Novel Treatment Approaches in Glioblastoma - Episode 3
Transcript:Maciej Mrugala, MD, PhD, MPH: The first step in the treatment and diagnosis of glioblastoma is typically a surgical approach. We need to find out what the diagnosis is, and that’s where the neurosurgery comes in. The type of intervention heavily depends on the location of the tumor. Some tumors are amenable to resection, and these can frequently be completely removed—completely meaning everything that’s visible, or visible disease. Because, we know that even most complete resections will always leave behind microscopic disease. However, what we call gross total resection can frequently be achieved in patients who do not have tumors in eloquent areas of the brain. In cases where the tumor is located in deep structures, let’s say in thalamus or somewhere in the brain stem, then surgical resection is not feasible because that would be associated with significant risk to the patient and cause neurological damage. And so, in those cases, patients would undergo a biopsy.
There are 2 types of biopsy that we can consider. One is open biopsy, which allows us to obtain more tissue. It’s sometimes called a ‘micro-resection.’ And then, there’s a needle biopsy. Each approach has pros and cons, the different risks associated with these approaches, but I think the major one that we fear in neuro-oncology is the fact that we may not obtain diagnostic tissue. There is a sampling problem with needle biopsies. We know that brain tumors, specifically glioblastoma, are not very homogenous, so they may harbor islands of histologies that are potentially higher grade, like grade 4. And some other parts of the lesion could be of a different grade. If we happen to encounter only the lower-grade areas, we might have a diagnostic error. So, in general, whenever possible, we prefer to offer either open biopsy or better yet, a resection. And the reason for that is also the fact that patients who can undergo more extensive resections have better survival. It has been shown by multiple studies that resections of the tumor, 98% of the tumor or more translates into better survival. So, our goal is always to offer resection to the patients whenever possible and safe.
Suriya Jeyapalan, MD, MPH: In glioblastoma, it’s actually been known for quite some time that surgery does really impact on the survival of the patient. And for a lot of time, that’s all we had; all we had was surgery followed by radiation. Chemotherapy only became important in 2005 with a first positive trial that was done in Europe and Canada. But, what they found was, if you could get at least 95% of the tumor out, you would impact positively on survival. That was basically back in the 80s that they did that with modern neurosurgical techniques. And then, more recently in the last several years, San Francisco published these really nice papers going back in their database of radiology to show that if they could get out 80% of the tumor or more, that they would impact on survival. So, I’m a firm believer in getting out as much tumor as you can safely. And if the surgeon thinks that they can get at least 80% of it out, we’ll definitely do that.
In other cases, I recommend surgery because patients in those cases who are getting treatment for glioblastoma need to undergo 6 weeks of radiation. That’s a small amount of radiation daily, but it does kill the tumor cells over that period of time. So, you have to have a large mass that’s there. The brain is a sponge in basically a very hard box. And when there’s swelling, there’s not a lot of room to go. The tumor basically pushes the brain down, and that’s what’s called ‘herniation.’ That could be threatening to life, actually.
So, what we’ll talk about very carefully in these tumor boards with surgeons, or even before where the person first gets admitted, is have the surgery and try and take at least even 50% of it out. Because, that gives space—for when we come after the tumor with chemoradiation—for the cells to die and swell, and then the patient doesn’t have a lot of side effects with it.
Maciej Mrugala, MD, PhD, MPH: In terms of novel imaging techniques, the research is rapidly evolving. We are now having the ability to use very strong MRI scans. The strength of the scan is usually given in teslas. We used to have the first or initial generation magnets that had small strengths of 3.0, 0.51, 1.5 tesla. Now we have MRIs with a strength of 3 or 3.5 tesla and even 7 tesla, which are mostly research machines. The higher the strength of the magnet, the better the resolution of the MRI scan, which can help the surgeon identify the lesion better and also can help us see if there’s any residual disease after surgical intervention. Some MRI machines also have the ability to obtain the test called MR tractography, which allows us to identify the location of the lesion in relationship to important motor or sensory tracts in the brain. And that, in turn, can allow a surgeon to plan surgery accordingly and hopefully avoid these structures during surgical intervention.
To take it one more step further, there’s also an ability to use MRI during surgery. It’s called intraoperative MRI. When the patient and the surgeon have the ability to use the MRI while the procedure is going on, this allows the surgeon to verify by MRI, every now and then during the procedure, how much of the tumor has been removed. Is there anything left that you need to go back and do a little more extensive resection? Intraoperative MRIs are becoming more and more popular. More hospitals are acquiring them, and more surgeons are comfortable using them. So, I think we’re going to see, in the future, expansion of this technology into the therapy of brain tumors, not just glioblastoma but probably also metastatic disease and in the low-grade gliomas.
In terms of other modalities, we sometimes use MR spectroscopy. This is a test that sometimes can allow us to identify if the lesion is more of a higher grade or a lower grade. This could potentially, in some cases, guide a surgeon in terms of obtaining a biopsy sample from the area of a high-grade versus low-grade. It’s not very specific technology, yet it’s certainly one of the adjunctive technologies that can help in treatment planning.
Other tests that we sometimes employ include brain PET scans. It’s a metabolic test that allows us to identify the areas in the brain where metabolic activity is abnormal. This, in cases of malignant brain tumors, can in turn tell us, help us distinguish a live tumor from, let’s say, scar tissue or radiation necrosis. We employ this test quite frequently at my center, especially in cases where we are suspecting that the lesion in question could be a result of prior treatment, mostly radiation, and that allows us to get better confidence in interpretation of the MRI in decision making regarding what should we do. Should we wait it out? Should we treat it as tumor? Or should we do something different for the patient?
Transcript Edited for Clarity