None — Dr.Khaled Aziz, M.D., Ph.D., explains how an experimental technique is giving brain tumor patients an edge over cancer.
What is your clinical trial about?
Dr. Aziz: Glioblastoma is a malignant or a primary brain tumor, so it's a primary cancer of the brain. This has been the most difficult tumor to treat so far in the brain, and usually patients will not get the most with glioblastoma. They will have short life expectancy despite the treatments we do, and so far it has been proved that the extent of surgery with resection can prolong the survival of the patients for an extra four to six months. Although there have been cases that can make it out of the range of the statistics and they can survive for years after. There are a lot of ways when we prepare for surgery for glioblastoma that we can achieve the maximum surgical resection. The 5-ALA it's a fluorescent medication. It's a pill that the patient ingests 6 hours before surgery. What happens is that some of the metabolites of the glioblastoma react with the fluorescence pill, and that lights the malignant tumor cells. The way it gets detected, you have to have a special equipment added to the surgical microscope that can visualize the fluorescent dye. Non-cancerous cells will light blue in color, the cancerous cell, they light more pink, reddish in color.
Why do only the cancer cells turn pink?
Dr. Aziz: Because there is a metabolite that is produced by the malignant cells that allow the dye to appear. It looks like cotton candy; it's hot pink or red.
What does that enable the surgeon to do?
Dr. Aziz: When we do the surgery, we do it under the microscope, and we are able to identify the difference between the normal tissue and the cancer tissue. There are certain areas which we can grossly identify with our eyes under the microscope. The question is other areas that are difficult to differentiate whether it is tumor or normal brain tissue. This is where we stop, and there is a lot of equipment which we use in surgery to help us. There is a navigation system that we use, just to identify the margins. What we noticed is that while we are using the 5-ALA, some of these margins which we thought we would stop, and it's not tumorous, looks like normal brain. It lights pink, and that increases the extent of surgical resection. Specimens have been taken from these parts and sent for lab analysis, for pathology, and it proved that it is tumor cells.
What is the maximum goal of this procedure?
Dr. Aziz: The goal is to maximize the resection. By maximizing the resection, we are able to resect above 95% of the tumor out. There is no question that the 5-ALA has been very helpful in this, and so far, we have done about 14 patients in our hospital. I did about six or seven patients so far, and all of my patients have above 95% resection if not 100%.
Why is glioblastoma something so difficult to operate on?
Dr. Aziz: It's a malignant cancer. It's a primary brain tumor. Primary brain tumors are divided into four grades, grade 1, 2, 3 and 4. Grade 4 is the highest malignant tumor or cancerous, which is as we call it, glioblastoma multi 4, or GBM. Gliomas in general, they are infiltrative tumors, especially when they turn into malignant it's very difficult to track it everywhere. That's the advantage with the 5-ALA because it allows us to track it, because sometimes you cannot differentiate between tumor cells and brain cells under the microscope grossly. When you get the 5-ALA rent, or hot pink, you can just follow it and dissect it. The other fact, malignant glioma (GBM) has very high tendency of recurrence. Sometimes that can be in multiple areas of the brain at the same time. There's chemotherapy and radiation therapy that patients receive after surgery. Despite all of the development and investment happening in the field of chemotherapy, there's still no cure for the tumors. The more we resect on the other hand, if we achieve resection above 90 or above 95%, you improve the response to chemotherapy and radiation therapy and reduce the percentage of recurrence.
How much time patients usually have with this type of cancer?
Dr. Aziz: Whenever a patient is diagnosed with GBM, they have about one year. That's what we say in generally. Me personally, I don't believe in time because I feel that all of us will die one day, but I believe we have to do whatever is for the patient safely. It depends on the location. There are areas of the brain that can allow us to maximize the resection. If we have 5-ALA, we use it in the frontal are of the brain; you can follow it until we resects it all. For example, the motor area, you cannot touch, but anything in front of or behind it, you can resect. If you have a tumor involved in the motor area or the speech area, we are limited of course. I have a patient with a frontal malignant glioma that I did before the 5-ALA four years ago. He is still alive, but we resected everything and we used the navigation system. We actually exceeded with ½ centimeter the limits (safety margin), so we have to go through normal brain just to make sure that we resected everything and he's still alive. But these are individual cases; you can't make statistics out of it. We're talking about the majority of the patients. If the patient will get a biopsy or a sub-total resection, the life expectancy is six to twelve months, you can extend it four to six months more once you maximize the resection because the less the residual tumor, the better the response to radiation, the better the response to chemotherapy.
Is there a possibility that by using this you're going to get more time?
Dr. Aziz: It's going to be a tool because there is a lot of stem cell research going on. The idea that you want to implant these stem cells to migrate to where the tumor is and function, you can load it with vaccines, we can load it with medications, we can load it with fluorescents to light. There is a lot of clinical trials and research for the treatment of glioblastoma, and I'm sure all the new surgeries are working in the field of brain tumors and all the neurologists are working in the field of neuro-oncology. The goal is to find the cure for glioblastoma.
How helpful is this tool going to be for the future of glioblastoma?
Dr. Aziz: I think the 5-ALA is a very helpful tool for neurosurgeons who are treating the glioblastoma or surgical procedures utilizing surgical procedures that will help the visualization. It will help identify normal brain tissue from abnormal brain tissue, and by that, you can maximize a safe resection.
How safe is this drug?
Dr. Aziz: This is a safe drug, and the patient has just to check liver functions before and after. It has been widely, there are thousands of cases that have been done in Europe. This is a standard of care, and they utilize it for all glioblastomas.
Can you describe this tool?
Dr. Aziz: It's a special camera lens that has to be added to the microscope, and the major microscope companies which are providing that technology for neurosurgeons have that tool to be added. We have to prove to the FDA that it's safe to use, and I know maybe three centers in the United States who are using it now. Once it gets approved, I'm sure it will be a standard preoperative medication for all of the glioblastoma patients when they come in the morning of surgery to ingest it and proceed with surgery after.
What is the time frame of the clinical trial?
Dr. Aziz: We are extending it for 50 cases. We'll submit our data to the FDA, so far we don't have any side effects or any complications from it, in fact, we have more benefits.
WFTV
