Proton therapy treatment for glioblastoma

MD Anderson Cancer Center
Date: 02-17-2014



Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host Lisa Garvin and today our guest is Dr. Paul Brown. He is a professor of radiation oncology here at MD Anderson and also Director of our CNS Stereo Tactic Radio Surgery Unit. Dr. Brown we talked a couple of years ago about proton therapy for brain tumors and it seems like there have been some advances since then.

Dr. Paul Brown: There have been. We've been developing some new techniques with protons. One of the techniques we've been developing is something called IMPT-intensity modulated proton therapy. What this basically does is it's a different way of delivering the protons where we use a very small point, kind of a pencil beam type to fill in the area we want to treat. It still has all of the typical advantages of standard protons, such that we decrease the amount of normal tissues that are radiated but the advantage is we're able to treat more complex shapes.

Lisa Garvin: And with intensity modulated therapy, isn't it like a series of leaves or gates that open up to kind of guide the beam as the gantry goes around the patient?

Dr. Paul Brown: That's very good, that's for normal radiation therapy, IMRT so exactly we use different basically use different tungsten leaves, or different leaves of heavy metal to form the radiation the shape where we want it to go. This is different in the sense it's essentially a very small pencil beam of radiation that fills in the volume that we want to treat.

Lisa Garvin: So basically you're combining the pinpoint accuracy of IMRT with proton therapies ability to reach the tumor?

Dr. Paul Brown: That's a great way of explaining it.

Lisa Garvin: So you currently are studying this method on certain types of brain tumors?

Dr. Paul Brown: Yep for a few years now we've been treating a type of tumor called Chordoma, they often form very complex shapes. We had tried in years past to treat them with the more standard proton plans and we did a good job with them. With IMPT we're able to treat them better, get better coverage of the tumor, and decrease dose to the normal surrounding structures. So for example it's very common that chordoma's wrap around a structure called the brain stem, that's a part of our brain that we essentially need for life, it's very essential, so by using IMPT we're able to cover the tumor better and decrease the dose to the brain stem. And in fact we've recently worked on a publication for that that should be going forward soon.

Lisa Garvin: And I understand that of course about two years ago the worst form of brain cancer being glioblastoma multiform was not treatable with proton therapy. That's changing?

Dr. Paul Brown: Yeah so in the past we were hesitant to treat glioblastoma or grade four astrocytoma with protons, now with some advancements in our proton technique we're much more interested in considering these patients for an ongoing trial we have using protons. Essentially what this trial is for patients with newly diagnosed glioblastoma, they're treated with either our standard radiation, as mentioned earlier, IMRT, or their offered protons. Most of the patients will be treated with IMPT and the reason for that is these tumors often have a very complex shape; with IMPT we can cover those complex shapes.

Lisa Garvin: Well, I understand with glioblastoma it often forms little tentacles so it's not like a little encapsulated tumor. How does proton therapy search out these microscopic little arms of disease?

Dr. Paul Brown: That's a great question. So we know from experience what type of margins to put on these tumors so we can do that with the more complex IMPT, cover these complex shapes and encompass those areas, something we couldn't do as easily before. The whole goal of the study is we want to have the same treatment outcomes with IMPT as we do with our standard IMRT but our hope is by doing IMPT sparing someone for example the contralateral, the other side of the brain, we can decrease the risks for the patients long term. In other words, the main goal is to decrease the risks of near cognitive decline after radiation therapy.

Lisa Garvin: Is it almost impossible to not take healthy tissue when you're trying to deal with a glioblastoma tumor?

Dr. Paul Brown: You always have to good point you always have to treat some normal tissue with the radiation therapy, the goal of IMPT is to treat the correct amount of normal tissue, yet sparing as much of the other brain as possible.

Lisa Garvin: So tell me about this trial. Is it open yet and what sort of candidates are you looking for this IMPT trial?

Dr. Paul Brown: The trial is open, we've been enrolling patients and the studies been doing quite well. So we're looking for patients with newly diagnosed glioblastoma. We typically and for all patients who have disease that is not widely disseminated across the brain, cause if it is involving the large portions of the brain, we couldn't offer a treatment like this. Thankfully most patients don't have that. So it's for patients who have newly diagnosed glioblastoma have undergone either a biopsy or a surgical re-section.

Lisa Garvin: Have you had enough accrual to have any sort of preliminary results or encouraging signs in this trial?

Dr. Paul Brown: We haven't had enough accrual to do that to take an interim analysis essentially, we haven't had enough accrual for the study. Saying that, we have enrolled patients on the study and I've been able to follow them over time and we've seen that the patients have done quite well. I haven't seen any increase in toxicity which is good, with new techniques you always want to look for that and in fact I've seen good tumor control with it as well, again with early follow-up.

Lisa Garvin:  Are you just doing adults in this trial?

Dr. Paul Brown: Just doing adults in this study and the reason for that is pediatric tumors pediatric glioblastomas behave differently than adult glioblastomas, plus there's the differences in the long term cognitive function of pediatric patients receiving radiation compared to adult patients.

Lisa Garvin:  Because it's a clinical trial they're not really being offered IMPT or proton therapy, or this sort of treatment just by their doctor. I mean it's something they have to be aware of.

Dr. Paul Brown:  Correct we're only offering the proton therapy for patients with glioblastoma on study, that's exactly right and the reason for that is we're investigating to see is this treatment going to be helpful for patients or not? We don't know the answer yet.

Lisa Garvin: And it seems like since 2006 when our proton therapy center opened here at MD Anderson, it seems like there have been a lot of treatment advances, we've really been kind of able to hone in and it seems like there have been a lot of advances in the brain area particularly.

Dr. Paul Brown: That's a great point, it's really a credit to the entire proton team and a lot of the credit goes to our physics team at the proton center, we have a very large experienced team that are always working on trying to solve problems. We're one of the few centers in the world that are actively using IMPT to treat patients.

Lisa Garvin: And of course we are seeing a proliferation of proton therapy centers but are all proton therapy centers alike with respect to brain cancer treatment?

Dr. Paul Brown: They're not. They're not going to have the experience a center like MD Anderson will have. It will be the clinicians, the dosimetrists who help plan the treatments and the physicists that are doing all the work behind and then also just our therapists, we have a very experienced team.

Lisa Garvin: And I know that treatment simulation is extremely important, I mean that whole you know making sure they map it correctly, that's not really standard across all treatment centers is it?

Dr. Paul Brown: Unfortunately it's not; so it varies quite a bit from center to center you're correct.

Lisa Garvin: So now with IMPT are there fewer treatments as opposed to IMRT?

Dr. Paul Brown: The number of treatments and the dose is the same whether it's IMRT or IMPT so we try to keep many of the variables the same between the two studies. The biggest difference is the amount of surrounding brain receiving radiation therapy, that bath of radiation therapy.

Lisa Garvin: But typically though I mean regular or standard radiation therapy is usually much longer treatment regimen.

Dr. Paul Brown: Both regiments are six weeks of treatment.

Lisa Garvin: Well, as you've talked about we've seen some great advances in very short time with treating brain tumors with proton therapy, has there been any movement in treating pediatric brain tumors with protons?

Dr. Paul Brown: There has. Along with we talked about the IMPT there's also we've been using IMPT also now for some of our pediatric patients as well. Again, they all have complex shaped tumors and the IMPT provides us advantages. Also, there's been more reports coming out showing the advantages of protons for pediatric patients. As we talked about earlier protons has the advantage of decreasing the amount of normal tissues receiving radiation therapy. That's important for adults but even more important for pediatric patients. They have growing bodies, growing brains so anything we can do to decrease the amount of surrounding tissue receiving radiation therapy is an advantage. In fact one of the fears whenever we radiate pediatric patients is something called second malignancy. What a second malignancy is a tumor that forms decades sometimes multiple decades after the radiation therapy treatment. There's a recent publication 2013 that Seer Database, Seer Database is a number of cancer registries that covers about twenty eight percent of the United States population and they found that there are less second malignancies in those patients, those pediatric adult patients that received proton radiation therapy than photon radiation therapy. So some initial reports are starting to come in showing the benefits of proton radio therapy over photon radiation therapy, or in other words standard radiation therapy.

Lisa Garvin: So I think that we're kind of at the break point here where we really are starting to see the results of proton therapy treatment, it seems like we're really starting to see the rubber meet the road.

Dr. Paul Brown: That's right.

Lisa Garvin: So for the adult IMPT trial for glioblastoma, what are your goals? I mean obviously survival, increasing survival would be one but what are your main goals in this trial?

Dr. Paul Brown: Our expectation and our hope is that there will be no difference in outcome with regards to survival or tumor control with IMPT compared to our standard IMRT, that's I have to say is our expectation. We're hopeful to see some benefit is a decrease in the toxicity long term of the radiation treatments. Many of our patients nowadays glioblastoma are living much longer than they have in the past. So trying to decrease the side effects long term is important. So again, as we talked about earlier, decreasing the amount of normal brain for example or receiving radiation therapy, we're hopeful the patients will have better cognitive function, better quality of life and that's meaningful not only for the patient but also for their family and caregivers.

Lisa Garvin:  Now after the course of IMPT treatment is over do you have to go back with imaging to make sure there's no microscopic disease left?

Dr. Paul Brown: That's right we'll follow our patients like we do standardly off or on protocol with MRI scans. We also have our patients undergo cognitive testing. What that essentially is is you do a series of tests with a trained professional that lasts about an hour. The trained professional also reviews those results with you.

Lisa Garvin: And if people are interested in this trial and want to know more what do they do?

Dr. Paul Brown: If they're interested we would ask them to contact the proton center and then we'll be in contact with them with more information.

Lisa Garvin: Great thank you very much Dr. Brown, very exciting news.

Dr. Paul Brown: Great thank you, thanks for having me.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact askMD Anderson at 1-877-MDA-6789, or online at MD Thank you for listening to this episode of Cancer Newsline, tune in for the next podcast in our series.