IP CHEMO: Maybe not such a step forward, after all

Linda and Ella

At the time of Linda’s ovarian cancer diagnosis there was excitement about a new method of administering chemotherapy.  Up to that time the stuff had been applied intravenously (IV), involving a needle or a port and trusting to blood circulation to deliver it to the tumor.  The new wrinkle was called Intraperitoneal (IP) chemotherapy, and it was widely deemed to be superior to IV treatment. IP worked by drilling a hole in the woman’s abdomen and injecting the poison directly into the target area.  Linda didn’t get IP chemo – and I have always wondered why.  See this commentary:

https://ljb-quiltcutie.blogspot.com/2015/08/intraperitoneal-chemotherapy.html

Now, however, it turns out that IP not only is no more effective than IV, but has more unpleasant side effects:

https://www.medpagetoday.com/hematologyoncology/ovariancancer/79415

So I guess I should be happy that Linda didn’t get IP treatment, but I’m not, really.  I have long chuckled at the frequency with which “health experts” change their minds.  About all they seem to regard as immutable advice is not to smoke and not to get fat!  However, I do not chuckle at suggestions that there are “fads” in cancer therapy.  Find it out and test it, guys, then put it to use.  Replace it if something better comes along, but never find yourselves in a position where you have to say “Woops”!  

THE FRED HUTCH NEWSLETTER

Finn & Grandma, a few years back

The Fred Hutch newsletter is out, and it contains lots of interesting articles for those of you who, like me, are dedicated to wrestling cancer into complete and abject submission.  The lead Hutch article concerns a new way to block metastases in breast cancer.  Another important offering is an essay on “liquid biopsies”, the detection and diagnosis of cancer by DNA-sequencing of tumor fragments floating in the blood stream.  The latter is somewhat discouraging, because it transpires that small (early stage, more easily eradicated) tumors don’t shed as much molecular debris , hence are harder to detect.

Other articles of note in the Hutch newsletter include the announcement of the death of Dr. Robert Hickman, at the age of 92.  Dr. Hickman was the inventor of the Hickman catheter, used for feeding, blood-sampling, and administering chemotherapy on the case of cancer.  Linda had one, installed by Dr. Hickman himself; he showed me how to check if it was okay.

Yet another article relates the excellent news that Dr. Kristin Anderson has received a grant to continue her work on immunotherapy.  I have been in touch with Dr. Anderson; she is a live wire!

If you mess around with the Hutch Newsletter you can find loads of interesting stuff.  I was particularly taken by a small blurb relating that Dr. Phillip Greenberg, Hutch immunologist, has been awarded an important honor.  (Kristin Anderson works in his lab.)  What I liked most about that article was his picture.  Dr. Greenberg has precisely the beard, mustache, and haircut that I aspire to – but I simply can’t grow enough hair!

https://mail.google.com/mail/u/0/#search/communications%40fredhutch.org/FMfcgxwCgLwzjtSVVsKTwqJNbGnZpmpm

THE NCI AGREES: We need more genetic testing.

W agrees

Amanda reads to the whole crew.

I have written many times about the deplorable lack of genetic testing for mutations associated with ovarian and breast cancer.  The NCI now agrees with me.  After some large trials and exercises in fancy statistics they have concluded that there is a grievous deficit in testing, especially among minorities and rural women.  Knowing a woman’s status vis a vis known cancer-related mutation is important in several ways, most of which you already know or can reliably guess.  New to me was the fact that mutation-status is an important factor in determining OVCA therapy.  For instance, PARP inhibitors will work well only for certain mutation signatures.

It would be worth your while to read this short, comprehensible article:

https://www.cancer.gov/news-events/cancer-currents-blog/2019/ovarian-breast-cancer-testing-inherited-genetic-mutations?cid=eb_govdel

The article ends with the words “Every woman with ovarian cancer should know her BRCA1 or BRCA2 status.”

This is pretty much what I said six months ago:

https://ljb-quiltcutie.blogspot.com/2018/10/all-women-should-know-their-brca-status.html

AN AMBIVALENT BOOK REVIEW

Magic mushrooms?

The title of this blog can be correctly interpreted in two ways: either an ambivalent review of a book, or a review of an ambivalent book.  Both are accurate.  After several somewhat unpleasant days wading through this book, I am ambivalent about whether or not to recommend it.  But also – the book itself is ambivalent about what it wants to be.  Is it a book about the immune system, or about the author’s buddy Jason – or is it merely an excuse for the author to publicize s his ideas about the human condition?  Darned if I know.  My bottom line is: read this book only for its occasional insights about how the immune system works.  And if you do read it, get it from your local library, or wait until abebooks has it for sale for $3.79.

The book I’m on about here is An Elegant Defense, by Matt Richtal.  Richtal is a free-lance writer with connections to the NYTimes, and has authored several other books – none of which I plan to read.  I bought this book retail, hoping to learn more about the immune system and how it affects our lives.  I did learn some stuff, or at least I was exposed to it – but it came in such randomly placed driblets that I was unable to form even a vestige of a coherent picture.  Maybe I could, but I’m not going to try – An Elegant Defense is straight on its way to the local bookstore.  Sorry, Matt: I know you loved Jason, and I know you tried.

If you want to read a serious cancer or bio-book, click on

https://ljb-quiltcutie.blogspot.com/2014/10/the-cancer-researcher-wannabes-bookshelf.html

and take your pick.

SURVIVORNET: A useful web site

Seamus, my Great Grandson, in a pensive mood

Happy Easter!  I have just discovered a most valuable web site – for those of us interested in the battle against cancer.  To access it, just Google “survivornet”.  Give it a try.  It has too much valuable information for me summarize.

READ THIS, IT WILL DO YOU GOOD

Linda and Carolyn, in a happy time

Wow!  This article speaks to multiple matters I think are extremely important:

Do we need better cancer diagnostic tools?  Damned right we do!  Lacking a cure or a means of prevention (these are still way in the future, I fear), early detection is our most important attainable goal.

Can you prevent cancer by “living right”?  Sadly, no.  You can increase your odds of evading the disease by not smoking, not drinking too much booze, staying skinny, etc., etc., etc., but malicious random mutations during normal cellular processes are still lurking out there somewhere.  Survival of the luckiest, in a way;  not an ideal situation, that’s for sure. But we’re probably stuck with it.

Do our expert know what we should eat?  Clearly no; they are forever changing their minds.  Cigarettes aren’t good for you, yes -  but chocolate?  My mantra: eat what you want, so long as it doesn’t contain ground glass.

Read this article.  It is short, easy, and packs a punch.  Actually, several punches.

https://www.curetoday.com/community/kelly-irvin/2019/03/ovarian-cancer-screening-tool-should-be-a-top-research-priority

PESTILENTIAL GARBAGE BAGS

Linda on Skye

As long ago as September of last year I introduced you to exosomes:

https://ljb-quiltcutie.blogspot.com/2018/09/exosomes-evolution-and-cancer.html

In that blog I related how recent research had found that exosomes, in addition to being molecular garbage bags, were – if emitted by cancer cells – also laden with a protein that could stifle the activity of immune cells, leaving them impotent as a weapon against cancer.

Only a few months later I “introduced” you to exosomes, apparently having forgotten all about my earlier post.  This blog described how people had perhaps discovered a way to prevent cancer cells from expelling their little garbage bags; I gloated that they might then die a painful death, of acute constipation!  This somewhat childish thought is elaborated in:

https://ljb-quiltcutie.blogspot.com/2019/03/molecular-garbage-bags.html

So now, Dr. Collins of the NIH continues the narrative:

https://directorsblog.nih.gov/2019/04/09/new-target-for-cancer-immunotherapy-exosomes/

It appears that work at U. Cal San Francisco (essentially a med school and lab complex, I believe) has verified that cancer-derived exosomes are laden with poison; specifically a protein named PDL-1.  PDL-1 binds with another protein, PD-1.  The problem is that some immune cells bristle with PD-1 receptors, and are summarily shut down by the binding of PDL-1.  Some types of immunotherapy are designed to prevent this sort of thing.

Well, it transpires that the molecular garbage bags we are considering go straight to the lymph nodes, a place where immune cells are perfected and readied for battle.  The PDL-1 carried in exosomes effectively shuts down the army before it is ready for battle.  Needed is a molecule that will effectively disable the bad guy – PDL-1.  They are working on it.  Many mice will die.

I admit to being slightly put out by Dr. Collins’ last paragraph, wherein he trumpets as evidence of rapid progress that 480 peer-reviewed papers on this subject have been published in the last few years.  Hell:  Progress is fixing cancer.  Some of those papers are valuable; specifically those that report findings essential to continued progress.  However, I’ll bet many of them are more of the “Hey, notice me, and give me a grant and/or a promotion” sort of thing.  We had a bunch of those in geology. Get back to your lab bench, guys!

MUCH MORE ON EARLY DETECTION

Cordova, Alaska, Coast Guard detachment

My daughter Kristen once echoed my sense of frustration, writing “Why isn’t there a simple blood test that will tell you whether you have cancer?”  At that time I was volunteering for a big-time research project aimed at developing exactly such a test.  We worked on it for several years, spent $8 million of your tax dollars – and failed.  Turns out the problem is not as simple as it ought to be.

The link below will bring you up to date with progress along this line.  The specific question addressed is: if you have a lump of stuff in your uterus, should you be referred to a specialist for possible surgery?  To answer that question several blood-sample tests have been developed.  Clearly, if CA 125 is elevated they send you off to a specialist clinic.  The other tests described in this article depend on multiple proteins in the blood plus menopausal status; as such they actually are computer algorithms.  One you are familiar with (if you read my blog) is ROMA: the Risk of Malignancy Algorithm.  Several more are described, possibly better than ROMA in some ways.

The bottom line is that your local doc should know about these things and make efficient use of them.  The article below makes it clear that applying these tests to the common asymptomatic woman who wanders in off the street is “inefficient” and is not recommended.  My take is: if it’s cheap and easy, go for it.

If you read this link (big “if”, I’m afraid) you might need to be reminded of some medical stat things:

Sensitivity: the probability that, if the test says you’ve got it you really do

Specificity: The probability that, if the test says you don’t have it, you really don’t.

PPV (Positive Predictive Value):  The number of true positives, divided by the sum of true positives and true negatives.

Bottom line: the bigger these things are, the better

https://www.contemporaryobgyn.net/ovarian-cancer/whats-new-biomarker-testing-ovarian-cancer

ANOTHER STAB AT EARLY DETECTION

Linda, with a Hunsinger grand nephew

I guess this is worth a blog.  I may have posted more news about diagnostic tests for OVCA than for anything else, possibly excluding immunotherapy.  This article, however, seems to be important.  Dedicated folks at U. Minnesota seem to have done what my now-defunct group at Fred Hutch was attempting to do; define a group of proteins, measurable in a blood sample that can detect the presence of ovarian cancer with high sensitivity and specificity.  They are pressing forward with their efforts.  It seems that this test might work for very early stages (this is the Holy Grail, of course) and even be easy – and inexpensive – to apply. 

Every few weeks I go into a medical lab and have my finger pricked.  A drop of blood is then transferred to a small contrivance the size of a standard flashlight.  The machine cogitates for a few seconds, and then spews out a number that describes my blood-coagulation time.  (I have atrial fibrillation, so “they” want my blood to be thin and syrupy).  I look forward to the day when women, present at the doc’s for any reason, can donate a drop of blood to a similar machine, to guard against ovarian cancer. 

https://twin-cities.umn.edu/news-events/research-brief-developing-blood-test-screen-ovarian-cancer

EXPLOITING NATURE FOR THE GOOD OF US ALL

Future NIH field investigators

I once tried to learn organic chemistry, from a Teaching Company on-line course – no lab, no tests, no flesh-and-blood teacher, not even a real-life textbook.  And, as you might have guessed –  no useful result.  Organic molecules consist of innumerable carbon and oxygen atoms with all sorts of stuff (other atoms, often hydrogen) hooked on.  These trellises of atoms extend out in all directions into three-dimensional space.  The precise atoms they contain, and the exact pattern they describe geometrically, are of vital significance in organic chemistry.  And, as I should have been able to predict, are inaccessible to the octogenarian mind.  All I can tell you about organic chemistry today is that there are innumerable organic molecules, the shapes and compositions of which are of vital significance in everything from medicine to beer-making.  Organic chemistry is important; too bad I never mastered it.

So, in early days – tribal times, let’s say – there were people, mainly women, who specialized in going into the forest and collecting herbs for use as medicine.  Mostly they didn’t work, but occasionally they did.  Part of the success no doubt was owing to the placebo effect; if you trust your “doctor” enough, you may well feel better – especially if the herbal potion was prepared by your maternal great-aunt, who happens to be the wife of the chief.  But more than likely some of the plants the old lady made you ingest contained organic compounds of genuine curative value; otherwise she would have stopped picking them.  At least, so reasons the NIH.

All of which is to tell you that our government is spending a bit of Cancer Moonshot money on creating a catalog of potentially useful organic compounds derived from plants and soil biota.  Turns out this is not a simple task.  How they do it, and why, makes interesting reading.

https://www.cancer.gov/news-events/cancer-currents-blog/2019/cancer-drugs-natural-products-nci-program?cid=eb_govdel