You just drink it?
Dr. Vogelbaum: Just drink it; it’s a very small amount of fluid that one has to drink. Then over the course of the next few hours it is converted primarily by tumor cells into that substance that glows under a blue light. The cancer cells do that conversion much more actively than normal cells. And then one can visualize the tumor cells as they turn pink or red while we’re operating once we shine blue light on them.
Is it hard without this liquid to tell the difference between normal cells?
Dr. Vogelbaum: When we’re removing the tumor there are parts of the tumor that are obviously, as we say grossly abnormal. It’s really at the margins where you start having the tumor cells blending in to normal surrounding brain where you can’t tell. Or it can be very difficult to tell where the limits are. One does not want to go too far, if you go too far then you’re removing normal functioning brain, which is what we all want to avoid. On the other hand we don’t want to leave the contrast enhancing tumor behind because we know that’s associated with a worse outcome.
When we’re talking about these cells can you give us an idea about how small they can actually be?
Dr. Vogelbaum: They are on the order of microns; twenty to fifty microns in size. So that’s micrometers, that’s one millionth of a meter.
When did you start doing this procedure?
Dr. Vogelbaum: We started using the 5-ALA here about a year ago. It has had limited use in the United States; it’s not actually approved, for this purpose, in the United States. It is approved in Europe, however and has been approved for a number of years now.
Is there any risk to it?
Dr. Vogelbaum: There are some risks associated with the drug itself. That is it sensitizes all tissues to bright light. So we actually keep the patients in a reduced light environment over the course of about twenty four to forty eight hours, in order to avoid skin burns associated with that.
You drink this, are brain tumors like breast tumors where breast tumors can end up in your liver and different places?
Dr. Vogelbaum: Brain tumors do not spread outside of the brain most often. They spread within the brain. The same principles that apply to cancers outside of the brain, that is when they spread to other organs that’s a much more serious situation, well the same is true within the brain. When these tumors spread within the brain that’s a very serious problem. That’s the biggest difficulty we have in trying to find a cure for these tumors is that they do spread microscopically within the brain.
Is it the skin burning problem is what’s keeping it from being FDA approved here?
Dr. Vogelbaum: No that’s a minor issue actually and very few reports of that being an issue because we know how to manage that. The other risk associated with it however is that one might go too far and remove too much tissue. We know that there’s going to be microscopic disease left behind. You can actually see evidence of it when you’re operating using this because you see a pink glow that remains even when you’ve gotten to the edge of the contrast enhancing tumor. So that could take the untrained surgeon in to areas that they don’t normally want to go in to. Where there may be tumor infiltration in functional areas that are still functioning just fine. We don’t want to take those parts out.
How important is it to get these small particles though?
Dr. Vogelbaum: We’ll never be able to get them with surgery, that’s not ever going to be accomplished with surgical removal of tissue, because the microscopic infiltration is so far away from the tumor mass that we would end up having to remove important parts of the brain. We wouldn’t do that, that’s one of the goals of surgery, is to remove as much tumor as possible, but the other equally important goal is to preserve function. And if we chase the microscopic disease too far we’re not going to be able to achieve that second goal.
How is this helping patients? Is it buying them time, years, months?
Dr. Vogelbaum: We have evidence that removal of the worst part of the tumor, the contrast enhancing part of the tumor is associated with an improved survival. So this helps us to be more effective at removing that part of the tumor and thereby giving the patients the best operation possible for extending survival.
When you saw Judy what was she like before surgery?
Dr. Vogelbaum: Before she had a surgery done at another hospital where some of the tumor was removed, but there was still a lot of the contrast enhancing tumor left behind. She was neurologically normal. Based upon the location of the tumor, I felt that it would be possible to remove all of the contrast enhancing tumor without putting her at undo risk of having a neurologic decline.
So do you think this is something you will use on all your patients?
Dr. Vogelbaum: The only way one can use it currently in the US is with a special permission called investigational new drug approval from the FDA. And in getting that one has to provide a fairly detailed and narrowly focused investigational protocol to the FDA for them to approve. So the one that we have really restricts this to a certain group of patients who are going to be operated on; who have gliomas; these people are going to be operated on using intraoperative MRI. We’re actually comparing intraoperative MRI to 5-ALA in terms of extended resection. So it’s not going to be for all of our patients, it’s going to be for ones where we think that we can remove all of the enhancing tumor safely.
What’s the next step for this?
Dr. Vogelbaum: There have been a number of efforts to try to see whether 5-ALA can be approved for general use in the US. My interpretation of the FDA’s stance, right now, is that the data from Europe are not sufficient in themselves to get approval in the US, despite the fact that it was approved in Europe. And that the FDA would like to see more evidence that a greater extent of tumor removal really causes a longer survival. That’s what they seem to be hung up on. That’s a very difficult thing to prove, because the best test of that is a randomized study and a study like that may not be ethical to do.
Could this be used for all cancers, does it highlight just brain tumors?