Brain Tumor Cath: Glioblastoma GPS
The survival rate for a type of brain cancer called glioblastoma is about 10 percent over a five year period. External beam radiation treatment has always been challenging because the beams must pass through healthy tissue. Now, a new method of increasing radiation to the tumor is showing promise.
David Williams entered a clinical trial to treat the recurrence of a malignant brain tumor called glioblastoma.
David told Ivanhoe, "Get rid of it. No more tumors, let's do that."
John Floyd, MD, Neurosurgeon at UT Health Science Center in San Antonio said, "This trial is very promising, because it's completely out of the box. It's not chemotherapy. It's not surgery."
The treatment is an infusion of radioactive isotope called Renium 186. Delivered directly into the tumor by catheter, the isotopes are enclosed in fat particles that stabilize them and keep them inside of the tumor.
"What I tell patients is it's like GPS for the brain and we can pinpoint just exactly where we want it to go," Dr. Floyd explained.
The radioactive particles stay inside the tumor, so radiation can be delivered in higher doses. David's treatment took about four hours.
His wife, Shannon Williams, was amazed at his quick recovery right after the treatment was over.
"He was already talking," she said.
Andrew Brenner, MD, PhD, Neuro-oncologist at the Cancer Therapy & Research Center at UT Health Science Center San Antonio says it was key that the Renium 186 stayed right in the tumor.
"There was no leakage of this drug anywhere outside of the area that we were targeting," Dr. Brenner explained." This clinical trial is giving hope to both doctors and patients.
David Williams is the first person in the U.S. to have this very focused radiation treatment. Doctors say if the trial goes as planned, it may be used in the future for initial brain tumor treatments. Research focusing on new treatments for glioblastoma has been highly publicized recently. Scientists at Duke University are testing a therapy involving an engineered polio virus designed to attack glioblastoma tumor cells.
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BACKGROUND: Glioblastomas are usually highly cancerous tumors that are generally found in the cerebral hemispheres of the brain. These are very deadly tumors that present about an 18 month survival period. Glioblastomas are caused by astrocytes, which are star-shaped cells that make up the supportive tissue of the brain. This type of tumor is so dangerous due to the fact that the cells reproduce quickly and they are supported and nourished by a large network of blood vessels. There are two types of glioblastomas: primary and secondary. Primary glioblastomas are the most common form of this type of tumor and tend to form quickly. Primary glioblastomas are very aggressive and tend to make their presence known quickly as well. Secondary glioblastomas are very aggressive but tend to have a longer, slower growth history. These tumors tend to be found in people 45 and younger and represent about 10 percent of glioblastomas. (Source: http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html)
TREATMENT: Traditional ways to treat glioblastomas can be difficult because the tumor contains so many different types of cells. Some of the cells may respond well to one type of therapy over another. Many treatments combine several approaches including radiation and chemotherapy. The first step of treatment is to make a diagnosis. After a diagnosis, doctors will want to relieve pressure on the brain and remove as much tumor as possible through surgery. Because of the tumor's finger-like tentacles, removing glioblastomas entirely through surgery can be difficult. Sometimes they are growing near parts of the brain that control important functions that surgeons do not want to harm. Doctors may also use radiation and chemotherapy to slow the growth of the tumors that cannot be removed with surgery. (Source: http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html)
NEW TECHNOLOGY: The first treatment in about eight years may potentially become the new genre of treatment for glioblastoma brain tumors. A dose escalation clinical trial is underway testing the effects of a one-time treatment of the injection of renium 186 nano-particles into the tumor. John Floyd, MD, Neurosurgeon at UT Health Science Center in San Antonio said, "This is the first- in- human trial that renium 186 has ever been used for brain tumors." During the trial doctors will give patients low doses of the drug and if the patients show low toxicity from the treatment, doses will be increased. David Williams is the first human to participate in this trial and was diagnosed with a brain tumor in September 2014. Before entering the trial he had surgery to remove the tumor, chemotherapy and radiation, but the tumor returned in January 2015. Dr. Floyd said, "This is very exciting to be part of something that's new, that has a lot of promise and can make a difference for our patients."
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Tell me about what this procedure is for, is it glioblastoma?
Dr. Floyd: Glioblastoma.
This is a very exciting procedure for that.
Dr. Floyd: Yes it is.
This is a new sort of genre of treatment for glioblastoma, which is a terminal illness. There is no cure. The five year survival rate is in the order of 3 percent. When I started my training in 2000, the average survival was about 11 months. Now, almost 15 years later, the average survival is around 18 months, so we haven't made that much progress. This trial is very promising, because it's completely out of the box. It's not chemotherapy. It's not surgery. It's a convergence of technologies and expertise. What we're seeing is a convergence of expertise in radiation therapy using renium and connecting that with nanoparticles. We're seeing a convergence with expertise with designing clinical trials and also with the delivery, with the surgical application and we're able to deliver this renium nanoparticle directly into the tumor through a catheter, through a catheter that can deliver very tiny, minute amounts of nano liposomes.
What is renium?
Dr. Floyd: Renium is a radioactive particle. It's beta emitting. And it has ideal properties for delivering localized radiation to brain tumors.
That is the element that is going to help the tumor? It's going to shrink the tumor or treat the tumor?
Dr. Floyd: That's right. That's the therapeutic element, the renium. Renium-186.
Renium-186. Has it ever been used before?
Dr. Floyd: This is the first time that renium-186 has ever been used for brain tumors, in a human trial. There have been some studies overseas with other applications, but not like this. This is the first in human.
What's new about this? It's the renium, but also the application by using this small system of catheter, delivering it directly into the tumor?
Dr. Floyd: That's correct. The renium itself, the way that it's conjugated to the nano liposome is what enables it to be stable and enables it to be delivered in high doses. That's something that the researchers here have pioneered and patented that process. Now that by itself is great, but we still have to have a way of getting it into the brain. In getting it into the brain, we use convection therapy using a catheter to insert it directly into the tumor to infuse. I think the catheter therapy is also equally as important, yet to have the product in a way to get it to the target. Previous studies using convection therapy and that's using a catheter therapy for chemotherapy have had failures in the past because of the design of the catheter. The one we're using is specifically designed for this kind of therapy, and we're only the second center in the country to use it in humans on a trial basis.
So this catheter allows you to put this drug directly into the tumor, where it stays, and it doesn't cause radiation to do any damage around that area. Is that correct?
Dr. Floyd: That's correct. Because of the particles, the renium particles, its physical properties- it doesn't disseminate through the body. What we're discovering is that where we place the renium, it pretty much stays in the brain tumor. After scanning for several days, the whole body, we don't see any reactivity so far anywhere else in the body other than where we placed it.
I've already talked to David a little bit. He looks great.
Dr. Floyd: He looks fantastic. He's only a week out. I think he tolerated the procedure very well. No complications whatsoever. No pain, no headache, no nausea. This is very exciting for us.
How many treatments of this will he have to have?
Dr. Floyd: It's just a one-time treatment. In theory, this could be repeated, but as we're starting the trial and looking at developing the trials, it's a one-time treatment. Then we follow it over time to evaluate the success.
Are you expecting the tumor to shrink as a result of this treatment he has had?
Dr. Floyd: We're hopeful. This is a dose escalation study. We start off with lower doses and work our way up to higher doses. We measure toxicities along the way. He's the first in human ever to receive this drug. It is at a lower dose, so we're mainly looking at any kind of toxicities or side effects, but as a secondary measure, we are very hopeful that even at this low dose, that there would be a positive effect on the tumor.
It's probably not going to cure his glioblastoma?
Dr. Floyd: We don't know. In some of our animal studies, we were able to give very high doses of renium. We were able to see complete sterilization of the tumor and again, with David, he is the first in human and it's a small dose. Over time, as we're able to escalate the dose and see, I think there's a lot of unknowns and questions to be answered. Is it possible that there could be a cure, eradication of the tumor? That's something that we're thinking about down the road.
Having done this since 2000, you've been kind of studying this. What does this feel like to have this sort of technology now at your fingertips?
Dr. Floyd: I think it's fantastic. When I was a resident, I saw Temodar come onboard. Temodar is a chemotherapy used in glioblastoma. That helped patients, gave an extra two or three months of survival. Then I saw Avastin come onboard in 2006. Since 2006 to 2007, there really hasn't been anything new for our patients to come out. That's been eight years. Since I've been in practice, we haven't seen anything new come out. This is very exciting to be a part of something that's new, that has a lot of promise, and that can really make a difference for our patients.
This is quite amazing.
Dr. Floyd: Quite amazing.
Describe what you've told me in terms of the procedure and how it works, in one sentence to somebody that was maybe in the sixth grade.
Dr. Floyd: A patient is identified when they have a tumor recurrence and usually it's along the area that had surgery before. What we do is we take a catheter, a very small one, and place it directly into the tumor using intraoperative navigation or techniques, almost like GPS for the brain. So we can identify coordinates in the brain and say that's where we want it to be delivered. Then we can get the catheter to those coordinates and give the medication through the catheter. What I tell patients is it's like GPS for the brain, and we can pinpoint just exactly where we want it to go.
How long does it take to deliver the medicine and to do the procedure?
Dr. Floyd: The procedure itself takes about an hour and a half, and then the infusion is a slow infusion, it takes about two and a half to maybe three hours to infuse.
This was a recurrence for David?
Dr. Floyd: Yes.
He had had radiation or chemotherapy before and he saw it on MRI, it had come back. Is this exclusively used for returning tumors or is it for someone who just is suddenly diagnosed, never had glioblastoma before?
Dr. Floyd: Right now, it's for recurrence of tumors. In the future, we'll see and our hope is that maybe we can incorporate this as a treatment for upfront diagnoses. Often times, patients present with large tumors causing neurological problems and still need to have surgery to remove it. But in the future, we think that this could be incorporated as upfront therapy at some point.
Is it just me that I know more people who seem to be diagnosed with glioblastoma or is there an increase in it that you know of?
Dr. Floyd: No, we look at population studies, and as a population's growing and awareness is becoming greater, diagnostic MRIs are more common, really the prevalence is about the same.
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