Childhood Osteosarcoma, a Rare Form of Bone Cancer

MD Anderson Cancer Center
Date: 08/29/2011

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Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from The University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, we're going to be talking about childhood osteosarcoma, more familiarly known as bone cancer in some circles. Our guest today are Dr. Najat Daw, she is a professor of pediatrics here at MD Anderson and Dr. Dennis Hughes who is an assistance professor of pediatrics here at MD Anderson as well. Dr. Daw, I think we'll start with you. Let's get basic and talk about what is osteosarcoma in children.

Dr. Najat Daw: Osteosarcoma is the most common type of bone cancer in children and adolescents. It usually affects the bones around the knee on either side of the knee and the bone in the upper arm, and it usually affects the metaphysis which is the largest part of the bone.

Lisa Garvin: Which would be the ends of the bone?

Dr. Najat Daw: Correct, towards the end of the bone. We see about 400 cases, new diagnoses of osteosarcoma each year in the United States and people who are younger than 20 years of age.

Lisa Garvin: And typically, you don't see this under the age of five, but how late do you see it into adolescents?

Dr. Najat Daw: Well, the peak incidence of osteosarcoma is in the second decade of life. So it typically affects adolescents during their growth spurt. We see it in adults, but it's much less common than we see it in children and young adults.

Lisa Garvin: What stage does we typically see patients upon diagnosis, Dr. Hughes?

Dr. Dennis Hughes: Well, they most often will present with what we'll call clinically localized disease, meaning to the best evidence that we can come up with, with all of our advanced imaging of CT scans and that kind of thing. We don't see any evidence that the tumor has spread, but osteosarcoma is what we would term a mesenchymal tumor which is just a fancy way of saying it's from the stuff in the middle of the body. It's not made out of skin and not made out of guts or anything like that. And this kind of tumor already has the behavior of knowing how to spread. So about 20, 30 percent of people might have had disease that spread. It most commonly goes to the lungs when it spreads and, otherwise, to bone. But even for the ones where we can't prove that the disease has spread. By the time we meet a child with this disease, we know they have microscopic disease that spread to the lung and perhaps elsewhere. And that's why we use systemic chemotherapy in addition to surgery as our mainstays of treatment. We know this about the biology from the history of how we treated this. If you go back to when I was a kid, if somebody had osteosarcoma, they got amputated the minute that their disease was found and they seemed okay for a while but, inevitably, between 6 months and 24 months later, 90 percent of those kids had metastatic disease so it must have been there when they showed up.

Lisa Garvin: So would you typically start with surgery and then adjuvant chemo or what is the typical treatment path?

Dr. Najat Daw: So the primary treatment of osteosarcoma is number one, surgery. You have to take it out and take it out completely and number two, a systemic chemotherapy. You have to treat with chemotherapy as Dr. Hughes alluded to even if we don't see any metaphysis or spread of the disease on CAT scan or/and bone scan. We still have to administer chemotherapy. Now, the sequence of events could be either/or. Most centers nowadays will give what we call neoadjuvant chemotherapy or a period of preoperative chemotherapy first and then they take the patient for surgery to take out the tumor, and then they follow with more chemotherapy. But there has been a study where they randomize the patients to either get up from surgery followed by chemotherapy or get chemotherapy then surgery, and there was no difference in outcome. The advantage of giving chemotherapy first is that it allows us time to manufacture a prosthesis that we can use for limb salvage surgery. So in the old days like Dr. Hughes said, most patients used to undergo amputation to completely resect the tumor but nowadays most of our patients are considered candidates for limb salvage surgery where we don't have to amputate their limb, but we can preserve it and use an endoprosthesis, a metal endoprosthesis to preserve appearance and relatively have very good function.

Lisa Garvin: Let's talk about limb sparing. In about how many cases and you don't have to be specific on the numbers. How often can you spare the limb?

Dr. Dennis Hughes: For the diseases that present in the typical locations, so immediately above or below the knee or in the shoulder area. The vast majority of those are able to have a limb salvage procedure. Really, these children are benefiting from the technology that was developed for older people that needed joint replacements and that has allowed the tech to be there to figure out how to do this for littler people. When you get into other locations that the tumor can show up, then it's a bigger problem. For example, about 4 percent of osteosarcomas will show up in the pelvis. There is an operation where you can remove that tumor and still preserve the leg being there, but it's not always very functional, and if the tumor is in the spine, the operation is very risky. And in fact, one of the things that MD Anderson has pioneered has been the use of radiation to control disease in those locations. We had a publication a few years ago now about how chemotherapy can be used together with radiation to control osteosarcoma tumors that cannot be removed surgically.

Lisa Garvin: What happens with children whose bones have not finished growing? What happens there?

Dr. Najat Daw: So in children who have not reached adult height or skeletal maturity, what the surgeons can do, they can place a type of prosthesis that they can later go back and change the middle part so that they will keep on extending that prosthesis so that it will match the height of the opposite leg that has a normal growth plate. The other type of prosthesis that has been around that also can be used as a type of prosthesis that you can lengthen it without having to do a surgical procedure. This is relatively a new type of noninvasive expandable prosthesis where you can expand the prosthesis by about half a centimeter each time by using a magnetic field applied around the leg and the prosthesis has a coil that when you apply the magnetic field, it will elongate by half a centimeter at a time. So this is the other type of endoprosthesis that we use in these younger children who have not yet reached skeletal maturity where their growth plate also has been removed as part of removing the tumor.

Lisa Garvin: And let's talk about prosthesis because I think most people think fake leg, fake arm. We're actually talking about prostheses that are inside like a replaced joint. Correct?

Dr. Dennis Hughes: Exactly. The problem with osteosarcoma is a cancer in a bone and only the bone has to get removed. So part of our amazing technologic advance in the last many years has been the ability to remove that bone without having to remove the rest of the limb that has that bone. So we call it a prosthesis. The kids call it their leg.

Lisa Garvin: Dr. Daw, is there a specific type of chemotherapy regimen that's used for osteosarcomas in children?

Dr. Najat Daw: Yes. So osteosarcoma, it has a relatively short list of chemotherapeutic agents that work against it. Most centers would use a regimen that has three drugs of chemotherapy to treat it. There are multiple regimens that combine these three and two other agents. So if the patient does not have a spread of metastasis, the most likely accepted regimen of treatment is with the three drugs. They get to treat it with three drugs. If the disease has spread elsewhere to the lungs and/or bone, then we treat them with more chemotherapeutic agents, more samples. We'll use four or five drugs. So usually, patients who have a localized disease, where the disease did not spread, they have a very good outcome, relatively good outcome about 75 percent survival versus patients who have a spread of that disease usually have about 30 percent survival.

Lisa Garvin: And Dr. Hughes, you're doing some work in the lab. What sorts of things are you looking at?

Dr. Dennis Hughes: Well, we're actually focused on what exactly are the signals that tell a tumor cell how to be able to get up and spread around the body with osteosarcoma as the model system we're using to ask those questions, and we're also heavily evaluating what signals promote the survival and chemotherapy resistance of osteosarcoma cells and we're narrowing in on a particular family of receptors that are normally responsible for regulating the growth and stability of skin and tissues like that, and these signals are co-opted by the bone cancer cells and used for other purposes. The reason why that matters so much is the same signals are often used in more common adult cancers and as a result, the big drug companies have made specific targeted therapies that specifically block these signals. Now, they're doing that because the adult cancers are relatively common and so there's a big market for them to do these treatments there. In kids, the diseases are so uncommon that we can really only plan to use the medicines they're going to develop anyway. So a major portion of our effort in the lab has been to figure out which of these noble therapies may be beneficial to kids. It's a bit of a tough go because we're kinda dependent on donor funds and philanthropy because pharma doesn't wanna give us the money, and when you apply for grants, if we're up against a disease that several million people a year will get, sometimes it's harder for us to argue why we're getting the grant moneys. But we're making some real headway and, in fact, some of our discoveries about sarcoma are informing the biology of the more common cancers.

Lisa Garvin: So targeted therapy is a big buzz word in cancer, a lot of them being developed here at MD Anderson. Is that kind of the path where we're going with osteosarcoma treatment?

Dr. Dennis Hughes: We'd like to think so. I think Dr. Daw is now very close to opening up a new clinical trial that combines a targeted therapy together with this conventional three-drug chemotherapy approach and we're very excited about that and we have other targeted therapies for patients that have recurrent or refractory disease that are already in clinical trials here at Anderson.

Lisa Garvin: Should--say you're a parent with a child who has been diagnosed with osteosarcoma, should you be looking at clinical trials? I mean is that--I mean should that--they be looking at that as well as standard treatment for their child?

Dr. Najat Daw: Yes, I think. Studies have shown that patients who are treated on clinical trials, they do--they fair better than patients who are not treated in the context of a protocol on a clinical trial. And what is very important in osteosarcoma and on all types of sarcoma is that for the patient to be treated in a tertiary care center where they have multidisciplinary care for the patient where you have a radiologist with expertise in this case, bone tumors, pathologist with expertise in bone tumors, surgeons, oncologist, radiation oncologist. It's very important to have all these members from the different disciplines together in the same institution and the same center so that we will have the best outcome for the patient.

Lisa Garvin: Because I know we're talking about children who have a lot of life ahead of them so quality of life is extremely important to their family. In closing, what would you--I mean, obviously, we want to increase awareness of the symptoms of osteosarcoma. What would you say to parents who maybe have a child with a sports injury who can't heal? I mean what advice do you have?

Dr. Dennis Hughes: One remembers that common things are common and most of the time, a bump is a bump and a bruise is a bruise, and an ache after a football game is probably because of an injury there. It's the injury that isn't getting better. It isn't doing what it's supposed to. The lump on the knee that's also warm and is getting worse over time even when you're resting it or you're doing what you're supposed to, or you're sitting out a week of your training. At that point, that's when, you know--when I'm giving CME lectures to pediatricians and family docs, I'd say that's when you need to get an x-ray just to convince yourself that there's not something that's a bigger problem there. So I do tell the doctors, have a low threshold for getting an x-ray.

Lisa Garvin: Any advice from you Dr. Daw?

Dr. Najat Daw: Yeah. I actually agree with Dr. Hughes that the parents do not have to over worry, but they need to worry when the pain or the lump, whatever, is not getting better. So they need to go back and follow up with their primary care physician or with the orthopedist to find out what is the problem. Most often we can tell from the x-ray that there is an abnormality. If the x-ray is easy [phonetic], did not give us the answer, we can investigate further. They can get an MRI. They can get a CT scan of the bone. Don't just let it go and sit on it for weeks and weeks, so.

Dr. Dennis Hughes: And one thing that we've developed here at the Children's Cancer Hospital at MD Anderson Cancer Center is a suspicion of cancer program that we administer through our clinic. So for doctors that have something where they're uncertain in the importance of this finding or this problem in a child, they can actually refer that child in before there's any formal diagnosis made on the basis of a worry, a concern, or a feeling that this child is at risk for a particular cancer, and we'll pick it up and run with it from there.

Lisa Garvin: Great. Dr. Daw, Dr. Hughes, thank you so much for being with us today.

Dr. Dennis Hughes: Thank you.

>> If you have questions about anything you've heard today, on Cancer Newsline, contact askMDAnderson at 1-877-MDA-6789 or online at Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.

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