ON STATISTICS AND SANDPIPERS

 

One of my favorite pictures

Linda and sister Carolyn

beautiful

 

As many of you  know, in my pathetic search for new ways to waste time I have begun to attempt birding.  I have most of the equipment – good binoculars, a professional grade (re, Brad Schram) spotting scope, and Sibley in book form as well as in the form of  apps on my iPad and smart phone.  So, last Sunday I went south to the Skagit Flats, to study water birds.  There was a bald eagle flying around, and a great blue heron fluttering from one bush to the next.  There were also shore birds in great profusion.  Therein lay my frustration.

Two kinds of birds were duck-like.  I think one was the American Widgeon and the other a Gadwall, although I would give long odds that I am wrong.  The others were “peeps” (small sandpiper-like birds).  Here the old reliable phrase “damned if I know” becomes appropriate.

One of these peeps was present in a great flock.  They were feeding in a shallow stretch of water, only an inch or two over a muddy bottom.  They had spotted backs, and were very small.  They behaved in a fascinating way – feeding for a while, then suddenly, simultaneously, taking off, swooping in perfect formation for a few seconds, then landing somewhere else and resuming feeding.  The precision with which they performed these complicated maneuvers – never running into one another nor breaking formation – made you wonder who was in control.  You remember an old sci fi movie involving the Borg (“we are the Borg – resistance is futile”)?  These birds behaved like the Borg; as if they were all controlled by a distant computer.  What were they?  Damned if I know.

There also were about a half-dozen of another, larger peep.  It was spotted, top and bottom, and had a small head.  I should have noticed the color of the legs and beaks, but I didn’t.  They roamed around, occasionally pulling goodies from the mud substrate.  They didn’t fly at all while I was watching.  Confidently I referred to Sibley on my tablet, and quickly determined that my bird was a – Sharp-tailed Sandpiper (Calidris acuminate)!  Then I read the fine print.  It appears that this bird is a “rare visitor from Asia”, although it is “seen annually in small numbers”.  Well, maybe it was a Western Sandpiper.  But, of course – damned if I know.

I will keep trying.

But – Oh wait! – this blog is about cancer, not birds.  Well, I found an article describing the improvement in cancer survival rates over the last 20 or so years.  Remember, five-year survival rates (used in this study) are far different from overall mortality rates, as discussed in a recent blog:

http://ljb-quiltcutie.blogspot.com/2015/04/survival-vs-mortality.html

Much back-patting is evident in this article.  The cancers studied were colon, breast, prostate, pancreas and ovary.  The sampled population numbered about 1 million.  The method used was to compare the survival statistics for people in the 50-64 age range during the period 1990-1994 with the same population in the years 2005 to 2009.  All but one of these cancer groups experienced significant improvement over time.  The one that didn’t was – can you guess? – ovarian cancer. 

I’m not a Greek statistician, but I will venture to say that this is mainly bullshit.  The five-year survival rates for most of these cancers have improved primarily because of earlier diagnosis.  Improved treatment may have helped, but I would guess it is not the most significant contributor.  As I have become painfully aware over the past three years (and, I hope, passed on to you), there has been no improvement in early diagnosis of ovarian cancer.  So, no big surprise that ovarian survival didn’t improve. 

I would like to see the mortality statistics for this same study group but, of course, that requires us to wait until all the subjects die.

Here is the article.  It is short, interesting, and easy to read.

http://in.reuters.com/article/2015/04/23/us-cancer-survival-idINKBN0NE2KD20150423

 



AN OVARIAN "DREAM TEAM"

At Carolyn's, a long time ago

Note that I had hair then.

She looks particularly beautiful, don't you think?

A little more than two years ago I introduced you to “Dream Teams”.  These were to be teams of diverse specialists all working together on a single project – that is, in this case, cure of some kind of cancer.  The organization pushing this approach was a product of the entertainment industry.  Its name was to be Stand Up to Cancer, or SU2C for short.  At the time I was hopeful, but slightly skeptical.  Then two years elapsed and I heard nothing about Dream Teams at all.

Well, now I have.  A consortium of funds and organization has announced a $6 million, three year attack on ovarian cancer.  Headed by SU2C, this is a genuine Dream Team venture.  At the same time a Dream Team project against lung cancer was announced.  Apparently SU2C has forked over $370 million for 16 projects since 2009; the fact that I haven’t heard about them obviously reflects on me, not SU2C.  Also, apparently SU2C was in operation long before my first Dream Team blog.  http://ljb-quiltcutie.blogspot.com/2013/04/dream-teams.html

Anyway: the approach to be taken in this research project is to investigate the activities (or lack of activity) of genes that affect DNA repair – such as our old friends, the PARP inhibitors.  They also will chase the Holy Grail of cancer treatment – prevention – by means not explicitly stated.  More power to them!

An interesting sidelight here is that the co-leader of this effort is Dr. Elizabeth Swisher, of U.W.  I have sat next to Dr. Swisher at several conference tables.  If I can summon the courage I will contact her and ask if I can help. –

Here is the link.  Note how many organizations are fighting ovarian cancer – and these are merely the largest.  How come OVCA is still around?

http://www.prnewswire.com/news-releases/new-su2c-ocrf-ocna-nocc-ovarian-cancer-dream-team-announced-6-million-grant-over-3-years-will-focus-on-dna-repair-therapies-300068296.html



SNIPPETS

In North Wales

Obviously we had been feasting on too many Welch pastries

I have lost that hat, but not that stomach

 

Snippets of fact observed while whipping through a week’s worth of Google Alerts on ovarian cancer, trying to get caught up:

Intraperitoneal chemotherapy now is the treatment of choice for ovarian cancer, and has been for some time.  (Linda wasn’t offered it.  I sometimes wonder why.)  It involves drilling a hole in your abdomen, inserting the chemo fluid directly into the peritoneal cavity, then sloshing it around by tilting the patient this way and that.  It works, but they don’t know why.  True to the spirit of investigation that I particularly like, they are trying to find out why it beats chemo-in-the-bloodstream.  The answer apparently involves changes in the miRNA and gene  population of the tumor.  Short article, easy going:

http://www.biologynews.net/archives/2015/04/19/seeking_new_targets_for_ovarian_cancer_treatment.html

 

A $249 test for the BRCA mutations, plus 17 other mutations known to be involved in ovarian cancer, is about to hit the market – even though the powers that be continue to insist on testing only women with a family history of breast or ovarian cancer.  Up theirs, say I.  The test involves saliva - you spit in a bottle and mail it in, I guess.  Here are a couple of links:

 

http://www.bloomberg.com/news/articles/2015-04-21/color-genomics-brings-245-breast-cancer-risk-test-kit-to-masses

http://health.usnews.com/health-news/health-wellness/articles/2015/04/22/at-home-saliva-test-gauges-breast-and-ovarian-cancer-risk

Delaying pregnancy until her mid-30s may reduce a woman’s risk of ovarian cancer, although the reason for this seems to be obscure.  I suppose that if the delay involved taking birth control measures that suppressed ovulation  this might be true.  Of course, delaying child birth potentially has several important negative consequences.  The statistics on this study seemed particularly skimpy.  I’ll bet that Dr. Ioannidis would read the report with wrinkled brow (see my blog http://ljbquiltcutie.blogspot.com/2014/04/metrics-scourge-of-sloppy-science.html)

 

The article discussed is the following:

http://www.inquisitr.com/2034690/delaying-pregnancy-until-mid-30s-may-help-prevent-ovarian-cancer-but-decreasing-fertility-complicates-issue/

Somewhere in all this skimming I ran on the statement that the mortality rate for ovarian cancer is not much different than what it was in the 1970s.  That grinding sound you hear derives from the collective teeth of Dr. Saul Rivkin, Dr. (of geology) Myrl Beck, and important published author Clifton Leaf - and no doubt a vast host of others

And, by golly, I’ve found something worth working on, but I will save it for another day.

 

 



A DUBIOUS MILESTONE

Linda at Richard and Raelyn's wedding

 

Sometime last night my blog’s “hit count” crashed through 20,000 all-time, thanks to 115 from Russia!  This is, of course, total baloney – most, if not all, of those late-night Russian  “hits” were recorded by a computer algorithm searching for something like the recipe for nerve gas or good stock market tips.  A fat lot of good it did them, those Cyrillic computer hacker!  According to this morning’s newspaper, Russian hackers have gained access to the innermost secrets of the White House, including even our President’s golf handicap!  May they soon smoke themselves to death!

But, anyway, the hit recorder says 20,044 since I started this blog in 2012.  Of those, 12,817 are from the U.S., which I tend to believe.   Five hundred-odd are from Canada and the U.K.  The rest are from places like Russia, Ukraine, Poland, South Korea and Cambodia.  These I discount.  I estimate that perhaps 14,000 actual human beings have read a blog at one time or another – but this includes multiple hits from faithful followers, of which there are at least six.  Still, I think I have reached a lot of people.  I would pat myself on the back, were I not so damned arthritic! 

On a totally different not: who has my copy of the movie The Big Year?  I plan on doing one myself in 2016, and I need to study up.



FLOATING DNA. MAYBE USEFUL

The Joyce sisters, on their way to Friday Harbor

They had fun

 

Dick Ingwall has sent me an important article from the NY Times.  I know it is important because the Bellingham Herald has copied it, word for word, and made it a front page article.  However, they stopped midway through, presumably because they had satisfied their need for column-inches.  The Herald on Mondays is too skimpy to ignite a campfire, so the column-inch limit must be very constraining.  I wish they would hire me to summarize, modify, and explicate these purloined pieces , but that would cost money and lower the bottom line (which I am afraid is pretty low as it is.)  So, anyway, you can read the whole thing right here:

http://www.nytimes.com/2015/04/20/health/blood-test-shows-promise-as-alternative-to-cancer-biopsy.html?smprod=nytcore-ipad&smid=nytcore-ipad-share

To summarize, modify and explicate:  All growing cells shed tiny fragments of DNA into the blood stream.  This was discovered in embryos, which almost by definition are growing masses of cells.  However, the same can be said for tumors.  Oncologists need to monitor the reaction of tumor masses to treatment: are they shrinking, or not, and what is the potential for recurrence?   Traditional methods, involving biopsies and CT scans, are clumsy, disruptive, and slow.  But now, thanks to The Cancer Genome Atlas and  rapid gene sequencing methods, it is increasingly possible to search the bloodstream for the presence or (hopefully) absence of tell tale scraps of cancer DNA.  – using only a blood draw. 

Oncologists are cautiously enthusiastic.  Again, this is no cure, but a step forward nonetheless.  Read more about DNA in the bloodstream at:

http://ljb-quiltcutie.blogspot.com/2012/04/wyoming-death-march-of-all-stupid-whims.html

 



OF ZINC, HEDGEHOGS, AND CANCER

Linda, daughter Kristen in Tucson

mid 1980s

 

Hedgehog  is

1.        The name of a cute little animal mainly encountered in British fiction.

 

              2.   The name of a gene, necessary for life in all biological symmetrical animals.

3.       The name of a protein coded for by the Hedgehog gene.

4.       The name for a biological pathway of unexcelled complication

5.       All of the above.

Zinc is

1         A metal, #30 on the periodic chart

2         Extracted from the mineral sphalerite.

3         A principal component of brass

4         A dietary supplement.

5         Necessary for life

The correct answers are, of course, 5 in both cases.

So what does this have to do with anything I should write a blog about?  Well, it turns out that zinc acts as a “regulator” of Hedgehog.  When we are developing – e.g., differentiating from a cellular blob into something with arms, legs, etc. – we need the Hedgehog signaling pathway to make the proper biological processes go.  However, when we are fully formed, we need Hedgehog to crawl back into its hole; improperly activated Hedgehog can lead to autism and several kinds of cancer, including ovarian.  Research performed at  Rensselaer University indicates that a zinc deficiency may be behind some (all?) of Hedgehog-related  mistakes.  Research is on-going.  Sounds hopeful.

http://medicalxpress.com/news/2015-04-zinc-deficiency-linked-hedgehog-pathway.html

I wrote about Hedgehog once before, long ago, when I obviously didn’t know how important it is:

http://ljb-quiltcutie.blogspot.com/2012/09/linda-with-chestnut-sprout-i-think.html

 

 



TENSORS: My God, whazat?

Grand Canyon, mid 80s

Man, wasn't she beautiful!

Tensors.  You know what they are, right?  They are sort of like vectors, only more so.  Does that help?  Well, that’s about all I can say about them.  Tensors are used in seismology and the study of rock stress in deforming rock bodies, so at one time I knew a little about them, and even tormented advanced students with the bloody thing!  The tensors I cared about appeared as a 3X3 matrix, and you could do all sorts of cute tricks with them.  Now, forget it.  I apologize to all those early grad students for the unnecessary suffering I put them through.

Why tensors?  Well, some people from the University of Utah have developed a mathematical model, using tensor analysis, to predict the outcome of various therapies on OVCA.  The input data is a scan of the tumor genome, compared to the genome of a normal cell from the same person.  The mathematical model, given this input, can tell a physician such things as how long her patient will live, whether the tumor will respond to platinum-based drugs, etc., etc.  Note that it just predicts the future; it doesn’t in any way alter it.  So, is it useful?  I guess so, but I wouldn’t want to be in the white coat and cheap tie of the oncologist who has to tell a woman that she has less than 18 months to live.  Maybe she’d rather not know.

So, math whizzes: How about an algorithm that will tell a woman how not to get OVCA in the first place?

http://medicalxpress.com/news/2015-04-method-accuracy-ovarian-cancer-prognosis.html



SURVIVAL vs MORTALITY

Linda at the humble log cottage built by Daniel Boone in his later years

 

That ponderous rag, the NY Times, has printed a very interesting  article on cancer statistics and how we can use them to fool ourselves about progress in the War on Cancer.  As you may already know, there are two “metrics” to describe such progress: survival rate, and mortality rate.  To illustrate:  Survival rate in ovarian cancer is measured by how many women are still alive  five years after diagnosis.  This has increased from roughly 33% in 1975 to 45% in 2010, a substantial gain, although in my opinion pitifully inadequate.  Mortality rate over that period also improved, from 10 per 100,000 women to 8; also progress.  Although in this case the two metrics yield similar results, in other cases they don’t.  Here is why:

Mortality rate can be affected only by changes in such factors as disease prevention and cure.  Survival rate, on the other hand, also is influenced by early diagnosis.  If early diagnosis doesn’t contribute to more effective treatment, all it will do is inflate the survival rate – without making a bit of difference in mortality.  Conversely, if it leads to more effective treatment – as is often the case – it will influence both survival and mortality. The Times article givers a clear example involving a mythical malady called thumb cancer.  You should read it; it will demystify cancer statistics to a degree.  Here is the article:

http://www.nytimes.com/2015/04/14/upshot/why-survival-rate-is-not-the-best-way-to-judge-cancer-spending.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

This short essay  was brought to my attention by Dick Ingwall, who generously took time off from the celebration of his 69^th birthday to send it to me.  Thanks, Dick: welcome to middle age.

Maybe some of you would be interested in a convenient source of cancer statistics furnished us by the NCI.  Play around with this web site 

http://seer.cancer.gov/faststats/selections.php?

 

 



BRCA MUTATIONS

On a beach somewhere, 1987

It’s funny how cancer news comes in “clusters.”  In a recent blog I described how Angelina Jolie’s brave public discussion of her medical problems and her chosen solution to them had resulted in a cluster of articles about detection and prevention of OVCA and BRCA.  Now comes a half-dozen pieces on what appears to be the same study, by researchers at the Perlman School of Medicine at the University of Pennsylvania, which discusses the probability of getting either of these cancers if you have mutations in either or both of the BRCA  genes.  The project involved over 33,000 (nearly all white) women from 33 countries, which I guess should yield reliable statistics.  A woman with a mutation in BRCA1 has a 46% chance of developing breast cancer, 12% chance of developing ovarian cancer and 5% of  encountering both.  This leaves 37% cancer free.  In the case of a BRCA2 mutation the odds were 52% for breast cancer, 6% for OVCA, and 2% both; 46% got off scot free.  (Note that a statistician might quibble with my interpretation of these data; I got scorched once before, long ago, for making a similar interpretation.  Nevertheless, if you read the article you will agree.)

So, the obvious conclusion:  If you have any reason to suspect that you have either of these mutations, get tested.  Good reason for such suspicion would be a first degree relative – mother, sister, daughter – who had either type of cancer.   At the very least, ask your gynecologist, and insist that he/she give the matter some deep thought.  Gene sequencing is no longer the bank-breaker  it once was, especially since the outfit that had a patent on the technique was forced to cough it up.  Insurance companies should be required to cover this species of diagnosis, at least for women with elevated risk.

If you read the article, below, you will be tripped up and disconcerted by discussion of something called “clusters”.  Don’t bother to Google this concept; you will get everything you didn’t want, and nothing else.   Both BRCA1 and 2 genes are thousands of “letters” (nucleotides)  long, and apparently the disabling mutations tend to occur in discrete sections of the gene.   The practical significance of this discovery is not explained, but – as I’ve said many times before – the more we learn about this (you supply the adjective) killer, the better off we are.  Also mentioned is something called “mutations with nonsense-mediated decay” which, despite its humorous name, is bad.  I will try to figure that one out.

Here is the link:

http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7B565b2918-c2eb-4b7e-9deb-25f024cf9a0d%7D/breast-ovarian-cancer-risks-vary-by-brca-mutation-location-type?sc_trk=internalsearch 



CANCER AND THE STOCK MARKET

Bryce Canyon National Park

Early 1980s

 

It is pretty interesting how many “alerts” to OVCA articles turn out to be in business/financial/stockmarket publications.  I guess it is obvious why this should be; any pharma company that is likely to bring  a “breakthrough” drug to market is a hot commodity on the Street.  This annoys me somewhat, but irrationally.  Yes, Jesus kicked the money-changers out of the temple, but what if they were making change for people who wanted to donate?  Profit isn’t always bad, no matter what you think.

However, the article that inspired this rambling, which appeared in TheStreet.com, has some interesting news.  It appears that Clovis Oncology (NASDAQ: CLVS) has a drug called rucaparib that is sufficiently promising that it has been awarded the designation of Breakthrough Therapy by the FDA.    (What that means doesn’t seem to have been explained, but I’ll bet it’s good).  Rucaparib is an oral PARP inhibitor (you remember those guys, right?).  It seems to be used with good effect on cancers caused by BRCA mutations.  And, of course, it merely prolongs life – it isn’t a cure.  But what the hell, it’s progress.

Read the article, but don’t buy the stock.

http://www.streetinsider.com/Corporate+News/Clovis+Oncologys+(CLVS)+Rucaparib+Receives+FDA+Breakthrough+Therapy+Designation+as+Ovarian+Cancer+Monotherapy+Treatment/10435403.html



MEA (dadburnit) CULPA!

Tucson sabbatical, early 80s

I dropped the ball.  Back on January 20^th I wrote that Ken Burns was doing a documentary based on the book The Emperor of All Maladies: A biography of cancer, which I have written about in several blogs.  I promised to let you know when to look for it.  Well: look for it a few weeks ago.  As I said, I dropped the ball.  I have managed to see  most of it, courtesy of Carolyn, Linda’s sister, who recorded it.  It is excellent, although tough going in places.  Try to find it; it will repay the effort