Durable medical equipment is the term used for equipment such as a hospital bed, wheelchair, walker, bedside commode and shower chair. Insurance coverage varies, so it is best to contact the patient’s insurance company or treatment team for more information.

Acute rehabilitation hospitals are sometimes an option for patients who have lost some of their mobility and have the potential to regain it. Typically, in order to be admitted to an acute rehabilitation hospital, a person must:

• Be able to tolerate at least three hours of rehabilitation exercises every day
• Be able to benefit from the rehabilitation exercises
• Have insurance coverage for acute rehabilitation services.

Most, but not all, health insurance policies have some coverage for acute rehabilitation hospitalization. For more information about this option, contact the patient’s treatment team.

Sub-acute rehabilitation facilities provide rehabilitation services for people who have lost some of their mobility and ability to perform activities of daily living. Typically, in order to be admitted to a sub-acute rehabilitation facility, a person must:

• Be able to tolerate an hour of rehabilitation exercises every day
• Be able to benefit from the exercises
• Have insurance coverage for sub-acute rehabilitation services

Most often sub-acute rehabilitation facilities are housed in skilled nursing facilities (also called nursing homes).

Skilled nursing facilities, also called nursing homes, provide 24-hour care to their residents, who live in rooms at the facility. Residents may be admitted for a short stay, such as to receive sub-acute rehabilitation services. People may also be admitted for longer stays, such as when they can no longer be cared for at home. Skilled nursing facilities vary in the accommodations and services they offer.

Medicare.gov contains information about skilled nursing facilities and a list of skilled nursing facilities, as well as the results of Medicare’s periodic inspections of these facilities.

Home health care can include many types of services provided in the home, such as:

• Durable medical equipment
• Home health aide services
• Medical social services
• Occupational therapy
• Part-time skilled nursing care
• Physical therapy
• Speech-language therapy

Most health insurance policies have some coverage for home health care, but a patient must generally have a “skilled need” (i.e., something a nurse or other professional can do that the family would not be capable of doing) in order for insurance to cover the service. Check with the patient’s treatment team to determine whether these services would be appropriate.

Hospice care helps patients who are no longer pursuing curative or life-prolonging treatment for their illness but who want aggressive symptom management. The goal is to enable each patient to maintain the highest quality of life possible for the duration of his or her life. Hospice care also provides support to the patient’s family, both before and after the person’s death.

Home hospice care

Home hospice care is the highest level of home health care. It is reserved for those who need it the most, generally people who are no longer pursuing curative or life-prolonging treatment for their illness but who do want aggressive symptom management. Home hospice care is provided by a team of providers, including a nurse, social worker, certified nursing assistant, clergy, volunteers and others.

The National Hospice and Palliative Care Organization has more information about home hospice care.

Inpatient hospice care

Inpatient hospice facilities provide 24-hour care and lodging to people at the end of life. Many home hospice agencies have an inpatient facility available for people who do not wish to die at home or who require care that cannot be provided in the home. Some inpatient hospice facilities are free-standing, while others are housed in skilled nursing facilities or hospitals.

The National Hospice and Palliative Care Organization has more information about inpatient hospice care.

Private duty care is a form of in-home care that can help with meal preparation, companionship, bathing and other tasks. Health insurance usually does not pay for this type of care, but it is always a good idea to check with the patient’s insurance company to be sure.

Fees range from less than $10 to more than $20 per hour. It is important to negotiate up-front with a private duty agency for the necessary services.

Considerations for private duty care

Before contacting an agency about private duty care, consider the following:

• What does the patient need help with, e.g., bathing, driving, lifting and/or shopping?
• How many days per week and hours per day does the patient need help?
• How long will the patient need this help (one week, a month, etc.)?
• What type of insurance does the agency carry (if their employee is injured while at the patient’s home)?
• Will the patient or a caregiver have the opportunity to interview the care provider in advance?
• If the agency employee is a “no show,” will the agency send someone else?

For more information about private duty care:

• Ask the patient’s treatment team
• Ask other people which agencies they have used
• Search online for “home care” or in the phone book under “nursing”

John Weingart: Hi, I'm John Weingart. I'm a professor of neurosurgery at Johns Hopkins, and we're going to be talking today about issues related to the brain.

Ellizabeth Tracey: I'm Elizabeth. Tracey, welcome to Brain Matters, your look at neurosurgery headlines for the month. This is our first one. This month we're going to start with something that was published about meningiomas.

John Weingart: Today we're going to start out with an article that was published recently talking about the risk of meningioma occurrence in association with weight and physical And this was an article reporting several observational studies, which means they looked at a large population of people, looked at the incidence of certain problems, and one of the problems that they looked at was meningioma. What they found was that in people who had higher weight, and the way they divided that up was BMI, and if they had a BMI of 25 to 29, they had a 20% higher risk for meningioma, and those who were obese, which is defined as a BMI of greater than 30, had about a 50% higher risk of meningioma. They also found that high physical activity levels conferred about a 25% lower risk for meningioma. The physiology behind why this might be isn't clear, and they postulated some issues related to insulin, but there's no clear explanation why this might be the case, but it's an interesting observation and certainly could be motivation for someone to get out and exercise several times a week.

Ellizabeth Tracey: That's in the Journal of Neurology. Help me to understand, you know, we talk an awful lot about this idea of biological plausibility. we look at what people speculate as mechanisms. So how biologically plausible do you find this explanation for an association between higher BMI and a greater likelihood of developing a meningioma?

John Weingart: Well, these things are always multifactorial. Sometimes a higher weight can reflect other health problems, which may play more of a role in the development of certain illnesses or tumors than just the weight itself. So it's a reflection of overall health, and certainly if you're physically active, and you keep your weight down. All health problems seem to be less in that circumstance.

Ellizabeth Tracey: I find it really interesting and tantalizing, and I know you're familiar with this also, this idea of fitness versus fatness and whether one can be overweight and very physically active and still ameliorate many of the deleterious factors relative to obesity. What are your thoughts on that? In this study, of course, they don't talk about that.

John Weingart: I would say that it's just not a number that you're shooting for. So one wouldn't want to starve oneself to get to a lower weight. One would be much better to do regular physical exercise, eat healthy, and then find whatever your natural weight would be.

Ellizabeth Tracey: Let's return then to meningiomas. In your experience, increasing, decreasing, staying the same?

John Weingart: Meningiomas are a problem that are more frequent in older decades of life, so that as people live longer, there will be a higher incidence of meningioma. There are more people alive who are older that could present with one.

Ellizabeth Tracey: Let's talk about presentation. How are most of these found? Are they incidentalomas?

John Weingart: They present in a variety of different ways. Certainly a lot of people get MRI scans for a headache, sinus disease. Oftentimes one will find a small meningioma on an MRI scan. Then there are people who have symptoms, headaches, seizure, weakness, numbness, that leads to them getting an MRI scan where something is found and can be a meningioma at times. Both people need to be evaluated. The patient that's having symptoms needs more rapid evaluation, and a decision needs to be made about intervention and what to do. For somebody that has a meningioma picked up by accident, say, there they need to be seen, but they have time to get information, be educated about what the problem is, think about the decision about whether to have treatment and the timing of that treatment. And that decision depends on size, location. Usually things that are asymptomatic are just monitored with regular MRI scans. The age of the person plays a role. A small meningioma, you're 30 years old, it starts to grow, probably best to have that addressed because the time period over which you're at risk for it to grow is very long. If you're 70 and you have a small meningioma picked up, one can tolerate a little bit of growth, really looking to control the problem for 15, 20 years. There, the hurdle, say, to propose intervention is higher than for the younger person where the risk of growth a much longer period of time.

Ellizabeth Tracey: The meninges, of course, are really kind of interesting in lots of ways. When these tumors arise, which type of tissue do they normally arise from?

John Weingart: Well, they arise from a cell that's normally in the dura. They grow from the lining of the skull, so they're outside the brain, and then they grow and push into the brain and cause symptoms in that way. And they occur everywhere. anywhere in the skull, anywhere where there's dura, they even occur in the spine. And the symptoms they cause are based on the location of the meningioma, and the issues associated for people in terms of treatment are different. So a meningioma on one area of the skull is much different than a meningioma in another area, even though the pathological diagnosis may be exactly the same. But located in the wrong spot, it can be troublesome.

Ellizabeth Tracey: When you're talking about treatment, then, treatment is largely surgical.

John Weingart: Primary treatment is surgery. Surgery to remove the tumor, remove the dural lining that it's growing from.

Ellizabeth Tracey: And not followed up with anything else. No radiation or.

John Weingart: In general, there's no radiation given as part of the standard first-line treatment. People do get radiation for meningiomas. The type of radiation given depends on location, size, and various other factors. As an initial therapy, however, we do favor removal of the tumor. Because it does completely take care of the problem, it also does establish diagnosis. There are different varieties of meningioma there's a Grade One, a Grade Two, and a Grade Three. The Grade One meningioma is the most innocuous, slowest-growing meningioma, and it represents about ninety-five percent of meningiomas. Grade 2 meningioma, what's called an atypical meningioma, represents about 4% of meningiomas. They have a higher incidence of regrowth and recurrence. Sometimes those get radiated after surgery or get radiated sometime in the course of caring for that problem. And then the final meningioma is a grade 3 meningioma, which is a malignant meningioma. It represents 1% or less than 1% of meningiomas. It is not that grade 1 meningiomas become grade 3 meningiomas. Typically, it's a grade 3 meningioma essentially from the start. So people shouldn't be worried that if it's monitored, that it could evolve into a more aggressive tumor. That is not what happens.

Ellizabeth Tracey: What do we know about the etiology of these things?

John Weingart: There's not a lot in terms of the mechanism of why they form understood. They're a little more common in women than in men. They do have estrogen and progesterone receptors on their surface. However, treatments that are aimed at blocking those receptors or interacting with those receptors have not really led to an effective treatment for the problem. There is an association with radiation in meningiomas. So years ago, people who had ringworm were treated with scalp radiation, and they have a much higher incidence of meningioma recurrence. In children that had radiation for leukemia or other childhood cancers, they have a higher incidence of meningiomas developing. So there is a clear association with radiation and meningioma development on a delayed basis. Doesn't mean people should stop getting CT scans or x-rays, but it's something to be aware of.

Ellizabeth Tracey: How many of these things do we see in a year?

John Weingart: They're one of the more frequent brain tumors, certainly here at Hopkins, several hundred a year that have surgery for this problem. It's a problem that needs to be managed to minimize the impact on the person in terms of their quality of life and length of life, but also to not impact their current life unnecessarily. Even when they're small, there should be a good reason to have surgery. So that's why people who have meningioma picked up that's not causing symptoms or the symptoms are not severe, they do have time They get opinions from different people and plan an intervention, a surgery, if it's appropriate, based on their life.

Ellizabeth Tracey: What else would you like to add?

John Weingart: In terms of resecting a meningioma and managing the problem, that a multidisciplinary approach is valuable. Although surgery is the main initial tool, there are a lot of other factors to come into play. And I think there's an advantage to being cared for at a center that does many of these types of surgeries, that has all the resources available to support the patient during their hospital stay and to manage the problem effectively after surgery. We have a multidisciplinary brain tumor group here. We have a meningioma center. These are problems that people are expected to blend right back into their normal life. So they have an operation, three, four weeks later, ideally they're back to work, exercising, doing all their normal things, almost like nothing happened. Since meningiomas generally are not such that you have to drop everything and have surgery tomorrow, there is the opportunity to get second opinions, to travel to a center where it's a frequent problem that they take care of so that you can get thoughts about management, and then the person can make the best decision for themselves about where they want to get their care.

Ellizabeth Tracey: But in general, you would say that the outlook is really quite good.

John Weingart: Oh, absolutely.

Ellizabeth Tracey: Thank you so very much.

John Weingart: Oh, you're very welcome. Look forward to the next month.

Elizabeth Tracey: All cells shed DNA into blood and bodily fluids when they break open, a fact that's being exploited in discerning whether cancers have returned or metastasized. Now the same technique has been used in looking at brain tumors, where the DNA is shed into the fluid surrounding the brain and spinal cord. John Weingart, a neurosurgeon at Johns Hopkins, explains.

John Weingart: This is a new concept that's been developed in cancer research. There's evidence that cells, as they die or break up in their natural growth or with treatment, that the DNA that's within them gets shed out into the bloodstream or into other bodily fluids. This DNA is different than the patient's normal DNA. There are unique fingerprints, so to speak, of the tumor DNA that can be detected elsewhere in the body.

Elizabeth Tracey: Weingart is one member of a group at Hopkins with a recent publication showing detection of over 70% of Tumor markers using the technique at Johns Hopkins. I'm Elizabeth Tracey.

Elizabeth Tracey: A helmet employing alternating electrical field pulses has been shown to improve survival from glioblastoma, one type of deadly brain tumor. A study published recently in the Journal of the American Medical Association found. John Weingart, a neurosurgeon at Johns Hopkins, explains the strategy.

John Weingart: It involves what's called tumor treating fields or low wave frequency electric fields that are applied to the scalp. The mechanism is to disrupt cellular biology such that it keeps cells from being able to divide. So it's a low-intensity microwave in a way that disrupts cellular division, thus would affect any process that requires cellular division to progress, which is what tumors do.

Elizabeth Tracey: Weingart says the helmet is custom-made and used alongside surgery and possibly also chemotherapy. People wear the helmet for the majority of the day and must shave their heads to do so. At Johns Hopkins, I'm Elizabeth Tracey.

Elizabeth Tracey: Welcome to this month's Brain Waves. I'm Elizabeth Tracey.

John Weingart: Hello, Elizabeth. I'm John Weingart, Professor of Neurosurgery at Johns Hopkins. Today, I thought we'd talk a little bit about if you're told that you have an abnormal MRI scan or a tumor, what do you do? How do you get access to Johns Hopkins? Some of the issues related to access have to do with the anxiety that's associated with being told by your family doctor or your primary care doctor that you have an abnormal MRI scan and you need to see a neurosurgeon. Patients fall into several categories. One is the patient that has symptoms not related to what's on their MRI scan. So they're having an MRI scan for a different reason. Maybe it's from migraine headaches. Maybe they had a car accident and they're ruling out concussion or some other problem. And while doing that MRI scan, something is found. The urgency of evaluation for that patient is different than the other patient who's having active symptoms. from what's found on their MRI scan. That person needs to be evaluated much quicker. For the patient and for their family, regardless of which category you fall in, there's a sense of urgency. There are many questions. People need plans. They need to understand. And so oftentimes, the local doctor will refer them to a neurosurgeon or may say, go to an emergency room, or you just need to be seen, and it's left to the family to identify a treatment location. So here at Hopkins, we've developed variety of different avenues for people to get access to the system. The speed of getting seen by neurosurgery here really is on the order of one day to within a week. The key, however, is to get the information here, and all that involves is usually just making a phone call. There is a number to access the neurosurgery department as a whole. We have a separate number for pediatric neurosurgery, and we have a separate number for people who are out of state. The Hopkins USA number is a route them to do that, but they can also call the neurosurgeon's office directly. We have an imaging uploading system that if somebody has their MRI disk on their home computer, they can upload the images onto a website, and we can do an initial screening to understand, one, the acuity of the problem, and then set up an appointment for the next day or an appropriate time for that person.

Elizabeth Tracey: This is all really great. I'm sure it developed in response to things that were probably going on, barriers for people being able to access the system. It's your standard then in this department that you would see people in a really short period of time.

John Weingart: Right, for someone who has a brain tumor, it's oftentimes the very next day. There's a small group of people that have a newly diagnosed brain tumor that need care immediately. But that's the smallest group of people that present with a mass. Most of the time, there is a period of time of a week to 10 days that is perfectly safe to get evaluated, figure out what questions you need to ask, what you need to understand the problem, and then to get seen and treated. People who have a problem like that are seen and they're usually operated on within a week. So there's always time to get second opinions. It's even possible for people to be transferred from other hospitals directly for more acute problems.

Elizabeth Tracey: One of the advantages, of course, here at Hopkins is that we have a wide range of specialists. And as you've told me before, sometimes brain tumors kind of fall into more than one. one specialty.

John Weingart: Oh, you're so right about that. Many of the things require doctors from different specialties to help take care of that patient. When somebody comes in to be seen in neurosurgery, if they have a problem that requires other services involvement to take care of that person in the best way, then we in neurosurgery arrange the visits, oftentimes on the very same day. One of the nice things about the kind of system that you have at a large academic center is that once you jump on the Plus, it stops where you need to stop.

Elizabeth Tracey: So that this comprehensive approach then extends not just to the consult and to the diagnosis, but also to the procedure and the treatment.

John Weingart: Absolutely, and the follow-up care. There are plenty of patients of mine that have a tumor that required surgery only, and they live two, three hours away. I don't ask them to drive two hours for a 10-minute visit to say your MRI looks great. They can get their MRI locally, they can upload it to the system, I can look at it, and we can have a phone Visit, so to speak, to say, Hey, your MRI looks fine, no problems, you know, how are you doing, any issues? It's more efficient for them, it works well for everybody. The system of being able to access information remotely, so to speak, is so efficient.

Elizabeth Tracey: Why don't we end with a note from you on clinical trials, because clearly in this place, that's a really big deal. And it certainly is an advantage to patients if they're eligible to participate in such a thing.

John Weingart: Yeah, the clinical trial thing is also a very difficult thing to access. And in terms of efficiency, to come for a visit and then say, yeah, you could be eligible for these trials, and you need to see this doctor and that doctor, you have to come back to see those doctors, well, that's not good for the patients. So they really need to come and get that evaluation all at once.

Elizabeth Tracey: Excellent. Would you like to share the phone numbers people can access?

John Weingart: Absolutely. For the general adult neurosurgery access line, the number is 410-955-6406. For the pediatric neurosurgery patients, it's 410-955-7337. And for the out-of-state patients, the number is 410-735-4306. 4872, which is the Hopkins USA number. But the other thing is patients can just call the doctor's office directly. So if someone has a brain tumor, they can look on the Johns Hopkins neurosurgery brain tumor site and you'll see listed all of the members of our faculty that take care of brain tumors. Just call that doctor's office. The doctor's assistant will take that information down and the doctor will get right back to them and they'll be seen immediately. So, you don't have to go through the general system. You can, but you don't have to necessarily go through the general system. You can go directly to the doctor's office, and for this kind of a problem, the person will be seen immediately, and sometimes... at least in my office, I have them ask the patient to upload their images even before the appointment so that I can see it so that if it looks like this is something that needs an operation sooner rather than later, I can be getting all that sort of orchestrated in my mind in terms of timing and getting even a pre-op evaluation, tentatively planned for someone on the same day that they're coming to be seen so all of that can be expedited for that person.

Elizabeth Tracey: Very good news. Thank you so very much.

John Weingart: Thank you.

Elizabeth Tracey: Welcome to this month's Brain Matters. I'm Elizabeth Tracey.

John Weingart: I'm John Weingart, Professor of Neurosurgery at Johns Hopkins Hospital.

Elizabeth Tracey: John, you picked something really interesting with a large number of patients in it for this month. Let's talk about it.

John Weingart: Elizabeth, this is a large experience at one institution. It happens to be our institution here at Johns Hopkins, but it involves really a small group of surgeons. One of the issues that exists with the high-grade astrocytoma is what is the true benefit of resection? It does give a diagnosis, but there's been some difficulty over the years in finding good evidence that better surgery results in better outcomes for patients. And so this was a retrospective study trying to get at that particular information. We felt that given that it was a small group of people that was doing the surgery, using the same technology, carrying out the surgery, post-operative care, post-surgery treatment in a very similar way, that we could hopefully get at that piece of information. So this This is a study that involves 1,200 patients. We looked at the post-operative MRI scan to assess how much residual enhancement was present on the MRI scan. And enhancement is where, when the contrast agent is given to the person during the MRI scan, the contrast agent accumulates in certain portions of the tumor. And that's the portion of the tumor that we want to remove at surgery. So we graded the quality of the resection by whether all of the enhancement was gone, compared to patients that had a thin rim enhancement to those that had bulky or nodular enhancement remaining. And we looked at patients that had had first-time surgery for what we call a grade 4 glioma, first-time surgery for a grade 3 glioma, and patients that had second surgery for a grade 4 glioma. And the bottom line was that for people with a grade 4 glioma, that if they had gross total resection or removal of all of the enhancing disease, their median survival was 13%. months. If they had just a small bit of enhancement left, then their median survival was 11 months versus eight months if there was still bulky disease left. If it was a second surgery, again, it was a similar type of benefit. For the grade threes, the difference was even more dramatic. The goal of getting an aggressive resection has to be taken in context with it being done safely. There are other secondary benefits to a resection that include better quality of life, less need for steroids, and a better, more accurate diagnosis. This clearly is a strong piece of evidence that supports people having a more aggressive resection as long as it's done safely.

Elizabeth Tracey: It seems curious to me that this was ever a question. And certainly there are plenty of examples in medicine where a priori, we have certain ideas about how things are going to turn out. And then when they're subsequently tested, we find out, oops, guess what? It's not exactly the outcome that I predicted. What was the basis of questioning with regard to search resection of tumors, of astrocytoma specifically.

John Weingart: Well, the astrocytoma is an infiltrator tumor, so there's no capsule, there's no edge, so there's always tumor remaining. And ultimately, how that person does is dependent on what happens to those remaining tumor cells. Before MRI scans, it was hard to know how much was really removed. A variety of tools over the years have been developed that have led to improved ability to resect things. We have interoperative MRI scan that can be used during surgery to assess the degree of resection. And then we have neuronavigation, which is like a GPS for brain surgery tool in terms of tabulating data and saying, yes, this group really had complete resection. You can now do that, whereas pre-MRI scan, it was really up to the surgeon's opinion about whether that had occurred.

Elizabeth Tracey: I'm really persuaded here by the difference between the stage 3 disease outcomes and the stage 4 disease outcomes. If you could create a tool that would help you to identify people earlier, that certainly would improve outcomes, right?

John Weingart: It's not always that a grade 3 becomes a grade 4. The grade 3 tumor can become a grade 4, but it tends to present as a grade 3 tumor. Oftentimes it's in a little younger population, so they're sort of in between the very low grade and the higher grade astrocytoma, their frequency is much less than the grade 4. But it highlights that in terms of the value of resection, the one thing about a grade 3 that probably is different than a grade 4 is that it's much less infiltrative. So therefore, the concept or hypothesis that if you can reduce the number of tumor cells to the smallest amount, that surgery itself can have an impact on the natural history of the disease, that or concept, the grade three data from this paper is proof in principle that that statement is true. For some grade four gliomas, it can be that it's so diffuse and infiltrative that surgery is not removing a significant amount of cells to really make a difference. And that's a segment of the disease that a group of patients that have this disease that needs another therapy that more diffusely can attack that, whether that be immunotherapy therapy or some other systemic therapy that gets to all areas, in addition to the standard treatment of radiation, will ultimately be required to impact those people that have a much more infiltrative process as opposed to one that's more focal.

Elizabeth Tracey: Here's my last question. This data is kind of old, and so what would you say about today's outcomes relative to resection?

John Weingart: The goal of, at least here at Hopkins, in treating people with this problem, whether it's initial surgery or recurrent surgery, is complete resection. And there are times when we use tools that we didn't have then to accomplish that, includes the intraop MRI scan. functional imaging we use to be a little more aggressive with resection. Again, all tempered with not creating a new neurological problem for the person because that does detract from how they do in terms of tumor control, but also obviously in terms of quality of life. This has highlighted our approach here for the last 20 years in terms of our goals at surgery. We're able to achieve complete resection of the most abnormal portion of the tumor.

Elizabeth Tracey: Excellent. Thank you so very much.

John Weingart: Thank you.

Elizabeth Tracey: Welcome to Brain Matters for this month. I'm Elizabeth Tracy.

Michael Lim: And I'm Michael Lim. I'm one of the brain tumor surgeons here at Johns Hopkins and director of the Brain Tumor Immunotherapy Center.

Elizabeth Tracey: Thank you so much for joining me this month. Recently, of course, on 60 Minutes, there was a major story that has gotten a lot of attention, and that was the use of poliovirus as a potential, what shall we call it, inducer of an immune response for people with a certain type of brain tumor. Please tell me more about that.

Michael Lim: It's an exciting for a tumor that's been very tough to beat. A genome glioblastoma is a very aggressive type of tumor. Oftentimes the prognosis is poor for patients. The concept behind the polio virus was initially to try to find a virus that would infect only tumor cells. As you know, polio is a type of virus. It's an RNA virus that infects brain or spinal cord cells. In the past, when the polio virus infected, for example, the spinal cord, it was a major cause of neurologic deficits in people. Finding a vaccine for it was a big deal. Now we're taking that idea of a very aggressive virus and trying to turn it against this aggressive tumor. I think initially the thoughts were to try to design this virus to specifically attack tumors, and they genetically modified these viruses to attack tumor cells. And as they started giving them to patients with glioblastoma, they found some really impressive results. One thought is that the viruses are eliciting an immune response, and perhaps this virus acted as a primer to generate a very vigorous immune response.

Elizabeth Tracey: So many things about this are just so very fascinating to me. Historically, of course, we've viewed the brain and the central nervous system as a protected space, where the thought for so long was that there wasn't much of an immunological response going on there. And it sounds like, wow, we're really learning a lot about that response.

Michael Lim: That's very true. I think that the brain is actually a place that can mount a very vigorous immune response. And we've seen that in patients who've had conditions such as multiple sclerosis, or brain abscesses. I think that the brain is a unique environment. We had a very neat paper recently that showed that the brain itself acts and behaves very different immunologically than the periphery. We did a set of experiments where we took mice and we implanted melanoma tumors in the flank, in the back of a mouse, and in the brain of a mouse, and we found that when the tumors were in the brain, the tumors themselves were actively deleting or getting rid of T-cells that would have otherwise acted against the tumor. And what we've learned is that the brain probably needs other ways to prime the immune response.

Elizabeth Tracey: This is so fascinating to me. Tell me about the migration of things like T-cells, because clearly they're not being developed in the brain. So how do they get into the brain? And gosh, did we even know that they were there for such a long time?

Michael Lim: Immune cells traffic in and out of the brain. The methods of surveillance in the brain may be a little different than in the body. For example, you need another partner to these lymphocytes or T-cells called myeloid cells, otherwise known as macrophages or dendritic cells and microglia. And it turns out that those populations of cells are the ones that alert the T-cells or the lymphocytes to come in and activate them. Like in the polio virus, they think that these myeloid cells play a very important role in mounting or turning the immune system on.

Elizabeth Tracey: This is so fascinating to me because I can recall a day when everyone was speculating on the role of microglia. And what in the world are they doing in there anyway?

Michael Lim: I think it's very exciting because now we've come another step in understanding the role of microglia. We think that there's a big role in surveillance.

Elizabeth Tracey: So let's return to the poliovirus and its neurotropic capabilities, if you will. Aren't there other viruses? And I'm thinking about the herpes virus family, for example, that are also neurotropic.

Michael Lim: There are other viruses that are neurotropic. herpes virus is, as you mentioned, one. There are other clinical trials that are ongoing looking at modifications of the herpes virus. With today's technology, they've been able to actually modify a lot of different viruses. They've taken adenoviruses and even cold viruses and re-engineered them so that they can specifically target molecules on different cells. So you may not even need to have a neurotropic virus.

Elizabeth Tracey: I guess one of the questions from a patient's standpoint might be, why did some people respond so dramatically to this particular intervention and others really didn't seem to respond much at all?

Michael Lim: I think it comes back to the basics of the tumor itself. When we say glioblastoma, I think it's the misconception to think that it's one disease. I think what we've learned is that the glioblastomas themselves are very heterogeneous. They're a very diverse population of tumors that look histologically or under the microscope very similarly, but there are variations in the way they behave. Like in other types of tumors, like for example with breast cancer and lung cancer, we become better at characterizing the subtypes of tumors and are able to now direct certain therapies. I think we are going to figure out which tumors are more susceptible to viral treatments. other tumors may be more susceptible to a vaccine. And I think we'll see other tumors that are going to be susceptible to targeted therapies.

Elizabeth Tracey: I've had other people who are cancer experts express to me the idea that there is a timeline relative to how tumors develop and the mutations that are present. Would that suggest to you that potentially vaccines might be important at one stage of the disease, but maybe something else is going to be required at another?

Michael Lim: So I think you brought up a great point. When I talk the heterogeneity of tumor. It's specific to one snapshot in time. We've had experiments in our lab where we found that when we simulate these glioblastomas earlier on, the T cells have a very different phenotype that mark what we call exhaustion compared to a late stage tumor. And so one set of antibodies that would cure a mouse at certain time points, but if you waited to a later time point, it turned out that we needed a different set of antibodies. Those are examples in our laboratory. We think that that's probably even more complex in a real-life clinical setting. And so I think you're absolutely right. We may not find a cure for glioblastoma, but we may find ways to keep it in check and that over time we may have cocktail A and five years later they may need to have cocktail B.

Elizabeth Tracey: Would you suggest then that in the designation of these cocktails that some genetic assessment and maybe even an epigenetic assessment might be necessary?

Michael Lim: I think that complements exactly what personalized medicine is doing today. As patients get treated, the whole concept of doing personalized medicine and getting your tumor, for example, genetically analyzed, I think that should be a moving target. So I think that as people live longer and progress through their disease states, that these tumors are reassessed and given different cocktails.

Elizabeth Tracey: If you had to sum up right now the state of immunotherapy with regard to brain tumors, what would you say?

Michael Lim: I think that we're at a very exciting time. We're building on some fantastic data from other tumors, as you know, with melanoma, renal cell carcinomas, or renal cell cancer, and lung cancer. And now with bladder cancer, there's been FDA approval of some of these immunotherapy drugs, like the checkpoint inhibitors. And if you look at their data, it's a revolution, because we are now seeing a subset of patients that what we deemed incurable are being cured. And so I think we all recognize that the immune system plays a critical role in potentially curing people with cancer. It's just that different tumors are going to require a different set of keys. I think we have a great set of initial keys to work with, and I think in the next five years to 10 years, I'm optimistic that we'll find something very exciting.

Elizabeth Tracey: Outstanding. One's brain matters. Thank you so much.

Michael Lim: Thank you.

• American Brain Tumor Association
• Brain Tumor Network
• Brain Science Foundation
• National Brain Tumor Society
• The Healing Exchange Brain Trust
• International Brain Tumour Alliance
• Musella Foundation for Brain Tumor Research and Information

Local Resources (Maryland, DC and Virginia)

• Hope Connections for Cancer Support (Bethesda and Landover)
• Life With Cancer (Northern Virginia)
• Smith Center for Healing and the Arts (Washington, D.C.)

National Resources:

• American Cancer Society
• Cancer and Careers
• Cancer Care, Inc.
• Cancer Commons
• Cancer Hope Network
• CURE: Cancer Updates, Research & Education
• National Association for Hospital Hospitality Houses
• National Cancer Institute
• National Coalition for Cancer Survivorship
• National Comprehensive Cancer Network
• National Hospice and Palliative Care Organization
• Oncolink
• Chemocare.com

• Caregiver.com
• Caregiver Action Network
• Well Spouse Foundation
• Visiting Nurse Association of America

• Aircare Alliance
• Corporate Angel Network
• Flights For Life, Inc.
• Lifeline Pilots
• Mercy Medical Angels
• Northwoods Air Lifeline
• U.S. Air Ambulance

• American Speech-Language Hearing Association
• Brain Injury Association
• Cushings Support and Research Foundation
• Epilepsy Foundation of America
• Food and Drug Administration
• National Aphasia Association
• National Center for Complementary and Alternative Medicine
• National Center for Learning Disabilities, Inc.
• National Institute on Deafness & Other Communication Disorders
• Patient Advocate Foundation
• The Sierra Group
• Vital Options