Friday, July 27, 2007

The Children Are Our Future

OK, that’s cliché, but clichés hang on because they contain a kernel of truth. This one certainly does, especially for someone like me, who spends every day working with kids. But why bring that up today? Well, last night I had the pleasure of participating in an event that was part of the National Youth Leadership Forum.

The National Youth Leadership Forum invited me to participate in small group discussions with high school students from across the country who would like to pursue a career in medicine. The format was very informal – I sat in a circle with the students, briefly introduced myself, and spent 35 minutes answering questions. The session was highly interactive, engaging and fun; but more importantly, I was surprised and moved by the complexity of their questions and by their motivations for wanting to pursue a medical career.

For example, there were very few questions about income, working long hours, or about how I got accepted into the schools I attended.

Instead, most of the questions were focused on more important concerns in entering a field like pediatric oncology. I was asked questions about how I balance family and work. I was asked about the difficulties a woman pursuing a career in pediatric oncology might face.. I was asked how one can maintain a social life during training. In short, I was asked serious questions by a serious group of young adults. If this is typical of the next generation, I’m full of hope for the future!

In my next entry I’ll address one of the most common questions that I answered last night – how I deal with the death of a patient.

Tuesday, July 17, 2007

Team Sarcoma and the Pan-Massachusetts Challenge

In these days of shrinking research budgets and increased belt tightening, the amount of government support for research into more rare disorders, such as sarcomas or childhood cancer, is steadily falling. This increases the burden on private foundations to pick up the slack.

I wanted to take this opportunity to support two very important endeavors: Team Sarcoma, and the Pan-Massachusetts Challenge .

Team Sarcoma is the brainchild of Bruce Shriver, who runs the Liddy Shriver Sarcoma Initiative. This is a private foundation honoring the memory of Bruce’s daughter, Liddy, who fought Ewing’s sarcoma from 2002 until her death in 2004. Bruce and his wife Beverly started this foundation to provide support to other individuals and families struggling with various sarcomas. In addition to an incredibly informative website, The Liddy Shriver Sarcoma Initiative funds laboratory research into the basic biology of sarcomas, in the hopes that their support will lead to the development of novel therapies that will one day spell the end of children and young adults dying of sarcomas.

Recognizing that sarcomas attract relatively little attention from the oncology community (representing only 1% of adult cancers), Bruce has also devoted his energy to raising awareness, predominantly through Team Sarcoma. The Team Sarcoma 2007 Initiative involves hundreds of people in 13 countries worldwide who are participating in more than 50 events designed to increase awareness of sarcomas (and hopefully raise money as well). The flagship event is the Team Sarcoma 2007 Bike Tour, going on now through July 21 in the Lake Champlain area in Vermont and New York.

I came across this video on YouTube. It features a Team Sarcoma 2007 member, Melissa Kramer, speaking about the bike ride and her reasons for participating. Although the voice is out of sync with the video, it is still an important video to see. After you watch, consider going to her website, www.ts2007mel.com, where you can find more information, including ways to contact your leaders in congress regarding increasing (rather than decreasing) funding for sarcoma research.



Finally, my fellow blogger, Sam Blackman , a pediatric hematology/oncology fellow from Boston, will be riding in the Pan-Massachusetts Challenge, a 192-mile ride from Sturbridge, MA to Provincetown, MA. All of the money raised by the Pan-Mass Challenge goes to support the Dana-Farber Cancer Institute. I rode my bike frequently and for long distances as a teenager (before I succumbed to the allure of a car), so I can tell you quite honestly that riding 192 miles is quite a feat. I wish him well!

Thursday, July 12, 2007

The (not so happy) Story of M (Part II)

I have to confess, I was a bit misleading in my last post .

I asked you to come back in a few days to see how the story ends. Although decisions have been made, there is no ending yet (and I think that’s a good thing). M’s father and I have been in near daily communication about his treatment, the family’s goals, their hopes, and their expectations. They realize that nothing I have to offer has any realistic hope of curing their son. They do, however, hope to find a treatment that is available in the US but not in Japan that might slow the progression of his disease, and perhaps even offer some palliation. They also seek the comfort of knowing that they have given their son every chance and tried every possible option to treat him.

Next Monday M and his family will return to my clinic and we will enroll him on a Phase I trial of a drug that is related to one of the more active osteosarcoma drugs, cisplatin. We hope that M will be one of the lucky ones who benefits from participation in a Phase I trial.

The statistic that I quoted the other day, that only 3% of patients benefit from being enrolled on a Phase I trial, uses a very narrow definition of “benefit.” They define “benefit” as the tumor having an objective response to the treatment (meaning the tumor shrinks or goes away). Using a broader definition of “benefit” would yield a very different statistic. M and his family will benefit from this trial, even if his tumors continue to grow. How will they benefit? They will have achieved a feeling of closure. They will know that they tried everything, that they went everywhere, and that they never gave up the fight. In the family’s eyes, this psychological benefit is worth another 6 weeks away from home.

And if the family sees this as beneficial, that’s good enough for me!

Monday, July 9, 2007

The (not so happy) Story of M (Part I)

Or… when is enough treatment enough?

A couple of weeks ago, I shared the story of my patient, K . Today’s story does not have the same happy ending. The case caused me to feel uncomfortable trying to balance my own beliefs against the wishes of two clearly loving parents, and I thought that I would share it with everyone who is reading this, and generate a bit of discussion about when to stop treating.

M is a 12 year old boy, and he was diagnosed with osteosarcoma of the right tibia in Kobe, Japan in 2005.

He was treated in the usual way, with chemotherapy followed by surgery to remove his tumor and replace his knee. Unfortunately, during the 2 months he was not receiving chemotherapy because of his surgery, he developed numerous metastases to other bones. He received 4 courses of intensive chemotherapy followed by a bone marrow transplant, but his disease did not respond. His doctors tried a different chemotherapy regimen, also without success. In October 2006 he was enrolled on a tumor vaccine trial in Osaka, but his cancer grew despite this treatment. Two further cycles of chemotherapy accomplished nothing. Desperate, his parents began to scour the world for novel therapies to try, and they stumbled onto a clinical trial that I am running. That’s how M came to be my patient in May of this year. Sadly, his response to my clinical trial was no better than his response to anything else he has been treated with.

Here is where the ethical difficulties begin.

M is now in the US, thousands of miles from home. His family has been told that there is nothing curative to offer him, and that they should take him back home to Japan for hospice care near his home, surrounded by friends and family. That advice, of course, comes from the medical team, and is certainly not what the family wanted to hear. The family has already shown a willingness to go to any lengths to find a treatment for their son. They are asking if there are any Phase I trials going on that he would be eligible for, because if so, they want to stay in the US and participate.

Let me step back and explain Phase I trials. Drug development in the US takes place in phases. In Phase I, a clinical trial is conducted to learn what is the best dose of the drug to give a patient. In Phase II, the goal of the trial is to learn what tumors are affected by the drug, and in Phase III the goal is to compare a new drug to either placebo or an old drug to see which works best. Because of the way Phase I trials are designed, most patients will not get the optimal dose (when the trial begins, the optimal dose is not known), and no one knows which types of cancer are affected by the drug. Because of this, it is estimated that only 3% of patients enrolled in a Phase I study get any clinical benefit. That’s great if you’re in the lucky 3%, but the overwhelming 97% of patients do not benefit from being in Phase I study.

So… the dilemma becomes what to do with M.

His family wants to keep trying new things. His doctor at home and I both think the time has come for hospice care. He is thousands of miles from home, in a foreign country, and he doesn’t speak the language. Should I do what the parents want, and enroll him on a Phase I trial, knowing how unlikely it is that he will benefit? Or should I refuse, essentially over-riding the family’s request, and not enroll him? If I do that, will they go home and get hospice care? Or will they take him to another American center for a trial that is unlikely to benefit him, but will increase the chance of him dying in pain?

There is a cross-cultural dimension to this case that makes it complicated. Here in the US, we are used to the idea that the physician’s role is to present options to a patient or family, and help them decide what the best treatment is. The physician’s role in Japan is different. Through the help of an interpreter, they were very explicit that they wanted me to tell them what they should do (as long as my suggestion wasn’t hospice care), because that is what they are used to. This, then, is the cross-cultural dilemma – I was trained to present patients and their families with options, but to leave the decision-making to them, but this family is used to a different model, where the doctor makes the final decision about what treatment will be pursued. So I was uncomfortable being asked to decide a treatment course for them, and they were uncomfortable having this decision left up to them.

Please check back in a day or two to see how the story ends.

Sunday, July 1, 2007

Medicine from the Sea

The internet has been positively buzzing with articles about a new cancer drug called Trabectedin (also known as ET-743) and its activity against a subtype of soft tissue sarcomas – myxoid liposarcoma. There have been articles on the BBC web site, in science blogs, and even on yachting websites. What’s all the fuss about? Well, there are two exciting things: first, there are precious few drugs that have any activity against soft tissue sarcomas, so the discovery of any new effective treatment is cause for excitement. Second, and possibly even more interesting, is that the drug is effective against just this single subtype of soft tissue sarcomas.

Why is this exciting? Well, the identification of a new chemotherapy drug for soft tissue sarcomas is a big deal. Granted, soft tissue sarcomas are not the public health menace that other cancers might be. But the number of drugs that are useful in the treatment of this type of cancer is very small indeed. The mainstay of treatment for soft tissue sarcomas remains surgery and radiation therapy, but these are local treatments, meaning that if the sarcoma has spread, these treatments have limited usefulness. Sarcomas that have spread have to be treated with chemotherapy, and the two most active drugs, doxorubicin and ifosfamide, have potentially devastating side effects, including heart failure, kidney dysfunction, and secondary leukemia. The results with trabectedin are brand new, and no one yet knows how to best integrate this drug into a treatment regimen, but with every new drug comes the promise of effective treatment without long term side effects.

The second big deal, which I suppose may be more exciting to us cancer doctors than to patients, is the selective effect of this drug on myxoid liposarcoma. Previously, the field of sarcoma treatment has been dominated by what I believe is an outmoded way of thinking – all sarcomas are the same. Clearly, this is not true, as the treatments for Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma (the most common types of sarcoma to affect children) are all different. Despite that, all other sarcomas are essentially treated the same, no matter what the diagnosis, no matter what they look like under the microscope. The finding that trabectedin is effective against a single type of sarcoma strengthens the idea that not all sarcomas are the same, that “histology matters” as we docs like to say, and that knowing precisely what kind of sarcoma you have will one day ensure that you get just the right treatment for your diagnosis.

Another really cool part of this finding is the source of this drug – the lowly sea squirt. What’s a sea squirt? Well, prior to these reports, I had no idea. Being the inquisitive sort, I looked it up. Apparently, a sea squirt is quite the interesting beast. The larva of the sea squirt is mobile and has a backbone, along with a brain, a balancing organ, and an eye. The larva swims around, finds a suitable place to land, and attaches itself, never to move again.











The adult has a spherical or cylindrical body attached to its substrate by a stalk. A siphon of sorts brings water into and out of its “pharyngeal chamber”, and feeding depends on the formation of a mucus net that traps plankton. The adult form has no backbone, no brain, no eye, and no balancing organ. It is, however, quite beautiful.



So… is this something unique in cancer therapy? Well, yes and no. Yes, in the sense that this is the first sarcoma-directed drug to be developed from a marine organism, but … this is NOT the first “natural” chemotherapy drug. Vincristine holds that title. Vincristine is derived from the leaves of the vinca, or periwinkle, plant. Periwinkles may even grow in your very own garden. I know my mother loves to grow them… they’re easy to care for and make pretty flowers. So it seems that the past and the future of chemotherapy will owe a huge debt to Mother Nature. More on this in future posts, I’m sure.