Glowing Tumors: Cutting Out Cancer By Lighting It Up
ATLANTA, GA (Ivanhoe Newswire) - Brain tumors will attack 40,000 Americans this year. Removing the malignant and most aggressive forms can be a tough task for surgeons. It's hard to see where the tumor begins and ends, but glowing technology is shedding light on the problem.
In those old sci-fi flicks, deranged doctors performed dangerous experiments in black and white. Now things are in color, and dedicated doctors are lighting up cancer to kill it.
"A patient drinks an agent that gets metabolized by the brain cancer cells into a fluorescent compound that stays within the cells," Costas G. Hadjipanayis, M.D., Ph.D. chief of neurosurgery service at Emory University Hospital Midtown, told Ivanhoe.
The drug Gliolan has been used safely in thousands of patients in Europe. Now, at Emory University, it's in its first U.S. clinical trial for patients with glioblastomas which are dangerous brain tumors that can be difficult to fully remove.
"You can see with the blood, spinal fluid it's very hard to visualize what's a tumor and what's not," Dr. Hadjipanayis said.
The drug, taken hours before surgery, makes the tumor cells light up, helping surgeons identify and remove more of the cancer. The glowing tumor technology helped safely remove an aggressive cancer from Boris Zeide's brain. Other doctors said it would be impossible.
"They were afraid he wouldn't be able to speak or walk. He's not just alive, he's talking," Liz Zeide, Boris' wife, said.
Using similar technology, the first fluorescence-guided surgery has been performed on an ovarian cancer patient. Doctors say it helped surgeons spot a tumor 30 times smaller than they would have been able to detect with standard techniques.
Phase two clinical trials for fluorescence-guided surgery started in January in conjunction with the Mayo Clinic. Gliolan is not FDA approved at this point, but more trials are expected. While the two methods can help with tumor removal, patients still need to go through chemotherapy or immunotherapy to lower the risk of the cancer coming back.
BACKGROUND: Glioblastoma (GBM) belongs to a family of brain tumors called "astrocytomas." These are tumors which arise from astrocytes – star-shaped cells of the brain which play a role in supporting normal brain tissue. There are four stages of astrocyomas and GBM is the fourth; it is also the most aggressive type of nervous system tumor. SOURCE: (www.abta.org); (www.ncbi.nlm.nih.gov/pubmedhealth); (www.webmd.com)
SYMPTOMS: General symptoms of GBM are essentially the same as for other brain tumors, they include, headache, weakness, seizures, clumsiness; and having difficulty walking. Specific symptoms will depend on the size and location of the GBM. The symptoms of brain cancer are numerous and not specific to brain tumors, meaning they can be caused by many other illnesses as well. The only way to know for sure what is causing the symptoms is to undergo diagnostic testing SOURCE: (www.cedars-sinai.edu); (www.webmd.com)
TREATMENT: The standard method of treating GBM has been essentially unchanged for many decades—surgical resection of as much of the tumor as is safe, followed by radiation therapy and chemotherapy (usually designed to damage DNA or to otherwise inhibit DNA replication) SOURCE: (www.ncbi.nlm.nih.gov/pubmedhealth)
SURVIVAL: Most people diagnosed with GBM die of this disease in less than a year. Even under the best of circumstances, in which essentially all of the enhancing tumor seen on MRI scan can be surgically removed and the patients are fully treated with radiation and chemotherapy, the mean survival of this disease is only extended from two to three months to one year. Only about one out of every four patients with this type of tumor survives two years. Prospects are better when:
The patient is younger than 45
All or most of the tumor can be removed
The tumor turns out to be an anaplastic astrocytoma, which is one stage less severe than GBM.
THINGS YOU DIDN'T KNOW: Although GBM brain tumors can occur at almost any age, they're most common after 50 years of age. GBM is hard to detect, thus a new drug called gliolan is used to light up the cancer cells. Gliolan is absorbed by cells in the body, where it is converted by enzymes into fluorescent chemicals. When illuminated under blue light of a specific wavelength, the PPIX in the tumor glows an intense red, while the normal brain tissue appears blue. This enables the surgeon to see the tumor more clearly during brain surgery and to remove it more accurately, sparing healthy brain tissue SOURCE: (www.cedars-sinai.edu); (www.ema.europa.eu)
LATEST BREAKTHROUGHS: Winship Cancer Institute researchers are testing an experimental therapy for GBM. The study uses brain imaging in an effort to detect whether the therapy is having an effect after one week. The therapy combines vorinostat, an experimental drug, with temozolomide, which is standard treatment for GBM. The goal of using the vorinostat drug is to turn genes that could suppress tumor growth back on while restoring normal metabolic behavior to the cancer cells, thus halting tumor growth SOURCE: (www.news.emory.edu)
Dr. Costas Hadjipanayis, Chief of Neurosurgery at Emory University Hospital Midtown discusses malignant brain tumors and new technology.
Are you also a professor of anything at Emory?
Dr. Hadjipanayis: I am. I am an Assistant Professor of the Department of Neurosurgery and a Georgia Cancer Coalition Scholar as well.
Let's shift gears and start talking about malignant brain tumors. What is the big challenge when you are trying to remove a malignant brain tumor as far as making sure you get all of it?
Dr. Hadjipanayis: The most challenging malignant brain tumor that we treat is called glioblastoma multiforme (GBM) and those tumors are very hard to see during surgery in the operating room when they blend in with the normal brain. At the margin of the tumor with the normal brain, there are cells that infiltrate into the normal brain and that region of the tumor is very difficult to visualize when we perform surgery.
And obviously the goal is to make sure that when you are closing up that you know you got everything you can see, right?
Dr. Hadjipanayis: The goal of surgery is to safely remove all what we can see during the operation. We perform what we call a gross total resection in as many patients as possible.
Now, there is technology that potentially can help you, help facilitate making sure you have removed the tumor more completely. Tell me about it.
Dr. Hadjipanayis: Yes, this is a new technology that has been used in Europe for some time where a patient drinks an agent that gets metabolized by the brain cancer cells into a fluorescent compound that stays within the cells. We use a special microscope that emits a blue light that excites those fluorescent metabolites in the cancer cells and they shine red. So, ultimately, the tumor mass turns red with the blue light and it allows the neurosurgeon to see remaining tumor that we need to resect during surgery.
It sounds so simple, but is it just a chemical reaction? What is it about this stuff that makes the tumor so visible?
Dr. Hadjipanayis: It is a neat agent. It is actually an agent that our body has already. It is called 5-Aminolevulinic acid (5-ALA). The brand name is called Gliolan that is approved in Europe. When the patient drinks this agent, it goes into what we call a heme biosynthesis pathway where it is broken down naturally within the mitochondria of cells. Brain cancer cells, specifically glioblastoma and other malignant gliomas more often breakdown this agent into the fluorescent compound, protoporphyrin IX, that accumulates in these brain cancer cells allowing us to see the tumor as red.
So how do you use it in surgery then?
Dr. Hadjipanayis: So, the way we are able to use Gliolan at Emory is by an investigator initiated trial we began under guidance by the FDA. We are the first to use the Gliolan formulation from Europe in North America as an investigational new drug (IND). We have patients that come in with, what we suspect have a malignant brain tumor, such as glioblastoma. They drink this agent 3-5 hours before surgery. We wait at least this time period so the agent can be properly metabolized by the tumor. The patients are kept in the preoperative area in a darker area because one of the side effects of the agent is that you can have photosensitivity. You can have a little skin rash, almost like a sunburn when exposed to bright light. Outside of that, it is a very safe agent. We monitor some of the liver function tests, etc. After the 3-5 hour time window, we take the patient to the operating room where we do our standard operation. We have a microscope that we can switch between white and blue light. The blue light excites the metabolite protoporphyrin IX and allows for the visualization of the tumor as red.
What does this mean for you as a surgeon, when you get into surgery and you are trying to do the best possible job getting rid of this tumor?
Dr. Hadjipanayis: I believe it is a great tool that can really help surgeons and ultimately benefit the patient. I think it really helps us with resecting the edges of the tumor. The main tumor mass we are able to get to in a relatively straightforward manner. We normally use the microscope for illumination/magnification, but the edges of the tumor, which blend in with the normal brain are really the challenge for neurosurgeons and that is the part of the tumor that we really want to get to, so we can resect out as much of the tumor as possible, and let patients then go onto other types of standard treatments such as radiation and chemotherapy as well as experimental agents in clinical trials.
This is just a trial now. Do you feel like this is something that is going to enhance your ability to get rid of these tumors and change brain surgery a little bit?
Dr. Hadjipanayis: I completely believe it will. I think it is something that 5 to 10 years from now, most neurosurgeons will be using in their practice. I think it is a tool that will help us and assist us in making more complete resections of these tumors. This technology will make it easier for us as neurosurgeons to identify the tumor and understand its relationship to other vital pathways and structures in the brain, so we do not hurt our patients.
I have been talking to you about this technology for long before you actually got into try it. It sounds to me like you are kind of excited about this technology. Tell me about it.
Dr. Hadjipanayis: Very excited. It has been years in the making. We have been collaborating with our German colleagues. The company in Germany is Photonomic and they have been very helpful. We also have a company here in the United States who is also helping us bring it to the United States, Nx Development Corporation. We have all just been working together to try to get this to neurosurgeons. We have opened this Investigator Initiated Trial at Emory, but the idea is that we want to branch this out into a multicenter randomized phase III trial so we can get this FDA approved in the United States. It is safe. It has been used in the thousands of patients in Europe and it can allow patients to have more of their tumor resected.
This is pretty exciting stuff.
Dr. Hadjipanayis: Very exciting.
Did I miss anything? Is there anything else I need to ask you about this?
Dr. Hadjipanayis: No. We talked about the microscope and we could take some pictures.
How many patients are there in the trial?
So, we have 33 patients that we will enroll. The trial that we plan on doing for a multicenter trial is going to probably involve 15-20 centers throughout the country and probably over 300 patients.
FOR MORE INFORMATION, PLEASE CONTACT:
Janet Christenbury Emory University Media Relations (404)727-8599 firstname.lastname@example.org
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