclusion criteria
1. Pregnancy/lactation (also, must AVOID PREGNACY DURING THERAPY AND X TIME AFTER)
2. Chemotherapy within 6 weeks prior to the PRRT
3. Second malignancies with short term survival (e.g. metastatic melanoma).
A part from this, patients should not be on cold octreotide therapy at least 6 weeks (e.g. SANDO)prior to therapy as it has been shown that there is a competitive inhibition of radiolabeled somatostatin analogues with cold octreotide for SSTR and PRRT. The authors have also shown that there is a significant reduction of 68Ga-DOTA-NOC uptake in SSTR rich normal organs/tumors in patients treated with somatostatin analogues (43).
Indications for PRRT
Based upon the clinical results gathered over the last decade, it is suggested that PRRT should be
reserved for patients with metastasized NET with documented evidence of disease progression after surgery or in some patients with inoperable tumors (e.g., inoperable primary tumors of the pancreas).
The definitive role of PRRT as first-line treatment modality has not yet been defined by centres
specialized in NET patient care. However, most patients who have been referred to our nuclear
medicine centre for PRRT were already in an advanced stage of disease.
In view of the authors, it would very likely be promising to apply PRRT to high risk patients immediately after surgery, rather than waiting for the tumor to metastasize on therapy with cold octreotide, chemotherapy, or interferon therapy.
Prior to PRRT, all lab values, morphologic and functional imaging results must be available.
Dosing schedule and quantity of radioactivity administered
After more than a decade of practicing PRRT, the issue of optimal dosing schedules still remains highly controversial. The most important criteria to decide upon when and how frequently PRRT can be and should be administered, are clinical stage of the disease, response to first PRRT, hematologic toxicity and renal function parameters.
As mentioned earlier, currently PRRT is indicated only after documented evidence of disease progression in patients with metastasized NET.
The amount of radioactivity chosen to be administered is primarily dependent upon renal function parameters, SSTR expression (quantitative and visual) on SR-PET/CT (if SR-PET/CT not available then SRS) and the extent of the disease (single vs. multiple metastases, tumor burden).
Many centres apply repeat PRRT (90Y-DOTATOC, 90Y-DOTA-TATE, 177Lu-DOTA-TATE) at
various and alternating time intervals.
Our experience in more than 1,000 PRRT cycles,administered in over 350 patients (with a maximum of 8 PRRT cycles in some patients) suggests that it is advisable to administer lower amounts of radioactivity at more frequent and prolonged intervals (3-6 months in between therapies), rather than giving high activities at short intervals. We dubbed this strategy the “Bad Berka PRRT concept” based on the rationale that slowly growing tumors are probably more susceptible to frequent low dose hits rather than to 2 or 3 “big bangs”.
Clinical results
The results of PRRT have varied widely depending upon which kind of radionuclide and somatostatin
analogue was utilized.
> In111: At first, the emission of auger electrons from 111In was utilized to treat somatostatin receptor positive tumor with up to 160 GBq of 111In-DTPA-octreotide. Partial remissions have been described in 8 % of patients as well as stabilization of disease in a higher proportion of patients (44-46) by some authors, whereas others did not see any objective response. Auger electron emission is a major drawback for the treatment of larger tumor.
>Y90: In contrast, using 90Y-DOTA-TOC in phase I and II clinical trials, complete or partial remissions were observed in nearly 27 % of patients (47,48). In these studies patients received 3 or more equal amounts of radioactivity. Waldherr et al. (49,50), using a different treatment regime (patients received or more single injections of 90Y-DOTA-TOC with increasing amounts of radioactivity administered at 4-weekintervals), showed a partial response in 24 % of the patients. A comparison of two different treatment protocols used in 400 patients at the University Hospital Basel (one group of patients received 4 equal injections of 1,850 MBq/m2 at 6 weeks intervals, whereas the other group received two equal injections of 3,700 MBq/m2 at an interval of 8 weeks) has demonstrated that patients receiving higher doses at an 8 week-interval had a slightly better response rate (34% vs. 24% PR). (11mm kill zone)
>Lu177: Kwekkeboom et al. (51) reported complete remissions in 2 %, and PR in 26 % of 139 patients (28% cr/pr) with GEP NET treated with 177Lu-DOTA-TATE with a very low toxicity profile.
>Lu177 & Y90: In our center,using 90Y-DOTA-TATE and 177Lu-DOTA-TATE either alone or in combination (mostly sequentially), partial remissions were achieved in 39 % of the patients and in 9/302 (3%) patients a complete remission was observed (unpublished data).
note- the data above does not include Stable Disease (SD) which in studies have shown to be the largest share of activity for this therapy. Progressive disease is typically seen in 10 to 20% of patient population.
A measurable clinical benefit (improvement of symptoms) was seen in over 90 % of the patients (Figure 6).- (usually patient stops needing MONTHLY SA injections!) A study conducted by Kwekkeboom et al. to assess the quality of life (QoL) in patients with GEP treated with 177Lu-DOTA-TATE demonstrated that global health/QoL improved significantly in patients post treatment.
Toxicity profile: PRRT vs. other (chemo) treatment options
The primary concern of many non-nuclear medicine physicians prior to referring a patient for PRRT is radiation-induced toxicity. In fact, radiolabeled somatostatin analogues are primarily excreted through the kidneys and, with regards to toxicity, the kidney is the primary organ of interest.
Therefore, PRRT is administered under nephroprotective agents such as amino acids (lysine, arginine) to reduce renal radiation damage.
A novel approach is the use of gelatine (gelofusine) prior to PRRT for reducing renal toxicity; initial results are promising (52-54).
With 111In-DTPAoctreotide, high cumulative radioactivity doses can be administered without any significant
deterioration in renal function (45).
Few studies have reported significant renal toxicity after 90YDOTA- TOC therapy, for the most part even in the absence of renal protection (55-60). With the advent of improved protective agents renal toxicity can be reduced even further. In our centre, in patients with normal kidney function before PRRT, no terminal kidney insufficiency has been observed so far at a mean follow up time of several years (Figure 7). Other adverse effects which are experienced, like hematological and liver toxicity, are usually mild and mostly reversible.
In a phase I study conducted in 47 patients in Rotterdam, Brussels and Tampa with 90Y-DOTATOC,
one patient with secondary myelodysplastic syndrome was observed, one showed liver toxicity,
and three patients developed grade 4 thrombocytopenia (39,61).
Studies using 177Lu-DOTA-TATE have documented less and mostly transient toxicity with only minimal bone marrow suppression (51,62,63).
In comparison to chemotherapy, PRRT using 177Lu DOTA-TATE have been shown to be less toxic
Kwekkeboom et al. (51) observed hematological toxicity in less than 2 % of the patients as compared to 5-61 % toxicity observed in patients treated with chemotherapy (20-22,64-67).
Similarly, renal toxicity was found to be much less as compared to that with chemotherapy (51).
Figure 7. Serial follow-up of hematological data by measuring hemoglobin, red blood cells (RBC), white
blood cells (WBC) and platelets (PLT) as well as serum creatinine. There is no significant hematological
toxicity after 3 cycles of 90Y- and 2 additional cycles of 177Lu DOTA-TATE therapy.
Multimodality Approach
In recent years, the value of combining different treatment modalities in order to achieve better
disease control in metastatic or inoperable NET has been increasingly investigated. Randomized clinical trials are underway to compare the efficacy of PRRT alone, and in combination with chemotherapy. The concept of COMBIERT (Combined Internal External Radiotherapy), developed by R.P. Baum, aims at combining internal and external radiation therapy for better efficacy. Initial results in patients with neuroendocrine tumors (e.g. inoperable primary pancreatic NET as well as in recurrent glomus tumors (Figure 8) and paragangliomas) are promising.
Similarly, the use of PRRT for tumor debulking prior to surgery (neoadjuvant therapy) should also be considered.
CONCLUSION
The significant and undeniable effects exerted by PRRT, even to the extent of being curative in
individual cases (Figure 9), has had a major impact on how patients with NET are treated in some
European countries. However, in spite of being an effective treatment option, PRRT is practiced in
Europe only at a few specialized centers (and even less in the U.S. and Canada), mainly due to the lack
of commercially available 90Y- and 177Lu- labeled somatostatin-derived peptides (radiopharmaceuticals).
(NOTE: THIS IS A 2007 STUDY. THIS IS CHANGING AS NOW PRRT IS IN AUSTRALIA, SINGAPORE, INDIA, AND I BELIEVE CHILE, PLUS MANY HOSITALS ACROSS EUROPE)
Studies that directly compare the clinical results of standard octreotide therapy with PRRT are unfortunately missing. These and other yet unresolved questions regarding the optimal therapy of patients with localized and metastatic NET should be addressed by newly designed, cooperative multicentre trials.
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STUDY #2
Overview of Results of Peptide Receptor Radionuclide Therapy with 3 Radiolabeled Somatostatin Analogs Another detailed, and excellent study, with many contributors, including some very prominent North American Md's (note-these Md's would be very familiar with PRRT) is the above study.
The study LINK for this data is BELOW.
This study is a combination of data which reviews PRRT options, therapy, drawbacks and results, objectively. Again, for progressive disease, this therapy, in my opinion, experience and research, is documented as overall the BEST NET THERAPY RELATIVE TO RESULTS IN TERMS OF DISEASE CONTROL, SYMPTOM CONTROL, COST EFFECTIVENESS AND SIDE EFFECTS and LENGTH for advanced disease, with intense sstr expression.
READ FOR YOURSELF AND COME UP WITH YOUR CONCLUSIONS!
(BTW, DR KVOLS, A NA MD WAS ONE OF THE PIONEERS OF PRRT AS THERAPY!)
IN READING STUDY DATA, THEY HAVE DIFFERENT FORMATS, AT TIMES COMPARISONS AND SPONSORS
(EG., ONE RECENT PRESENTATION COMPARES ONE DRUG WITH "MONTHS TO PROGRESSION" AND HOW WONDERFUL IT IS, THEN COMPARES IT TO ANOTHER THERAPY (PRRT!) ON "TUMOR RESPONSE", AND QUESTIONING THE STUDY INTEGRITY- QUESTIONING THE EFFECTS AND STUDY DATA, ETC............."APPLES TO ORANGES", I THINK, NO?
HOPEFULLY, I CAN PUT SOMETHING MEANINGFUL TOGETHER ON ALL STUDIES...and my CLINICAL TRIAL EXPERIENCE, RESULTS AND WHERE I ENDED UP ON THE "CLINICAL TRIAL RESULTS CHART" AS COMPARED TO MY DISEASE STAUS BEFORE AND AFTER FOR UNDERSTANDING ON HOW THIS PROCESS WORKS.......JUST FOR THE HELL OF IT....!
.JPG)
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