Microchips Cause Cancer

Microchips are tiny radio-frequency computer chips (typically no larger than a grain of rice) that can be implanted into domestic animals, cars, and laptops. They are used for information storage – in dogs, for example, they contain the owner’s contact information and serve as a GPS tracking device in case the dog is lost.



In 2004, the FDA approved microchips for health-care use in human beings. They gave this approval to a company called VeriChip Corp.

In humans, these implantable chips act as high-tech electronic medical records. Imagine it: your entire medical history can be instantly accessed in a single computer scan because you have a data chip under your skin. Sounds convenient doesn’t it? In case of an emergency your medical provider would not be at a loss, even if you forget important details or can’t communicate at all..

…but do these microchips cause cancer?

Well, according to a report by The Associated Press, they just might.

A series of veterinary and toxicology studies, dating to the mid-1990s, stated that chip implants had "induced" malignant tumors in some lab mice and rats.

What? I thought these things were supposed to SAVE your life, not give you cancer! How did these devices get approved by the FDA if they cause tumors in mice? I’m not usually a conspiracy theorist, but I could offer one reason for their approval:

The FDA is overseen by the Department of Health and Human Services, which, at the time of VeriChip's approval, was headed by Tommy Thompson. Two weeks after the device's approval took effect on Jan. 10, 2005, Thompson left his Cabinet post, and within five months he became a board member of VeriChip Corp. According to the AP article, he was compensated in cash and stock options.

Hmmm…

OK. Leaving conspiracy theories aside for the moment, it’s not like this is a public health menace or anything, right? I mean, do you know anyone with an implanted microchip? Well, you might be surprised, I sure was, to learn that….

To date, about 2,000 of the so-called radio frequency identification, or RFID, devices have been implanted in humans worldwide, according to VeriChip Corp. The company, which sees a target market of 45 million Americans for its medical monitoring chips…

Yes, you’re right, 2,000 chips implanted in humans amounts to just 1 in every 150,000 people in the US. But what if it were 45,000,000? Now THAT’S a lot of microchips. And don’t forget that these devices have been implanted in tens of thousands of pet dogs and cats in the US to aid in their recovery should they get lost.

So what lesson can we learn from all of this?

Well, maybe VeriChip paid off Tommy Thompson to ensure FDA approval of their product and then further rewarded him by offering him a lucrative position as a board member. Maybe not. Figuring that out is what investigational reporters are for. What I think we can learn from this experience is the importance of ongoing research even after a product is approved by the FDA. The studies required by the FDA in order to demonstrate safety are usually very small, enrolling fewer than 100 patients, so that rare side effects may not be seen in these trials.

For example, if microchips cause tumors at a rate of 0.01% (1 in 10,000), and if they were tested in 100 people prior to approval, no tumors would have been expected to be seen in those studies. However, if 1 in 10,000 recipients get a tumor, and if 45,000,000 chips are implanted, that’s 4,500 tumors, which is not an insignificant number.

Post-market evaluations are a valuable mechanism for identifying these problems, as demonstrated by the Vioxx case that was so prominent several years ago. And because some of these side effects are rare, detecting them after the drug or device has been approved by the FDA does not imply fault on the part of the manufacturer or on the part of the FDA. It just means that it is hard to detect rare side effects.

The other lesson to be learned is on the value of animal testing. Thus far, no study has determined that tumors have been detected in humans, but given the small number of humans with chips implanted, this is not a surprise. However, having detected these tumors in animals alerts us to the possibility that something similar could happen in people. This will increase our vigilance in looking for this side effect, and that will ultimately benefit us all.

The Inspiring Story of T

One of the recurring topics of this blog has been end-of-life issues, and how patients and their families face this most difficult part of the fight against cancer. So far I’ve written about a family that wanted another clinical trial to be on, even when there was no potential for cure, and I’ve written about how I deal with the death of my patients. One patient who faced the end of his life with amazing maturity was a teenager named T.

T was 14 when we first met. He had been diagnosed with, and treated for, acute myeloid leukemia (AML) at another hospital. Unfortunately, less than a year after completing his chemotherapy, he relapsed. He needed a bone marrow transplant to survive, a procedure not available at his hospital, so his doctors sent him to me.

T and his family moved to Baltimore and began the next phase of his treatment. The drugs we usually use to treat relapsed AML didn’t work for him. Our second attempt at treating his leukemia made him much better, but was still not enough to cause a remission. We had some long, difficult discussions at that point, and T knew the odds were against him, but he decided to keep fighting, so we went ahead with the transplant.

His course was very complicated, and T spent several weeks in the ICU, but when it was all over, he was in remission! He did so well, in fact, that he was finally able to go home, after spending 8 months in Baltimore, away from his friends, his school, and his dog. I wish I had a picture to share of the smile he had on his face the day we told him he could go home!

After being home 2 months, though, T suddenly became very ill again, and had to be flown back to Baltimore and back into our ICU. His ICU stay this time was only a couple of days, and within 2 weeks he was discharged again. He and his family chose to stay in Baltimore for a while, to be sure he was going to be OK. Sadly, the next month he relapsed again.

At this point, T and his family were faced with an awful dilemma. On the one hand, they had the option to pursue aggressive chemotherapy and other treatments, with an almost certainty of making T terribly sick and only the slimmest chance of another remission, let alone a cure. On the other hand, they could choose hospice care – going home and only treating his symptoms to ensure he was comfortable while dying. A third possibility we presented to them was low dose chemotherapy aimed at slowing the progression of the leukemia but not really aimed at curing it.

The family thought long and hard about the decision. In private conversations I had with his parents, it was clear that they wanted to pull out all the stops and go for the cure, despite the long odds and difficult path.

But… they knew that T was the one who was destined to suffer if this was the path they chose, and despite his relative youth (he was only 15 years old by that time), they decided to leave the final decision to him.

And here is where T did something mature beyond his years, and in my mind, truly inspirational. He spoke with his parents. He spoke with his sisters. He knew what they wanted him to say. He knew they wanted him to keep on fighting, no matter what.

But he told us all he was done.

He chose quality over quantity of life.

All he wanted to do was go home, see his dog and his friends, drive his father’s truck on the beach, and get ribs from Rendezvous in Memphis, Tennessee. If he could do those things, he said, he could face death unafraid.

So that’s exactly what he did. Within 24 hours we arranged for his discharge from the hospital and transportation home. He went to Rendezvous (and sent me a t-shirt). He drove his father’s truck (he wasn’t 16 and didn’t have a license, but at that point did it matter?). He saw his friends and his dog. And he died three weeks later, in his own bed, surrounded by loved ones, in no pain.

Two weeks ago I was in Memphis and had the pleasure of eating at Rendezvous for the first time. The ribs were excellent (maybe the best I’ve ever had) but all I could think about while I was there was T, and how I hope that if I’m faced with a tough decision like he was, I can make the choice that’s best for me, regardless of what others want, just like T did.

The Stem Cell Thing

One of the best parts of my job is that not only do I have the pleasure of taking care of children and young adults with sarcomas, but I also run a laboratory where we conduct research that we all hope will eventually lead to new treatments for my patients. I am going to talk a little about my laboratory research today.

One of the hottest new ideas in the world of cancer research is the concept of the “cancer stem cell.” As many of you who have been involved with Ewing’s sarcoma patients know, the correlation between response to therapy and cure is not very strong. In other words, although patients with widely metastatic disease can respond well to chemotherapy and to radiation therapy, relapse is frequent and cure rates remain less than 25%.

Why is this?

One possible explanation is the existence of a cancer stem cell. Cancer researchers used to believe that all cells within a tumor were the same, and that any one of them is capable of unlimited growth and of spreading to distant sites. We now know that this is not the case. Only a small fraction of the cells in a tumor are capable of unlimited growth. The rest will only divide a few times before dying. This recognition led to the development of the Cancer Stem Cell Model.

The Cancer Stem Cell Model predicts that the small number of cells capable of unlimited self-renewal would have properties similar to other stem cells, such as bone marrow stem cells and the embryonic stem cells that we read about in the papers all the time. These cells would be responsible for maintaining the primary tumor population and should be relatively resistant to chemotherapy. This would make them the primary cells causing relapse because of their ability to survive the treatments that kill the majority of the other cancer cells. Cancer stem cells have been identified in several types of cancer, including leukemia, breast cancer, brain tumors, and others.

So…. Are there sarcoma stem cells? That remains an open question, but one that we are in the process of studying in my lab.

We have some very exciting preliminary data that makes me think that we may have identified Ewing’s sarcoma stem cells. This, of course, is just the first step. After we are able to prove that these cells exist, the real fun will begin! We have a plan in place to learn as much as we can as quickly as we can about the basic biology of these cells.

Hopefully our research will have a big impact on many aspects of the care of sarcoma patients:

1. We can isolate sarcoma stem cells and try to find drugs that can kill them.

2. We can devise a rapid test for sarcoma stem cells that might allow us to better predict who will relapse and who will not.

3. We can devise strategies to identify these cells in biopsy specimens to be able to determine if treatments have killed stem cells in the patient.

4. We can devise new treatment strategies specifically targeting stem cells that hopefully will result in higher cure rates than currently used chemotherapy with fewer side effects.

It is an exciting time in cancer research…. This new theory goes a long way toward explaining why chemotherapy can make a tumor go away but might not cure the patient. Identifying the cells responsible for relapse will allow us to make big strides in treatment and hopefully dramatically improve our treatments.

I’m lucky to be able to work in both worlds (the lab and the hospital) and be in a position to guide research findings from the laboratory into the hospital and witness first hand this revolution in cancer treatment – away from toxic chemotherapy and toward targeted therapy* more precisely aimed at the cancer.

*An article I wrote for ESUN, the newsletter for the Liddy Shriver Sarcoma Initiative, on targeted therapies for sarcomas

When My Patients Die

On July 27th, I posted about my participation in the National Youth Leadership Forum, where I discussed my career with teenagers who have expressed an interest in the field of medicine. One question that I was asked more than once was:

“How do you handle it when a patient of yours dies?”

Whenever I’m asked that question (and given my profession, I get asked that a lot!), I’m reminded of a scene from my favorite old TV show, Homicide: Life on the Streets. In one episode, a new character, a female Chief Medical Examiner named Julianna Cox, is introduced. Dr. Cox is young and beautiful, and one of the detectives, Bayliss, is clearly attracted to her. He tries to make small talk, and he asks her how she deals with her job, doing autopsies and dealing every day with death. Her answer? “Sometimes I drink too much, sometimes I drive too fast, sometimes I fall in love with the wrong people.”

So how do I handle it?

I remind myself that just because the patient died doesn’t mean I didn’t do some good, it doesn’t mean I didn’t help the patient, and it doesn’t mean “we lost.”Helping a child with cancer can mean providing treatment that results in a better quality of life, relieving pain and suffering, and allowing the patient to have as normal a childhood as possible. These things have immense value to the patient and the patient’s family.

I also find it important to remind myself of the patients whose outcomes have been better. I’ve taken care of many patients that everyone thought would not do well – patients like K, who was the subject of my second post here, and others. Although I know I can’t cure everyone, after one of my patients dies it’s reassuring to remind myself that there are others who lived.

Finally, I try to attend the viewings, wakes, or funerals of my patients who have died. I have found over the years that this allows me a certain amount of closure. Perhaps more importantly, it gives me a glimpse into the life my patient had outside of the hospital. It reminds me that they were children and young adults with full, rich lives, not just patients with a disease. Unfortunately, doctors rarely get this view of their patients, and almost never see their patients outside of an office, a clinic, or the hospital.

Does any of this make the death of a patient any easier? No. Nothing makes that easy. Even when the patient was suffering and we all knew that death brought relief that I was unable to provide with medicine.

However, in order to go on treating children with life threatening illnesses, doctors and nurses have to develop strategies to allow them to cope. Everyone is different, and what helps one may not help another. The fictional Dr. Cox drinks too much, drives too fast, and falls in love with the wrong people. The non-fictional Dr. Loeb tries to recognize that he might have helped a patient even if he did not cure their cancer and he gains strength from recalling the patients who did survive and have gone on to really wonderful lives.

A Gift

When I returned to work Monday morning after a week of vacation, I was surprised to find a box from UPS on my office chair. I was even more surprised when I opened the box and found these inside!



A patient I took care of a while ago had sent them to me as a gift. I wore them proudly today.

Thank you, Logan!

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.

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!

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!

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.

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.