WHAT IS CANCER, ANYWAY?

Linda with French-Canadian goat
Or is that a sheep?

 

Well, Summerun North 2013 is part of history.  About two dozen people walked through the tourist swarms in Old Fairhaven on a warm and sunny Sunday, wearing their “Linda’s Team” T-shirts.  They accosted anyone who couldn’t creep away fast enough, and gave them potentially life-saving literature, furnished by the Marsha Rivkin Center.  Then they came back to my house and lunched delicately on hot dogs (cooked by Joe Mortimer), beer (I opened the bottles), and many sorts of salads and desserts provided by the nice ladies of Linda’s various organizations, quilting and otherwise.  I seriously over-estimated the thirst of the participants, resulting in an ambient beer supply sufficient to open a bar.  I think everyone had a good time, and we raised almost $2K – a bit more than the $750 I had hoped to raise.  Stay tuned for Summerun North 2014.  Thanks to all, but especially to Linda’s sister Carolyn and Linda's good friend Florence.  And, by the way, our shirts really looked good.

So, anyway, Dick Ingwall has again spotted a story in the NYTimes concerning cancer – in this case, what it is & what it isn’t.   A “working group” of the National Cancer Institute has just published the results of its deliberations concerning what we should call cancer, and what we should call something else.  To boil the issue down to its dry essence, there are lots of things our medicos refer to by long names including words like “carcinoma”.  Many of these things are being detected as direct results of progress in early detection (I almost said early “cancer” detection, but maybe I shouldn’t.)  Some of these things may in fact develop into full blown metastatic cancer and do us grave harm, but many of them won’t.  The problem arises, then, because, given the current state of medicine, telling which is which is an uncertain at best.  So, if your doctor says that you have (to make it up)a squamous neoplastic porous yellow lesion” you might go home content, but if she says you had a squamous neoplastic porous yellow protocarcinoma you might be terrified – and demand to have the damned thing cut out immediately.  This, says the working group, results in lots of unnecessary surgery and needless anxiety.  So, they say, ditch the word carcinoma (sarcoma, etc.).  Call it something bland, until you know what the damned thing really is. 

Do you agree?  I guess I do, somewhat.  What I really want my doc to say is: “Well, the path report says you have this thing with a long name.  As far as we know, it has a 5% or less chance of growing into a full-blown cancer.  As far as we know, yeah, but we really don’t know all that much.  I would suggest watchful waiting.”  If he phrased it that way I probably would take his advice.  But if he said “…. 30% chance…..”  I might say “Take it out.  Now.”  I don’t think our docs need to worry overmuch about disillusioning us with their lack of certainty.  In my somewhat post-disillusioned state I realize that much of diagnosis, despite the multiply fortunes being spent on bio-medical research,  remains a cosmic crap-shoot.    

But – progress is being made.  I have faith.

To read the story yourself:  http://nyti.ms/1aSMm6a

 

 

DO CLINICAL TRIALS WORK?

Linda Joyce Beck, pro miniature golfer

 

Leavenworth

 

You know how clinical trials work.  Let’s say that a research team develops a drug that cures (or more likely inhibits) lung cancer in mice or chickens or monkeys.  To check if it works in humans they first perform a Phase I trial to determine maximum safe dose.  Then they get permission and funding for a Phase II trial, perhaps involving a few dozen to a hundred or so people.  In Phase II they seek to determine whether the drug does humans any good, while continuing to monitor for side effects, etc.  If the drug still looks promising after Phase II, Phase III may be attempted, involving several hundred to several thousand subjects.  If once again the drug appears to be effective they leap with joy, order their BMWs, and apply to the FDA for permission to market.  (Most likely they actually wait for approval before buying the BMW.)  Most drugs never even make it to Phase III, and fewer still are approved for use.  Drug development is a costly, tedious, and frustrating process. 

The “gold standard” for Phase III trials is the “double blind” version.  The trial cohort is divided in two; half receive the drug and the other half get a placebo*.  Neither the patient nor the doctor administering the drug knows which is who.  Only the computer back at headquarters knows that patient A is getting the real stuff and patient B is getting a sugar pill.  When the trial has run its course, that same computer assists sage statisticians to determine (with impecable mathematical rigor) whether the drug arm of the study experienced better outcomes than the placebo arm.  If it did, head for the FDA office nearest you…

Now, however, an article appearing in the NYTimes (thank you, Dick) questions the validity of even “gold-standard” trials.  The example cited is Avastin, which targets angiogenesis in tumors.  (No, I did not use that big word just to impress you.)  Angiogenesis is the process whereby fast-multiplying tumor cells build a blood supply; without sufficient blood they will croak, like any other cell.  Avastin was used to combat a nasty species of brain tumor.  The drug had helped significantly in an earlier, much smaller Phase II study, but the double-blind Phase 3 trial showed no significant difference in survival between the two arms.  In other words, from a much larger selection of patients, very few benefitted from Avastin.  The odd thing was, though, that some benefitted a lot.  Which brings us, I think, to the point:  maybe clinical trials of the traditional sort don’t work mainly because cancers are so heterogeneous.  Maybe it doesn’t make sense to speak of “pancreatic cancer”, for instance, as if it were a single disease that can be confronted by a single remedy.  If one were to examine the genetic damage that lead to cancer in the pancreas, one might find that several different kinds of genetic errors were involved.  Thus a treatment that worked on tumor A might not work on tumor B, even if both were located in the pancreas.  Get my drift?  We come once again to the necessity of matching the treatment to the individual genetic (or epigenetic?) mistake.   More laboratory analysis, more testing – and more money.  

There is a lot more stuff in the original Times article, but I’ll let you read it for yourselves.  It is lunchtime and I’m hungry.  http://nyti.ms/12vDZvw

*Commonly Phase III trials are run with the “standard of care” treatment used in what I have called the placebo arm.  That way you can see if the new drug, which almost certainly is expensive, will do a significantly better job than the usual treatment regimen.

 



EVEN THE ARMY GETS INTO THE ACT

WHAT A DIFFERENCE A FEW DECADES MAKE!

Did you know that the Department of Defense (DoD) funds ovarian cancer research?  If you are like me, your initial response probably was – what the heck?  When I was in the Army very few soldiers had ovaries, that’s for sure.  Some did, of course – WACs, nurses, and maybe a few others, but I wouldn’t have thought that there were enough to merit a special research program.  Even now it seems odd, to a dinosaur like myself.  However, it’s true and it’s well appreciated, even by dinosaurs.

It turns out that, in 1992, Congress established something called the CDMRP, which codes for Congress-Directed Medical Research Program, which has been funded to the tune of $7.4 billion to date.  Funds for medical research are added to the annual DoD budget.  The DoD then divvies these funds up between various programs, one of which is the OCRP; Ovarian Cancer Research Program.  OCRP was initiated in 1997 and so far has spent $216 million on a large number of disparate, promisingly innovative, projects.  Several of the people I work with at the Hutch are partially funded by the DoD. 

 

So, I tend to be a bit incredulous that these funds are being administered by the Department of Defense.   Don’t these guys spend billions on advanced weapons systems that, just occasionally, don’t work worth a damn?  Isn’t $216 million a rounding error for them?  Pocket change, that you might toss in a change dish?  I would have thought that, just maybe, the NIH could look after the money better.  But what do I know?  I’m  a dinosaur.

 

But, anyway, the CDMRP exists, and it has put out a document – a readable document - stuffed with interesting information about ovarian cancer.  You can read it yourself at the following web address:

 

http://cdmrp.army.mil/ocrp/  For the easy-to-understand pamphlet, click on the image on the left of the page. 

 

On another matter, I am pleased to report that I have finally met Dr. Saul Rivkin, the founder of the Marsha Rivkin Center for Ovarian Cancer Research.  He just retired, at 77, from active duty as an oncologist at Swedish Hospital.  I admire (and envy) his energy – but, after all, he IS younger than me.  His wife Marsha died early of OVCA, earlier even than my own Linda.  I imagine that his dedication to eradicating that particular disease is at least as great as mine, if that is possible.  He has the advantage of a medical education, good contacts and – as I said before – a surplus of energy.  He is going to be devote full time and attention to ovarian cancer, now that he’s retired.  I  hope I can help.



THE SEQUESTER HITS HOME

 

A quilt shop in Mahone Bay, Nova Scotia

She could smell 'em at 50 miles if the wind was right!

 

 

Remember back on March 2^nd when I told you (TIME TO BURN SOME SHOE LEATHER) about the effect this moronic thing called the “Sequester” was about to have on the NIH and NCI budgets”   and politely exhorted you to write your Congresspersons to complain?  Sure you do, because I kept hounding you for weeks thereafter.  I am certain that most of you did the right thing and raised hell.  However, as you certainly know, all your efforts did no good – “Sequester” not only took, but now seems to be permanently installed as the new norm.  Well, yesterday I learned something that again rubbed my nose in this monumental stupidity.  I had a talk with Dr. Bonnie McGregor.

You will remember Dr. McGregor.  I wrote about her in my blog “CHEMO BRAIN AND CROWDSOURCING” on May 26^th.(Well, after actually re-reading that little contribution I see that I didn’t say anything at all about Dr. McGregor – although if  (as I am sure you did) you followed the link I gave you would know her and her project).  Anyway, she has given us several tote bags, which I will dole out to the winners of various aspects of Summerun North 2013, on July 28^th.  She also wanted to attend, but has other commitments.  Anyway:  Dr. McGregor told me a little of what is happening because of the big “S”.  She is awaiting word on how much her various grants, already awarded, will be cut.  Some salaries will feel the pinch as well.  I know that the unit I work with is sweating bullets trying to get their master grant re-funded.  I suspect that terror roams the halls of most cancer research institutes these days.   And all because Congress (and the body politic at large, it seems) has forgotten the arts of compromise. 

I have several times lately used  the Aussie expression “Goodonem” -  translated” Good on you, them, it” whatever.  It may be time for a similar expression:” Apoxonem”.

I know, I wrote two blogs today, and two per day is too many.  It’s just that my cats have stopped barfing on the rug, so I had some time on my hands.  It won’t happen again.

By the way: http://community.swedish.org/page.aspx?pid=608&tab=0&frtid=1183, and of course
 http://www.customink.com/signup/3a9v6j52



DISCOURAGED: but only temporarily

 

Linda and her Mom, on the latters wedding day

Both gone now, unhappily

The world is a far sadder place without them

 

One must not become discouraged.  The fight must go on until victory is achieved.  Be of good cheer.  Or, as Linda would have said “Buck up, Buck!”

No, I’m not talking about General Eisenhower during the Battle of the Bulge.  I am talking to myself, after reading a depressing news article.

If you read these blogs instead of just looking at the pictures you will be aware that one of the hot approaches in cancer research is “targeted therapy”.  Targeted therapy consists of using genomics to determine which mutation (or mutations) is driving the uncontrolled cell reproduction that is at the heart of cancer, then developing a specific treatment to cancel its evil activities.   Expensive for sure, but effective.  Well, maybe not.

Dick Ingwall alerts me to an article in the NYTimes: Studying Tumors Differently, in Hopes of Outsmarting Them.  (http://nyti.ms/1cnNE8n).  The opening paragraphs are what brought on my depression.  They relate the story of an unfortunate man who was covered with melanoma blotches, with only weeks to live.  His oncologist treated him with a new targeted therapy drug, vemurafenib.  Like magic his melanoma blotches disappeared, all of them.  Unfortunately, 16 weeks later they all returned,  every single one.  He died a few weeks later. 

The problem, clearly, is that vemurafenib didn’t get all the mutated cells.  There are literally billions of cells in a solid tumor, so if you kill 99.999% of them you still leave of the order of a million cells to mount a counter-attack.  Why didn’t you get them all?  That’s because, as I keep reading everywhere, tumors are “heterogeneous”.  Because they are tumors they divide rapidly.  The chance for a spontaneous mutation occurring is greatest at cell division, when the DNA is duplicated.  Errors occur, and although most are repaired right away and many of those that aren’t fixed are harmless – still, some bad ones may get through.  Thus a tumor caused by a single mutation may spawn other deleterious mutations as it grows.  This puts us in a pickle.

The way out of the pickle, this article implies, is to give two (or more?) targeted drugs simultaneously.  This means even more genomics, and more messing around in the laboratory to create the drugs.  And, of course, more money.  

We were meant to be born, grow up, reproduce –  and then,  shortly -  die.  If we all died at 40 cancer wouldn’t be much of a problem.  But the problem is that we don’t WANT to die at 40.  I sure as hell didn’t.  So we keep on wrestling with cancer.  Maybe targeted therapy will someday be feasible, reliable, and cheap.  Maybe immunotherapy will experience a break-through.  Maybe epigenetics is the way to go.  Damned if I know.  But I still think that early detection is the most immediately promising avenue of research.  That’s what my group does.

By the way, another gentle reminder.  Summerun North 2013 is only 25 days away – and only 11 people have signed up, and seven of them can’t be here!  Don’t make me drink all that beer by myself!  To sign up, go to http://community.swedish.org/page.aspx?pid=608&tab=0&frtid=1183.  Recommended donation is $20, but feel free to give anything you want.  Of course, you always can give me money, checks or stolen property on the 28^th,, but if you want your name on the web site you must use the link.  Big deal, of course.

Even more imminent is the deadline for signing up to purchase a Linda’s Team T-shirt – only five more days..  If you want one of these elegant shirts, go immediately to http://www.customink.com/signup/3a9v6j52. 

 

Anyway, I hope to see you on the 28th.  For those who can't be here, send good vibs..Or, of course, money.