Beating cancer with beads

September 28, 2009 8:51:06 AM PDT
More than 1 million people are diagnosed with liver cancer every year. The majority die within the next 12 months. That's because 90-percent of the patients have tumors that are too large or too complicated for surgery. Now doctors are turning to a powerful treatment that uses tiny glass beads to kill the cancer. BACKGROUND: Liver cancer begins in the cells of the liver -- the football-sized organ that sits in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It is one of the most common cancers in the world, and rates of liver cancer are increasing in the U.S. According to the National Cancer Institute, in just the first eight months of 2009, more than 22,000 people in the U.S. had been diagnosed with liver cancer and more than 18,000 people died from it. Typically, most cancer that occurs in the liver begins in another area of the body, such as the colon, lung or breast.

SYMPTOMS: Possible signs of adult primary liver cancer include a lump or pain on the right side, caused by swelling of the liver. Other symptoms include a hard lump on the right side just below the rib cage, discomfort in the upper abdomen on the right side, pain around the right shoulder blade, unexplained weight loss, jaundice, unusual tiredness, nausea and loss of appetite.

TREATMENT: Many times liver tumors are too large to operate on or treat with chemotherapy. A new treatment called radioembolization takes advantage of your body's anatomy to deliver a large dose of radiation to the tumor and minimal amounts to those areas not affected. The radioactive particles are about the size of talcum powder particles and are delivered to the tumor through a catheter inserted in the groin. The small tube is threaded up to the liver. The radiation is in the form of beta particles, which travel about 2 millimeters through the tissues and do not cause any significant radiation outside the patient's body.

The outpatient procedure takes about an hour and patients are given a local anesthetic. It is a powerful treatment and can make a patient sick for a couple days or weeks. Patients may be candidates for radioembolization if they are not a candidate for liver transplantation, surgery or chemotherapy.

The prognosis for primary liver cancer is usually poor when surgery is not an option. For these patients, radioembolization is typically used as a palliative therapy to improve quality of life, improve length of survival, and in some cases, it may be chosen as a therapy to shrink a tumor in order to prepare a patient for a curative liver transplant. In some rare cases, however, the radioembolization itself is enough to kill the liver tumor.

Riad Salem, M.D., an interventional radiologist at Northwestern Memorial Hospital in Chicago, Ill., explains how a technique called radioembolization is used in the treatment of liver cancer.

What is radioembolization?

Dr. Riad Salem: Radioembolization is a procedure that has been around for about 20 or 30 years. The concept was to try to optimize the way to deliver radiation therapy. The traditional techniques involve administering radiation from the outside in. What if you could catheterize and advance a radiation therapy from inside the tumor? Since we were developing techniques to catheterize tumors and get access directly through the blood vessel, what if you could inject the radiation therapy as opposed to administering it through other tissue? Radioembolization involves the injection of microscopic small particles that are very radioactive. Because tumors have a lot of blood flow in them, the microspheres will concentrate in the tumor and emit a very high dose radiation.

What exactly are microspheres?

Dr. Salem: They are tiny beads. It's really very difficult to see one microsphere. Each microsphere is really the size of a human hair, if not smaller. When we do an infusion of these microspheres, we're typically injecting millions of microspheres. Despite the fact that we're injecting millions of microspheres, the volume is very low of what we are injecting, so really, it is a very high dose of radiation concentrated in a very, very small area.

What types of tumors does this technique benefit?

Dr. Salem: We have been doing a lot of the research on this therapy in conjunction with transplant surgery, medical oncology, like Dr. Mulcahy and Dr. Benson in hepatology. We have been working very closely to get on this therapy. The tumors, we've noted, that have particularly good benefit or good response to this, are the hepatocellular carcinomas -- primary liver tumors where there are very few treatment options, have a very good response to that. Some colorectal cancer tumors respond very well to that. What we call neuroendocrine tumors, very vascular tumors that can metastasize to the liver and give you symptoms like shortness of breath and weight loss and diarrhea, respond very well to those.

There are other more rare cancers that we have studied, although because those cancers are very rare, we don't have as much of a rich supply of evidence as opposed to the other therapies, but primarily liver cancer, HCC, particularly those with what we call portal vein thrombosis where the tumor has invaded in the portal vein, as was the case with Mr. Waldron. We have seen very impressive results. Certainly, impressive enough to push us to the next step of research and try to see where else we can take this field.

How long has this technique been available?

Dr. Salem: The United States is where most of the research has been going on, and in Europe, as well, recently. About 10, 12 years ago is when things were introduced in the United States and about 10, nine or 10 years ago in Europe. Most of the research comes from Europe and the United States now. It was about 10 to 15 years in development -- clinical trials, clinical development, optimization of the microspheres to make sure that they can be manufactured properly using all the appropriate safety and regulatory concerns that exist with new devices -- but really, in a high level clinical practice, about 10 years.

How was the treatment used in your patient, Mr. Waldron?

Dr. Salem: We work very closely with the referring team and the medical oncologist. In this case, Mr. Waldron was seen by Dr. Mulcahy, and usually we discuss all cases together in a conference to see what sort of therapies we believe the patient might benefit from. In his case, he was seen by Dr. Mulcahy, who really devised a strategic plan. He had a few conditions that needed to be dealt with -- the lung cancer being one, and the liver cancer being another. I personally have never seen this kind of combination in one patient.

Dr. Mulcahy's plan was, let's see if we can treat this with radioembolization to see if we can get an effect, and if we get an effect, maybe we can then tackle the lung cancer. Both of these independently still have a relatively poor outcome compared to other more benign conditions.

We discussed Mr. Waldron's case at length and we said, 'Let's try to treat the liver tumor itself first to see if we can get a benefit and then tackle the lung cancer after.' To Dr. Mulcahy's credit, this worked brilliantly. We had a dramatic effect in Mr. Waldron, and really, there are a few things that we learned from his case. First, it confirmed that in this kind of therapy it takes two to three months before you see your effect. You don't get an immediate effect at one month, and that's really keeping in line with other treatments -- chemotherapy and other options take time for the tumors to shrink. The liver has to heal, the tumor has to shrink, and the body has to sort of get rid of the excess tissue, so it takes a few months.

What was unique in his case was the level of the response and the dramatic effect that I personally have never seen, and I've treated thousands of people now. From an 18 centimeter tumor with portal vein thrombosis came near complete disappearance of the tumor. I don't want to say complete because there's a little scar left, but an 18 centimeter tumor responding at that level, I've never seen before, and to create just a small scar with one treatment was very dramatic and really inexplicable. To this day, I still can't explain it. From there, Dr. Mulcahy's plan really worked very well in that we targeted the liver. Now, it's time to target the lung cancer, and he responded to that beautifully He had that taken care of, and the patient is thriving, really.

One of the things that I think we under appreciate and really don't discuss enough is quality of life with some of these patients. In Mr. Waldron's case, one of the advantages of this therapy was he came in, he received one injection and he was able to continue with his life without really significantly altering his activities. In general, after these therapies, patients can go back to work, but they are home and they are recovering at home as opposed to other therapies, such as chemotherapy that involves IVs, potentially hair loss, and other side effects where you have to recover from this before you continue with chemotherapy.

This is really something that we need to study more. If you look at how we report data and outcomes, we're always focused on survival. What is the survival and does survival really improve? I would say that if the survival is going to be minimally improved or even if it's the same survival, but one therapy has no side effects or minimal side effects or minimal sort of detrimental effect on your quality of life, this is a very important thing, and I think this is something we need to study further.

What are the risks to this therapy?

Dr. Salem: There are risks to this therapy. All therapies have risks. One of the risks here, depending on the health of the liver, is liver failure, but with proper patient selection, we have minimized this to well below one percent the risk of liver failure. There are risks of injury to organs near the liver -- the gall bladder, the stomach. Sometimes little microspheres can flow into the vessels and cause ulcers or cause injury to the gall bladder. That can be a risk, but these are really the main things.

The biggest side effects patients have are fatigue. They can have some vague nausea and some vomiting. Often, that's because of the sedatives we give them in interventional radiology, so they have to recover and metabolize these drugs that we gave them. Fatigue is by far the most common side effect that they have. 60 percent of patients experience this. How much of it is because of the treatment or the fatigue they had before because they had cancer is difficult to quantify, but clearly, fatigue is something that is reported by a lot of patients.

Who is the best candidate for this treatment?

Dr. Salem: One of the things that we just recently learned a few years ago is studying patients in terms of trying to convert them to transplant candidates. If you can, if you have a primary liver tumor, really your best option is to resect them, to remove them by surgery, or a liver transplant. The problem is many patients present with advanced disease, which means they're outside transplant criteria or surgical resection criteria.

One of the things that we have actually learned very recently is trying to see who the ideal patients are that might benefit from this. In patients that have primary liver tumors, hepatocellular carcinoma, surgical resection and transplantation are the only known curative options. The problem is many of these patients present with what we call advanced disease where the tumor is too large or it has spread already, so we can't offer these therapies, but what about some patients where we could potentially shrink the tumors to have them undergo a potentially curative treatment like resection or transplantation?

We have just published some research from our center showing the beneficial effect of this therapy in shrinking these tumors so that the transplant surgeons will accept them for a potentially curative procedure. It's very interesting because you've converted a patient from an incurable condition to now a potentially curable condition, and we have, in fact, transplanted many patients that are alive five, six, seven, eight years later after being able to, what we call, downstage them to transplantation. We have also down staged some patients to surgery. For example, a young 40 year old patient of ours had a huge tumor. Surgeons could not resect it, but after we treated him with radioembolization, the tumor shrank from 18 centimeters to six centimeters and he underwent surgical resection. He is cured.

There are patients now where you can actually convert to curative options whereas really, it's not an option if you can't undergo resection or transplantation, so there's a new paradigm at identifying patients that might benefit from this therapy.

As someone who uses science to explain everything, is it difficult to explain why someone like Mr. Waldron ha such great results?

Dr. Salem: I fully admit, and I've admitted many times when I speak at panels or meetings, that I cannot explain certain cases that we have observed. I think all of us have these in our practices and our careers. Certainly, Mr. Waldron is one of these cases. I have no scientific rationale as to why he would have such a dramatic response compared to others. This is what we're looking for when we treat patients -- we are looking for the Mr. Waldrons. We want to identify those patients, and I think with some of the new research, we might better be able to identify those patients that might benefit best.

I cannot explain it. I'm a scientist and a clinician and I cannot explain the findings of Mr. Waldron. It is a miracle case and I would take those every day if I could. The Mr. Waldron cases are sort of a handful in my career and we keep looking for them, and really it's a wonderful, wonderful result for him, but you are correct, I cannot explain the findings in his case. It's what we look for, and that's what I'm hoping to see every time I look at a scan, a follow-up scan on a patient. That's what I'm hoping to see.

There's a clinical trial that we're going to be developing to try to validate some of these outcomes to see who is really eligible for this -- which are these patients that we can really benefit because ultimately, we want to cure people. It's hard to cure people in cancer, but in some cases, particularly with transplantation and resection, there are some cases where cure is possible. That one possibility is what makes you sort of strive to try to identify that patient. Shrinking a large tumor into a small one and having a surgeon resect it and a surgeon look at it and tell me it's a completely dead tumor, and having the pathologist confirm that this is a dead tumor means a lot. It means a lot to us as clinicians. It means the most for patients that really didn't have that option before. Most options are those that really are palliative, which means cure's really not a possibility, so these are new things, and I think this is really something we should investigate further. In fact, we are doing so at our institution.

How many centers are using this treatment?

Dr. Salem: There are now probably over a 100 centers worldwide because this has really caught on. This approach and this tool have been recognized as just another tool in managing patients with cancer, and this is not an answer to everyone. There are other tools for other conditions, but this is one of them, and it's a particularly powerful tool. I think the fact that it has spread very quickly and it is being adopted as a real option sort of says that this is a viable therapy and that there's certainly a bright future to this kind of therapy. It's a change in paradigm in how to inject radiation therapy. We've never really done this before. We place prostate seeds right in the tumor. What if we can inject the tumor with these radioactive seeds and have them distribute? This is really what this is, so it just justifies that this is a very good therapy that has certainly a lot of investigative work that needs to be done, but certainly the proof of concept has been demonstrated over and over.

FOR MORE INFORMATION, PLEASE CONTACT:

Northwestern Memorial Hospital
(877) 926-4664


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