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.