TO SCREEN OR NOT TO SCREEN?

 

CANCER SCREENING: WHEN IS IT WORTHWHILE?

A Michigan Fall

She loved dry leaves

Essentially the entire issue of the November 27, 2012 NCI Cancer Bulletin is devoted to a discussion of cancer screening.  As both of the groups I try to help are engaged in just that, I read it with interest (and more than my usual comprehension.)  It is really good stuff, and (as always) I urge you to read it.  However, I know you won’t, so I will toss out a few observations and maybe some analysis.  I am tempted to weave a few egregious lies into some future blog, to see if anybody notices and checks.  I promise not to do it this time, though.

First, there is a long piece by Dr. Virginia Moyer, who is the head of the USPSTF: that is, the United States Preventative Services Task Force.  This is the group that has caught so much flack over their recommendation that healthy men not be screened for prostate cancer using PSA.  (All males over 60 will know very well what that is.)  To get current with the Prostate Cancer Wars, re-read the blog of the same name (3/27/12) and especially the appended Comments. 

It turns out that the USPSTF is an all-volunteer group of 16 and is substantially independent of control by government or anything else.  They were set up in 1984 to counter the perception that the medical community was neglecting prevention for cure.  They make recommendations for preventative measures, including screening.  They have had their bad days; one especially bad occurred in 2009, when they issued guidelines for mammography.  They recommended that women under the age of 50 – and over 75 – be not screened at all.  The AMA went ballistic.

Dr. Moyer does a good job of explaining their reasoning.  Any screening regimen involves false negatives.  False negatives engender anxiety, discomfort, and expense.  In the case of cancer, there are some which are easily cured – and others that are incurable.  It doesn’t make sense to screen for these.  Pancreatic cancer is a case in point; there is no viable treatment.  For the rest of cancers, screening might save lives, and whether to screen or not is a judgment call.  I reason that ovarian cancer is one of these.  If caught early, it’s completely curable; if later, rarely so.

The problem here is that one does not know how to value a few lives saved relative to a whole bunch of needless treatment and anxiety.  I tend to think that one live saved easily balances a mountain of anxiety, discomfort and expense.  But that’s just me. 

Another great article concerns the role of statistics.  You know Mark Twain’s famous analysis of statistics.  Well, it seems still to be at work.  Some statistics show that the life-span of cancer victims from diagnosis to death has lengthened dramatically in recent decades.   Good news.   But there is a problem: does this represent better treatment, or is it simply an artifact of screening?  For instance, assume treatment for cancer X is totally ineffective.  Persons not screened will be diagnosed later than persons in the screening arm of the trial.  Thus, the diagnosis-to-death interval will be shorter for the first group than the second, and it will appear the “progress is being made”, when in fact it hasn’t.  In fact, the screened group is less well off in that they had to live longer with anxiety.  So, I guess that screening is useful only for those cancers that are easier to cure in an early stage.  Ovarian is one of these.

 

SHE COULD DO ANYTHING

 

Thursday, February 7, 2013

MRC RESEARCH GRANTS

Why I married here: she could do anything.  1967
Most likely a car load of college boys came by 12 seconds later.
I know I would have stopped

Encouraged by the Comment of my granddaughter Amanda, from time to time I am going to “profile” one or another of the cancer researchers we at the Marsha Rivkin Center help support.  We (MRC) offer support in three categories, but it is clear that each emphasizes innovation.  We try to identify people who may have spied an incipient crack in the armour (of ovarian cancer), and  then  help them pry it open.  Once they are inside, we leave it to the far deeper pockets of the NIH to fight the war.  To me – I had no part in the design of any of our programs – this seems to be a remarkably promising approach.  I wish I were 30 again and a biochemist; I’d rather be one of those smart young people than simply an old guy  writing about them.  But, you do what you can with what you’ve got.

Rather than jumping right in, I will describe the kinds of grants we award.  In ascending order of dollars available, and – probably – difficulty in getting funded:   we award Scientific Scholar Awards, Pilot Study Grants, and Challenge Grants.   

 Scientific Scholar Awards:  These go to young, bright, early-career scientists.  The purpose is to enable them to try out new ideas (which the young have in profusion, I am told – I can't  remember.)  Needless to say, the ideas chosen have relevance to ovarian cancer.  A grant amounts to $60,000 for one year, which isn’t much these days but may make the difference between trying out an idea and shrugging it off.  This year (2012, actually) we gave out three of these, to young women in England, Canada, and the United States.

 Pilot Studies:  These are worth $75,000 for one year.  In 2012 we awarded ten of them.  I gather that the successful applicants tend to be better established in their field, but need help and encouragement in developing some novel approach to ovarian cancer.  One of these awards went to a scientist in Helsinki.

 Challenge Grants:  I don’t precisely understand the nature of this award, so I will simply quote what is said in the MRC Website:  “Challenge grants in scientific research revolve around posing a grand scientific question to the research community and asking researchers to submit their best ideas for meeting the challenge with creative solutions. With help from our Scientific Advisory Board, the Rivkin Center will identify areas in ovarian cancer research in which the greatest strides can be made today and offer a 2-year, $150,000 Challenge Grant to the research group that proposes the best solution.”

 The 2011-2013 MRC  Challenge Grant was awarded to Dr. David Bowtell, who works in Melbourne, Australia.  Dr. Bowtell is testing the hypothesis that ovarian tumors, especially of the most lethal type – serous – leak pieces of DNA into the blood-stream  in quantities sufficient to serve as an early marker of the disease.  Specifically, he is looking at a mutated version of the gene TP53, which apparently is associated with numerous kinds of cancer.  Incidentally, it appears that serous “ovarian” cancer originates in the fallopian tubes.

 Regarding  Dr. Bowtell’s very important  work:   as an Aussie friend of mine was fond of saying, “Goodonyah”!

 

Myrl Beck

 

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HEIDI GRAY, M.D.

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Monday, February 18, 2013

PROFILES IN RESEARCH EXCELLENCE, 2: Heidi Gray, M.D.

 

Linda at Welburn gourd farm

She was good at gourding

She was even better at quilting

 

Remember back on  June 14^th of last year when I wrote about “chemo-brain”?  Actually I was writing about CIPN – chemotherapy-induced peripheral neuropathy, but in two Comments to that blog I introduced   CICI – chemotherapy induced cognitive impairment – chemo-brain.  Linda didn’t have it, thank God, except perhaps in her last few weeks when she wasn’t herself.  However, some women do suffer from  it, and for some of them it last a lifetime.  Thank goodness then for Heidi Gray, M.D.  Dr. Gray is one of our (MRC – Marsha Rivkin Center) grantees for 2012.  She is going to do something about chemo-brain.

What is she going to do, you might legitimately ask?  Well, I don’t rightly know.  Her MRC citation states that she “will examine the ability of a 7-week cognitive rehabilitation intervention to improve memory and thinking abilities in ovarian cancer survivors.”  Additionally, she will “measure changes in brain activity patterns from the treatment using neuroimaging”.

The reason I don’t rightly know is that nowhere can I  find what is meant  by “intervention”, precisely.  It isn’t the administration of drug; that much is certain.  Maybe if I had a proper education the matter would be clear, but I’m just a dumb geologist.  When a geologist stages an “intervention” he usually is breaking up a fight between two of his graduate students over which one gets the last  beer.

But I don’t need to know – Dr. Gray obviously is a smart cookie (actually, you probably shouldn’t refer to cancer scientists as “cookies), as is amply demonstrated  by the fact that she has been  involved in over 20 original research papers in the last five years. The work is innovative (she got an MRC grant didn’t she?), and, given her record, will be well done. She is on the faculty of the U.W. medical school.  She got her M.D. degree at UCLA in 1997.  She is fortunate enough to work with Dr. Elizabeth Swisher, who collaborates with my group at the Hutch. 

And, - I must say it – she looks like she is 25 years old.  Studying medicine and biochemistry apparently imparts a certain ability to resist time – at least to women.

 



 

 

LESS IS MORE more or less

 

Friday, May 3, 2013

LESS IS MORE, more or less

 On Rhodes, mid 80's

This was a "Stations of the Cross" for a medieval monastery

 

I find the number of important cancer-related articles that are floating  around in the popular press to be remarkable.  Has it always been this way, or am I just paying more attention?  Probably the latter. 

Anyway, the Economist for April 13-19 has one such, an interesting, and blessedly short,  description of research done by  Dr. Meghan Thakur of the Novartis Institute for Biochemical Research.  (Full disclosure: I have a little bit of Novartis s stock – and I wish I had a lot more.)  The article, on p. 81, is entitled Less is More.    Dr. Thakur has discovered that sometimes discontinuing use of a cancer drug  will cause the tumor to shrivel and, one hopes, die.  And there is a good explanation for this, one we all can understand. 

It seems that some drugs do a good job of killing tumor cells the first time they are administered, but eventually their efficacy wears off.  It appears that, if the drug doesn’t kill every last tumor cell, the tumor may return – mutated into a form that is resistant to the drug!  (Talk about bad planning!)  This is illustrated in the article by the drug vermuafenib, used to combat advanced melanoma.   After testing the technique on mice (what would we do without them?), it was tried on 19 patients at a London hospital who were not longer responding to vermuafenib; in 14 the tumor growth slowed.  Unfortunately, the tumors don’t seem to have disappeared, just slowed down.   (That’s progress, I guess, but we could wish for a lot more.)   

The article also has a short, simple explanation of just what is going on, biochemically.  Because I know all of you are eager to absorb more biochemistry, I will let you read it for yourselves.

By the way, I have several more topics to discuss, courtesy of Dick Ingwall, but I will be busy with Cinco de Mayo and other things for the next few days.  If you become restless, re-read some earlier blogs  and write Comments.

.

Profiles in Research Excellence: BRIGITTE THERIAULT

Even windblown she was beautiful

 

As promised, from time to time I am going to “profile” a young cancer researcher; specifically, those that have received a grant from the Marsha Rivkin Center for Ovarian Cancer Research.  To kick off the series we consider Dr. Brigitte Theriault, Ph.D. 

Dr. Theriault currently works for the University Health Network, in Ontario, Canada.  She earned her Ph.D. from Dalhousie University, Nova Scotia, in 2007 at – judging from her recent youthful photo –  about the age of 16.    She later Post Doc’d at the University of Toronto.  She has published 13 papers on ovarian cancer in the last few years, received several awards (including ours – MRC) and helped organize  an important conference on ovarian cancer.  It should give us confidence in the eventual extinction of ovarian cancer that people like Brigitte Theriault are on the job. 

I would like to give you the biochemical lowdown on Dr. Theriault’s work, but – quite frankly – I don’t understand it.  Instead, I will quote from two documents describing her research – documents that quite obviously are not meant for the likes of me.

"Her efforts focused on studying how differential regulation of autocrine transforming growth factor beta (TGFβ)/bone morphogenetic protein (BMP) superfamily signalling between ovarian cancer and normal ovarian surface epithelial cells regulates cellular processes such as proliferation, adhesion and migration".  This from her Ph,.D. work in Halifax.

And this, from the MRC citation:

Brigitte Thériault, PhD

Ontario Cancer Institute

Modulation of KIF14 overexpression in ovarian cancer

Dr. Thériault's lab had previously discovered that the gene KIF14 is present in high amounts in the majority of ovarian cancers, and that patients with high KIF14 have much worse survival than patients with low KIF14. KIF14 is normally found in cells that are growing and dividing and is usually not found in adult human tissues. Her prior research in cell cultures and in animal models has shown that accumulation of KIF14 leads to tumor spread and blocking KIF14 causes tumor cell death. Dr. Thériault's goal in this project is to understand how tumors accumulate such high amounts of KIF14 so that she can find ways to block KIF14 production, stop tumor cell growth, and improve the survival of ovarian cancer patients. (The italics are mine.  I am pleased when a cancer researcher relly wants to get at the basic science - to understand something.)

All I can say is that, although I may not understand what she’s doing I can tell she is dedicated and smart smart – and I wish her Godspeed.

 

 

 



MRC GRANTS FOR OVARIAN CANCER RESEARCH

She could do anything

 

Encouraged by the Comment of my granddaughter Amanda, from time to time I am going to “profile” one or another of the cancer researchers we at the Marsha Rivkin Center help support.  We offer support in three categories, but it is clear that each emphases innovation.  We try to identify people who may have spied an incipient crack in the armor (of ovarian cancer), and  then  help them pry it open.  Once they have are inside, we leave it to the far deeper pockets of the NIH to help them fight the war.  To me – I had no part in designing any of our programs – this seems to be a remarkably promising approach.  I wish I were 30 again and a smart biochemist; I’d rather be one of these young people than simply an old guy  writing about them.  But, you do what you can with what you’ve got.

Rather than jumping right in, I will describe the kinds of grants we award.  In ascending order of dollars available, and – probably – difficulty in getting funded -  we award Scientific Scholar Awards, Pilot Study Grants, and Challenge Grants.   

Scientific Scholar Awards:  These go to young, bright, early-career scientists.  The purpose is to enable them to try out new ideas (which the young have in profusion, I am told – I am too old to remember).  Needless to say, these ideas have relevance to ovarian cancer.  The grant amounts to $60,000 for one year, which isn’t much these days but may make the difference between trying out an idea and shrugging it off.  This year (2012, actually) we gave out three of these, to young women in England, Canada, and the United States.

Pilot Studies:  These are worth $75,000 for one year.  In 2012 we awarded ten of them.  I gather that the successful applicants tend to be better established in their field, but need help and encouragement in developing some novel approach to ovarian cancer.  One of these awards went to a scientist in Helsinki.

 

Challenge Grants:  I don’t precisely understand the nature of this award, so I will simply quote what is said in the MRC Website:  “Challenge grants in scientific research revolve around posing a grand scientific question to the research community and asking researchers to submit their best ideas for meeting the challenge with creative solutions. With help from our Scientific Advisory Board, the Rivkin Center will identify areas in ovarian cancer research in which the greatest strides can be made today and offer a 2-year, $150,000 Challenge Grant to the research group that proposes the best solution.”

 Thr 2011-2013 MRC  Challenge Grant was awarded to Dr. David Bowtell, who works in Melbourne, Australia.  Dr. Bowtell is testing the hypothesis that ovarian tumors, especially of the most lethal type – serous – leak pieces of DNA into the blood-stream  in quantities sufficient to serve as an early marker of the disease.  Specifically, he is looking at a mutated version of the gene TP53, which apparently is associated with numerous kinds of cancer.  Incidentally, it appears that serous “ovarian” cancer originates in the fallopian tubes.

Regarding  Dr. Bowtell’s very important  work:   as an Aussie friend of mine was fond of saying, “Goodonyah”!

 

 



WECOME BACK

This is me in December, 1952.  I had just survived my first quarter at Caltech, racking up a GPA of 2.985.  (Yes, in those days, Tech calculated GPAs to the third decimal place.)

It seems that from time to time people blunder on this long-abandoned blog by accident.  They should go immediately to "Myrl'sBlog", which now has 106 entries.  However, it occurs to me that I can put whatever I post on BOTH blogsites, so from now on I will.  If I remember.