Nick Doble, Caregiver

I’m going to pose a question now to everyone. How can the medical team improve the care of patients with brain metastases? Perhaps we can start with having Ivy and Katie speak to that.

Patients need information. That’s probably the most important thing. When you’re diagnosed, everything is thrown at you. I think patients need to understand what brain metastasis means, how that can impact their lives, if they’re asymptomatic versus symptomatic, what the options are for treatment, both short term and possibly long term. That needs to be laid out to people in an easily understandable way up front. I also think patients need to understand what the ongoing management is going to be for brain metastases, how often they’ll be scanned, if you have certain symptoms, when you should bring that up and maybe recommend moving a scan up earlier. But basically, what it comes down to is increased information.

I agree. We’ll have Ralph, after Katie has a chance to speak, but that’s exactly what the ABTA [American Brain Tumor Association] survey results showed us, too. But Katie, do you want to add to that?

I agree with everything Ivy said, although I have already said I’m the patient who doesn’t want to hear all the worst-case scenarios. I don’t know how I would have responded if a doctor said, “Listen, I need you to be looking for these things,” because then I would be like, “Oh my god, I think that symptom happened to me last week, I think I have a brain tumor, I think you need to scan me right now.” But I think I’ve gotten a little bit better now that I’m seasoned at dealing with this.

Another thing that was shocking to me was, I’m not claustrophobic, I didn’t think I was, until I got a brain scan. That’s a very different scan. If you think, “Oh, I’ve done scans, I know what I’m doing,” and suddenly you’re going headfirst down a very narrow tube with a cage on your head, it’s terrifying. To this day, if I ever hear of someone having to go in for a brain scan, I’m always very careful with how I present information to other patients. But I always do say, “That one is a little harder for me, and I take a Valium for it.” I call that a cancer perquisite. But Nick has to drive me to those scans now because they still, to this day, I get a lot of anxiety around that particular scan.

 I think your experience is not a rarity, I think other patients have had similar experiences. Ralph, do you want to add to that?

Sure. I think you all know this very well, but patients and caregivers trust you and respect you. When you take the time to sit down and give them clinical trial treatment options, they listen, they absorb it. But it’s important that you also involve your team, your nurses, and your social workers, so that when they leave the office, they trust you, but sometimes they don’t fully understand everything that you have said. Having your support staff following up, working with them on clinical trials is important. Second, the survey shows how much they lean on, and want to know more about, organizations like the ABTA. You can trust us to work with them where they are and then afterward. People like Nick, who is a phenomenal caregiver, we can talk to him about whether he’s interested in being a mentor to others after he feels like Katie is at a place where he can give time to other caregivers.

 I completely agree, Ralph. Dr. Gondi, did you want to add to, how can we as a field improve the care of a patient with brain metastases?

As I listen to Ivy, Katie and Nick speak, it reminded me, at least in my clinical experience, that when systemic cancer goes to the brain, there are a lot of emotions, understandably, there’s a lot of fear, there’s a lot of confusion, consternation. And it’s not just on the patient’s perspective, but even some medical oncologists. What I’ve appreciated is that sometimes medical oncologists, as a brain tumor specialist, and I’m sure Dr. Brastianos, you probably do the same, I just say, “You know what, I’ll take care of the brain. Everything above the neck, I’m going to watch and keep an eye on, and everything below the neck, your systemic oncologist can keep an eye on it, and we’ll do it together.” That collaboration becomes useful. Just during this Zoom call, I’ve gotten a couple of texts from medical oncologists about patients we have, and I think that gives patients and their providers some sense of calm and comfort, that everything is taken care of up here, that we’re OK. If I have a headache, call that doctor who specializes in brain stuff and let him know, so that they can address it. I do think that there is tremendous opportunity to help and augment the care of patients and their providers, especially when we’re talking about the brain.

Of the two concepts I tried to cover, one is that the neurological team, whether they are a surgeon, radiation oncologist, or whatever, they have the knowledge and expertise pertaining to the brain and to the central nervous system. That team is bringing that expertise to help the medical oncologist treat the patient in a complete way. The second concept is that it’s a complicated world, and one specialist within the neuro field cannot handle all the problems of brain metastasis. It does require a whole team of a surgeon, oncologist, radiation, radiologist, and so on and so forth. Bringing all these together in the brain metastasis concept is a great advantage for patients.

 I completely agree. On that note, we can be providing more support to caregivers. Nick, you already alluded to that earlier, but tell us more about how we can help caregivers.

This morning was a good example, my first question to Kate was, “How are you doing?” I think that’s a nice question also to ask a caregiver, how are they doing. I think I would like to see more proactive support offered, and if you do need support, here are avenues you can use to find support and information. Then what do you need as well as a caregiver, what can we do to support you, because we’re here to help the patient. The more that we can be supported to be in a better place to help the patient, the better that could be for us. Even Ivy talked about how she was the patient, she looked after the kids. I’m sure while her husband was working, that was a huge impact on him, as much as there was when I had to go to Pittsburgh, change my schedule, and be there to support Katie in the hospital every day. It would be great for a little more attention to the caregiver, to make sure things are well there, because we’re here to help the patient, and we’re part of the overall story and on the journey together.

That’s so important, Nick, thanks for saying that. Again, thank you to Katie, Nick and Ivy for sharing these deeply personal journeys. We’re so inspired by your stories. Thank you, and we hope that you’ll continue to do well and respond to therapies. I think we’ve reached time. Thank you to everyone who participated in today’s 

® program. I want to thank Ivy and Katie for sharing your story, and my colleagues, Vinai Gondi, Ray Sawaya, Manmeet Ahluwalia, and of course, Ralph DeVitto, for this incredible discussion. To our viewing audience, we hope you found this presentation to be useful and we’ve provided you with practical information that you can discuss with your health care provider. Thank you so much, everyone.

Videos

Improving Outcomes for Patients With Brain Metastases

How do you define treatment success for Katie?

It’s a good question. I was thinking about that as I heard Ivy and Katie talking. I think one of the things that she talks about is living to old age, and she has a number, 89, that is like a targeted area for her. I think for us, to be able to enjoy our life and live our life. I’d love to grow old together. If we can do a treatment and get back to the closest sense of normality and to be able to, as Katie said, go traveling and see friends and family and enjoy our lives, I think that’s the most important thing for me and for us.

Another question for you. What are your thoughts or feelings when Katie does enroll in clinical trials?

I do feel that I’m part of the decision-making. Like the TIL [tumor-infiltrating lymphocyte] therapy, we did have a pamphlet for that, and I read through what the situation was with that. We had a couple of options before going into this clinical trial, one of them, embolization, which we’d done, and then TIL. And the doctor explained what the tools in the tool belt were to help, to a reference earlier on. I felt part of the decision-making and confident about the treatment options. I think clinical trials are very good for patients. As Katie explained earlier, the initial treatment option that we were offered right back when the cancer had metastasized wasn’t the best option. Clinical trials, if we could do something new that might have a huge impact on this type of cancer and prove successful for her, is very much something that I would advocate for.

I think this last treatment had the most disruption on Nick’s life of all of the treatments that I’ve had, because we bought a one-way ticket to Pittsburgh, Pennsylvania, at the beginning of September, and we didn’t know when we were coming home. We spent the whole summer, we’d go on walks with our dog every day, and we would talk about, “What does that look like for you, what does that look like for me?” There were a lot of logistics. We found an Airbnb, and Nick stayed there. We had a friend of a friend who lived in town, who lent him a monitor so he was able to set up and work, so that it wouldn’t disrupt his work. We found a chef who would deliver about four or five meals a week, so that he could pop those in the oven and not have to cook but eat a healthier meal than eating out every meal, so that he could get to the hospital every night and visit me before visiting hours ended. That trip was as much of an impact on me as it was on him, and he has always been so supportive and takes it as it comes and never complains.

As a caregiver, if I can avoid FMLA [taking unpaid leave through the Family and Medical Leave Act], that’s the biggest success, to be able to continue my life while supporting Katie in Pittsburgh. That was starting work at 10 am for the times that we were here, working through to 6:30 pm, chucking food into the oven, and then straight to the hospital after I’d scarfed it down, basically. Whatever I could do to try to live a normal life for myself and for her, allows me to be the best caregiver I can be for her, too.

That’s incredible, Nick. It sounds like you’re such an amazing support for Katie.

A Caregiver’s Perspective on Treatment Success

Ivy and Katie, do you feel supported during your treatment by your medical team, your loved ones? You’ve already answered the question, that you both have amazing support networks. But tell us more about whether you feel supported by the community around you?

Yes, I really do feel supported. My oncologist and her staff are absolutely fantastic and if I have any questions, I know exactly how to reach out and get answers. I have a great group of friends here in my community who, along with me, have learned a lot about lung cancer over the past seven years, including the fact that anyone can get lung cancer, you just need to have lungs, which none of us knew before I was diagnosed.

I would say that I feel very supported by pretty much everyone in my life, and I am very grateful for that. Like Katie said before, I too feel that having cancer has changed my life. I also focus more on the present and try not to sweat the little things. It’s even changed my whole career focus because I’m a full-time patient advocate now, and I help others. It really has changed my life in many ways, and as a result of having had good support myself, I feel that I can support other people and help advocate for them as well.

Both of your stories are so moving, I have to say. Nick, you’ve been waiting patiently, thank you. Let’s turn our attention now to you as a caregiver. Again, thank you so much for joining us today and for being so supportive of Katie. How much of an effect did you have on treatment decision-making through this whole process?

Thanks for inviting me to speak today and to represent caregivers and to share our story and my story. Treatment diagnosis, I think Katie explained a little bit about it. It happened quickly when it spread to the brain. I was at work when she had a lot of the calls with the doctors and the results were shared and pieces like that. We knew that there were problems going on, so I was relieved that we’d found what the situation was. We had a lot of trust in the oncologist as well. I think building rapport is very important and we had that trust in him, Dr. Gonzalez. It really helped when he said, “Hey, this is what we’re going to be doing and why we’re going to be doing it, and we need to move quickly to do this.” For me, I felt at ease, that, OK, there’s a brain tumor, but here’s the next step with that.

Also, we’re very lucky to have Katie’s dad, who is a doctor. She refers to him as her agent in this as well. He’s always a good person to reference to and see how he is responding and reacting to what we’re doing. I can tell if he’s looking for different options, whether he’s worried about it as well. I feel if he’s like, “Yes, that’s fine, we’re going to do this,” then obviously that reassures me, and then I can focus on supporting Katie, too.

Do you discuss your concerns or beliefs with Katie and the medical team?

When the question comes, “Are there any questions?” I feel like it’s always open for me to chip in, and if it’s not open, I just chip in. I don’t think it’s often asked specifically to the caregiver, or in my experience, a lot of the time not. It’s normally to the patient, what are the patient’s questions, and the caregiver has to take that backseat while the patient goes through a lot of personal things that are going on with them. It’s very much related to the patient. But I do have a lot of questions, I have an analytical mind. I think what Ivy said is true, sometimes there can be a lot of information. Even as a caregiver, and I like to think I’m very detailed, I miss things as well, so it’s great to have that support. We both talk about what happens after meetings as well.

Do you feel like you have enough support as a caregiver, and as a medical field, do you think we could do better in supporting caregivers?

I don’t feel that supported by the medical field, to be honest. There’s a charitable organization, First Descents, that has helped support caregivers who are part of that charity. Getting people outdoors and living in the outdoors is very much a part of what they do. They had a caregiver “Rock program,” they called it, where we went rock climbing with 16 other caregivers from multiple different cancer diagnoses and treatments and where their partners were. For caregivers, that was a very big resource. But I don’t think, in the medical field, I’ve ever had anyone say, “How are you really doing; what resources can we offer to you?” Even when we recently had TIL [tumor-infiltrating lymphocyte] treatment, there wasn’t too much of a focus on the caregiver. I think that’s something that needs to be developed because we do have an impact on helping the patient, and we’re going through a lot at the same time. Helping us to be in a better situation to help the patient really helps.

I always go back to Kate’s diagnosis for brain cancer when it metastasized, and I was telling her, “Oh, you’re probably just dehydrated.” I didn’t think there could be other scenarios going on and feel quite guilty about that. Perhaps if I was educated more, it would have been like, “Well, maybe we should check in with your doctor.” We should report this to your doctor earlier than having to wait for the week after, and then go do the scan and then the doctor says, “Actually, there could be an issue here.” I think there’s a lot of room to help caregivers to be a better support function to patients. I try my best now to advocate after we just had TIL and say, “Maybe you should report that to your doctor. Have you told your doctor about that?” I think stating those expectations and talking openly with a caregiver very much benefits us and also makes us feel heard and valued at the same time.

Thanks so much for sharing that, being so open about that. I think what resonates here is that number one, we do need to do better in supporting caregivers and there needs to be more resources. There is, I think, more interest in that in the field, which is important. Even now, there are data coming out during COVID-19 [coronavirus disease 2019], that there’s a lot of caregiver burnout, caregiver fatigue, and not enough resources. I do think you highlight something that’s really important. The other thing you highlighted is that we need to be better about educating not just patients, but their caregivers, about what kind of things to look out for, and how to best help patients. Thank you for sharing that with us.

Feeling Supported During the Diagnosis and Treatment of Brain Metastases

Tell us, what effect did treatment have on your quality of life and how important is quality of life in all of this?

My quality of life, other than the first three months post-diagnosis when I needed to wear a neck brace, has been fantastic, to tell you the truth. I feel good, I have minimal side effects, I have lots of energy. I’m able to do whatever I want. People who don’t know me would have no idea that I’m living with stage IV lung cancer, seriously. I have no issues with my quality of life. Even when I had surgery in 2020, I was able to bounce back from that really well. I continue to work out on a daily basis, and I really am living very well despite the cancer.

That’s amazing. It also speaks to what an amazing person you are. Katie, how about you?

The same. I honestly think my quality of life has improved so much compared to pre-cancer. I’m a happier person, I think I’m a kinder person. It opened my eyes to how lucky I am, so I appreciate that. One of the lasting side effects of one of my treatments is that I struggle to breathe when I am deep belly laughing, which is one of my favorite things in life, because when you’re really deep belly laughing, you know life is good. That happens with us on a daily basis because Nick is funny, and our dog is hysterical. At least once a day I’m laughing so hard that I can’t breathe, and yes, it’s a side effect from treatment, but it makes me live in that moment. It makes me realize you are lucky to be experiencing this joy in this moment. I always say I wouldn’t go back and change my diagnosis. It’s made me live life so much richer than I was before. I treat my body better, I treat others better, we soak up every day, and we know how lucky we are that we get to be here.

That’s incredible. Dr. Gondi can also speak to this, but I’ve had several patients who have told me that a cancer diagnosis was a blessing to them because it changed their life in multiple positive ways. I don’t know, Dr. Gondi, if you wanted to speak to that, too.

I wish all Zoom calls had a reference to Seinfeld and Transformers. But your stories, honestly, they touch all of us. It touches anybody who is watching this and listening to this. It gives everybody hope. I say that oftentimes with my patients, and ironically with my kids. Memories and milestones, that’s what life is all about, and sometimes a cancer diagnosis gives us an unfortunate reminder of that. But I’m glad you are doing well, and I’m glad you are reaching those memories and milestones.

Effect of Brain Metastasis Treatment on Quality of Life

Tell us, how do you define treatment success?

For me, at the very beginning of my treatment, I was too nervous to look too far toward the future and plan too many things. But when I was diagnosed, since my boys were young, treatment success to me meant being around in order to raise them. The fact that my older son is a sophomore in college and my younger son is a senior in high school and applying to college right now, to me, is an incredible measure of success because they were 10 and 13 years old when I was diagnosed. I didn’t even know if I would be around to see them start high school, let alone finish high school and start enrolling in college. So to me, treatment success is making certain milestones in my family’s life. Next year, my husband and I will celebrate our 25th anniversary. I never expected to see that either. It’s those milestones that make it all worthwhile and are important to me.

Oh, that’s amazing. I’m tearing up just hearing it. Katie, how about you? How do you define treatment success and what aspect is most important to you?

It’s very similar to what Ivy just said. We haven’t been able to start a family, and my goal in life is to be the fun aunt, and I think I’m succeeding wildly at that. We’ve got four nephews now and two nieces, and my life goal, what I envision, and what I visualize is celebrating drinking a first beer with them when they turn 21 and dancing at their weddings. In the day-to-day now, it’s being able to spend time with them, obviously not this year, but to be there for them, to do sleepovers, and to just be part of their lives. My nephew had his 12-year-old physical yesterday, and the doctor asked him, “Who do you talk to when you’re down?” My sister said she was all ready for him to say, “My mom,” and he said, “My aunt.” So, for me, it’s being a part of their lives.

For me and Nick, it’s making plans, still being able to travel, really living our best lives, and taking advantage of the fact that we don’t have kids and that we can take vacations. Nick is from England, so we go back, we travel to Europe frequently, of course, not this year because of the pandemic. All along treatment success has been buying me time, and now that I’m farther away from my initial diagnosis, it’s making sure that I can still do the things that I love. The TIL [tumor-infiltrating lymphocyte] treatment this year was really challenging, but there was always a light at the end of the tunnel. I always knew it was going to be tough, but it’s 17 days in the hospital, then you go home, you get stronger, and then you can live your life again. As long as I have something to look forward to, there’s something on the horizon, and I get to spend time with people I love, then that’s when I feel like we’re succeeding.

It sounds like both of you are lucky enough to have had that, where the treatment has allowed you to live your lives and be there for the milestones.

Individual Assessment of Treatment Success With Brain Metastases

Another question for Ivy and Katie, what was your biggest concern and biggest fears when the treatment goals and options were being presented to you?

I think I had two main concerns. The first one was how well this medication that I was taking—I was thrilled to find out that I was going to be taking a targeted therapy medication, meaning a pill once a day as opposed to traditional chemotherapy or radiation. It just seemed so much easier. But my initial concern was how long was this going to work, if it worked for me at all? I was very worried about that. I was 47 years old when I was diagnosed, my husband and I had two boys, they were 10 and 13 years old at the time. I was a stay-at-home mom, so I did everything. I drove them everywhere, to school, to extracurricular activities, ran our household, and I was worried. Targeted therapy on average, I was hearing, could work for maybe a year. I was very worried about what would happen next and whether there would be another option for me after the one that I started on. I was also worried about the side effects and the impact of treatment on my daily life and my ability to care for my family.

I was fortunate when it came to side effects of the targeted therapy. Other than some mild issues, I didn’t really have anything happen. But that initial pain that I had in my neck when I was first diagnosed ended up being the biggest thing that my doctor was worried about. It was a large tumor high up on my cervical spine on my neck, and I visited a neurosurgeon, in addition to my thoracic oncologist and the radiation oncologist, on my first work-up appointment and there was some discussion about whether I might need to have surgery on my neck prior to starting the targeted therapy treatment. Again, the decision was made to start the targeted therapy treatment, but I ended up wearing, on the strong recommendation of the neurosurgeon, a neck brace for the first three months of my treatment, and having to frequently come back and have CT [computerized tomography] scans of my neck to make sure that my spinal column was no longer in danger of collapse because they were very worried about that.

That made it difficult for me to do a lot of things. I couldn’t drive, it made it difficult for me to do things in the home like laundry, cooking, etcetera. I immediately had to tell everyone that I had stage IV lung cancer, which was hard to do because people wanted to know why I was wearing a neck brace and they never expected that would be the answer. It brought my diagnosis really out to the public, and I felt myself constantly needing to explain what was going on to people, which was quite hard.

I would imagine how hard that was. Katie, what about you? What was your biggest concern and fear when treatment options and goals were presented to you?

Is this specific to the brain metastases or in general? I think this whole time I’ve always said I’m just along for the ride. For me, I’ve been lucky that I’ve had breaks in treatment, and I recognize that a lot of patients with cancer are in this marathon fight where their body is constantly being beaten down. I was coming off of a long break from treatment. For me, I was getting used to the comfort of pretending like life was normal, so I was a bit irritated and thinking, “I don’t have time for this.” I was lucky. Honestly, I bounced back from Gamma Knife radiosurgery better than I did any other therapy or treatment I’ve ever had. So while it was not fun having four screws drilled into my skull, wearing headgear, and looking like a Transformer, the actual procedure was 17 minutes. The pre-scan was longer than the actual treatment itself.

One of the things I did was invited all my friends and family to send me a song that reminded them of our relationship, or a motivational song, and the night before the procedure, my dad and I sat up, and I made this playlist and we listened to music. I got through three songs. I was a little annoyed, I had more to play. But it was quick. Then that night we ordered pizza, and I was sitting at the kitchen table eating with my two caregivers, my husband and my dad. I had a banging headache the next day, but it was a quick recovery, and I felt very lucky in that sense, that we were able to address the issue, and I was able to then move forward and get back to my kind of normal life that I had been living.

Personal Concerns With Treatment Options for Brain Metastases

At what point do we talk to patients about clinical trial enrollment? Please talk a little bit more about what are the risks and benefits of participating in clinical trials.

Clinical trial enrolment is crucial for many reasons. One important reason is it is shown that patients who enter clinical trials generally do better, maybe because they get much more attention, closer follow-up, and care. It’s not clear, but it is shown that they do better. Number 2, unfortunately, there are still too many questions that we have not answered, and to be able to advise a patient as to which treatment is superior and in what circumstance, that requires a clinical trial. It’s very important to have those trials available for patients.

Number 3, in terms of patients accepting a clinical trial, the overwhelming majority of patients will agree to enter a trial. The problem is when we present a patient with two options that are so different one from the other, they may not accept having a computer decide which way to go. As an example, we had a clinical trial comparing surgery with radiosurgery for brain metastasis because we wanted to show which patients will do better, depending on the size, etcetera. Well, half of the patients refused to enter the trial because it was comparing an invasive procedure with a noninvasive procedure. It’s very important for us, when we design a trial, to find equipoise, to find situations that are fairly similar, so that it’s not too hard on the patient to make the decision.

All patients, I believe, should have an opportunity for clinical trials, whether they have brain metastases or not, patients with any type of cancer. That’s good not just for that patient, but it’s good for the community of oncology and the future patients who come through our doors. But in the area of brain metastases, there are so many questions that remain unanswered. When we think about clinical trials—for instance, systemic therapy trials for patients with brain metastases—where we run into challenges oftentimes is that we’ve treated a lesion with radiotherapy and really don’t have any other options from a radiotherapy perspective because of the risk of causing harm. That’s where there’s tremendous opportunity to use drug therapy in those situations. But even preceding that, it becomes important to evaluate those drug therapy scenarios in a situation very similar to Ivy’s, where we have some time to watch these lesions and see how the systemic therapy works. In Ivy’s case, it was a remarkable success and that’s fantastic. In other cases, it may not be, but that’s OK because we can follow it, we can catch them early, before they cause symptoms. I do think, from a systemic therapy perspective, as a radiation oncologist who manages these patients, it’s always something that I’m considering. Do I need to treat right now, and if I don’t, is there a systemic therapy off-trial that’s available or on-trial that allows us to help this patient delay time to radiotherapy and perhaps help the next patient coming through the door?

From a radiotherapy trial perspective, we’re doing a lot of trials in this area to continue to improve our technology and our ability to safely treat patients using these modalities that I spoke about earlier. One of the unique aspects of the radiotherapy trials that we’ve done in the brain metastases sphere, is that, thanks to our patients and their caregivers, they have been some of the fastest accruing clinical trials I’ve ever been a part of, and that speaks to our patient population—that they’re so interested in trying to help us move the field forward and take care of patients.

I want to add to that point. It’s incredibly generous of patients like Ivy and Katie to participate in clinical trials. It’s inspiring and heroic because you’re often first getting to trials where you don’t know that there’s going to be a benefit for you. But you’re doing this to help others and that’s moving to see patients who are so generous with that. What are the benefits? You have access to potentially novel therapy that can help you. There are risks because it is a novel therapy, so we don’t know what the side effects are. It’s incredibly important for the field and for other patients and we thank you and we’re grateful to you, Katie and Ivy, and other patients, that you’re participating in these trials.

I can speak a little bit more to some of the systemic therapy trials. Dr. Ahluwalia already mentioned some of the targeted therapies that people are looking at. Now there are novel targets that people are discovering, particularly even in patients with brain metastases. There are a number of targeted therapies that are showing great promise in different histologies. For example, in breast cancer, tucatinib is a HER2 [human epidermal growth factor receptor 2] agent that shows activity in brain metastases, and then in lung cancer, we’re seeing promising results with EGFR inhibitors, with RET inhibitors such as selpercatinib and pralsetinib, with MET inhibitors such as capmatinib, and now there are KRAS inhibitors that are being investigated in clinical trials. We also have a genomically guided brain metastases trial that’s national right now, that’s open at more than 300 hospitals throughout the United States, and we have three drug arms to that study. We have a PI3 kinase inhibitor arm, we have an NTRK arm, and we have a CDK inhibitor arm, with the goal to add more arms in the coming months and years. With that trial, we’re genetically screening tumor samples from the brain and from extracranial sites that were taken out as part of clinical care, and then if a patient has that specific mutation, they receive that particular inhibitor.

We’re trying to get it open at as many sites, particularly even out in the community too, so that other patients can have access to it. There are a number of current clinical trials, and we hope that patients will have access to those trials.

Importance of Clinical Trial Enrollment for Patients With Brain Metastases

What factors do you consider when weighing efficacy vs physical and cognitive effects of treatments?

 The whole issue of cognitive impairment is a critical one, and it has become an issue when patients receive whole-brain radiation therapy, something our radiation oncologist will expand on. But because the whole-brain radiation concept has been associated with diminished cognition, diminished memory and executive functioning, most specialists try to avoid whole-brain radiation. Therefore, we go back to the focal therapy, such as surgery plus radiation or radiation alone in a focal way, like stereotactic radiosurgery. When you do that, then it’s very unlikely that the patient will suffer from cognitive deficits because of the treatment.

This is now a question for Vinai. You alluded to it a little with the memantine. But tell us a little more about how you weigh patient-reported outcomes with potential treatments. Why don’t you tell us about that?

It’s an area of my research, as you guys know, and something we really try to focus on is how we can optimize that with the radiotherapy approach. There’s no blood-brain barrier for radiotherapy, so that’s helpful. We can treat the lesions in the brain with over 90% control. But there is a recognition of whether radiotherapy should be utilized in a situation. If you have a patient who is going to be on a systemic therapy and has the capacity to offer some activity in the brain, similar to what happened with Ivy Elkins’ situation, then probably the best thing—from a patient-reported-outcomes cognitive perspective—if they’re having no symptoms and they’re small, is to do nothing. From a radiotherapy perspective, it’s better to just follow and see how things go, recognizing that you can keep that tool in your back pocket for some time down the road.

However, there are scenarios, and unfortunately, the majority of patients with brain metastases just don’t have systemic therapy options that do have activity or compelling activity in the brain. If they happen to have lesions in parts of the brain where you get a little question, you wonder: If there’s any more growth, there could be some symptoms that develop. In those scenarios, we weigh the two radiotherapy approaches that work effectively—radiosurgery, but also the whole-brain radiotherapy. We ran a number of clinical trials. We talked about this drug memantine. Research that was published a few years ago showed that we can effectively prevent cognitive toxicity from whole-brain radiotherapy. But even more recently, when we used hippocampal avoidance using IMRT [intensity-modulated radiation therapy], we showed that we can offer even more cognitive protection. Of those results, most important was that we were able to show that patient-reported outcomes were better when they were treated with hippocampal avoidance. It speaks to the ability to control lesions in the brain and the associated symptoms as well as preventing some of those cognitive outcomes.

In my clinic, I’m fortunate to have all these options available to patients, and I go through each one individually. It really depends on the type of cancer. If it’s Ivy’s situation, where she has a systemic therapy that’s very effective, I say, “Hey, looks great. I’ll see you in a couple of months. I think we’ll just watch it.” If it’s Katie Doble’s unfortunate situation, where she had something in a very sensitive area, in the pons, and causing symptoms, we need to act quickly so we can reverse these symptoms. Because there’s only one lesion, we focally treat it and watch carefully.

There are certain scenarios where patients come in with what I call brain-dominant disease. Everything is controlled in the body systemically, but they keep popping up with new lesions in the brain, and we’re chasing our tails a little. To some extent, it speaks to the importance of intracranial control. In those situations, we then think about optimizing that, maybe using hippocampal avoidant whole-brain radiation in those scenarios.

Everybody is different, and every patient is different. One of the unique things about brain metastases, unlike perhaps primary brain tumors, is there are so many histologies that can feed into this machination of brain metastases development. It becomes interesting, it becomes fascinating, but it becomes personalized. We take each patient individually and weigh all those factors.

 The whole concept of “the expert decides, and that’s the end of the story” is old news. We are treating a patient, we are treating a family, and those treatments have to be done in concert with their understanding, with their preference to the extent that they’re able to make the decision. Sometimes they tell us, “Well, you’re the expert, you tell us what to do.” But in reality, most patients and caregivers are quite sophisticated and have done a lot of reading, on Google or otherwise, and they come prepared with excellent and intelligent questions. Our role is to provide the information as we know it. Sometimes we don’t have all the answers, and that takes us into the concept of clinical trial, which I know is very much on your mind and on patients’ minds. We don’t always have the answer, but we share what we know with the patient and come to a decision collectively.

I want to bring up one concept that is beginning to be applied more widely in the United States, and that is the concept of the brain metastasis clinic. Dr Brastianos, our leader today, is very familiar with this concept. It’s worthwhile to share the idea with patients and caregivers. It’s a patient-focused clinic where the patient meets all the specialists who will potentially be involved in their care and their treatment. That includes a medical oncologist, the neuro-oncologist, the neurosurgeon, the radiation oncologist and the neuro-radiologist, because the brain metastasis are usually diagnosed with imaging, with an MRI scan. We need the input of the neuro-radiologist as well to define what is a tumor, what is not a tumor, what may be a scar and what may be swelling. The whole team gets together in one location, where the patient is, and that is the whole idea behind a brain metastasis clinic.

Factors Considered When Selecting Treatment for Brain Metastases

Dr. Ahluwalia, tell us broadly about systemic therapies. I know we can write an entire textbook on this, but tell us about systemic therapies for patients with brain metastases.

Sure. As I’ve mentioned, traditionally we use cytotoxic chemotherapies. These would be like DNA-damaging agents that we would give to patients, and they had limited blood-brain barrier penetration. The benefits of these therapies were 5% or less in most patients, and there were sizable toxicities that were associated with these agents. But in the last 10, maybe 15 years, we have identified genetic mutations that can be driving the cancer in patients’ cases. As Ivy Elkins alluded to, she had an 

 lung cancer drove the initial drug development in solid tumors, especially with brain metastases, where we had therapies working in the brain—first-generation drugs like erlotinib and gefitinib—and then second- and third-generation drugs like afatinib, as was mentioned in her case. Now we have osimertinib, which has even better blood-brain barrier penetration. These precision medicine approaches or targeted therapy approaches are also getting better.

I’ll use a couple of examples to highlight this. 

 is a mutation that occurs in those who have lung cancer, in around 10% to 15% of the Caucasian population and up to 50% of the Asian American population. The first-generation inhibitors, drugs like erlotinib and gefitinib, had good efficacy, but the second-generation drugs like afatinib, and now third-generation drugs like osimertinib, have even better efficacy. They work in around 70% of patients where the lesions can decrease or shrink in size when we treat them.

Another alteration that we find in lung cancer is ALK, and there the first-generation drug was crizotinib, and the benefit was around 20% to 30%. In 20% to 30% of patients, the lesions shrank when we gave these drugs. But now we have second- and third-generation drugs like alectinib, lorlatinib, brigatinib, and ceritinib, and the benefit with these drugs, because they’re better blood-brain barrier penetration compared with the first-generation drugs, is 50% to 70%. About five or seven of 10 patients we treat will have shrinkage of lesions or their brain metastases. So not only are there precision medicine–based approaches, but those approaches are getting better with time, because the newer drugs are more precise to deliver or act on the brain metastases and have better outcomes for the patients.

The next aspect, which I had alluded to before—it has been really exciting for me as an oncologist—is the use of these immunotherapies. They have really changed the landscape of lung cancer, melanoma, types of breast cancer and head and neck cancer, and they are undergoing evaluation in a number of other cancers as well. We initially used to think that brain was an immunotherapy site, that the immunotherapies wouldn’t work in the brain. But now we know that these immunotherapies can have benefit even in the brain, independent of the benefit in the body. In Katie Culos’s case, she is being treated with TILs [tumor infiltrating lymphocytes] and IL-2s. Ten years back, we wouldn’t have thought that this was possible. Now we know that these approaches—which target the immune component of patients, because we actually boost patients’ immune system to fight the cancer—can work extremely well in brain metastases. It’s very heartening as a health care provider but even more important for patients and their caregivers.

Thank you so much. That was a great summary, Dr. Ahluwalia. I just want to emphasize the point that Dr. Ahluwalia made, that there is a lot of hope now for patients with brain metastases because there are new drugs constantly being developed and new drugs showing efficacy. Granted, we still have a long way to go because not every patient will respond, which highlights why we need to do more work in this area. But there’s a lot of hope for better treatments coming for patients.

Systemic Therapies Used for Cancer That Has Spread to the Brain

Let’s talk about treatment options. I want to highlight how important multidisciplinary care is for the management of these patients.

The overarching points related to treating brain metastases are effectiveness and quality of life. We could do things like give very high dose of radiation that may be effective but could harm the patient. First and foremost in our decision-making is how can we maximize the effectiveness and minimize the side effects. To give you a specific example, when you get a large brain metastasis—by large, I mean over an inch, over 3 cm—although radiation could help, it may not be as effective as having the tumor removed and then radiation provided. This way, you minimize the side effects and you increase the effectiveness of the therapy.

Talk to us about the radiation, the radiosurgery options for patients, and tell us a little about the modalities.

From a focal therapy, this is a general term used when we apply very localized therapy—in particular, surgery or stereotactic radiosurgery [SRS]. The benefit of SRS is that it is noninvasive. That’s a great advantage and benefit for patients because we are not admitting them to the hospital. We do the procedure as an outpatient setup, and the patient is home the same day. The question is when is radiosurgery preferable to surgery, and when is surgery preferable to radiosurgery? That goes back to the concept of effectiveness and side effects. The larger the tumor, the less effective is SRS. You have to balance the size or the volume of the metastasis and the number of metastases because some patients will have more than one metastasis.

The larger the tumor, the better it is to apply surgery first and then radiation, most likely radiosurgery. If the tumors are small—and by 

, I mean less than 1 inch, less than 2½ cm in diameter—then radiosurgery becomes an excellent option with high rate of local control, meaning the tumor would remain without growth or even shrink or sometimes disappear. That’s the goal of the treatment: to be effective in stopping the tumor from growing and not causing damage to the surrounding brain.

Radiotherapy is remarkably effective for lesions in the brain. One of the things that has been fun to be a part of in the last 10 years is we’ve made a number of innovations in the delivery of radiotherapy to maintain that effectiveness but also to do it more safely for our patients. In general, we break it into two broad categories when we’re deliberating therapies: the delivery of focal radiotherapy to gross macrometastatic disease, meaning lesions that we can visualize on an MRI. Keep in mind, it takes almost a billion cells for a tumor to show up on an MRI. For it to actually be there means there’s a lot of tumor cancer cells in that focus.

Then there’s the micro metastatic disease, meaning it’s not visible on the MRI. The fact is that—to Ivy Elkins’ point, or maybe her radiation oncologist’s point—the brain is an organ, so it’s possible for cells to spread elsewhere in the brain. Radiosurgery, the delivery of a high-dose radiation to a focal lesion, treats gross macrometastatic disease. It treats lesions that we can see on an MRI. It doesn’t treat micrometastatic disease, and as a result, it becomes important to follow that brain with MRI surveillance, typically every couple of months after treatment.

One of the great innovations we’ve had in the last five to 10 years is our technology for radiosurgery—a couple of people have mentioned gamma knife radiosurgery. There are a number of modalities for radiosurgery that are widely available and are allowing us to treat more and more lesions safely in a single treatment, which becomes very convenient and also easier for patients undergoing that procedure.

The second option that we think about is something that Ivy mentioned, which is whole-brain radiotherapy, where we’re treating what we see and what we cannot see. We’ve come a long way with whole-brain radiotherapy in the last five years, developing techniques that are sparing the memory zones in the brain, called the hippocampi, and providing certain pharmacological neuroprotectants in the use of a drug—called memantine, or Namenda—that allows us to treat macrometastatic and micrometastatic diseases effectively and safely without some of the cognitive issues that we’ve seen with conventional whole-brain radiotherapy.

Both of those strategies, from a radiotherapy perspective, are available. They’re on the table every time a patient comes in with brain metastases. It’s complementing it in a multidisciplinary manner with all the other therapies that are available, trying to discuss the pluses and minuses and framing it within the context of the goals of care for that particular patient.

Role of Radiotherapy and Radiosurgery for Brain Metastases

How do you discuss these goals with patients and their caregivers, and what challenges do you have when you’re presenting these issues to patients and their caregivers?

Patients are not experts in the field, so our job is to explain the options that are available to them. Fortunately, there are many options available to patients when they are diagnosed or found to have brain metastasis. Our role is to provide the information in a clear way and to help them make a decision. Sometimes the decision is not obvious, so we need to lay out the pros and cons of each treatment.

 It’s an assessment of what their current situation is doing. Katie Doble’s is a good example of an unfortunate situation where she presented acutely symptomatic, with a lesion in a tough spot in the brain, the pons. What her team did is exactly what we do—get her in, get her treated, shrink it down, hopefully reverse the symptoms and maintain her quality of life as much as possible. To some extent,we take situations like Ivy Elkins’ situation, where she was not having any symptoms. In that case, we had room to think about alternative options to maintain her quality of life and use drug therapy. It’s understanding how patients are presenting, understanding the type of systemic cancer that they have, the type of systemic therapies available off trial and on trial, and then complementing all that information with what we know can work with focal therapies to the brain, including radiotherapeutic and surgical options.

Adding to that, it’s taking what the goals and the needs are for that particular patient, whether it’s quality of life or wanting to go on to a clinical trial. Putting out what we have to offer but also combining that with what the patient hopes for. Dr Ahluwalia, can you tell us a little more about some of the issues you confront when treating brain metastases—the challenges—and speak a little to the blood-brain barrier?

As we all know, treating brain metastases is a complex issue. As Dr Gondi alluded to, you have a two-compartment disease. When someone has brain metastases, often they’ll have a systemic cancer as well, which is ongoing. With the brain, we have an additional challenge that our traditional chemotherapies do not cross this lining around the brain called the blood-brain barrier. A lot of these patients, when they were treated with the traditional chemotherapies, had response rates of benefit in less than 5% of the cases. In the past, these patients were mostly handled by our neurosurgical colleagues or our radiation oncology colleagues, who either operated on these patients or delivered some form of radiation. It used to be whole-brain radiation and more focused forms of radiation, as has been described in the cases before.

In the last decade or so, a lot of drug development has taken place, and we are in the era of precision medicine. We’re in the era of immunotherapy. Really exciting times as physicians, but more important for patients, because a number of these therapies can penetrate the blood-brain barrier, especially the small-molecule tyrosine kinase inhibitors, as Ivy described to us that she was treated on. She had eight brain metastases, which very nicely disappeared. In her case, she got a complete response with use of these small-molecule tyrosine kinase inhibitors.

Overall, I would like to highlight that whenever someone has brain metastases, as Dr. Gondi alluded to, we need to take into account whether patients are symptomatic or asymptomatic and what the goals of care are—keep patients and their caregivers central to the discussion. Involve them in picking the choices they would like, depending on what their goals are for themselves, and then picking the therapy that will have the least toxicity profile and the best chances of outcome. But a lot of times this is managed in a multidisciplinary manner using tumor boards, where we all deliberate and say, “What’s the right choice for this patient?”—whether it’s just a targeted therapy by itself, a combination of a focused form of radiation with targeted therapy or using immunotherapies that are showing benefit in the brain. Every patient is unique, and individualized care in a multidisciplinary manner—keeping the patients and the caregivers central to the discussion—is the key way to move forward.

Discussing Goals of Treatment With Patients and Caregivers

 I think we’re going to talk now more about the treatment of brain metastases, and here we’re going to include Dr. Gondi, Dr. Sawaya and, of course, Dr. Ahluwalia in this discussion. What are the goals of treatment for brain metastases?

First, thank you to ABTA [American Brain Tumor Association] for asking me to be a part of this wonderful panel. If you don’t mind, I just want to speak to the wonderful patients and caregivers. Katie and Nick, you guys remind me of a patient I just saw not too long ago. What an amazing story you’ve had and I’m so happy for you guys and everything you’ve accomplished to this point. Keep everything up and I wish you guys all the best. Ivy, you remind me of a couple of patients I’ve seen in the last few months, and I’m so happy for you in so many ways; that you’re leading such a long-term survivorship role and a good quality of life. Keep it up. All of you are inspirations to all of us. Ralph, thanks for everything you’ve done. A couple of years ago, Ralph and I talked about how there is an absence, a void for brain metastases patients, for patient education and support groups, and I’m so glad that ABTA has filled that void so well. I’m glad to be a part of this with Dr. Brastianos and Dr. Ahluwalia.

So, the question of Dr. Brastianos. The goals of care are multi-fold. One of the challenges with brain metastases is they tend to happen in the brain. To Ralph’s wording, semantics, the computer of the brain, but the brain is also an enclosed space, so there’s not a lot of wiggle room. Unfortunately, some of our patients do come in with symptoms similar to what Katie, unfortunately, experienced. One of the goals of treatment for brain metastases is symptom improvement, neurologic symptom improvement. Then the second goal that we think about is controlling the brain so that future lesions do not arise, and/or if there are existing lesions that are not causing symptoms, they don’t grow to the point of causing symptoms. That process of maintaining patients in a symptom-free or minimal symptom state preserves their quality of life and, in certain cases, prolongs their timeline as cancer survivors. I see those as primary goals of care.

One of the amazing things that we have now in 2020, moving into 2021, is more tools, more technology, more bullets in the gun to fire at this thing, so we can achieve those goals of treatment, and we’ll talk about some of them. But I think Katie’s story and Ivy’s story reflects on how far we’ve come in the last 5 to 10 years in terms of how many different opportunities we have to achieve those goals.

When cancer travels to the brain, then it goes out of the field of the medical oncologist that is treating the patient with cancer in the first place. Our role, collectively, is to control or help control the metastasis when they go to the brain because that’s our expertise, whether we’re a neurosurgeon, neuro-oncologist or radiation oncologist specializing in controlling the brain metastasis. That’s our main and foremost goal, is to help the medical oncologist control the disease when it goes to the central nervous system.

Goals of Treatment for Cancer Which Has Spread to the Brain

Ivy and Katie, were your caregivers with you during these conversations and what role did they play?

Yes, my husband was with me throughout all the conversations that led up to my diagnosis and treatment. We were both so shocked and surprised. His role was to be there with me and to provide some support and help try to make sense of what was said. But we were both so shocked, I’m not sure who was supporting whom to tell you the truth.

But one thing that was very helpful and something that I always tell newly diagnosed patients when I speak to them now is that when you’re diagnosed with cancer there’s so much new terminology, new phrases, scans and treatments that are being talked about, that it’s really important to have someone with you, like my husband. Because I would find, after some of these appointments, we would go home and I remembered half of what I was told and he remembered about half what was said, and by putting it together, at least we had more information. It wasn’t because we weren’t paying enough attention, it was just so overwhelming. It was very helpful to have someone who was there going through everything with me.

Katie, tell us a little bit more about your experience, too.

For the experience with the brain tumor, Nick was with me at the doctor’s appointment when the brain MRI [magnetic resonance imaging] was ordered and he took me to that appointment, to that scan. Then the next day, I’ve been doing this long enough that I’ve figured out you can call and get the results instead of waiting for the results. So, I called my nurse. I have her number on speed dial. And she was hesitant. She said, “Something did show up and we need to have Dr. Gonzalez look at it and we’ll be back in touch.” So that was sort of this, “Oh crap, something’s wrong.”

Nick was at work and I was off that day and I remember calling my sister. I have two sisters. I called one of my sisters who was golfing, and she stepped aside, and we said a prayer together. I was just terrified. Then the next day I got a phone call from my oncologist himself, letting me know what was going on, and I was at work that day. I hung up the phone and my co-worker and I, we still are very close, and I just lost it. She was there with me and we left work and went and got a beer. My dad flew in, I think, the next day. We had a busy weekend planned. My sisters were both going out of town and we were watching all of the children — we have five nephews and a niece. My sister said, “We can cancel our trip, what do you need?” I said, “That’s the perfect distraction for us right now, is to have five kids.” My dad came out and stayed and helped us. For me, that’s always been what I need, is I just need to take my mind off things. Nick, of course, is always supportive. We hug every day, but I think that day and that weekend we hugged a lot. We were both scared for what was happening and the threat that was happening.

But for me, if I have a plan, that’s when I do better emotionally. The good thing about this diagnosis was it came with a plan. There wasn’t additional waiting of what’s next and what’s going to happen now. It was OK, a week from now we check into the hospital at 6 am and zap this thing and that’s what’s going to happen next. So just get through it.

Nick, thanks so much for supporting Katie. Katie, you’re very lucky to have Nick as your caregiver.

The Importance of a Support System During a Diagnosis of Brain Metastases

Let’s turn our attention now to Ivy and Katie again. Again, thank you so much for the time you’re taking to talk to us today and for telling us your story. Tell us a little bit more about your emotions when you were diagnosed with the brain metastases.

I was completely shocked when I was diagnosed with brain metastases because as I’ve mentioned, I didn’t have any symptoms. I didn’t have any idea that I had brain metastases. But even though I was already devastated to be diagnosed with stage 4 lung cancer, it even seemed worse to have it spread to my brain. You always, as a person just living in society with a non-medical background, you always hear, “Oh my gosh, the cancer went to so-and-so’s brain and that was it.” That’s the impression you have of brain metastases, or at least it was certainly the impression I had. I felt like that was the worst possible thing that could happen. That’s why it was very important when I spoke to a radiation oncologist and she told me, “The brain is an organ and can be treated like other organs can.” That settled some of my initial concerns. But I was very worried about how I didn’t have any symptoms initially, and how treatment might impact that. Would the treatment cause cognitive issues if I needed to have, say, whole-brain radiation? It was very, very concerning when I first found out about the metastasis.

Yeah, I’m sure. It’s incredibly scary. Katie, what about you? Tell us a little bit more about your experience.

 As I said earlier, all along I have had doctors telling me it doesn’t spread to the brain. For me it was a total shock as well and it was just another hit. In my whole cancer journey, what we’re trying to do is buy me time. Getting a hit like that when we had gotten the liver under control was devastating. It was shocking and I was terrified because the brain is controlling a lot of things going on, and because I was having the side effects, it was scary what was happening with my body. I remember sending out Mother’s Day cards and I had licked three envelopes and my tongue became numb and then it sort of crept up the side of my face. It was about 10 o’clock at night and I called my dad in Omaha, Nebraska, and I woke him up, and he kind of laughed at me. I think I’m having a George Costanza’s fiancée moment from 

 where she licks all the envelopes and dies. What’s happening to me? Again, even my dad was like, “Katie, it’s not in your brain.” I kept being told, “It’s not in your brain,” and “You’re fine, you’re fine.” It was such a shock, but the doctors were so quick in their actions. When my doctor called me to confirm it, he already had me scheduled for gamma knife surgery, and so there was relief. I think there was relief that there was an explanation for what was happening with my body. There was validation of, “You’re not crazy, something is wrong,” and then relief knowing that there was a plan in place already to take care of it and that it was effective. I had heard of gamma knife before. I knew that it was a highly effective treatment, so there was hope that this would take care of things and then we would move on like we always do.

Experiencing a Diagnosis of Brain Metastases

Now we’ll move on to the next segment. Let’s talk about the diagnosis of brain metastases. Dr. Ahluwalia, tell us about how brain metastases are usually diagnosed and what do you look for? We already heard a little bit from Katie and Ivy about their diagnosis. Dr. Ahluwalia, do you want to expand on that?

 Absolutely, and thanks to both Ivy and Katie for sharing their incredible journey, and thanks to Nick for being such a supportive caregiver. These are inspiring stories, and every time we take care of these patients, we are just in awe of how much they go through and how valiantly they encounter this disease. I always say to the patients that it’s a journey and that we all take together, right? We’re all in this as stakeholders and we all need to support the patient who is the center of the whole mission. Thank you for sharing your journeys, both of you. I’m so incredibly happy with you getting the outcomes you have been getting and best of luck to keep going strong.

With that, whenever we have patients who have lung cancer, and in Ivy’s case this was done, we do a screening MRI [magnetic resonance imaging] at diagnosis of a stage 4 lung cancer, and we like to do MRI unless it’s contraindicated, because we know MRIs are much more likely to pick out a small brain metastasis. As Ivy had mentioned, she had eight small metastases at diagnosis and she was asymptomatic. We all are humbled. We have seen a number of patients who are asymptomatic and have brain metastases which are small, and they’re picked up by MRI that may be missed by a CAT [computerized axial tomography] scan. Clearly, the morality of choice is an MRI whenever you need to screen for brain metastases.

Then we had worked with the American Cancer Society and we had put out a campaign, and kudos to Ralph and the ABTA [American Brain Tumor Association] for doing the survey, picking out these findings where, as Ralph outlined, as physicians and health care givers, we feel we are doing a good job informing our patients, but we are finding out from patients and caregivers that we can all do better. This is a nice wake-up call for us that we need to inform our patients in a better manner. We heard from both Ivy and Katie that it was discussed, but not to the degree that they would have liked. I clearly feel that we could all do better.

As a part of the campaign, we had brochures in our patient work rooms that informed patients of general symptoms to look for. Obviously, you can give a general overview and depending on where the brain metastases happens in the brain, they can lead to a neurological dysfunction the patient might have. Maintaining a high degree of awareness is helpful, especially in patients who may have a greater chance of developing a brain metastases — that’s stage 4 lung cancer, HER2-positive breast cancer, triple negative breast cancer, especially with stage 4 diseases in these — and then patients who have 

 mutations in their melanoma, which is 50% of patients with melanoma. Talking about awareness, talking about telling patients and their caregivers what to be on the lookout for, is always helpful. Then there’s always a suspicion so ordering a brain MRI sooner rather than later is helpful and at least ruling out if someone has a brain metastasis or not.

Great, thanks so much. Again, you highlight the importance of patients being aware of letting their physicians know if they’re having new neurologic symptoms.

The Diagnosis of Brain Metastases

That’s actually a very nice segue into the role that the American Brain Tumor Association [ABTA] is playing and the importance of the role because that is one of the important tasks that the ABTA is doing right now. That ties very nicely into the next segment. Ralph, let’s talk a little bit more about the recent initiative of ABTA, the surveys that ABTA has conducted. Tell us a little bit about the methodology, the surveys, and the overall findings.

Thank you, and Ivy, Katie, and Nick, thank you for sharing your journey. We learn so much because you are willing to be so honest, transparent and vulnerable in settings like these. It means a lot to the entire community, especially to the American Brain Tumor Association, just speaking directly from our organization. First, I want to thank 

® for the opportunity of the ABTA to be a part of this important educational program. The mission of the ABTA is to improve, to extend and ultimately save the lives of those diagnosed with a brain tumor, and we do it by funding brain tumor research. We especially fund early career investigators and we’re proud of that and the ongoing work that they do in their careers.

We serve brain tumor patients, both primary and secondary. Before we get into the survey results, let me answer, “Why did we do it?” Back in 2017, there was enough known; about 200,000 to 300,000 cases of brain metastases and a lot of emphasis and focus on the about 87,000 people a year that have a primary brain tumor. The initiative was launched in 2017 — and I really want to thank those that helped fund part of this work at least, Accuray, Agios, Bristol Myers Squibb, Brainlab, Genentech, Novocure —and then we worked with other patient advocacy organizations, and I think, Katie, you mentioned one of them, the Melanoma Research Foundation. We worked with LUNGevity, Melanoma Research Foundation, Kidney Cancer Association, Living Beyond Breast Cancer, Fight Colorectal Cancer and the Society for Neuro-Oncology [SNO]. Some were with us from the beginning and some are more recent partners, all playing a vital role.

I became CEO in 2018, and so we continued the focus on this important work of brain metastases because the great news is the oncology community is really extending lives of people diagnosed with breast and lung cancers, or melanoma — that is great news. While the challenge, as you know, is that there’s a greater risk of that primary cancer traveling to the brain. The brain, our complicated, vital organ, it’s our computer. We have got to find a way to work together with other organizations to inform and engage patients and caregivers and the physician community. Just a broad comment is that all physicians are brilliant and dedicated, but there’s a difference if you’re treated, in some cases, in a private setting versus an academic setting. We can touch on that more in a moment.

But I am proud of the survey results. We engaged, Penn, Schoen & Berland [PSB] out of Washington, DC. We had an amazing clinical advisory committee, including yourself and Dr Ahluwalia, thank you, and Joe Barnhardt Sloane, Dan Brad, there’s Mehta and patient advocate Robin Page. All were a very important part of our clinical advisory committee. We did the surveys. We had a clinical advisory committee, and between August and September we surveyed a few hundred patients with cancer. Working through our patient advocacy partners and SNO, we reached out by email and had them do an online survey of approximately 90 questions in each of the cohorts of the patients, caregivers and physicians. We redid our survey tool when we partnered with SNO so that we’d be particularly sensitive to the neuro-oncology community. I will say from what I remember, there were a higher propensity of neuro-oncologists to respond versus the entire spectrum of specialists. We had more men than women respond, but it was a broad spectrum of physicians, and as I mentioned, in private practice, larger practices, academia spread throughout the country. That physician survey happened in June 2019. We were pleased that we had such a wonderful response from patients like yourselves, caregivers, Nick — the role that you play is huge. It would be great if every patient had a caregiver who was so engaged, and quite frankly not all patients have someone as a caregiver that travels with them through their entire journey. We see that, we understand that, and we are here to play a role. As you said, Priscilla, the ABTA does have a plethora of patient services that either we directly deliver, or we refer to other organizations.

Ralph, we’re so grateful for the stuff that ABTA does for patients in the community. Can you tell us a little bit more about the survey results? Can you give us a sneak preview before they’re published?

We can. In fact, thank you for setting it up. We are about to publish, we hope, in Neuro-Oncology, a peer-reviewed journal, early next year. We have a phenomenal team. It’s amazing that so many of you have been willing to step up and give hours of your time to this effort. A little preview. One of the things that we learned, and it was touched on earlier, is that depending upon where your physician practices, some of the treatment options that you get are going to vary.

Let me just point out one and that’s in the area of neuroradio-oncology. We have found in our survey results that those who have brain metastases, if they are being treated in a private setting, they are more than likely to get whole-brain radiation as a recommendation, where if they go to an academic or larger setting, stereotactic radiosurgery [SRS], are more than likely to be offered. Dr Gondi can speak to the significant advances and the ability to treat numbers of regions and different locations and complexities that are available. Often, as our survey found, that can be offered to a patient when they’re treated at an academic setting or a setting where there are more resources, a larger team, and, quite frankly, more options.

One other thing that I just want to point out, that was touched on a little bit, that will come out more in our manuscript; physicians believe that they’re sharing important information about brain metastases, and they are, but it’s more of an overview. The patient experience, according to our survey, is they don’t get what their risk is for their type of cancer to spread to the brain. Patients and caregivers want physicians to be earlier in explaining the risk and then explaining the treatment options. I love the fact that Ivy and Katie were so open to clinical trials because that is another thing that we need to be advocates for, and that is for every patient to be given the option to explore clinical trials. Now, there are barriers. If you have brain metastases, unfortunately too many of you are excluded from trials, and we have to find ways to address that issue, and I assure you we will do that.

Just one final thing, Priscilla. In the survey findings, the role of the federal government was uniformly identified by physicians, caregivers and patients as needing to play the leading role in funding more brain tumor research in this area and really making sure that they’re a partner in breaking down the barriers for patients to enroll in clinical trials.

I think we can all agree here that it would be great if there was more funding available for patients, research, and clinical trials to help further the field.

Importance of the American Brain Tumor Association (ABTA)

 Ivy and Katie, do you remember your oncologist discussing the risk of brain metastases when you first received your cancer diagnosis?

 When I was diagnosed, I knew I had stage 4 lung cancer, and initially I had no idea that it could even spread to the brain. I had my PET [positron emission tomography] scan and some other scans done when I was told by my oncology nurse that I should also get a brain MRI [magnetic resonance imaging] to check on things. She told me that there were no indications that it had spread to my brain, but they like to do that for any new stage 4 diagnosis of lung cancer just to make sure. Of course, that made me incredibly nervous because I already found out that I had stage 4 lung cancer, which I didn’t even have any symptoms in my lungs, and now I started worrying about whether I was going to have anything in my brain as well.

When I went for my first appointment with my brand-new thoracic oncologist, who I love and I’ve been with for my entire seven years, that’s when I found out that I had the eight small brain metastases. I was really surprised and shocked, and that changed the discussion from whether I should start on the targeted therapy that they had planned to start me on for my EGFR [epidermal growth factor receptor] mutation, or whether I needed to take care of or treat the brain metastases first. I went that very same day to speak to radiation oncology in the hospital, and I still remember the radiation oncologist who I spoke with — because I was freaking out about having brain metastases — saying to me, “The brain is an organ like other organs and it can be treated like other organs.” That stuck in my mind and I’ve thought of that a number of times since.

At that point, since the targeted therapy, I went on a drug called afatinib; it had been recently FDA approved and no one knew whether it would penetrate the blood-brain barrier and have impact on the metastases in my brain. The radiation oncologist said to me, “We may need to consider brain radiation at some point in the future, possibly whole-brain radiation, because if there’s eight small metastases, there’s a good chance there are others that we haven’t been able to detect.” That obviously wasn’t something that I was happy to hear. I do remember asking about gamma knife surgery, but they thought that there were probably too many brain metastases to make that a possibility.

My oncologist conferred with the radiation oncologist, and together they decided to start me on the targeted therapy and see how I responded. I was very fortunate to have my brain metastases disappear. I almost couldn’t believe it. As a result, I haven’t had any forms of brain radiation.

Unfortunately, the experience you described as being shocked with the initial diagnosis of brain metastases is common in the United States. A lot of patients are not aware of brain metastases before they’re diagnosed. Katie, what about your experience? Do you remember your oncologist discussing the risk of brain metastases before you developed them?

 I never had a doctor discuss it with me. In fact, the ocular melanoma community is pretty small, and I remember meeting a woman at the Melanoma Research Foundation’s Wings of Hope for Melanoma Gala in Denver, Colorado, in 2017. She said she was also an ocular melanoma patient, and she told me that it had spread to her brain. I remember thinking, “I can’t unhear that. I don’t want to know.” When it happened to me, I had more than one doctor say, “That’s interesting, it doesn’t typically spread to the brain.” I remember thinking, “How can you say that when I know of another patient and I had heard of other patients who had had this experience?” I think in my case, there are so many unknowns in the ocular melanoma world, so it surprised me that these doctors were surprised. But my oncologist, who is treating me here in Denver, Colorado, is a cutaneous melanoma specialist, because there isn’t an ocular melanoma specialist here, and so he was a little more familiar with it. I’m so thankful that he, when I described my symptoms, said we’re going to do this brain MRI. But that was really the first that we had heard of this possibility in the whole experience.

One last question before we move on to the next segment. What types of educational materials did you receive related to brain metastases, and what information did you seek out on your own?

Honestly, I didn’t really receive any educational information, I don’t believe. It was all tied up in a very confusing time because I found out I had lung cancer, which I knew nothing about — and then I found out I had brain metastases, which I knew next to nothing about. There was just so much going on. I do remember once I started on my targeted therapy my oncologist said to me that she thought that this would work better. There were two choices of targeted therapy, but the other targeted therapy that was out there and FDA approved for people who had brain metastases.

I do remember going online. I do like to Google and it’s not always good for me. I Google way too much. I read stories about people who did have a targeted therapy medication for lung cancer penetrate the blood-brain barrier and have an impact on their brain, and I read stories where they didn’t. I read some articles about my targeted therapy in scientific journals about that possibility. I pretty much sat back and kept my fingers crossed until my first scan, my first MRI, just to see what would happen, because there really wasn’t anything else I could do at that point. I just remember hoping that this would take care of it and I wouldn’t need to do the radiation.

I don’t remember getting any specific information about it, and it honestly all happened very quickly. My cutaneous melanoma oncologist called me, and he said, “It’s confirmed and we’re going to have you do gamma knife, we’re scheduling you next week.” I didn’t even meet with the neurologist before I went in for the procedure. My dad, again, flew out so he could be there with us for the procedure. I’m sure that Nick, my dad, my sister and anyone else who knew me was Googling it, but I wasn’t. I just want a high level, what can I expect, but I don’t want to know the nitty-gritty details. But I didn’t get any, not that I recall, do you recall getting?

— specific information or pamphlets or anything like that given to us.

Understanding Your Risk for Brain Metastases

Thank you, first of all, for having us here. Ivy, thank you for sharing your story. It’s always inspiring for me to hear of other stage IV thrivers. Thank you. I am 38 years old, and when I was 31 years old, I was experiencing some issues with my vision. I called my ophthalmologist after a black line sort of danced across my windshield while I was driving one afternoon, and they had me come in the following morning. I went in, and they told me there was a bump on my retina and that it could potentially be a tear, which could be serious, and they wanted me to get into a retina specialist immediately. I went straight to a retina specialist, where I was diagnosed with ocular melanoma. I was by myself that day. I was totally blindsided—I have a lot of eye jokes if you want to hear them—and I didn’t know what to do. I called my sister, who is a nurse and lives in town, and she came to the doctor with me that afternoon, where we went through what this meant and what my options were.

I have always been in the camp of “I don’t want to know.” Some people like to google everything and know everything. I have not once googled ocular melanoma and what that means. But my sister did, and we learned it affects six in 1 million people and that the standard treatment of care is to have plaque therapy to the eyeball. We underwent the radiation to my eyeball shortly after my diagnosis. It was a weeklong radiation, and it left me 100% blind in my left eye. That was it: I became a cancer survivor. They biopsied my cells during the radiation procedure, and they told me that I had a less than 2% chance of metastatic disease. I thought, “I’m good; life goes on. I’m blind in one eye, with no depth perception, but I’m going to be fine.”

A few months later, I met this young man, and we quickly fell in love. A year later, I went in for a routine liver ultrasound, which was what they had suggested as follow-up care. I had had one in April that year that was totally clean. I went in, it was November 2014, and I got a call that afternoon from the oncologist herself telling me that I had 12 suspicious lesions on my liver, that it was likely that I had fallen into that 2% category and that it had metastasized. We had a liver biopsy. My dad flew out the next day and was there for my liver biopsy—my dad is an internist in Omaha, Nebraska—and it was confirmed that I had developed stage IV cancer.

My oncologist told me, “You’ll get started on Yervoy [ipilimumab], the only FDA-approved drug for your disease. We’ll get you started next week.” My dad said, “That’s not good enough. I want to know if clinical trial options are available.” That doctor replied, “That would be really expensive.” We left her office that day, and my dad was on the phone with every single doctor across America who would speak with him about my case. He presented my case to the tumor board of Nebraska, and he got in touch with some doctors at Memorial Sloan Kettering Cancer Center about a clinical trial there. I never talked to that doctor again. If she saw me today, she might think she saw a ghost. But I started in January 2015 at Sloan Kettering for my first clinical trial. Two days after my metastatic diagnosis, by the way, Nick proposed, and so we had that going on as well.

I had my first clinical trial in 2015, and by August of that year I was booted from that trial because of tumor growth, and I had my first liver embolization at that point. Actually, sorry, I had a second clinical trial at the University of Colorado here in Denver and was booted from that trial as well. I’m good at getting in and out of trials. So, that trial I was booted from. I did a liver embolization, which is a targeted therapy to the liver, and I’ve responded well to that. They treated only half my liver because they wanted to have a baseline to see how I would respond.

I went about six months in 2016 getting a break from treatment, which was glorious, and then in June 2016, there was additional growth. I entered my third clinical trial, and I was in that trial for about three months when there was growth again, and the doctor said, “We want you to go back and have the rest of your liver embolized because you’ve responded very well to that therapy.” I went back and I got the other half of my liver, had the embolization done, and then 2017 was great. We finally took our honeymoon—I had no treatment that year; it was a great year. And 2018 was going really well. I was living with stage IV cancer, but you never would have guessed it.

But midyear 2018, I started presenting with stroke-like symptoms. I remember one morning getting out of bed and feeling like a drunken sailor on a ship that was in the middle of a storm. Everything was moving. I was clipping door frames, trying to go up the stairs was a huge effort—I kept tripping. I knew something was wrong with me, but I didn’t know what was going on with me.

Nick and I carpool to work sometimes, and I was driving us into work and we got rear-ended. I remember thinking, “I can’t even get out of the car right now. I can’t deal with anything.” I thought I was just dehydrated. I had scans the following week, and I mentioned what was going on to my oncologist. He said, “We should get a brain MRI.” Sure enough, something showed up in the left pons—as if I know where that is—and then we found out that it was likely a brain tumor. It’s still unknown; they didn’t biopsy it. I underwent gamma knife the following week, and my brain has been stable since. I had been, as of earlier this year, doing great. I was stable nearly two years in my brain, I had been stable in my liver for about three and a half years.

But on brand with 2020, my scan showed massive growth in my tumors in my liver earlier this year. I ended up enrolling in my fourth clinical trial at the University of Pittsburgh Medical Center and that was TIL [tumor-infiltrating lymphocyte] therapy. I went to Pittsburgh; we went for the month of September and I was in the hospital most of the month. Got my free haircut, got my TIL, and got my IL-2. We just got off the phone with the doctors this morning before this call to get my updated results from my latest scan, and things are going well. The tumors are slightly shrinking, and so we’re pleased with the results. That is, in a nutshell, what we’ve been doing the last seven and a half years.

That’s an incredible story. Thank you for sharing that. I’m thrilled that things are going well with this trial.

Katie’s Journey With Stage IV Ocular Melanoma That Has Spread to the Brain

I want to turn to Ivy and Katie. A special thank-you to the two of you for sharing your deeply personal stories. For each of you, please share with us the journey from diagnosis that you have had with your cancer. Ivy, if you want to start, and then we’ll have Katie also share her journey.

Sure, thanks so much for having me here to talk about my journey. I was diagnosed at the end of 2013, pretty much seven years ago, with stage IV non–small cell lung cancer. It was a diagnosis for me that came out of the blue. I didn’t have any known risk factors. Prior to my diagnosis, for about six months, earlier in 2013, I had some problems with my right elbow. I couldn’t completely straighten it, it hurt a bit, and I also had some trouble with the left side of my neck. It was a little painful—not horrible pain, but it was bothering me.

I eventually ended up going to my primary care physician, whom I had been seeing for a long time. I otherwise was very healthy and active. He thought that since I was in my 40s, it was just an overuse injury—I was using my computer too much, maybe not bouncing back the way I would have when I was younger. He sent me to physical therapy, and for about six months, I did different physical therapy exercises, I visited an orthopedist and had cortisone shots in my elbow, I went to a rheumatologist, and no one could really figure out why my elbow wasn’t getting better. They thought it was a condition called tennis elbow, and it just wasn’t responding to any normal treatment. Ironically, my neck started feeling a lot better, but no one really knows why that was the case.

Eventually, one of the orthopedists—I had seen two at this point—did an MRI of my elbow and found that there was a mass that had eaten away some of the bone. He didn’t really know what it was either. He sent me to an orthopedic oncologist, who basically took one look at me and said, “You know, the way you present and the way you appear, I’m telling you that otherwise, if you presented differently, I would look to see if this was a metastasis from a different type of cancer. But I am 95% sure this is a benign large cell tumor. Let’s do a biopsy, just make sure. I’ll take it out, and you’ll be all set.”

I remember going into that biopsy worried about how long it would be, if I had to have surgery, before I could drive again. I had that biopsy and the results came back that they were malignant as opposed to benign, as they had expected. And I was told that it was adenocarcinoma, but I had no idea what that was. That’s when I found out that adenocarcinoma doesn’t originate in the bone; it came from somewhere else in my body. I remember asking my orthopedic oncologist where it could have come from, and he said adenocarcinoma could come from your lungs or from your breast. I was sure I had breast cancer initially.

To make a long story short, I had a full work-up at that point, a PET [positron emission tomography] scan that identified the source of the cancer as my lungs. It had spread to my bones, neck, elbow, pelvis, and ribs, and I had eight small lesions in my brain, which was also found through a brain MRI. A lot of cancer, no symptoms other than the bone pain in my elbow and neck, no neurological symptoms, no coughing, no wheezing, no shortness of breath, nothing like that. I ended up having my biopsy tissue tested, and found out that I had a specific mutation called 

 and was put on a targeted therapy for that, which I responded to extremely well. My brain metastases disappeared, my bone grew back in the areas where I had metastases, and my main lung tumor shrunk but didn’t disappear.

After three years on that targeted therapy, I had a little progression in my lung tumor. I had another biopsy and qualified for a new targeted therapy, which didn’t exist when I was first diagnosed, and I’m still on that to this day. My brain metastases never came back, and earlier this year I had surgery to remove my upper right lobe, because that was the area of my originating lung tumor, and it was the only area that still showed up as active cancer within my body. I had that removed, and I am considered NED, no evidence of disease. That’s my journey—probably not a short summary, but that’s my journey.

That’s incredible, Ivy. We’re keeping our fingers crossed that you’re going to continue to be NED. Wow, that’s incredible.

Ivy’s Journey With Stage IV Non–Small Cell Lung Cancer That Has Spread to the Brain

At what point do you discuss the potential for brain metastases with patients, given that we know that the incidence is rising and we know how common brain metastases are in certain histologies?

Great question. For someone with stage IV lung cancer, you have to talk about brain metastases often from the outset, because 20% or 25% of these patients may have brain metastases even at diagnosis, and NCCN [National Comprehensive Cancer Network] recommends an MRI screening for these patients. For example, we know patients with hormone-positive breast cancer have less likelihood of developing brain metastases. But those who have triple-negative disease or who have 

+ [human epidermal growth factor receptor 2-positive] disease may have a greater propensity. If someone has a stage IV breast cancer, their chances of having brain metastases is around 9% to 12% based on a recent review from Boston that looked at the SEER [Surveillance, Epidemiology, and End Result Program] data. It might be reasonable to alert such patients to be looking out for neurological symptoms they may encounter. If someone has brain metastases, we are able to find out sooner because we know we are able to manage those brain metastases, if someone has a limited number of brain metastases, better compared with someone who has a number of brain metastases.

The same goes for patients with advanced melanoma to a metastatic melanoma, where about 50% of those patients develop brain metastases too. It’s really important for patients to be aware that this is a possibility and that if they do develop neurological symptoms, they should let their physician know fairly early. At what point do you discuss clinical trial enrollment with patients?

As oncologists who are involved with clinical investigations, we know that trials are the way to move the field forward. We like to bring up trial discussion at the very onset if someone is diagnosed. We always try to look if there’s a clinical trial for such patients because a lot of times management of brain metastases is a multidisciplinary effort, and we want to make sure we are providing the best care to our patients. In the past, most of the clinical trials excluded patients with brain metastases. However, several of us who have been involved in the field and who have been leading in this aspect have worked hard to get trials that primarily focus on brain metastases. Every time someone has a brain metastases, we screen through a portfolio to see if there’s a clinical trial for those patients. We like to talk about it because if we do not have a trial and maybe you have a trial, we are always happy to refer, because these patients with brain metastases are those who have complex cancer, and we always feel a complex cancer should be managed at a tertiary care center, a place that has access to clinical trials while providing best possible care or maximum potential…for such patients.

I completely agree. And in the current era, there are more clinical trials for patients with brain metastases. As you said, in the past, there were very few. Encouraging patients to enroll in clinical trials when they’re feasible is a good idea. Final question for you, Dr. Ahluwalia, do you usually meet with patients and caregivers together to discuss these things? Who else in your office participates or manages these discussions?

We like to meet with the patient and the caregiver together, because when someone has a diagnosis of cancer, it becomes a family perspective. A patient, specifically when they have brain metastases, may have neurological symptoms, and at that time their needs substantially increase depending on how symptomatic they are. The caregiver’s role is of immense importance in such patients. We like to understand what the patient’s situation at home is and who is going to take care of them. We like to talk about potential risk for seizures and potential risk for falls. And we like to make sure that the patient and their family, which includes caregivers or friends who are going to be involved in the care of the patient, are actively involved in that discussion.

When we manage patients with brain metastases, we like to take care of such patients in a multidisciplinary manner. We like to talk to the neurosurgeons, our radiation oncology colleagues, medical neuro-oncology colleagues, to pick the best modality to give these patients. I would highlight the role of our nurses, who are going to be extremely important because they interact with these patients most of the time and they’re the first to take the phone call. They’re an important link in the chain of communication. We also like our patients to meet social workers. We like to even see if these patients are willing to undergo neurocognitive battery, so we need research nurses and coordinators for that aspect. There are a lot of people who are involved in the care of these patients.

Then we like to give them support group information, organizations like ABTA [American Brain Tumor Association], NBTS [National Brain Tumor Society], organizations which support patients with brain metastases. Several systemic cancers also have foundations, such as Susan G. Komen and several other foundations, which can help such patients. We like to offer that. A lot of times at our place, either a nurse or a social worker will meet with the patients and caregivers to provide them this information.

Discussing the Potential for Brain Metastases With Patients

® program titled “Management of Cancer That Has Spread to the Brain.” Because of the tremendous multidisciplinary approaches being implemented and novel treatments being investigated, the treatment of cancer that has spread to the brain has advanced, showing better effectiveness and safety outcomes.

I am Priscilla Brastianos, the director of the Central Nervous System Metastasis Program at Massachusetts General Hospital, Harvard Medical School, in Boston, Massachusetts. I’m joined by two patients: Ivy Elkins, who will be sharing the details of her journey of being diagnosed with lung cancer, and Katie Doble, who will be sharing the details of her journey of being diagnosed with ocular melanoma. They will share their experiences with learning that the cancer had spread or metastasized to the brain and the care that they received.

We’re also joined by Nick Doble, Katie’s husband and caregiver; Dr. Manmeet Ahluwalia, a brain tumor specialist from the Cleveland Clinic in Cleveland, Ohio; Dr. Raymond Sawaya, a neurosurgeon from The University of Texas MD Anderson Cancer Center in Houston, Texas; Dr. Vinai Gondi, a radiation oncologist from the Northwestern Medicine Cancer Center in Warrenville, Illinois; and Ralph DeVitto, patient advocate representative from the American Brain Tumor Association in Chicago, Illinois. Thank you all so much for joining us. Let’s get started.

First, let’s talk about the risk of brain metastases from different cancers, and let’s start with Dr. Ahluwalia. Dr. Ahluwalia, tell us about which cancer types are most associated with the development of brain metastases, and how prevalent are brain metastases in terms of the overall cancer diagnosis?

Thanks so much, Dr Brastianos, for the invitation to participate in this roundtable with these patient advocates and these luminaries. As you know, brain metastases are a common clinical problem. It is estimated that every year, 200,000 to 300,000 patients will be diagnosed with brain metastases. We do know that there are some cancers that have a propensity to go to the brain. The most common cancer that results in brain metastases is lung cancer, followed by breast cancer, melanoma, and renal cell. These four cancers typically constitute 85% to 90% of the cases of brain metastases that we encounter in our clinic every day.

What is also very important, and this session is very timely, is that the incidence of brain metastases is increasing because although we have systemic therapies that are taking care of cancers in a better manner, the brain is a sanctuary site. So there is a higher likelihood of brain metastases resulting from good systemic control.