Music Is Medicine

No, the title is not a cliche.  It's the name of a fabulous organization founded by the daughters of one of my colleagues here at Johns Hopkins.  Leora and Ariella are musicians themselves, and they firmly believe that music can truly help in the healing process.  Founded when the girls were still teenagers, Music is Medicine is now an organization with national reach.  Quite a feat for two sisters from Baltimore.

Last year, I wrote about a visit one of my patients had from Drew Seeley, her favorite singer.  He wrote her a song, and I'll never forget the look on her face when he showed up in her hospital room to sing it for her.

Yesterday, lightning struck twice, when my patient, Bo, received a visit from Savannah Outen, who flew to Baltimore to serenade him with a song she wrote just for him.

 Bo is a musician himself.  In fact, I've seen him play at a fundraiser to help raise money to cover some of his medical costs.

So after Savannah played, Bo picked up the guitar, and in a truly priceless moment, played for her as she sang his requests.  Her version of Landslide (performed here by Fleetwood Mac and here by Smashing Pumpkins) was absolutely beautiful.  Moments like this, unscripted and real, remind me of all that is good in people.

I was there to hear the music, but Bo and his family had a surprise for me, too.  A framed picture of me and Bo... in one of my... uh... better moments in clinic.  Yes, that's me, hard at work curing cancer!

The song Savannah wrote and sang for Bo, "Brave and True," will be available soon on iTunes.  If you can't wait that long, check out this song to hear what a beautiful voice she has.

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The Power of Social Media

In the past, I've discussed the financial challenges facing those of us who conduct research on rare diseases and the important role private foundations play in facilitating our work.  What I haven't mentioned before is the role social media can play in linking researchers with foundations.

As some of you may know, I'm on Twitter.  Well... sort of.  I've been on Twitter recently about as much as I've been posting on my blog.

But through Twitter, I found the Rally Foundation.  Honestly, I'm not sure I would have found them otherwise.  I'm sure glad I did, though.  They're a fabulous organization.  Founded by Dean Crowe, they have raised a ton of money to support childhood cancer research, and they have supported projects at 35 cancer centers across the country.  I'm honored to be on their medical advisory board.

And today I was thrilled to learn that they are going to fund a new project in my lab.

We have been studying a gene called WT1, which is turned on in a large number of sarcomas, including many cases of Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma.  The role of WT1 in childhood cancer is unclear.  We have a theory -- that WT1 helps tumors to coax blood vessels into supporting their growth.  Money from Rally Foundation will allow us to test this theory, and to begin the process of identifying drugs that will block the activity of WT1.  Our hope is that, since WT1 is turned off in almost all noncancer cells in growing children, a drug that targets WT1 will be an effective treatment for childhood cancers with very few side effects.

We're obviously a long way from developing such a drug, but with the help of Rally Foundation, we're a step closer today than we were yesterday.

And every journey begins with a single step.

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Welcome Back!

It's a warm, sunny day today.  Spring is finally here, from the looks of things.  That means it's time for a new beginning.

On my way home from work last night, I stopped for a drink with an old friend of mine.  When I say old... I've known this friend since we were kids.   I can't remember a time when I didn't know him.  We were joined by two of his other friends, who I was meeting for the first time.  When I first meet people, and they ask what I do, my answer evokes either a blank look, a look of pity, or a lot of questions.

Thankfully, this time I got questions.

The two most common questions I'm asked are how I ended up doing what I do, and what is the most rewarding part of my job.  I'd like to share my answers here, as a part of my new beginning.

How did I end up as a pediatric oncologist?  I wasn't one of those kids who knew at age 5 he wanted to be a doctor.  In fact, I went to college hoping to be a research scientist.  It was only after my sophomore year that my father suggested to me that if I wanted to do medical research, a medical degree might be helpful.  So I started medical school in the Medical Scientist Training Program, on a track to get both an MD and a PhD.  Thankfully, just seven years later, I graduated with both degrees, ready to take the next steps.

Why oncology?  I was attracted to the science.  Understanding how cells work fascinated me, and when I realized that cancer is a perversion of the normal processes of cell biology, I knew what I wanted to study.

Why pediatrics?  That's even easier.  I love kids.  I love their undying optimism, their boundless enthusiasm for life, they neverending need to explore the world around them, and their seemingly limitless ability to love those around them.

The choice to become a pediatric oncologist turned out to be pretty easy for me.

Source

What is the most rewarding part of my job?  That's pretty easy, too.  Earlier this week, I received an email from an old patient.  He wrote to tell me that it was the 15th anniversary of the day we met and I told him he had cancer.  He has now lived more time post-diagnosis than pre, and felt moved to tell me how much he loved his life and how happy he was to have met me.

I received a similar message two years ago.  An old patient wrote to me on her birthday.  She told me she had recently been researching her diagnosis... and realized that someone with her type of leukemia, who had the chromosome mutations that her leukemia had, ought to have died.  Not only was she celebrating another birthday, but she was preparing for her wedding, and she wrote to thank me for taking such good care of her.

How could I ever have considered any other career?

It's spring.  Time for new beginnings.  Time to renew my efforts in the lab, so that even more kids will be able to look back on the day they were diagnosed and be thankful for the modern treatments, born of an intense research effort, that have erased the day when a childhood cancer diagnosis was a death sentence.

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Childhood Cancer Awareness Month

September is Childhood Cancer Awareness Month.  If you are a regular reader of my blog (even if I'm not a regular writer), you are already aware of childhood cancer.  But perhaps you didn't know that cancer is the Number 1 disease killer of children.  The only more frequent cause of death in childhood is trauma.  Or perhaps you didn't know that 10,400 children will be diagnosed with cancer this year in the US, but that many women will be diagnosed with breast cancer every 2 weeks.  This might be why a paltry 4% of the National Cancer Institute's annual budget goes to pediatric cancer research.

So now you're aware.

But here's a more important thing to be aware of:  pediatric cancer is weak; although it can kill the body, it can't kill the spirit of childhood.  Don't believe me?  Check out the spirit of the kids I take care of every day.

A Challenge for Personalized Medicine

Personalized medicine is the new Holy Grail of cancer therapy.  The drugs we currently use are stupid.  They don't actually target cancer cells, they target rapidly dividing cells.  Cancer cells divide rapidly, which is why chemotherapy works, but plenty of other cells in our bodies divide rapidly, and that is why chemotherapy causes so many side effects.

Not only that, but not every tumor of the same type responds similarly to the same chemotherapy.  For breast cancer, some tumors respond well to cyclophosphamide and doxorubicin, but others do not.

Cancer is, at its root, a genetic disease... meaning that changes in the genes within a cell cause it to transform from normal to cancer.  A lot of recent work has gone into identifying the specific mutations that lead to a particular tumor type, and using this information to gauge risk and make treatment decisions.

A by-product of this work has been the development of so-called targeted therapies... drugs that interfere with the abnormal function of a mutated enzyme, for example.  Because these drugs act only in cells that have that particular mutation, which presumably only happens in tumor cells, they are thought to be more specific and less prone to side effects.  The ultimate goal, then, of personalize cancer medicine would be to identify mutations in an individual's tumor and prescribe a regimen of targeted therapies that are specific for that tumor.  Not for the type of tumor... for the individual tumor.

An article in today's issue of the New England Journal of Medicine makes it clear that this approach is going to be more difficult than previously believed.

Most work aimed at identifying mutations in a specific tumor is based on a single biopsy of the tumor, the idea being that the important mutations will be present in every cell in the tumor.  Today's article addressed this issue directly by comparing the mutations found in multiple different biopsies from the same tumor.  What they found raises serious concerns.  Only about 1/3 of the mutations this group identified were present in every biopsy specimen from the same tumor.  The other 2/3 were found in only a subset of the biopsies.

At one level, this is not news.  Cancer scientists have been aware for years that tumors are heterogeneous... that is, not all of the cells are the same.  It stands to reason, then, that not every cell will have all of the mutations.  That there will be some cells with fewer mutations, and some with more.  And today's article does suggest that some mutations, probably the ones important for the original development of the tumor, are found throughout the mass.  However, if only a single biopsy is performed and used as the basis for making treatment decisions, most of the identified mutations will NOT be common throughout the tumor.

Photo Credit

It's not the end of the world, but it does mean that developing and testing this kind of treatment approach is going to be a lot messier than people have previously believed.

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Music Can Heal

Well, maybe music can't cure cancer, but it can certainly heal the spirit.

Drew Seeley released a new song today that he wrote for my patient.

Watch the video here.

If you buy the song on iTunes, the proceeds go to support childhood cancer research.  Even if you don't buy the song, watch the video and enjoy the bliss on Brooke's face when Drew came to sing for her.

Priceless.

This is not a drill!

 Today was the day.


I recently wrote about chemotherapy shortages.  They've been in the news more and more over the past 12 months.  But until today, at least in my practice, they were worries.

But now the drug in short supply is methotrexate.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children.  Cancer is the most common cause of death (other than trauma) in children.  Upwards of 80% of children with ALL are cured with modern treatment regimens.

But I don't know how to cure ALL without methotrexate.

Or osteosarcoma.

Or lymphoma.

There are several companies that supply methotrexate in the US, but all are experiencing production or distribution delays or suspensions.  The net result?  We had a meeting today to figure out if we have enough methotrexate to treat our current patients.  And, if we have a shortfall, to figure out who gets treated... and who doesn't.

The good news is we found a few vials we didn't know about yesterday, and for at least the next 2 weeks, all current patients can get treated on schedule.  But, if we don't get another shipment in 2 weeks, or if an adult-sized patient is diagnosed with Burkitt's lymphoma presents to the hospital tomorrow?  We won't have enough drug. 

And someone won't get treated.

I have already discussed the many reasons for drug shortages.  The list of drugs in short supply is mind-bogglingly long.  But we can work around a lack of Zofran.  We can find alternatives for Gentamicin.

But I can't cure ALL without methotrexate.

What's Sauce for the Goose May Not Be Sauce for the Gander

Avastin has been in the news a lot lately, and most of the press has been negative.  In November, the FDA revoked its approval of Avastin to treat newly diagnosed metastatic breast cancer.  Then, in December, Genentech, who manufactures Avastin, announced it would not seek FDA approval for the treatment of ovarian cancer, based on studies showing an improvement in progression-free survival but not overall survival.  Of course, whether Avastin helps women with ovarian cancer remains a controversial question, depending how you value progression-free survival. Compare this report with this one, for example. 

In tomorrow's New England Journal of Medicine, there are two reports of clinical trials evaluating Avastin for patients with newly diagnosed HER2-negative breast cancer.  In both this study and this one, women with newly diagnosed breast cancer were given chemotherapy with or without Avastin.  The women with HER2-negative tumors had a higher rate of "pathological complete response" if they received Avastin.  "Pathologic complete response" means that when it was time for surgery, not living tumor could be found.  Women with a "pathologic complete response" tend to live longer than women who do not respond as well.

What does all this mean?  Will these studies "reignite the debate" about Avastin in breast cancer?  I guess that depends on who is doing the debating.  I think the role of Avastin in breast cancer, indeed the role of Avastin in treating any cancer, remains unclear.  In the end, I believe it will be shown that Avastin helps some cancer patients and not others, and it will all depend on the biology of each tumor type.  Clearly, not all breast cancer is the same, and breast cancer is not the same as ovarian cancer, let alone osteosarcoma or lymphoma.  Today's studies simply reinforce the fallacy of extrapolating from one tumor type to another.  A drug may be very helpful for one type of cancer, and useless for another.


That's why we do clinical trials like this one, sponsored by St. Jude Children's Research Hospital, in which we are participating, trying to see if Avastin helps osteosarcoma patients.

These studies do raise another important point, which I will discuss very soon.  These studies relied on a "surrogate end point."  That is, the studies were designed to see an effect on "pathologic complete response," but only because that is thought to correspond with improved overall survival.  Only time will tell whether the women who received Avastin do actually live longer.

More to come...

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Yes, we have no...Zofran?

Photo Credit



The issue of chemotherapy drug shortages has made the news a lot over the past 6 months or so, including an OpEd piece in the New York Times last August that pointed out that the situation is so bad that, in effect, cancer care is being rationed in the US.


How did this happen?

Well, the situation is quite complex, but much of what is going on was summarized beautifully by my colleague Michelle Hudspeth, Director of Pediatric Hematology/Oncology at Medical University of South Carolina (and graduate of our residency and fellowship programs), when she testified before Congress (her testimony is here).  Briefly, the problem can be traced, in part, to a rule by The Centers for Medicare and Medicaid Services (CMS) called the ASP + 6 Rule.  This rule limits what a private oncologist can charge for a chemotherapy drug to the Average Sale Price plus 6%. 

Why does that matter?  An article by the Director of the National Library of Medicine, and one in the New England Journal of Medicine, outlines the financial issues.  Because so many of the older chemotherapy drugs are available as generics and are consequently very inexpensive.  Consider the case of carboplatin.  A vial of carboplatin once sold for $125, but recently the cost has fallen to $3.50.  Add 6% to that, and you certainly don't recoup the cost of administering the drug in your office. Similarly, paclitaxel costs $312 per vial, while Abraxane (albumin-bound paclitaxel) costs $5,824 (all cost data come from this article in the New England Journal of Medicine).  There is almost no financial incentive to pharmaceutical companies to make generic chemotherapy drugs, nor is there a financial incentive to private oncology practices to use generics.

But this is just part of the problem.  There is currently a nationwide shortage of Doxil (liposomal doxorubicin), which is not a generic.  Why?  Through industry consolidation, there are fewer and fewer plants that manufacture these drugs, so when something happens at even a single plant, the entire market is affected.  Quality control issues at the only plant in the world that makes Doxil shut the plant down and with it, all drug production. 

 Photo Credit

So, it seems that industry consolidation, downward pressure on pricing of generics, as well as contamination, other quality control problems, and shortages of raw materials have conspired to create a perfect storm.

The consequences of these shortages go beyond just drug availability.  As the New York Times article discussed, and Dr. Hudspeth mentioned, medication errors are increasing as oncologists are forced to use less familiar drugs.  Research is affected, too. This article, published in the scientific journal Nature in October, discusses the effect of drug shortages on clinical trial enrollment.  Closer to home, the clinical trial I am running looking at Doxil and temsirolimus for sarcoma patients is on hold because Doxil is unavailable.  We haven't enrolled a new patient in months, and there is no end to the shortage in sight.

Photo Credit

The shortages are not limited to chemotherapy drugs (which, of course, is evidence that the problem is not due to the inability of oncologists to make a profit giving drugs to patients).  Drugs for ADHD, the components for iv nutrition, anesthetics, and many others are affected.  In fact, on Friday I was told our hospital has only a 5 day supply of Zofran, the mainstay anti-nausea drug used for patients receiving chemotherapy. 

I sure hope they get more.  I'm not looking forward to giving chemotherapy without it.


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Entering the Fray

The vast majority of biomedical research conducted in the United States is funded by taxpayers through grants distributed by the National Institutes of Health.  This includes investigator-initiated laboratory research (the work we do in our labs) as well as clinical trials, both large and small (NIH is a large supporter, for example, of the Children's Oncology Group).  In the not-too-distant past, the results of all of this research were published in scientific journals which were available to anyone who could gain entrance to a medical library.  With the rise of the internet, journals began publishing online, and charging a fee for viewing these articles on their websites.  Those of us who work at academic centers generally have free access to most (but not all) of these websites because our universities buy institutional subscriptions.  Others, including people who work at smaller centers and the general public, have less (or no) access to this work.

All of this changed in 2008, when the NIH instituted a Public Access Policy that stated, in brief, that results of research funded by the NIH had to be made freely available to the general public.  Along with NIH's Public Access Policy came the advent of the Public Library of Science, a non-profit organization co-founded by Michael Eisen, a professor at UC Berkley (and blogger), dedicated to open access to scientific research.  I have published in one of their journals, PLoS ONE.  I am a strong supporter of open access to the results of research, mine and everyone else's.

This concept of free access to taxpayer-funded research is under attack by a bill introduced into the House of Representatives last month, the Research Works Act.  In essence, this bill would forbid the NIH to require that its grantees provide copies of their papers to the National Library of Medicine for online, open access.  There are innumerable reasons to oppose this bill, and Dr. Eisen discussed them far more eloquently than I ever could in an Op-Ed piece published in the New York Times. 

If you agree that the results of research paid for by your tax dollars should be freely available, please contact your congressperson and express your opposition to the Research Works Act.  As the PLoS journals have demonstrated, high quality research can be published online and made freely available to all, and the research enterprise will flourish because of this, not suffer.