proton therapy and pediatric cancer webcast june 8, 2010...

Proton Therapy and Pediatric Cancer Webcast June 8, 2010 Anita Mahajan, M.D. Denise Rager Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer

Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care

from your own doctor. That’s how you’ll get care that’s most appropriate for you. Introduction Andrew Schorr: What is proton therapy and how is this cancer treatment option different from others? Coming up you'll hear from a leading radiation oncologist and also the mother of an eight-year-old brain cancer survivor as they discuss latest in proton therapy for pediatric cancers. It's all next on Patient Power. Hello and welcome to Patient Power sponsored by M. D. Anderson Cancer Center. I'm Andrew Schorr. Well, cancer in anyone is a really tough diagnosis. It is really, really tough in kids, and imagine if your child had a seizure, they do imaging, they see a mass and it turns out to be brain cancer, and then what do you do and where do you go and what therapies are available today. We're going to hear about proton therapy, very, very targeted, very effective, very precise radiation, and how it's used in children. I want you to meet the mom of a little boy who had such a diagnosis, a brain tumor. So we're going to go east of Los Angeles, just a little bit down the road to Corona, California, and meet Denise Rager. Denise, tell us about that day when you brought Matthew, who I guess was about, what, just before his sixth birthday, right? Denise: Right. He was five years old. He had a seizure at three in the morning. My husband and I both woke up, thinking it was our other son having a seizure. Our oldest has epilepsy. And we called the paramedics. They came out. They all knew us because they had come out before for my other son, and we went to Loma Linda emergency room and we didn't think anyone was wrong. We had had seizures in our life before, so we just thought maybe it ran in the family. But after being in the emergency room for a couple hours and wanting to go home we realized the doctors were all talking amongst themselves, and they came and told us that they saw something on the CT scan and that they'd have to admit us. Andrew Schorr: Now, seeing something in a child could be nonmalignant. Is that what they thought first?

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Denise: Actually, they thought it was just some kind of artery problem in the brain, the arteries were tangled because they couldn't see a mass. Andrew Schorr: Right, a malformation. Denise: A malformation, that's the word I'm looking for. Andrew Schorr: And that could be corrected, surgery, but it's not cancer. So this goes on for a while, trying to figure out what's going on. Denise: Yeah. We didn't even know there was a mass for four days after that. We were actually in ICU for three, almost four days before we actually got an MRI done, so it was on that day that the doctor told us there was a mass, that he thought--it was very large, it was 11 centimeters by seven centimeters. Andrew Schorr: That's big. Denise: Yeah, he felt he would be aggressive and get it all out. Andrew Schorr: So you have surgery, but it turns out to be malignant. Denise: Right. Andrew Schorr: So you do your research, your husband does research, and you learn that surgery is the first step but it's not the only step, and often chemo and radiation are needed. How did you end up going from California to M. D. Anderson? Denise: Well, we prayed a lot, and we started doing our research, and we got involved with an online support group of pediatric brain tumor parents, and they all encouraged us to go to a top hospital in the country, and so it was actually by me doing a Google search on the web that I came to find M. D. Anderson. And they had actually just opened a Proton Center I think a year before we were treated, so we knew that they had protons, and so I called them the next day. Andrew Schorr: And you said what about protons for kids.

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Denise: I knew they had proton for kids. I wanted that because I didn't want damage to the brain. I wanted to spare as much damage as I could. I knew radiation can cause cognitive deficits, and I didn't want to have to face that in the future if I could avoid it. Andrew Schorr: Absolutely not. So you went to M. D. Anderson, and he did have proton therapy. How long were you there for? Denise: Our proton therapy I believe was six weeks, and we had two weeks of appointments before that started, so eight weeks. But we ended up being there I think three to four months our first time, and we went back every 90 days after that for a few years. Andrew Schorr: All right. Well, now he's eight years old, and I understand Matthew likes to read and play strategy games. How is he doing? Denise: He's doing great. He is really a miracle. He is actually three grades ahead in math. He's in third grade and actually starting seventh grade algebra. Andrew Schorr: That's not my kid. Denise: And he loves to read. So, yeah, I don't really see any deficits for Matthew from the proton radiation at this point. Andrew Schorr: You must be very thankful. Denise: I'm very thankful. Andrew Schorr: All right. Well, let's hear from a doctor who is very involved in the care at the Proton Center there at M. D. Anderson, and that's Dr. Anita Mahajan, who is a radiation oncologist and really focuses particular on kids. Dr. Mahajan, first of all, you must feel great hearing a story like Matthew's and where proton has really helped give them their life back. Dr. Mahajan: Yeah, I think Matthew's story is fantastic. I wish we could have the same type of outcome for all the kids we treat. I remember first meeting with Matthew and his

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mom, looking at the original tumor, and this tumor was really quite large. And the surgeons actually had done a fantastic job and removed the entire thing, and we did have quite a question about what type of tumor this was. We had an agreement that it was malignant and that it would require radiotherapy and chemotherapy, but there was a bit of a debate of what specific type of tumor it was, and we were hoping that it was going to have a good outcome, and it's really great to hear that he has so far. That's really fantastic. Proton Radiation vs. Standard Radiation Andrew Schorr: Well, let's understand proton radiation versus other ways of delivering it and how it, particularly for kids, and we'll talk about maybe brain tumors first, but we can talk about other applications for it too, how it really may offer a benefit to a child. Dr. Mahajan: So in any child we treat we're always trying to maximize treatment outcomes by treating the tumor effectively but really trying to spare everything around the tumor that doesn't need to be treated. So all of the therapies that we use these days we are thinking about that and we use conformal radiotherapy. And there's many ways of doing that. Common ways are three-dimensional conformal radiotherapy using x-rays, intensity-modulated radiotherapy, which is also commonly with x-rays. But the nice thing about proton therapy is that if you treat a child from the right side, as we did for Matthew, the radiation goes in a certain distance and then it stops, whereas with x-ray therapy it would continue and exit through normal tissues and normal brain. So those physical properties of protons really help us target the areas we want to without treating the other areas that don't need to be treated. Andrew Schorr: So I know these terms "entrance dose" and "exit dose." So entrance dose is what tissue may receive before it gets to its target and exit would be radiation to maybe healthy tissue on the way out. So you're trying to limit that and give as high a dose as you can right where it needs to be. Dr. Mahajan: Correct. Andrew Schorr: All right. So protons are different from x-ray. So you have a really big center, there are not many in the country. I would imagine there are not many that are particularly set up for children too. Dr. Mahajan: Yeah, I think proton therapy is very complex in its delivery. It requires a lot of technical support, engineering support, physics support, so I think that in itself makes it challenging. And then treating children, it does require another additional

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level of commitment, teamwork and expertise. For children in particular we need the support of our pediatric oncologists who are helpful for any complications that may occur during radiation, the use of chemotherapy. There is a team approach to following patients after treatment. Our younger children require anesthesia because they can't sit still and they are unable to cooperate. Matthew was really smart and he was able to, but for many of our younger children we need sedation on a daily basis, so anesthesia support is really mandatory. And also we need to have all of the expertise from the neuropsychologist, from the ophthalmologist to help us really develop a plan that's going to be looking at all the facets of the patient's care. Andrew Schorr: So it really requires a team. Dr. Mahajan: Absolutely. Andrew Schorr: That's for sure. Now, let's understand what tumor types it could be used for. So, Denise, your son was diagnosed with a glioma. Is that right? Denise: They called it a malignant glioma because they couldn't sub classify it. Andrew Schorr: Doctor, tell us about the various different types for parents who are probably listening and saying, does this apply to our child. Dr. Mahajan: Sure. Almost any type of tumor in the brain could be treated with protons. Those that have potential for a long-term control with radiotherapy in general, historically. So I think there are certain situations unfortunately, whether we use protons or not, it won't help that patient and sometimes we have to really look at those cases very hard and make some difficult decisions. But otherwise, benign brain tumors such as a craniopharyngioma or a pituitary tumor or any other curative type tumors, such as a medulloblastoma, pineoblastoma, the list goes on, are candidates for proton therapy. Andrew Schorr: Now, I've also interviewed a child where she had sarcoma, I think. So sarcoma would be another one. Dr. Mahajan: Correct.

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Andrew Schorr: So a wide variety. How do you decide when proton is right versus. I don't want to say more traditional approaches, and certainly you've made those much more targeted too, but how do you decide which tool, M. D. Anderson has them all, is right in which child? Dr. Mahajan: That's a challenging situation because we have to think of many different levels of the patient's existence and care. A lot of the time for me even though we've been doing this for several years now I do run plans comparing both protons and x-ray therapies to see if there's any big difference and to see if there's a great advantage. Typically, whenever I do that, protons does come ahead. So in many ways I wish I could treat all children with proton therapy, but sometimes it's just not possible. Andrew Schorr: But it's not where you say, well, we have this proton center and we're going to use it on everybody. You're very selective on where you think it gives the patient the best benefit because you have all the options. Dr. Mahajan: Right. I think that the patients who would benefit the most are the younger patients. The younger a person is the more susceptible they are to radiation injury. They have developing brains, and low doses of radiation can increase the risk of late problems and toxicities. Children with retinoblastoma, for instance, have an incidence of secondary tumors from the radiation that was traditionally given, and those are kids I think who can really benefit from proton therapy since we limit the lower doses of radiation. We have a huge experience with kids with craniospinal radiation, which is needed for certain types of brain tumors. And there is no exit dose into the body cavity, and we're hoping that that will limit certain late toxicities. Pelvic tumors are something that we're learning more and more about, and it turns out that there are certain advantages. So it is a situation where you can use proton therapy in many, many different ways. It's not a cure-all, it's not magical, but there may be a certain reduction in side effects that we may experience otherwise. Andrew Schorr: So, Denise, you and your husband did your research. This whole issue of not only beating the cancer but also giving Matthew a long life without complications from the treatment he received, that was very much on your mind. Denise: That was very important to us. We knew we wanted protons when we started looking at hospitals to go to.

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The Actual Treatment: What to Expect Andrew Schorr: Okay. So, Doctor, help us understand just for a minute the procedure. So somebody contacts the department there and it works out that they're coming to M. D. Anderson and they may be there for an extended period of time. But give us a given day. So Denise and Matthew come in. What happens to Matthew? How long is he there? I understand some children may be sedated, so it may vary some, but how long is an actual treatment? Dr. Mahajan: The preparation for coming here actually starts even before the patient arrives here. What we try to do is have everything set up so there's as little down time once they get here as far as preparation, getting insurance clearance, which is sometimes quite burdensome, before the patient arrives here. Once they're here, we meet, there's a consultation time, there's an evaluation of the patient, question and answer time for the parents. They get to see the facility and get to meet all the different personnel, the nurses and the therapists. The first step once that's been done is a simulation which is where we do the setup and the preparation with the CT scan. Oftentimes we'll get another MRI scan to make sure we have a sense of what the tumor and what the brain and the geometry of the issue right then and there is. We also get a full evaluation of neurocognitive function, hearing, eyesight, just to understand where that child is so that we can continue to follow those factors as we get more follow-up and time from the treatment. And then we finally get the treatment. The whole preparation time may take about anywhere from three to five days. And the actual treatment itself once we get going is anywhere from, I would say, 30 minutes to 60 minutes, depending on complexity. Andrew Schorr: Well, we're going to get Denise's perspective on that in just a minute because I'm sure other parents listening will say, well, just kind of what is it like from the parents' perspective or the patient's perspective. So we're going to get more of that on pediatric use of proton therapy when we continue our program right after this. Welcome back to Patient Power. On this program we're talking about proton therapy for pediatric cancers, and we have with us Denise Rager from east of Los Angeles, Corona, California, talking about Matthew, who is now eight, but just before his sixth birthday they discovered a malignancy in his brain, and then mom and dad decided to take Matthew, and they were there for a while, down to M. D. Anderson. He did have proton therapy. Also with us is Dr. Anita Mahajan, who is a radiation oncologist and works on pediatric cases with proton therapy.

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Denise, we were talking just before the break, Dr. Mahajan was describing the preparation and timing, but she's involved in this all the time. Talk from the point of view of a parent coming in first time with your child. What do you feel, and how does it turn out to be? Denise: Well, I was terrified. Radiation scared me. Chemo scared me. Yeah, I was very scared. But, you know what, M. D. Anderson made everything go smoothly. I think I saw Dr. Mahajan on my second day in Texas, and they had Matthew all ready for proton radiation within I think eight or nine days. It was really quick. My son was six at the time, he just turned six, and for him, he had no problems with radiation. He actually enjoyed radiation, which sounds weird to us as adults, but him being so young and not understanding cancer made it easier for us, and he really enjoyed just going to the facility every night and being with the same people. You see all the same people every night for six weeks, and he really had no--he wasn't scared at all, so he helped me get through my fears. Andrew Schorr: There's a lot of technology. I mean, Dr. Mahajan, I've actually seen a proton center as they were putting it together, and there's a lot of stuff. There's a lot of technology, but, Denise, is it daunting for you the mom coming there or for Matthew? Denise: Not at all because you don't really see the technology unless you ask them to show you behind the gantry door, and then you're in awe. Andrew Schorr: Yeah, it's like the space shuttle. Denise: It's like the space shuttle, but just going in, it's very comfortable. The waiting area is very comfortable. They let me in to see Matthew as he was getting screwed into the table, and, you know, it was just a nice environment. It was very warm and friendly. All the techs were great. They made it comfortable for not only me but for Matthew. Andrew Schorr: I just want to say, when you say "screwed into the table," it's not like his flesh is being screwed in, it's not the middle ages. Denise: He actually had a mask that they would screw into the table. Andrew Schorr: Right. You don't want him to move.

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Denise: You don't want him to move, right. But the techs had painted Matthew's mask as Spider-Man. Andrew Schorr: Oh, cool. Denise: So he enjoyed it. They even joked that he liked watching the lights. So, yeah, it was a great experience. Andrew Schorr: So what about, you know, there are various, let's say, drug therapies where you can have sometimes significant side effects right away, and he's gone through chemotherapy as well. Is that right? Denise: Correct. Andrew Schorr: So how would you relate radiation therapy with proton to that, you know, as far as side effects or any… Denise: The only side effects we had is I think after about three and a half weeks he started to get what looked like a sunburn where the radiation was entering, and he lost his hair at about the three-and-a-half-week mark. But other than that he didn't have any issue, no side effects. Side Effects Andrew Schorr: And often we talk when we talk about radiation or chemotherapy we talk about late effects. Anything you've noticed now? We're, what, a couple of years out. Anything you've noticed? Denise: The only thing we had was about two months after radiation ended he went through maybe a three-month period where he was wanting to sleep a lot. Andrew Schorr: Fatigue. Denise: The fatigue. So he would have a nap every day, but so far the only side effect we've had.

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Andrew Schorr: Doctor, you see many patients of course. Help our listeners understand potential side effects. Dr. Mahajan: So what Matthew experienced is not uncommon for the patients that we treat. There is the hair loss, the skin irritation that happens in some, not all patients. The fatigue can linger for a period of time, and that timing again is pretty classic for patients who have gone through brain irradiation. We're waiting to see our results for late effects, but so far the overall sense of what we're experiencing and seeing seems to be quite be favorable, and we want to study that closer as time goes by. But those are the big ones. If there's chemotherapy involved we have to look for side effects from chemotherapy, and that does involve nutrition and blood counts and infection. But some of those side effects are not from the proton therapy but from other things that are also going on. Andrew Schorr: Denise, did you move the whole family to Houston? How did that work out? Denise: We did. Through a friend of a friend a charity heard about us out there, the Jimmy Burns Foundation, and they actually called me up before we even left for Houston and told me not to worry, that the rent would be paid for. Andrew Schorr: Wow. Denise: So that was an amazing miracle that that even happened because housing is expensive out there. Andrew Schorr: Right. Right. So did you feel comfortable? This was sort of Matthew's job for a while, and the family's focus was beating the cancer that was in Matthew's brain. Denise: Right. Andrew Schorr: And you felt that M. D. Anderson and the family were totally aligned? Denise: Completely aligned. We even want to move to Houston. Andrew Schorr: All right.

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Denise: It changed our lives. The History of Proton Therapy Andrew Schorr: Wow. Well, that's quite a story. Dr. Mahajan, now, some people say, well, this whole idea of proton therapy sounds kind of new to me. So somebody would say, well, sounds good now and a child like Matthew is doing well, but what about years later. Is the concept of proton to fight cancer, is that really new or did it just take a while to finally get the finances together and all the logistics to build the centers? Dr. Mahajan: It's actually been around for many, many decades. The first proton therapy patients were treated back in the 1950s, and one of the oldest centers was treating patients in the 1960s. What's caught up with protons is technology, is the ability to develop a gantry system and the machining for developing these large medical-level type facilities. Used to be that patients were treated in a physics lab, and the medical side of things were just kind of offshooting from the proton source in a physics environment. So I think there is a safety record for proton therapy. And what we're trying to do now is really gain more and more confidence and information about reduction of late effects, and there's certainly the theoretical advantage and everything points towards the fact that we should be getting those advantages as we get more robust data on our patients. Prevalence of Pediatric Cancer Andrew Schorr: Now, we talked about kids, but we haven't really talked about ages. So here is Matthew who was just six at the time. Cancer can be discovered in kids even younger than that. What about age? Where does that come into play? Dr. Mahajan: In general, we do get more reluctant to treat very young children. Having said that I have to say that we have treated a child who was as young, she was seven months old. Andrew Schorr: Whoa. Dr. Mahajan: And that was a typically, that was a very difficult situation, and it was out of necessity that we thought radiotherapy would be in her best interest. But a lot of our children are under the age of three, and we ourselves as well as other proton

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centers have noted that we do get referrals for a lot more younger children because the thought is again that we're sparing more critical structures in them, developing brain, and hopefully reducing treatment-related sequelae. Available Support Andrew Schorr: Denise, there may be parents who are listening to this program and they've been searching in the middle of the night because cancer has been diagnosed or suspected in their child and they're looking all through the corners of the internet for information, and where they live the medical community may be relatively unfamiliar with proton therapy or certainly unfamiliar with it in children. What advice would you give parents as far as connecting with resources, getting accurate information and then maybe making the decision to get on a plane to go to a center such as M. D. Anderson where they do this? Denise: Well, with us I know we joined an online support group. It was a Yahoo! Group, pediatric brain tumors, and that was what convinced us to pick up from where we were living and travel to Houston. Because we had parents online who had been through similar situations. They knew of therapies, they knew of hospitals, they knew of doctors. We talk about everything in our support group, so I would encourage any parent whose child is newly diagnosed to get into one of these support groups online because we're out there and there's people that understand what you're going through. Andrew Schorr: But what about if in your local community, though, you have people maybe even doctors saying, I never heard of it and why are you going to uproot your family and, you know, this is… Denise: That's actually a common response to it from a lot of doctors. Andrew Schorr: Yes, so what do you say? Denise: I always tell the families that I talk to, you need to get a second and third opinion on not only a doctor but on the pathology. You need to be in charge of your child's medical situation. Don't rely on doctors to tell you what to do. You need to understand what you're getting into. Because otherwise you're going to look back and have regrets, and I didn't want to have any regrets with my son.

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Andrew Schorr: Right. Dr. Mahajan, now, you at M. D. Anderson I imagine you get calls from patients, parents, physicians around the country if not around the world. Do you welcome those calls to say, well, we want to learn more about that case and let's talk about whether we think we can help? Dr. Mahajan: We do that on a daily basis, and I do believe that our knowledge, and we may actually have some insights into non-proton therapy options for certain situations, and that does come up on occasion. But, yes, we are very open to discussing cases to try to help the patients and try to give information out. Andrew Schorr: So, Denise, one step would be where parents might call but if they have a doctor that they like but is unfamiliar with it they can also make that connection to get everybody on the same page, I imagine, as well. Denise: My experience with a lot of doctors is that they, on my online discussions is doctors won't make the call. It's the parents that have made the initial call. Andrew Schorr: Right. Right. Well, this program is called Patient Power. You know where I'm coming from. And I'll tell you just my story. I recap this every once in a while. So I live in Seattle, and I did not know of any specialist in my leukemia here, even though it's a very reputable medical community, and it was through an online community, just like you, Denise, connected with people with the same illness that I'd never heard of--and certainly brain tumors in children is a very uncommon, cancer is fortunately uncommon in kids--and it was those other people around the country and around the world who helped connect me with specialists, and in my case it was flying to Houston. I'd never been there. Denise, had you ever been there before? Denise: I'd never been there. I never thought I would travel to Houston in my whole life. Andrew Schorr: Right, because when I went there all I knew about was to go shopping for cowboy boots… Denise: And barbecue. Andrew Schorr: …and barbecue, and it turned out of course where for me too I think it was lifesaving technology and medical wisdom. Well, Dr. Mahajan so we're on a journey together. A child may go through radiation for several weeks, and as we mentioned

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there could be other modalities like chemotherapy and there's surgery that's probably come into play. Is it usually typical where surgery will be first? Dr. Mahajan: Surgery. We rely on surgery to provide the diagnosis. So typically at the very minimum there's a biopsy. I would say that most tumors if they can be removed completely it's an advantageous thing. However, sometimes it's not possible, and so we proceed after biopsy with radiation and chemotherapy if needed. Andrew Schorr: And it could be that the tumor might be in a place where surgery is not really doable, if you will, too, right? Dr. Mahajan: Correct. Andrew Schorr: So then radiation. Now, might someone need proton therapy again? So could you have a course, unfortunately, maybe down the line, there's some tumor that shows up again, that it could be repeated? Dr. Mahajan: Yeah, it's a challenging situation because a lot of questions need to be answered and part of it would be where it did it come back, why did it come back, when did it come back. And given the right set of circumstances repeat radiotherapy could be recommended. But of course at any point in time such as that we would consider all of our different options again including surgery or chemotherapy and/or radiation. Andrew Schorr: Does having proton close off any options? Dr. Mahajan: Not really. Andrew Schorr: Okay. Well, you must be very encouraged that you have this tool. It hasn't been around a long time. And also it's a busy place now, right? Since M. D. Anderson has had it it's sort of been in full swing, right? Dr. Mahajan: Yes. e've had a very, very active program in particular for children over there, and since our first patient back in August of 2006 we've treated about 300 kids, kids being patients under the age of 18. We've had great results, nothing unexpected, and we're again following our patients for studying and trying to get a better sense

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of the reduction in late effects. And we cooperate with all the cooperative groups. So patients on trials through Children's Oncology Group or PBTC, which is another cooperative group, we have access to those trials with protons. And another exciting development we have is the use of the pencil beam, which is going to give us better control and possibly even further reduction of dose to the normal tissues. So a very exciting time. Andrew Schorr: So when you talk about the pencil beam, making it yet more precise. Dr. Mahajan: Correct. So the current technology in most centers, all but one in the world, they're using what's called a scattered beam, essentially. It's as if you're using a diffuser to generate the radiation field that needs to be delivered to the patient. With a pencil beam it's almost like using a marker, and we're coloring in the area of concern and by doing that we are able to remove some of the hardware that's in between the nozzle and the patient, and that does reduce some of the scatter radiation that we know exists. And so it's a further advance that will allow us to be even better and hopefully provide even a better therapeutic index for treating our patients. Andrew Schorr: Wow. Well, all the best to you, Dr. Anita Mahajan, with the work you do, your dedication to patients, children, parents, families, and may there be more stories like Matthew's. Denise Rager, I want to just find out now what you'd say as a final word to parents who may be listening where there's a diagnosis like Matthew received and trying to decide what to do. Denise: Just I always tell people no regrets. You want to make sure you research everything, that you understand everything, you can actually understand what the doctors where saying to you. Research all your options, get lots of opinions and move forward. Andrew Schorr: Well, I hope you move forward for many years and dance at Matthew's wedding, okay? Denise: I hope so too. Andrew Schorr: And that he'll be reading his kids bedtime stories, right? Denise: That's my prayer.

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Andrew Schorr: That's our prayer too. Thank you so much for being with us. You tell that little boy all the best for us, okay? Denise: Thanks. Andrew Schorr: And thank you, Doctor, for being with us, too. Dr. Mahajan: Thank you. Andrew Schorr: And thanks to M. D. Anderson for being such a long-time sponsor of Patient Power. I get to meet great inspiring professionals, parents, and patients, and it just moves my heart, it really does. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all. Thanks for joining us.

Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer

Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care

from your own doctor. That’s how you’ll get care that’s most appropriate for you.

proton therapy and pediatric cancer webcast june 8, 2010...

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