Friday, February 28, 2014

Dr. Rajkumar, and my "Grand Unified Theory" on the curability of Myeloma

I participated in a very interesting conference call / panel hosted by the good people at Cure Talk this week.  Our guest this time was Dr. Rajkumar from Mayo, MN. 
Dr. Rajkumar was the lead author of the paper on secondary MGUS that helped assuage my concerns when I noticed this in my blood last year.  As such, he is one of few people qualified to directly speak to the topic so I was sure to ask him about it.  He didn't tell me too much more than I'd already read in his paper, but there were a couple of new insights and it was quite interesting overall:
* A significant number of post-transplant patients have been seen to have a secondary monoclonal signature in their blood that typically disappears after about six months.  They have observed it in about 30% of patients that they've seen at Mayo post-transplant, and it is likely underreported since not all patients commit to regular follow-up and it only shows up on detailed IFE blood tests, not in standard SPEP blood tests.
* In cases of secondary MGUS (as opposed to disease recurrence), the monoclonal protein that appears does not come from the same clone that presented at baseline.  In many cases, it will come back in a different region of the immunglobulin spectrum (e.g., if somebody had IgG Lamba myeloma, the secondary MGUS might be IgA Kappa).  In my case, it was in the same part of the spectrum -- IgG Lamba -- so it wasn't as clear that it wasn't disease return.  But it was a faint light chain only, no heavy chain, and ultimately it went away so it was simply a different manifestation in the gamma globulin spectrum.
* Patients that exhibit this transient protein -- provided it is eliminated without treatment -- have an overall survival twice as long as those who do not exhibit this condition.  That's a good sign for that it's gone away of course.  : )
* He posited that appearance and elimination of the protein was a good sign because it was reflective of an immune system that was able to eliminate the clone.  The clone is there in the first place because the immune system is manufacturing immunoglobulin to repopulate itself after treatment, and when there isn't enough normal immunoglobulin to fill up the "cup" that represents the system, benign monoclonal proteins can emerge unchallenged.  However, even if benign, the clone is superfluous to immune function and if the immune system is able to get rid of it, it's not just a sign of an immune system rebuilding: it's a sign of an immune system functioning effectively.
* He did note that in the majority of cases, this phenomenon is seen within the first year of transplant.  He didn't assign any particular importance to the fact that mine showed up four years after transplant, although he said it was very unusual.  However, UAMS uses a lot more medicine than Mayo and it's simply possible that it took longer for my immune system to recover than would be the case were I treated less aggressively (this is my guess -- he did not opine).  I was still on Velcade up to a couple of months prior to the disappearance of the protein.
My question came late in the panel.  The rest of his talk was primarily about the main topic for the conversation: cure versus control.  It's a topic covered increasingly on these calls, and certainly one that I continue to address in these pages.  You can listen to the entire call by clicking on the link here, below the picture of Dr. Rajkumar, but the highlights were as follows:
* He believes that some patients are being cured today.  In fact, he believes in very rare cases people were being cured 20 years ago.
* He noted that approximately 40% of Total Therapy patients remain in complete remission after five years and acknowledged that if the data holds, many or most of them are likely cured.  He basically said that we have to wait to see what the future has in store.  Recall, however, the 40% includes the subgroup of high risk patients who do not respond to any current treatment.  Remove them and the 40% becomes 50% -- which is consistent with what UAMS has said of late with respect to "low risk" patients.  Also, the published data is old as all published data is because of the demands of third party oversight, peer review, etc. that slow down the publication process.  The newest data confirms the curve does plateau -- which indicates cure in the same way that the plateaued curves for certain other blood cancers do.
* He noted that "we do not need to cure MGUS -- we need to cure Myeloma" and that many people could experience long-term remission even if they have trace levels of monoclonal protein in their blood, as it might be a benign clone unrelated to the Myeloma.  This is consistent with UAMS' assertions that there are those who are functionally "cured" with an ongoing MGUS signature.
* He noted -- appropriately, in my view -- that an issue with saying TT is a cure is that not everybody is eligible for it.  And that for a disease to be considered curable, it would have to be something that could be applied broadly across all patients.  I don't disagree with this -- although I do think he underestimates the eligibility for TT.  But there's no escaping the fact that the elderly will get less of an incremental benefit from TT versus less aggressive therapy, and those who are not healthy enough to undergo treatment or who can't afford to take 6-9 months off work (or who can't afford the treatments) or who are unable to go to Arkansas are not able to have the opportunity at this treatment, even if it is potentially curative.
* He acknowledged the importance of MRD testing but in discussing its use, he said (unintentionally) something slightly misleading when he referenced other UAMS data that suggested quick remissions were among the least durable.  This is true in the case of high risk disease reponse to Total Therapy -- remission is easily achieved but rarely meaningfully sustained.  In the case of the 85% of newly diagnosed patients with low risk disease, the speed of remission is not associated with a bad outcome.
* Importantly, he implied that the UAMS data shows a potential plateau while other doctors that have good survival durations do not show plateau.  In other words, a certain renowned anti-transplant doctor might say his patients survive for 7 years or what-not, but the mortality rate eventually turns up, whereas with UAMS the mortality rate (from Myeloma) may not.  This is consistent with BB's comment to me that "the curves for progression free survival and overall survival are essentially superimposable."  In other words: the people that are dying have no Myeloma when they die of something else.  When you have a median age of 71 at diagnosis, you are going to see deaths -- Father Time is, after all, undefeated.
This all leads me to an important crystalization of my own viewpoint on the curability of this disease, which has been refined through this conversation, discussions with several other patients with well-informed points of view on the subject, and discussions with BB and other experts.  By rephrasing my belief per the below, I'm hoping it makes room for those that don't support Total Therapy, or who don't think it's as broad a cure as is necessary to cause us to say "Myeloma is a curable disease."  The term Grand Unified Theory refers to a scientific concept in physics that attempts to reconcile three disparate theories under a unified banner that explains the physics of everything in the world.  That's a more messianic metaphor than appropriate for the following entry, but you get the idea.  Plus it was punchy as a headline for this post.  : )
I believe that Total Therapy represents a potentially curative option for a meaningful subset of newly diagnosed patients and can exceed a 50% cure rate for patients in the right population.  Patients who have (1) not undergone meaningful amounts of previous treatment for the disease, who are (2) young enough to benefit from the additional lifespan beyond the potential 5-10 years that less invasive therapy generally provides in a successful case, who are (3) healthy enough to receive multiple courses of chemotherapy including two high-dose courses of Melphalan, who are (4) psychologically prepared to embrace an aggressive treatment protiocol and who are (5) prepared for the logistics of an extended stay at a center of excellence for this treatment (whether Little Rock, Iowa, etc.) should consider that, if they are in the 85% of patients with "low risk" disease, they have a better than 50% chance of being cured.
Does this statement with all its qualifications mean that Total Therapy constitutes a cure for the disease?  Biologically, it probably constitutes a good shot at it for those that are otherwise healthy.  Psychologically, not all patients are prepared for it -- and I think that's in part because they have been led to be terrified by the concept of a transplant, which is a shame.  For the older diagnosed patient (Tom Brokaw comes to mind), the incremental few years of life in his late 80s may not be worth the added intensity of treatment versus the less invasive program he is receiving at Mayo.  For the high risk patient, unfortunately, few if any cases are cured through existing treatments.  But still -- for someone like me, diagnosed at 40, otherwise healthy, and prepared to fight like hell -- the chance of a cure is not some shot in the dark, 2% chance.  It's even money or better -- and once one achieves remission and maintains it for a period of time, it approaches certainty.  Whether that period of time is 6 years, as BB and team now maintain, or some longer timeframe as Rajkumar appears to suggest, it's out there.  Dr. Rajkumar agrees with that much, and notes that people were cured 20 years ago with Melphalan and Predisone -- just not very many.
BB and Total Therapy are curing a meaningful portion of patients that undergo Total Therapy.  Patient empowerment and a gradual broadening of the centers that offer Total Therapy as a choice should increase the reach of this alternative, and that's a good thing.
Patients that come across this blog likely already can figure out where to go to learn more about MIRT and UAMS.  But if you need a link, here it is.
Ultimately, this is another element of a movement in treatment towards care that is individualized, taking into account each person's biology and preferences.  Knowledge is power, and more options are better than fewer options.  I'm glad I had the option of choosing aggressive treatment in pursuit of a cure.  And I'm glad BB was iconoclastic and insisted on pursuing this approach instead of settling with mere control, where other options exist.
With that, I wish you all a great weekend!

Monday, February 10, 2014

Part three of the three part post: cure versus control.

Regular readers will likely remember that I take part, time to time, in a series of panels on Myeloma hosted by the wonderful people at Cure Talk, with help from Priya Menon who has done a remarkable job of assembling this program.

At 5PM Eastern on February 26th, there will be a panel discussing "Cure vs. Control" and featuring noted Myeloma expert Dr. S. Vincent Rajkumar of Mayo, Rochester.

This is of particular interest to me for two reasons.  First, Dr. Rajkumar took part in a very thoughtful debate with my doctor a few years ago, and this debate can be found on youtube here (this is part 1 of 4).   I'm looking forward to learning if Dr. Rajkumar, in light of the progress made in the last two years and the announcement of the Black Swan initiative by the IMF, has reconsidered his stance that the disease is not curable.

Second, and probably more important to me personally, is that Dr. Rajkumar was the author of the paper that discussed the presence of transient monoclonal protein after transplant being a good thing.  I'm interested in learning why we are just now observing this (when for years we knew that oligoclonal bands appear during immune system recovery), what difference if any there is between the two types of bands appearing post-treatment, and what impact it this might have on assessing the effectiveness of treatment.   Since I exhibited both oligoclonal and -- much later -- monoclonal bands during recovery, I'm particularly intrigued.

For instructions on how to participate on the call, including the opportunity to ask a question of the panel or Dr. Rajkumar, click here.

You can also post a comment here with a question for me to ask the good doctor!

...and why cure matters

The cure versus control debate has been gaining steam in the past few years.

I've been accused of favoring Arkansas in the past, so I will be careful to make the below claims with appropriate caveats and considering all I've learned, and the contributions of others.  For example, I claimed that Barlogie was the first to use Velcade in up-front therapy.  Evidently others began at or around the same time.  It doesn't matter, really, to the argument I'm making.

When I was diagnosed in October of 2008, there may have been other voices in the wilderness talking about a cure, but UAMS was the only center openly discussing it as the objective of their therapy, and touting that Total Therapy was curing people.  Many did not believe them then; many still do not believe them now.  And many of the non-believers are very smart people, and many of them are learned doctors.

The startling statement of being curative was just one of several aspects of Arkansas' approach that led some others to call it "crazy" (whether in that word or a more polite variant thereof).

In addition to the fact that common wisdom said the disease was incurable, here are a few other things that common wisdom said:

- Velcade should be reserved for relapsed patients.  Barlogie used it up front.

- Revlimid should be reserved for relapsed patients.  Barlogie used it up front.

- Maintenance therapy did not make a difference in outcome.  Barlogie has had it as a mainstay of his protocols for 20 years.

- Complete Remission doesn't matter; there's no real difference between a minimal M spike and the absence thereof.  Barlogie, in contrast, uses CR as a prognostic precursor to cure.

- Tandem transplants won't make a difference in outcome.  Barlogie has used them from the outset -- it's not about the transplant iself, it's about administering more melphalan.

- Focal lesions do not resolve and are meaningless as a prognostic factor once no longer active for cancer.  Meanwhile Barlogie has maintained they resolve, though it can take years -- and believes that until they are resolved they can represent microenvironments where cancer can lurk, awaiting recurrence.

Now, fast forward five years.

- Velcade is the standard of care for newly-diagnosed patients

- Revlimid is the standard of care for newly-diagnosed patients

- More and more evidence exists (I'm not going to research the publications right now -- there are too many now and can be found via a google search) that maintenance prolongs overall survival as well as progression free survival and it is becoming the standard of care if it isn't already

- Complete remission is being recognized as an important marker with more advanced tests designed to investigate for the traces of any remaining disease

- I've seen at least one study that confirms the superior outcomes of tandem transplants

- My own focal lesions continue to resolve.  I had at least 10 (I think 12?) and all but four are now gone.

- The IMF has announced the Black Swan Initiative, which at a minimum is a tacit acknowledgement that some patients are being cured

- More doctors are admitting that some patients are likely cured.  I'm not going to "out" them, here, but they exist.

This is not about a "neener neener, I was right / my doctor was right."  This isn't about bragging rights.

This is first and foremost about giving patients as many options as possible.

But this is also about getting on with life as normal for a good subset of patients who have families that depend on them.

Some people phrase it as "isn't a long remission as good as a cure?"

The answer, for me at least, is no.

Long remission doesn't let you buy life insurance.

Long remission doesn't let you buy disability insurance.

Long remission introduces questions like "will this person hire me if they believe I have incurable cancer?" I'm not sure of the legality of this -- but common sense dictates that it's a concern.

With other cancers, after five years of remission, you're considered free and clear.  But until such time as enough of the medical community agrees that Myeloma is curable, that window will not be available for those of us with this disease.

I want to be very clear on my perspective here:

* Each person's biology is different.  I have enjoyed a favorable response (thus far) to a curative approach.  That doesn't mean other people will.  The most aggressive claims of Arkansas acknowledge that 15-20% of newly diagnosed patients have dire prognoses despite the success of Total Therapy with other patients.  Most might not be cured regardless -- although time will tell.

* Each person's choice is their own.  Some people don't want to sacrifice quality of life for quantity of life.  Some people simply don't want aggressive therapy and are prepared to accept a different set of odds as a result.  Some people don't believe in the Arkansas protocol -- and it could certainly be proved wrong.  This is not about asserting Arkansas being right over anybody else's choice.

* That said, patients need to be aware of their options, and make their own choice about their own treatment based on a fully informed perspective, understanding the pros and cons of each alternative.

Arkansas and Total Therapy are not for everybody, for a variety of reasons: age, health, philosophy, individual disease biology, etc.  But patients should be informed enough to know that this treatment approach exists.  Because cure, in many cases, does matter.

Why I love my doctor...

Here it comes: an end to the initials of those involved with Arkansas.

There are going to be three posts from me today, I think, broken up for easier digestion.  Each is related, but each also has its own little piece of the message.

The first is a bit about why I love Dr. (B)art (B)arlogie and his team.

In the interest of not putting off people that chose a different therapeutic path, I've generally backed off any kind of zealous proselytization of Total Therapy in the past few years, however for these next few posts I'm going to be a bit more assertive.

Some people that have disparaged Arkansas refer to adherents of its program as "cult members" because of the faith that we place in Total Therapy and/or the larger-than-life personality of Dr. Barlogie.  One of the most vocal online denigrators of this dynamic has actually become a valued friend  of mine -- and though I respect this person and acknowledge that this person's individual disease characteristics make Total Therapy much less appealing for them than for others, I nevertheless must disagree with this person about the "cult" commentary and about this person's overall opinion of Barlogie.

Those who are passionate about UAMS, Barlogie and Total Therapy are thus because (1) we believe it works and that a meaningful proportion (call it 50%) of newly diagnosed patients can be cured of this disease through this protocol, (2) our doctor ENCOURAGES patients to become educated about their disease, their therapy, their biology, etc. and (3) we are passionate just as our doctor is passionate.  If we strongly encourage a newly diagnosed person to learn about the Arkansas program, it's because we believe there is a better way than just saying "well, the disease can't be cured, it will always come back and I'm eventually going to die from it unless a cure is found."  I realize that's a little like an Evangelical Christian wanting to force the "Good News" on others in order to save their soul...but even the most spiritually minded among us have to recognize that our mortal life is a bit more tangible than our soul.  Extending our life is knowable and measurable.

I will address the issues of curability and being an informed patient in my next post, but I want to talk about my doctor's passion and knowledge here.

I have developed a privileged relationship with Dr. Barlogie, his wonderful wife Kathy, his awesome son Bart Jr., and his amazing chief of staff Bonnie Jenkins over the years.  When I go back to Arkansas for regular visits, I usually try to get together with as many of them as possible for a drink or dinner.  Often, one or more of them is traveling or (particularly in the case of Dr. Barlogie) too busy.  But this last week, I was very fortunate.  I had dinner with Bart Sr., Kathy and Bonnie three nights in a row, and Bart Jr. was able to join for two of them.

On the first night, Bart was at the clinic until after 9PM.  It was another routine 12+ hour day for him and it would continue after dinner.  He was late because he was personally editing FIFTEEN articles that were about to be submitted to ASCO (the American Society of Clinical Oncology) for potential publication.  Dr. Barlogie is approaching 70 years old, but still sees between 15-25 patients a day including around 20 new patients a week.  His dedication is tireless.

I often speak of the need for people to see a specialist.  Virtually all of Dr. Barlogie's patients have Myeloma (a few may have related diseases like Waldenstrom's Macroglobulinemia or the like) and this has been the case for 30 years.  He has likely seen more Myeloma than any practicing physician in the world.

Because of this, he knows the disease as well or better than any practicing Myeloma physician in the world.  And that takes nothing away from the many learned physicians including a dozen or so absolutely brilliant specialists (this is my estimation only) who I am sure Dr. Barlogie fully considers his peers.  He may not be smarter than other top doctors -- though he certainly is brilliant -- but he's simply seen more of the disease.  If your car is mangled in a wreck, do you take it to a brilliant mechanic who has worked on 500 cars, or a brilliant mechanic who has worked on 5,000 of the same make and model?

I spoke with Dr. Barlogie at dinner this first night for two hours about the disease: why he believes it responds the way it does to some kinds of therapies and not others; why he feels the new classes of immunotherapy agents (e.g., elotuzimab, daritumimab -- both of which are receiving a lot of press now) are not ready for prime time and not as effective for Myeloma as similar agents are for lymphoma; why he feels the disease is curable.  And why he believes Total Therapy works.  As he ultimately put it to me:
"I was counseling one of our new doctors.  He had seen a patient and based on his previous training, had suggested a course of action that involved a few well known drugs in small doses, but not the newest drugs, and not a widespread group of drugs that would attack all pathways.  He said to me that he was saving the best for recurrence.  I told him you don't get it, son...we use the best we have NOW, so that there will BE no recurrence."
This falls somewhere between philosophy and treatment reality.  But Bart knows too much about why things work and do not work for this to be written off as a stab in the dark.   I have too many friends with Myeloma who went for non-aggressive approaches and are now relapsing and having dire outcomes.  I have seen too many friends with doctors that are supposed specialists guessing at what to do next, disagreeing with other doctors and with patients, and not having any real plan other than picking some agents that might work and throwing it at the disease and hoping it sticks.  Having a doctor that has a plan, can articulate it, and knows why it works and when it doesn't is a HUGE asset as a patient.

This is not to say that Total Therapy works for everybody.  It does not.  As I have always noted, 15-20% of patients  have high risk characteristics -- or, if you prefer, have a biology which Arkansas' Gene Array test indicates will not be cured by Total Therapy.   Then, of the remaining 80-85%, only about 80% or so are likely to be cured according to UAMS.  However, those are compelling statistics for a supposedly "incurable" disease.  Even if they are off by a factor of two, it's still 30% of low-risk patients being cured.

Included in the 20% that Arkansas recognizes will not be cured by TT despite low-risk biology are those who have standard risk disease (or, if one prefers, disease which has attributes that, according to Arkansas' Gene Array test, are likely to respond well to Total Therapy) but who lose remission.  These are sad cases, because often times the disease returns with very aggressive characteristics and prognosis is not good.

One such case is a friend of mine, and I was discussing this person with Dr. Barlogie over dinner (within the confines of patient confidentiality as appropriate).  Where other doctors would say "well, we could try X, or Y" Dr. Barlogie shared with me that he had researched additional therapies that work on a specific cellular level since this patient didn't have trouble reaching remission, but had difficulty remaining on therapy due to his blood counts (white cells and platelets) being knocked out by the therapy.  So Barlogie's new therapeutic choice for this individual was to select chemo agents that work at a stem cell level and don't damage mature cells, so that the counts would not be as impacted.  Barlogie not only knows what to do, he knows WHY he is doing it.

When he sees a patient that has been heavily treated elsewhere -- and I have personally referred patients from Los Angeles to Canada who were told by their supposed experts that they would be dead in three months only to be given a new lease on life in Arkansas -- Barlogie knows what the options are and why.  This can include experimentation, particularly in those that have received all the common treatments before.  But when one can either update one's will and sign up for hospice, or sign up for experimentation and live 18 months to who knows how long, that's a meaningful choice to have, even for those who choose the first path.

As another example, because he has seen so many patients, Barlogie knows that certain procedures ENCOURAGE plasma cells and Myeloma.  In patients that are not in remission, something as simple as removing a central line (a catheter placed subcutaneously for infusions, and which requires an incision) can sometimes cause the eruption of plasmacytomas at the incision site.  Patients with serious disease might even experience this at the site of simple injections.  Doctors that haven't seen thousands of patients and haven't observed this phenomenon dozens if not hundreds of times simply won't know this is happening.

Similarly, I have friends that receive radiation.  Radiation can possibly cause the same thing -- plasma cells rush to the area that experiences the radiation.  This could strengthen the Myeloma over the long haul.  This is why my doctor favors "melting tumors" with chemotherapy.  A doctor that hasn't seen this many times over might be quick to radiate something that won't help the situation.

Now, some of this is theory -- and some of it is likely the age-old difference between chemotherapists and radiologists whom, I am told, haven't always gotten along well (this is not specific at all to UAMS, where the departments work well together).  But a lot of this is experience.  Experience that few doctors in the world have.

Over the course of the next two nights, I had other conversations with Bart, his family, and Bonnie.  About the disease, about what we learn from going through it, about their own lives and families as well as my own.  Bart and his family become profoundly emotionally involved in the outcome of Bart's patients.  Some may say this is a bad thing -- they prefer a doctor that is detached and unemotional.  I can understand that -- but there's also something about having a specialist being emotionally invested in one's case and wanting that person to beat the disease.  Not to qualify for more funding, not to validate or invalidate a particular drug's efficacy -- but because Bart hates this disease and loves his patients.

That is not a cult.  That is a family of care.

I've seen an unfortunate few of those in Bart's care -- both newly diagnosed who arrive full of hope, and those who have been treated elsewhere that aren't able to hope for a cure through Total Therapy because being pre-treated means the TT approach isn't as effective -- die.  These people are not bitter.  Uniformly, they are at peace.  Because they know that they have been seen by the best and there could not have been a better outcome.  That, too, is not a cult.  That is the result of a dignified grace conferred at least in part by confidence in one's medical team.  I am not certain I would experience such grace in the face of imminent mortality.  I hope I never need to find out.  The UAMS people don't sugar-coat things...Bonnie once told me "I can help you beat this disease, but should the time come, I can also help you prepare to die from it."  That's both awful and pretty remarkable at the same time.

I have a privileged relationship with Bart and his family, as I've said in the past and said earlier in this article.  He doesn't visit everybody in the hospital, as he did with me (and did with my friend who experienced relapse, whom I mentioned above).  Kathy, who doesn't even work at UAMS, doesn't visit everybody in the hospital either -- yet I remember when I was basically in a coma from Dilaudid, I opened my eyes once to see her sitting there holding the hand of my terrified wife.    Yet this privileged relationship didn't come from anything special and isn't unique to me.  I reciprocate and invest in it, because it's good for my care clinically but mostly because I love these people.  This privileged relationship arises for me and others BECAUSE of the commitment that Bart and his team give to their patients.

If that collectively means I'm part of a cult, then sign me up.  So long as it doesn't involve purple jumpsuits or Kool-Aid.  :)

As to curability and why it matters, that's coming up next.

P.S.  As part of being in the cult, I provide free advertising for associated businesses.  :)    If you are in Little Rock, make sure to check out The Fold, which is Bart Jr'.s restaurant featuring farm-to-table, high-end tacos and other small plates.  Calling them tacos is a bit of an understatement.  It's a very relaxed, reasonably priced and cool place with a wide variety of good eats.  I've now put it in my rotation along with certain BBQ and pizza places when I go my weeks in Little Rock.

Saturday, February 8, 2014

A good checkup

I will post more on this soon, but here are the highlights:

* The monoclonal signature in the blood is gone.  Which means all along it was the secondary MGUS phenomenon that Mayo research indicated is a good thing.  Hurray!

* Bone marrow is negative for Myeloma, minimal residual disease test looked at 2.1 mil "events" (not sure if this is a cell or a receptor on a cell) and found no Myeloma.

* Formerly active focal lesion at my 12th thoracic vertebrae is gone.  Formerly active lesion at T10 remains but is slightly smaller.

Unchanged lesions remain at T2, T3 and T4.  These lesions were too difficult to aspirate with a fine needle so I thankfully only had two holes dug in my hip (one for marrow, one for gene array) and none in my spine.

So now we are down to four lesions.  Stay the course.

I will post more detail soon, but a spoiler: I love my doctor and I am utterly convinced that this aggressive approach is by far the best one to use.  I would urge any newly diagnosed patients who come across this blog to go to Arkansas for treatment.

Oh, and just to prove the old dog can learn a new trick, my doctor now thinks curcumin "can't hurt."  :)