Respectful Insolence

One major point I’ve tried to make over the last few years is that the so-called “individualization” or “personalization” of treatments claimed by practitioners of “complementary and alternative medicine” (CAM) is not “individualization” at all, but rather a sham that appears superficially like individualization but in reality is not. I say that because the “individualization” promoted by CAM practitioners is not based on science and clinical trials. Another point I’ve been trying to make is that the true “individualization” of treatments will require science, and it will not be easy. In fact, it will be very, very hard.

This point was driven home over the weekend in an article by Gina Kolata in the New York Times entitled In Treatment for Leukemia, Glimpses of the Future. While the story is basically one long anecdote that shows what can be done when new genomic technologies are applied to cancer, it also shows why we are a very long way from the true “individualization” of cancer care. It also turns out that I’ve discussed the same basic story before, but here I’ll try to discuss it in a bit more detail.

As hard as it is to believe, it’s been nine months since Steve Jobs succumbed to a metastatic neuroendocrine cancer of the pancreas. Last November, the authorized biography of Steve Jobs, written by Walter Isaacson, revealed that after his cancer recurred for the second (and final) time Jobs became one of the first twenty people in the world to have all the genes of his cancer and his normal tissues sequenced, which was done by a collaboration of research teams at Stanford, Johns Hopkins, and the Broad Institute. At the time (2010-2011), it cost $100,000 to do. Scientists and oncologists looked at this information and used it to choose various targeted therapies for Jobs throughout the remainder of his life, and Jobs met with all his doctors and researchers from the three institutions working on the DNA from his cancer at the Four Seasons Hotel in Palo Alto to discuss the genetic signatures found in Jobs’ cancer and how best to target them. Jobs’ case, as we now know, was, alas, a failure. However much Jobs’ team tried to stay one step ahead of his cancer, the cancer caught up and passed whatever they could do.

Kolata’s story, in contrast, appears to be that of a success. It is the story of Dr. Lukas Wartman, a recent graduate of the Washington University hematology-oncology fellowship who is now an Instructor in the Division of Oncology:

Genetics researchers at Washington University, one of the world’s leading centers for work on the human genome, were devastated. Dr. Lukas Wartman, a young, talented and beloved colleague, had the very cancer he had devoted his career to studying. He was deteriorating fast. No known treatment could save him. And no one, to their knowledge, had ever investigated the complete genetic makeup of a cancer like his.

So one day last July, Dr. Timothy Ley, associate director of the university’s genome institute, summoned his team. Why not throw everything we have at seeing if we can find a rogue gene spurring Dr. Wartman’s cancer, adult acute lymphoblastic leukemia, he asked? “It’s now or never,” he recalled telling them. “We will only get one shot.”

We learn later in the article that Dr. Wartman had first been diagnosed with acute lymphoblastic leukemia in 2002, when he was a fourth year medical student ready to finish up and move on to residency. During trip out to California for a job interview, he began to experience overwhelming fatigue. Upon his return, he found he couldn’t run anymore and started having night sweats. At first he thought it was mono, but then he started having bone pain. He finally went to an urgent care center, where at first it was thought that he might be suffering from depression, but it was also noticed that he had a low white blood cell count.

The rest of his story can be summarized in a manner that is still too common among leukemia patients. He underwent nine months of intensive chemotherapy, which was followed by 15 months of maintenance chemotherapy. Five years later, his leukemia recurred, and he underwent a bone marrow transplantation, which is the usual treatment for recurrent ALL. Thus far, he had beaten the odds, having not realized how bad they are for recurrent ALL:

Seven months after the transplant, feeling much stronger, he went to a major cancer meeting and sat in on a session on his type of leukemia. The speaker, a renowned researcher, reported that only 4 or 5 percent of those who relapsed survived.

“My stomach turned,” Dr. Wartman said. “I will never forget the shock of hearing that number.”

In the vast majority of cases, a patient like Dr. Wartman would be dead. As is pointed out in Kolata’s article, we are not even sure of the expected survival rate of someone who has relapsed twice with ALL, other than that the odds are clearly very, very low. However, Dr. Wartman was very fortunate to have friends who had access to technologies to which few have access. Because he is a researcher at the Washington University and knew Dr. Timothy Ley, a world-renowned leukemia researcher and Associate Director for Cancer Genomics for the The Genome Institute at Washington University and because he was apparently well-liked there, Dr. Ley offered to do what was described in the introduction of Kolata’s article. It was a massive undertaking, as well:

Dr. Ley’s team tried a type of analysis that they had never done before. They fully sequenced the genes of both his cancer cells and healthy cells for comparison, and at the same time analyzed his RNA, a close chemical cousin to DNA, for clues to what his genes were doing.

The researchers on the project put other work aside for weeks, running one of the university’s 26 sequencing machines and supercomputer around the clock. And they found a culprit — a normal gene that was in overdrive, churning out huge amounts of a protein that appeared to be spurring the cancer’s growth.

Even better, there was a promising new drug that might shut down the malfunctioning gene — a drug that had been tested and approved only for advanced kidney cancer. Dr. Wartman became the first person ever to take it for leukemia.

And now, against all odds, his cancer is in remission and has been since last fall.

As is often the case when I’m reading an article in the lay press, I sometimes have to read a bit between the lines and make an educated guess as to what exactly it was that Dr. Ley’s team did. The first analysis appears to be a next generation sequencing (NGS) analysis of both the leukemic cells and normal cells. NGS techniques allow the sequencing of complete genomes in a matter of weeks. In “old-fashioned” automated sequencing using Sanger techniques, the rate-limiting step in the sequencing process was the need to separate reaction products on a polyacrylamide gel in order for the sequence to be read. Next generation sequencing (NGS) techniques overcome this limitation by arraying DNA molecules on solid surfaces by anchoring and copying single DNA molecules on glass slides or or array of beads. Going into the details of these new sequencing techniques is beyond the scope of this particular post (maybe some day), but for interested readers who know a bit about sequencing and PCR, there is a decent general description here. The long and the short of it is that NGS techniques allow the massively parallel sequencing of a genome such that 30 gigabases of DNA sequence, which is the equivalent of approximately 10 haploid human genomes, can be obtained in a week at a cost of approximately $15,000. By way of comparison, the draft human genome reference that was reported in 2001 to six-fold redundancy took five years of sequencing by several laboratories and cost billions of dollars. That is how much technology has advanced in a single decade. It’s truly astonishing.

The second analysis that was performed is almost certainly another NGS techique known as RNAseq, which is the common name for whole genome shotgun sequencing (WTSS). Again, the details of the technique are beyond the scope of this post. However, RNAseq overcomes the major limitation of cDNA microarrays, which is that it is only possible to measure the mRNAs whose sequences are known and therefore have been placed on the gene chip. Consequently, cDNA microarrays can’t discover previously unknown transcript and in general do not cover noncoding RNAs, such as microRNAs and long noncoding RNAs (lncRNAs). RNAseq does. As a result, using RNAseq it is possible to identify every sequence of every mRNA transcript, coding and noncoding, being made by the cell and how much. Of course, cDNA microarray techniques are by no means dead yet, the primary reason being that RNAseq is a lot more expensive than cDNA microarray techniques, at least ten-fold more, and cDNA microarray experiments can be completed a lot faster.

Taking the results of the sequencing of the entire genome and RNAseq data and analyzing them allows scientists to probe the genome and transcriptome of cancers in a way that was never before possible. It produces an enormous amount of data, too, terabytes from a single experiment. At cancer meetings I’ve been to, investigators frequently refer to a “firehose” of data, petabytes in magnitude. Indeed, the sheer quantity of data from these experiments challenges the bandwidth of universities doing them, and, in fact, it’s not at all uncommon for the preferred means of sending experimental data to be to load up a hard drive with the data and send it by the quaint but effective method of overnight mail to other investigators because it’s faster and more reliable that way. Not surprisingly, serious computing power and major advancements in computer algorithms have been necessary to develop the methods of analyzing data from these experiments.

What I’m trying to convey is that what WUSTL did for Dr. Wartman was not a little deal. It was a big deal that took a lot of resources and effort and likely cost well over $100,000. Apparently it was paid for through research grants, and Dr. Ley claims that no patients were neglected while all that sequencing and computing firepower were transferred to sequencing Dr. Wartman’s cancer genome and transcriptome, having done the same thing for a previous patient. That might well be true, but does anyone believe that Dr. Wartman would have had access to so much genomics goodness if he hadn’t been a researcher at The Genome Institute? Be that as it may, Dr. Wartman’s luck didn’t end at having friends willing to go to such great lengths for him. Here’s what happened when all that sequencing was done and analyzed:

The cancer’s DNA had, as expected, many mutations, but there was nothing to be done about them. There were no drugs to attack them.

But the other analysis, of the cancer’s RNA, was different. There was something there, something unexpected.

The RNA sequencing showed that a normal gene, FLT3, was wildly active in the leukemia cells. Its normal role is to make cells grow and proliferate. An overactive FLT3 gene might be making Dr. Wartman’s cancer cells multiply so quickly.

Even better, there was a drug, sunitinib or Sutent, approved for treating advanced kidney cancer, that inhibits FLT3.

In brief, for whatever reason, Dr. Wartman’s leukemia cells appeared not to have any mutations in the FLT3 gene, which would have been found in the DNA sequencing, but for some reason (probably a mutation in a regulatory region) was making lots and lots of the kinase coded for by FLT3. FLT3 has also been implicated as a molecular target in acute myeloid leukemia (AML). Indeed, this is the very reason why sequencing the genome and transcriptome both are frequently needed to understand what is driving the cancer. Of course, as I’ve discussed before, the genome of your typical cancer cell is so messed up that it’s impossible to identify a single gene that is primarily responsible for the cancer, but in this case Dr. Wartman was again incredibly lucky. His recurrent ALL was being driven primarily by FLT3, a single gene, and there exists a good drug to target that oncogene. Even better, as predicted by the biology, treating Dr. Wartman with sunitinib worked! His blood cell counts started to normalize within days, and he rapidly went into remission.

There was a hitch, however. Sunitinib is very, expensive ($330 per day), and Dr. Wartman’s insurance company wouldn’t pay for it, given that it was being used off-label. Basically, Dr. Wartman scraped together enough money to buy a week’s worth of the drug, and that’s what demonstrated such remarkable effects. Later, the doctors in his division pitched in to buy him more drug. After a few weeks, Dr. Wartman was in complete remission. Fantastic news, but it presented a dilemma: Should Dr. Wartman keep taking the drug, or should he undergo another bone marrow transplant? Ultimately, the decision was made to do another bone marrow transplant because of fear that the leukemia would soon evolve resistance. When evolution meets modern medicine, evolution nearly always wins. In another stroke of luck, Pfizer decided to supply Dr. Wartman with the drug free of charge until he underwent a bone marrow transplant. As of the running of the story, Dr. Wartman remains, as far as the best tools of modern medicine can tell, free of cancer, although he is suffering from graft versus host disease due to his transplant.

There’s no doubt that “individualized” medicine will become increasingly a part of modern medical care, with the individualization based on sequencing the genomes and transcriptomes of patients. In just a few years, the price of a complete genome sequence has fallen from hundreds of thousands of dollars to around $15,000. True, that doesn’t count all the analysis and that’s $15,000 per genome, which means at least $30,000 to sequence a normal and cancerous genome. There are, however, lots of things we do in medicine that cost $15,000. The price doesn’t have to come down much more before whole genome sequencing starts to look doable for individual patients. After all, gene tests like the OncoType DX cost on the order of $3,000 to $4,000, and we now order this test fairly routinely for patients with estrogen receptor-positive, node-negative breast cancer because in the end it saves a lot of patients from unnecessary chemotherapy.

The problem with the individualization of care based on genomics are well-illustrated in this article, which, let’s not forget, is nothing more than anecdote. The question of its generalizability remains to be determined. Using genomics to individualize treatment worked in Dr. Wartman’s case. What his odds of long-term survival are now, no one really knows, but we do know this much. There’s little doubt that, without the discovery that sunitinib would be an appropriate drug to treat his cancer, he would almost certainly be dead by now. Unfortunately, his example can be countered with that of Steve Jobs, whom sequencing his tumor ultimately didn’t help, and Christopher Hitchens, who according to this article also had his cancer sequenced.

How many will have results like Dr. Wartman’s and how many will have results like those of Steve Jobs or Christopher Hitchens? Most cancers are not driven by just one gene that can be targeted, nor are most other diseases and conditions that we might wish to use genome and transcriptome sequencing as a guide to therapy. We’re drowning in genomic data right now, and we just don’t know how to use it yet. Nor will we know until a lot more research is done. The problem is that, with a relatively few exceptions like the case of Dr. Wartman, we don’t know enough yet to translate genome and transcriptome sequences into therapies. We also don’t have drugs for anywhere near all the potential molecular targets that can be identified this way, and the targeted drugs that we do have tend to be enormously expensive. For all the promise it shows and for the now occasional success story like that of Dr. Wartman, the genomics revolution will, like most revolutions, be messy.

Comments

  1. #1 James Sweet
    July 9, 2012

    in fact, it’s not at all uncommon for the preferred means of sending experimental data to be to load up a hard drive with the data and send it by the quaint but effective method of overnight mail to other investigators because it’s faster and more reliable that way.

    Heh, it reminds me of a quote I heard at one point, can’t remember who it was attribute to, that still nothing can beat the bandwidth of a Volkswagen loaded up with tapes (that dates the quote for ya, eh?). The same sentient is true today.

  2. #2 Sullivanthepoop
    July 9, 2012

    Well, there is a two fold problem with individualized cancer care. There is the cost of sequencing, which would go down rapidly if it was used diagnostically. Then there is also the problem of drug availability. In a study done on 12 cancer patients RNAseq found good molecular targets in all 12, but only 3 of those targets actually had a drug available for treatment. All three were for treating different types of cancers than the ones the patient was suffer from and one was even contraindicated for the type of cancer because it usually makes it worse . So, not only will it take time for sequencing to be economical enough to be useful, once it does we still have the problem of not enough drugs for the proper molecular targets.

  3. #3 Todd W.
    http://harpocratesspeaks.com
    July 9, 2012

    Wow. Dr. Wartman’s colleagues must have really liked him. I can’t imagine they have all that many sequencing machines lying around. Not to mention the time of lab techs and assistants working on crunching the data that comes out!

    This is definitely not something that your average Joe is going to have access to. Heck, even those who do have the money might not be able to get this level of attention without the right connections.

    It would be great to see technology advance far enough that we wouldn’t blink at processing petabytes of data, but that’s quite a ways off, I imagine.

  4. #4 Todd W.
    http://harpocratesspeaks.com
    July 9, 2012

    Just reread and caught the “26 sequencing machines”. So, they do have quite a few, but that’s still a significant use of resources.

  5. #5 Lawrence
    July 9, 2012

    Trying to figure out the resources necessary to apply this to even a small fraction of the Cancer community – and it boggles the mind. The technology exist to do this on a very small (and expensive) scale, but to think of the hundreds of thousands of individuals who would want this, plus that not every Cancer is going to be as accommodating….well, sounds like a great way to get peoples’ hopes up, but little else at this point.

  6. #6 Composer99
    http://composer99.blogspot.ca
    July 9, 2012

    I’d say by the end of the decade we should have the tech to reliably process petabytes of information in reasonable timeframes.

    After that, I couldn’t guess when it all translates into effective clinical therapies. Another decade or two, perhaps?

  7. #7 Anj
    July 9, 2012

    thanks for the breakdown.

    I saw the story and didn’t read the details because I suspected I’d find the usual media coverage of a technical medical issue. Your work is as great as ever.

    Thanks again

  8. #8 Mike
    July 9, 2012

    @James Sweet

    You beat me to it. It’s an old IT adage that predates the Internet as we know it. There are a number of variations, but the one I remember hearing first was “Never underestimate the bandwidth of a station wagon loaded with backup tapes.”

    More on-topic though, it’s actually heartening to hear of this kind of success. Individualized treatment really is possible, at least in some cases. But here, the difference between Quacks making the claim and scientists actually making it happen is that the scientists really DO make it happen.

    Expensive as hell, in resources and monetary terms, but real.

    The only thing the Quacks share is the expensive part.

  9. #9 Heliantus
    July 9, 2012

    @ James Sweet

    Re:

    in fact, it’s not at all uncommon for the preferred means of sending experimental data to be to load up a hard drive with the data and send it by the quaint but effective method of overnight mail to other investigators because it’s faster and more reliable that way.

    As usual, xkcd touched on this.

  10. #10 Calli Arcale
    July 9, 2012

    On a project I was on, we actually did this. For reasons I’m not going to go into, our download time was pathetic to try to get this tool we needed, so one guy went home, downloaded the piece of software on his home computer, burned it to a CD, and then drove back to work with it. He beat the original download. :-D

  11. #11 Anton P. Nym
    July 9, 2012

    http://en.wikipedia.org/wiki/IP_over_Avian_Carriers#Other_avian_data_transfer_methods

    PigeonNet (and the earlier StationWagonNet and SneakerNet) transfer protocols can still beat some modern carriers in unusual circumstances.

    That being said, we should keep in mind that technology gets better and cheaper as development goes on; air travel was a risky sport for the ultra-rich when the Montgolfier brothers were wowing crowds, but now it’s all-but taken for granted. In a decade or two the sort of gene sequencing described in the article could very well be practical for front-line medicine. *fingers crossed*

    — Steve

  12. #12 bad poet
    July 9, 2012

    Before Sneakernet, there was “telegraph, telephone, tell-the-neighborhood-gossip” and air freight/other couriers before there was FedEx.

  13. #13 Calli Arcale
    July 9, 2012

    Ah, sneakernet….

    We had a lab where that was implemented as the sole transfer protocol, and added USB ports to the test stations specifically to support it. (This was to remove the interference of IT pushing out upgrades and patches to the OS that didn’t actually belong to them — this was customer hardware.) Logs were usually put on USB sticks; software was delivered via CD. As the build manager, I went through a whole lotta CDs.

  14. #14 Mrs Woo
    July 9, 2012

    In its way this could be a glimpse of the future. What is sad is that purveyors of woo will glean bits and pieces out of this, offer an “alternate” (bogus) process to make it sound like they are doing the same thing and make their woo-filled suggestions based on “cutting edge” technology.

    One thing I’ve noticed is that a lot of the more realistic-sounding woo treatments/cures are often based on research from one promising case or from a small in vitro study. They take a supplement, etc., and run with it, selling it based on that information even when later studies cannot replicate original results or it is determined that dosage has to be too high to be safe.

    I fully expect some alternative health people to take this one article and use it to create (or in Dr. B’s case, further support) their treatments and their “every one is unique and needs unique treatment” mantra.

    This man was incredibly lucky. In a different place in life (say a co-manager at Walmart) he would have had a death sentence and collections would be being made for the family. He definitely had a lot of things coming together to provide this for him.

  15. #15 peebs
    somewhere just short of retox
    July 9, 2012

    As usual, I have nothing practical to add to the discussion. But I do have an observation.
    Sunitinib backwards reads ‘bin it in us’

    Hardly reassuring if you’re a Brit who happens to have the rarely useful talent of reading backwards.

  16. #16 AdamG
    surrounded by HiSeqs
    July 9, 2012

    I’m a researcher at a major sequencing center working on many, many NGS projects for medical applications. I can tell you that this technology is coming, and in many ways it’s already here. Currently there are several RCTs underway that directly measure the difference in outcomes between patients who receive WXS and those who don’t. I’m involved in a couple of these, notably one for patients with colon cancer. This is coming folks, sooner than you think.

    Just reread and caught the “26 sequencing machines”. So, they do have quite a few, but that’s still a significant use of resources.

    As an aside, I can tell you from personal experience that this isn’t really true. The article paints this as a major undertaking and use of resources, but in reality this sort of stuff happens all the time at sequencing centers. Extra sequencing space comes up pretty often due to the way sample prep is done, and pet projects like this get thrown into the extra space.

  17. #17 Chris
    In the same city as AdamG...
    July 9, 2012

    AdamG:

    I’m a researcher at a major sequencing center working on many, many NGS projects for medical applications.

    And when we went to the medical geneticist at the Medical Center (and her other office at the EEU), my son’s blood was sent to Maryland. Perhaps it has to do with the specific genes for the genetic diagnosis. Who knows?

  18. #18 AdamG
    July 9, 2012

    Chris, this is pretty common for routine clinical tests involving small numbers of genes. Do you know if the sample was sent to a clinical testing company or to a research institution? It also depends on how recently this was…UWMC has really stepped up its CLIA sequencing load in the past year or two through our lab and our affiliates.

  19. #19 Chris
    July 9, 2012

    Sheet of paper with results in front of me: Gene Dx, a search for eighteen known genes causing hypertrophic cardiomyopathy.

    None of the known ones were found, but they encouraged us to pay for full panel. Um, we declined since there is no known genetic treatment. It was best to surgically remove the extra heart muscle.

  20. #20 AdamG
    July 9, 2012

    Ah that makes sense, I know GeneDX is based out of a large facility near the NIH in Bethesda.

    You might be interested to know that there is a lot of work being done right now on HCM genetics, even right here in Seattle. Our lab is very involved with one of the largest sequencing efforts to date. A part of this project is looking at how rare variation in known HCM candidate genes and novel candidates contribute to the phenotype. There are some really cool findings that I can’t discuss here yet, but the papers are on their way out!

    For more info on this project, and to browse 6500 exomes worth of data, check out our site:
    http://evs.gs.washington.edu/EVS/

  21. #21 Chris
    July 9, 2012

    Thanks a bunch for the extra info on the company. We did discuss that his blood sample would be held there as extra data for any research. Plus we agreed that if they needed more samples from my son we would be glad to provide it.

    The UW cardiologist and the geneticist have plans to set up a special HCM clinic. The geneticist wondered if there was a relationship between the heart issues and my son’s history of seizures and speech issues. She also researches autism genetics.

    We figure that genetics medicine is still heavily in the data collection stage. (We were also encouraged by the clinic in Minnesota to get the full genetic panel, they want data too!)

  22. #22 bad poet
    July 9, 2012

    Sorry off topic, Trine Tsouderos up on Trib re Durbin response to her excellent article on sleazy supplements and the scammers that make them.

    http://www.chicagotribune.com/news/chi-120709dietary-supplements,0,2880369.story

  23. #23 Autistic Lurker
    July 9, 2012

    Newbie question, is it possible for me to get my entire genome (or exome)? I know about 23andme but I’d also like to contribute to a research team.

    A.L.

  24. #24 AdamG
    July 9, 2012

    Unfortunately no, A.L., you can’t get your exome or genome done yet, 23andMe is as close as you can get right now. Even subjects who are enrolled in genome/exome studies are unable to obtain their raw data due to issues with incidental findings and liability.

    Personal exomes are coming soon though! 23andMe is about to roll out their massive $1000 exome initiative…stay tuned.

    https://www.23andme.com/exome/

  25. #25 Mrs Woo
    July 9, 2012

    When I began having symptoms of neurological deficits, I wanted to be tested for a hereditary illness that runs in my family. My father is dead, so I asked his widow which genetic abnormality he had. His sister also has the illness, so I asked her as well. They both answered with different genetic abnormalities. The testing center wanted $750 per genetic abnormality to do the testing. The cost was prohibitive and there was no treatment at that point except dealing with symptoms. The neurologist also assured me that I didn’t want to be “tagged” with that diagnosis so early in life because it would make me uninsurable. With another ten years or so that I might be able to get by and no treatment available anyhow, he counseled not pursuing diagnosis at that time.

    Nice to know that it’s getting cheaper to look for what’s causing the problems. If I keep developing new symptoms I can reinvestigate what is causing them and maybe have them do a broader test for a similar or (less expensive) “look.”

  26. #26 Sullivanthepoop
    July 10, 2012

    I had some genes sequenced when they were trying to figure out why I kept having problems with low blood sugar. They knew it was from fructose malabsorption disorder, but they found that I was also not absorbing sucrose which is usually not a problem because their is enough glucose in it to pull it in. My insurance company paid 95% for the testing, even though the only place that offers it here is out of my network. It ended up costing me $275 and didn’t really answer any questions.

  27. #27 Mrs Woo
    July 11, 2012

    Was that recently, Sullivan? When we came to “what to test for” I was told $750 for each test. My father’s widow was adamant that he had one genetic version of the illness, but his sister, who has the disease assured me that Johns Hopkins did her diagnosis and it was different mutation.

    I didn’t like the idea of almost $1000 and not knowing for sure if I was even testing for the right disorder.

  28. #28 Chris
    July 11, 2012

    Mrs. Woo, the cost depends on how many genes they are looking for. If there are fewer things to look for, the cost is less.

    Perhaps, like the 18 genetic sequences known to cause my son’s heart problem, there may be several more known to cause Sullivan’s blood sugar issues.

  29. #29 Kathryn
    Silicon Valley
    July 11, 2012

    This is mostly OT, but it’s about cancer in general, so not completely OT.

    More bad news about Jacob Steieler refusing chemotherapy:

    http://www.woodtv.com/dpp/news/local/grand_rapids/parents-v-som-over-sons-chemo-treatment

  30. #30 Rose
    July 11, 2012

    Jacob is ten. He can’t imagine anything worse than chemo. At ten he should not be able to. At my age and with my life experience I know here are things that are worse than chemo.
    So his parents asked him and he didn’t want to do any more chemo. He does not have the life experience to make that decision.
    It is not the same as asking him if he wants spinach or Twinkies for dinner. Both decisions a ten year old boy would be likely to make would probably have bad consequences but not of the same magnitude.
    The comments reflect the staggering lack of knowledge that most people have about cancer and chemo.

  31. #31 Sauceress
    July 17, 2012

    A little late as usual…
    Great write up Orac. I so love it when you go all molec bio/biotech. (smiley showing lot’s of teeth)

  32. #32 Sauceress
    July 17, 2012

    Bah..lots
    Free apostrophe there if anyone wants it.

  33. #33 Mrs Woo
    July 17, 2012

    @Chris – I quit following how many genetic variants they found that cause this. There were the two different ones reported by my father’s widow and his sister and at least another 14 more I think, but the numbers began having space in between them like researchers suspected there were other places it would show up and that the order they would list them ultimately would make more sense if they didn’t do it by date the researchers found a new trinucleotide repeat that didn’t belong.

    Oh Rose. That is terrible. I can imagine how hard it is for a parent to watch their child go through the cancer diagnosis, treatment, etc. An experience recently, though, brings home exactly how much difference there is between the view of a child vs. an experienced adult:

    My son’s girlfriend somehow got a razor blade underneath her one fingernail cleaning the bathroom. She’s 13. When they asked her how much pain she was when she went to the emergency room (with my history of taping myself back together here and there after a good solid cleaning and some antibiotic ointment, I really had to marvel that her mother took her to the ER for something like that) she told them on a scale of 1 to 10 she was an “eleven.” Hyperbole aside, as someone who has had a few more painful episodes in my life than the girl, I would have probably put a similar thing at a three. I know it can hurt, but it’s not that terrible, especially if you’ve done natural child birth, broken a few bones here and there (including a nose), etc. When she left, they asked her again what it was and she told them down to a seven.

    Now, if she had been someone who was severely injured, that kind of response would merit some kind of pain medication; however, doctors and nurses both kind of took her numbers with a grain of salt. I realized suddenly that the girl has had a pretty kind life if at 13 she is saying a cut under her fingernail equals an 11 on a 1-10 pain scale.

    So kids definitely cannot fathom what a life-changing decision choosing that chemo is “too tough” can really be. They cannot see that a year of misery and a lifetime of remission (hopefully) is better than a year of misery followed by death. It is a very hard thing for an adult or a child – I am not minimizing the misery of the treatment (though it depends on the treatment these days too). Having to go through the hard things because of the possible end results is something that doesn’t make much sense to a child who will also think having to go without television for a week might be the end of the world, or that graduating from high school is too far away to ever imagine getting there.

    That’s why we parents were created – to take over and make decisions based on our experiences and to educate our children based on them. I can’t believe the parents don’t have a bit more stick-to-it-iveness themselves – I would be scared to death of my child dying, even moreso if I skipped finishing science based treatment. If they died as a result I could never forgive myself.

  34. #34 Narad
    July 18, 2012

    Now, if she had been someone who was severely injured, that kind of response would merit some kind of pain medication; however, doctors and nurses both kind of took her numbers with a grain of salt.

    I found involuntarily screaming when something was moved the wrong way to be a pretty effective communication technique in this regard. (The 4 mg of subcutaneous morphine didn’t really do it, either.)

  35. #35 Mrs Woo
    July 18, 2012

    @Narad – I had to take a deep breath and look away at her “seven” – I didn’t want anything on my face to show any kind of amusement – I wasn’t amused that she hurt, but very amused at how high her numbers were, and immediately realized it was life experience that made the difference.

    A neighbor actually called and begged me to ask for pain management at one point in my disease journey. After all the horror stories I read on the internet about being treated as a drug-seeker, etc., I was waiting to be involuntarily writhing on the floor in agony before being willing to hope I would be treated as someone with a valid complaint. When the pain would get bad I would change color and the top of my upper lip and a few other discrete patches on my face would begin sweating. My blood pressure had also gone up higher than normal once things got really bad. However, since I still was too reserved to fall screaming on the floor, I assured myself it “wasn’t that bad.” I haven’t had it get that bad (to involuntary screaming) yet. There have been times when I have temporarily doubled over no matter how much I tried to stay erect, but no screaming.

    I know my idea of a seven was much different than this girl’s idea of a seven. I was lucky – I found a functional pain scale by a support organization for my illness. It didn’t just give you numbers – it described how you would have to modify activity to work around the pain levels. That one helps me a lot more with being honest or at least being consistent, because I’m a rare person that tends to downplay my pain (must be part of that older generation – though nowhere near as amazing as Mr Woo’s aunt, who had a farm truck accidentally back over both of her legs and was so ticked off to have let herself get into the situation that she insisted on walking to her house (not making this up) and taking a bath first before allowing her husband to take her to the ER). She had broken both of her legs. That woman is probably tougher than me, and there aren’t a lot of people I have met in person that I would say that about.

  36. #36 Sauceress
    July 21, 2012

    Don’t mind me…just after a cookie. Laptop housekeeping time.

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