First, tell us the name of the brain cancer that we’re talking about and how common is it.
Dr. Khagi: The brain cancer that I unfortunately treat the most of is called glioblastoma, also known as a GBM. Its prevalence in society is about 20,000 people diagnosed per year.
Is that considered uncommon?
Dr. Khagi: On the spectrum of all cancer, it’s one of the more rare cancers. Unfortunately though, it is one of the most common brain tumors that you can get and it’s certainly the most common malignant type of brain tumor. But compared to, say, breast cancer where you have about 200,000 to 250,000 diagnosed per year, it falls on the lower end in terms of the overall incidence.
Are you seeing different age groups? Who is most likely to be stricken with this? Give us an idea of ages and gender.
Dr. Khagi: There is an age predisposition as well as a gender and ethnic predisposition to it. Caucasians are more likely to have it, individuals that are greater than fifty, fifty five are more likely, and males have a higher risk as well. However, I have male and female patients with glioblastoma who range from their late teens to their eighties, and come from all sorts of different ethnic and socioeconomic backgrounds.
How does this present itself? What normally happens with the patient?
Dr. Khagi: Presentation can be fairly variable from patient to patient because it affects the brain, and any part of the brain can be affected. A patient may present with things as simple as headaches that start very acutely to things such as seizures and even paralysis in different parts of the body.
That’s why when something like this happens, people may think the person is having a stroke or something else is going on. Is it a tumor in the brain and does it originate in the brain?
Dr. Khagi: Most clinicians don’t consider a tumor when they initially meet a patient with a seizure or perhaps even an area of paralysis in one part of the body. With common things being common, it’s going to be things like stroke that are suspected to cause weakness in one part of the body. And a seizure can come about from many different types of sources. So, it isn’t at the top of everyone’s radar when a patient comes in and that at times can lead to a delay in diagnosis.
That’s a critical issue I would imagine, because you’re talking about a very aggressive form of cancer.
Dr. Khagi: Right. It is a cancer that originates within the brain or even the spinal cord, but within the brain is the most common area and it can be very aggressive and very fast growing. Its biological behavior from patient to patient can vary. No one glioblastoma is the same and a lot of our research here at UNC is trying to understand the mechanisms of what makes certain tumors more aggressive than others.
Do we know what the causes are at this point? I’ve heard everything from being too close to electrical fields and holding the cell phone at your ear too long. None of that has been proven to be causing something like this, right?
Dr. Khagi: There’s been a significant amount of research into that question and I think it’s valid to question how much sort of background radiation we are being exposed to. Whether it’s coming from our cell phones or electromagnetic radiation from large towers and things like that. The research thus far has been equivocal to say the least. It has not really pointed the finger or indicated an association with background electromagnet radiation. Part of that is also evidenced by the fact that the incidence of glioblastoma especially has been relatively flat over the past 15 years. It has not spiked after the introduction of smart phones and our culture using them more and more frequently. So, in a way, it’s kind of a good thing that despite a higher prevalence of technology and cell phone use, we have not seen a spike or an increase of the prevalence of glioblastoma.
When a person is diagnosed with glioblastoma, what would the treatment be and is it pretty immediate?
Dr. Khagi: We try to start treatment as soon as possible. The standard therapy, as it has been for decades, is a good surgical resection, if possible. You try to get out as much of the tumor as possible that’s causing all these symptoms. However, we know that surgery is not curative by any means because the tumor has already put down roots or tentacles throughout the brain, extending beyond what we can see on an MRI and what a surgeon can see when they open up the patient’s skull and see the tumor. But surgery is a very important aspect nonetheless. The next step is to allow the patient to recover from their operation and then follow that up by starting a three to six week course of radiation combined with chemotherapy. The range is different because it can depend on how physically fit the patient is and whether they can tolerate a full six week course of radiation combined with chemotherapy. After that, we try to keep the tumor at bay by using a maintenance dose of the same kind of chemotherapy and that ranges between six to twelve months.
Can you tell us if there has been anything new on the horizon for glioblastoma? In Ashley’s case, and I’m sure other patients, you are using some new technology. Tell us about that and how it works.
Dr. Khagi: The newest technology for the treatment of glioblastoma is the use of Optune, which utilizes Alternating Electrical Tumor Treating Fields. This technology is basically a device that uses just about palm sized arrays with ceramic electrodes that are applied to the shaved scalp. The hair has to be completely removed and it’s applied to the scalp on either side and one and one in the back so there are four arrays that are used for treatment. These arrays are then connected via wires to a power source. Sometimes it’s a battery pack when the patient is out and about, or a satchel, or they’re connected to a power source at home such as when they’re sitting on the couch or lying in bed so they can continue to generate that necessary electrical field within the brain. That technology was recently approved for the treatment for newly diagnosed glioblastoma where we combine the Optune device and their maintenance chemotherapy. In a large randomized control study of five years, pretty mature data that was just recently published showed a survival advantage of about five months. Those individuals that took chemotherapy alone were living to about 16 months and those who used the device plus chemotherapy were looking at about 21 months. It’s a fairly significant difference in survival when you consider that the overall survival rate for this disease is in the range of about 16 to 18 months—it truly is light years.
Five months, a lot of people think that’s really not a lot of time, but when you are dealing with such a critical diagnosis and you are a parent or you have people to take care of, this is ground breaking technology.
Dr. Khagi: Five months is potentially a birthday, a graduation, or other important events in people’s lives and because of this technology we’re helping patients to live a little bit longer to those milestones. The device was actually shown to increase overall survival beyond the median, but even at three, four, and five years, the percentage of patients was higher compared to those individuals that only got chemotherapy. We classically quote that survival at five years for this disease is 5%, so in five years you know 5% of patients are alive. In this study, we saw that survival jump to 13%. So it’s greater than double. It may not seem like much, but to have 13% of patients still alive at the end of five years with such a deadly disease is quite remarkable.
Tell us about your experience with Optune because you’re treating patients and your patients are wearing Optune, but you also put yourself in some of the patients’ shoes. Talk about that a little bit.
Dr. Khagi: So from the patient experience to end point, I do prescribe this device. I recommend it to all my glioblastoma patients who start going through maintenance chemotherapy. And folks like Ashley, who are very busy moms and have very busy schedules don’t want to be tied down to something. But I know that they do it because they have things that they’re looking forward to and they know the data—I always discuss it with my patients to justify why they have to wear this device at least 18 hours a day, when they’re sleeping and when they’re out and about. It’s a huge commitment. So I try to empathize and understand what my patients are going through. I decided to actually see what it’s like to wear an Optune device, and I thought that our annual 5-K race where we raise funds for research would be a great opportunity to do that. So I challenged all the teams to raise as much money as they could and the team that raised the most would have the opportunity to shave my head. That alone I thought would be good enough, but at the same time, I did want to know what it was like to experience wearing the Optune device. So along with that, I put on the device and I ran the five kilometer race for many different reasons, but mostly just in the solidarity of my patients to sort of analogize the struggle that they’re going through. In a way, this race represents the struggle of being diagnosed with a glioblastoma. As much as I wanted to quit because it was a very hilly course and a very hot day and I was wearing this device and this backpack, I really wanted all of this to mean something and it helped me understand their struggles a little bit better. I think it resonated with my patients and their families because I can’t take chemotherapy and I can’t do radiation, but I can try to do this and try to understand what they’re going through on a daily basis. I don’t necessarily need to convince more people to wear the device because I think the data speaks for itself, but in the future when I have a conversation with my patients about wearing this device, I can actually say that I did it and I know what it feels like. So if anything, it brings me closer to my patients and I think there’s a lot of value to that.
You did the whole thing and I think that’s extremely impressive. I jumped the gun because you were saying patients need to wear this for 18 hours a day. Tell us what it is actually doing. Is it stopping cancer cells from reproducing?
Dr. Khagi: The mechanism of action of Optune is multifold, in that it acts on many different aspects of the cell cycle and division process. First of all, it only affects dividing cells, and the frequency which the electromagnetic field is calibrated to will only impact a certain size of cell. In this case, it’s calibrated to the size of a GBM cell, so not the size of a neuron or the size of a skin cell on a person’s scalp. Furthermore, the normal cells like neurons and skin cells and things like that aren’t dividing like glioblastoma cells, so this field doesn’t affect those types of cells. When an electromagnetic field is introduced into the brain via this device, it alternates rapidly between the arrays that are on the scalp, hence why there are four apposing arrays. When the field is on, it interferes with something called the spindle complex which the cells have to form in order to take their DNA, which is found in the middle when they’re about to divide to each daughter cell equally. It interferes with the spindle complex so the cancer cell can’t assemble it properly because it has to be polarized so that the little, dimmer units that have to assemble to make these spindle complexes attach from north to south and south to north like a magnet. When you have that field on, it confuses the cell and it can’t assemble these little sub units for the microtubule complex. Furthermore, it can’t equally divide the DNA from one cell to the next because it has to go to a north end and a south end. When the cell is confused and doesn’t know which direction to divide into, that further complicates the entire process. There’s also the effect on the little organs of the cells called organelles that also have to be equally divided. In this case, the organelles are unequally divided and the cells can’t go through the normal process. What that leads to is a thing called apoptosis, which is cell death, because in this case the cell can’t divide its genetic material equally between daughter cells. It’s not as easy as a pill, but it’s a very novel approach and we’re actually looking at using it for lung cancer tumors that have traveled to the brain to see if it could impact that disease as well. I know there are national studies looking at things like mesothelioma, lung cancer, ovarian cancer, and pancreatic cancer where they’re using these very large chest sized arrays that they’re placing on patients and using the same sort of concept to try to impair the cell division process. So I think it’s a very promising technology that went after, I would say, the worst of the worst kinds of cancers and came out on top. They really made a difference in these patients’ lives and when combined with chemotherapy, it really adds to the overall benefit as was demonstrated in the large clinical study.
Are there any side effects that patients report?
Dr. Khagi: Really the biggest side effect is dermatological, so skin toxicity. Wearing the device at least 18 hours a day is hard and it can be hard on people’s skin, especially when it comes to humid conditions like in North Carolina. Patients do have to wash the skin, make sure it’s clean, and make sure that any raised, bumpy areas are addressed with creams, maybe topical steroids and sometimes even topical antibiotics to make sure the skin stays healthy. As long as people stay on top of it, it’s very, very tolerable. It doesn’t have the side effects that chemotherapy would. So blood count problems, infections, all of that which comes with chemotherapy, this device has none of.
Is there hope that new generations of this device will eventually prolong life even more or stop cell division even longer?
Dr. Khagi: Absolutely. We’re just scratching the surface of the potential of using external alternating electrical fields. We don’t really know how far we can go and when we potentially get more experience with this device out in the community, more data starts coming in from the experience that on the ground practitioners have with it. Perhaps we’ll even see a trend towards a greater survival number. We usually see that, even when we were using chemotherapy back in 2005, which is the same chemotherapy that we use now. Survival has increased by a month or two, so we have gotten better at using it and people do live a little bit longer and I suspect that this will probably happen with this device as well. We could be combining this device with other methods and other chemotherapies that could be even more helpful. In the era of immunotherapy, perhaps this device may also have a role where we can add a sort of an immune stimulating agent plus the device to try to stop cancer growth entirely.
And this, I assume, will be covered by insurance?
Dr. Khagi: Some insurance companies do have problems covering this device because it is quite expensive. There is sort of a company support mechanism for allowing the patient to use the device at a very nominal cost, though patients would have to qualify for that program. But there are some insurance companies that are changing their minds about it because they actually see the benefit of using this device and prolonging people’s lives while they’re on it. So I think hearts and minds are changing.
You seem very positive about the research and the direction where this is headed and I hope you continue working on a cure for glioblastoma.
Dr. Khagi: We are actively doing that here at UNC. We have some amazing research going on.
If folks wanted to learn more about glioblastoma, is there a specific web site you want to send them to or should I have them just go to UNC? I could send them to Optune, right?
Dr. Khagi: A really great website to learn about the disease and actually quite a bit of brain tumor information would be a website called headforthecure.org, which is actually a foundation that helps raise money for the cause. They also have a website called brainsforthecure.org, which has a plethora of information on treatment strategies, clinical trials at various centers, as well as contact information for experts in the field, including myself.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Bill Schaller, UNC Cancer Center
919-962-3405
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