Dr. Priya Kumthekar
Dr. Priya Kumthekar is a neuro-oncologist from Northwestern University who treats primary brain tumors, but has a specific interest in metastatic disease to the brain from cancers like breast cancer. She leads multiple clinical trials to advance the field of neuro-oncology to improve care for patients.
Dr. Kumthekar is a UCNS certified neuro-oncologist from Northwestern University dedicated to patient and care and moving the field of brain tumor forward primarily through her leadership on clinical trials.
She is currently involved in and leads many clinical trials including being the overall principal investigator of five investigator initiated treatment trials as well as the site principal investigator (PI) of over a dozen additional collaborative brain tumor treatment trials. Dr. Kumthekar is the planned study chair/overall PI for a multicenter, international breast cancer leptomeningeal clinical trial scheduled to open in Q4 2020.
Dr. Kumthekar has also been actively involved in the NCI funded clinical trials for many years. Within the NCTN (National Clinical Trials Network) and serves in leadership roles, particularly with the Alliance for Clinical Trials (Alliance”) for several years.
In 2016, Dr. Kumthekar was appointed as the national Executive Officer of Neuro-Oncology at the Alliance. In this role, she oversees the conception and development of clinical trials in these two areas from early phase through registration studies. Dr. Kumthekar has teamed with various scientists both at Northwestern and at other institutions with the goal of using translational research to advance the field. These partnerships allow for cutting edge scientific discoveries to be successfully brought to the clinic for brain tumor patients to benefit.
Full Transcript
Christine Hodgdon:
Thank you for joining us today. My name is Christine Hodgdon. I’m a metastatic breast cancer patient and advocate, and I’m here today with Dr. Priya Kumthekar. And I am very excited to talk with her about all the wonderful work she does, especially for patients living with brain metastasis.
A little bit about Dr. Kumthekar. She is a neuro-oncologist from Northwestern University. She primarily treats brain tumors, but has a specific interest in metastatic disease to the brain from cancers like breast cancer. She leads multiple clinical trials, which we’ll talk about a little bit later, and all these trials advance the field of neuro-oncology to improve care for patients. So Dr. Kumthekar, thank you so much for joining us today.
Dr. Kumthekar:
Thanks for having me.
Christine Hodgdon:
The first question is just very simple. Not everybody might know what a neuro-oncologist is. Could you explain what you do specifically and how it relates to breast cancer?
Dr. Kumthekar:
Absolutely. So neuro-oncologist is almost exactly as it sounds. So, we are interested in the treatment of patients with both primary brain tumors, so tumors that start in the brain, as well as secondary brain tumors, so tumors that start in the body and then go to the brain. And so that’s where it relates to breast cancer because we’re often treating patients with breast cancer that then spreads to the brain and in and around the brain, as breast cancer is one of the primary cancers that leads to brain metastasis.
Christine Hodgdon:
And I know that some cancer centers don’t always involve neuro-oncologists when they’re caring for their breast cancer CNS disease, but it can depend on the hospital. Do you have any comments about that? Is that something that a patient should be concerned about?
Dr. Kumthekar:
No, I don’t think that patients need to necessarily be concerned about not having a neuro-oncologist involved in their care. It’s just an added dimension and an added specialty that can be quite helpful. Not all hospitals actually physically have a neuro-oncologist onsite to have, to be able to include in their care. But we’re a pretty small network of doctors. As a specialty, we’re quite small compared to say medical oncology or breast oncology. And so if there are questions about neuro-oncologists and neuro-oncologists in your area, we can often connect you with those folks because we’re often connected in one network anyway.
Christine Hodgdon:
That’s great. And so we commonly hear the term brain metastasis. I think we’ve mentioned that already today. But there is this separate type of metastasis called leptomeningeal disease. And I was hoping you could explain to us what leptomeningeal disease is and how it differs from brain metastasis.
Dr. Kumthekar:
Yeah. So brain metastasis is pretty straightforward, right? It’s metastasis that go to the brain itself. But what a lot of people don’t know anatomically, is that, the brain and the spinal cord live in this fluid, right. This basically floats in this fluid and that fluid is called Cerebrospinal fluid. And so what leptomeningeal disease is, is essentially the involvement of cancer in that fluid. So basically it’s the presence of cancer cells in your Cerebrospinal fluid.
The name of that space is called the subarachnoid space. I don’t want to get too detailed on the anatomy, but I think just generally speaking, the way to think of leptomeningeal disease is cancer cells that are in the fluid that surround the brain and spinal cord.
Christine Hodgdon:
I think that’s an excellent explanation. I think many people, we often in the advocacy community hear people kind of using that term, lepto, when in fact it might actually be brain metastasis. So I just think it’s important to make that distinction. And I wanted to ask too, can patients present with both brain metastasis and leptomeningeal disease? Is that possible?
Dr. Kumthekar:
Absolutely. Similarly to having, you know, two sets of metastases, let’s say to liver and lung, present at the same time, it’s just the same concept except different anatomical spaces. So absolutely, you can have brain and leptomeningeal disease present at the same time, just like any other metastatic site.
Christine Hodgdon:
Understood. Like you can have metastasis in your liver and you can have in your brain. And for patients that are living with brain metastasis, is there a risk factor then of developing leptomeningeal disease, or is that unrelated?
Dr. Kumthekar:
So yeah, there is a little higher risk factor of developing leptomeningeal disease. We’re still understanding the depths of that. And we do know that some subtypes are more likely to then go on to develop leptomeningeal disease. So it’s really hard to target that exactly.
Similarly, you know, we know that patients with lung mets are at greater risk of, let’s say, developing brain metastases, but we can’t quite pinpoint who they are. And that’s kind of the same analogy for brain to lepto. It’s hard to say and to complicate things further, you can have leptomeningeal disease alone, without having brain metastasis. So, really they’re truly, you know, separate anatomic compartments that you can get metastasis in.
Video #2
Christine Hodgdon:
Are there any other risk factors that you are aware of for developing leptomeningeal disease?
Dr. Kumthekar:
Yeah. There are a few different ones and they’re very similar to that of brain metastasis. So, in terms of subtypes, very frequently, we might see this in the HER2+ population or the triple negative population, basically populations that we know that have a predisposition for the central nervous system.
Christine Hodgdon:
I see. I think I’ve even heard, so correct me if I’m wrong, does lobular breast cancer have a propensity to potentially develop into leptomeningeal metastasis?
Dr. Kumthekar:
Yeah, absolutely. That can as well. I mean, truly it’s – any breast cancer could. So even outside of the two examples that I provided, any breast cancer subtype could. But the top two of that list would be HER2+ and triple negative.
Christine Hodgdon:
Understood. And speaking of that, how common is leptomeningeal disease in breast cancer patients? I don’t know if we have a statistic on that.
Dr. Kumthekar:
Oh, we do. I mean, I would say for all comers, if you’re looking at breast cancer as a whole, it’s a very small minority, right. We’re talking like five percent-ish, you know. But it’s, again, those risk factors that you refer to. So, for example, in the HER2+ population, depending on what statistic you’re looking at, 30 to 50% of patients with HER2+ disease have CNS mets. And of that, you know, a fraction of – a significant fraction of that – is leptomeningeal disease. So, you know, the subtypes really do matter. But all comers, it’s actually a much smaller risk.
Christine Hodgdon:
But I think – are brain metastasis more common than leptomeningeal disease?
Dr. Kumthekar:
Yes, correct.
Christine Hodgdon:
We’re going to see more brain mets than we will lepto.
Dr. Kumthekar:
Correct. So even in that figure of 30 to 50% of HER2+ disease going on to develop CNS or central nervous system metastasis, it’s still just probably around, you know, depending on what you read, 15 to 25% of that, then that goes on to develop lepto. So it’s still going to be a minority population, even within the CNS population.
Christine Hodgdon:
Okay. And I think I’ve also heard and read that we are now seeing metastatic breast cancer patients living longer with their disease. So might that incidence actually increase as we might start to see more CNS, brain metastasis, lepto.
Dr. Kumthekar:
It’s a very insightful question and it’s actually totally accurate. And we’ve already started to see that over the past, you know, a handful of years plus. And beyond that… so the answer to your question is yes. And then beyond that, we’re seeing a lot more patients who are dealing with disease only in their CNS compartment, be it brain mets or lepto, because of exactly those same reasons.
So, I think we’re doing great as a field, as a breast cancer field, moving forward with great new therapies and advancing the field. It’s not necessarily an exact parallel advancement in the brain, although there are CNS advancements occurring as well. But for that reason, we see a lot more patients who, with the given therapies, are doing great systemically or, neck down, if you will. And we’re really primarily dealing with the CNS, or central nervous system disease.
Christine Hodgdon:
Yes. I think this is really why we started this whole project and website is because we want to see the advancements that we see in breast cancer in the central nervous system as well.
Video #3
Christine Hodgdon:
I want to switch gears just a little bit. And I’m wondering if you can tell us about the symptoms of leptomeningeal disease. Some patients may be concerned that they’re experiencing something that might be indicative of lepto, but maybe they’re similar to brain metastasis. So maybe you can comment on that.
Dr. Kumthekar:
Yeah, they are similar, but there are a few distinctions that we like to keep in mind. So, you know, similar to brain mets, you can get kind of focal neurologic symptoms, your quote, unquote sort of stroke-like symptoms, where your thinking, speech and motor deficits and so forth, depending on the location of the mets.
But lepto is similar, but a little bit different. So when again, when you go back to that original question of “where is leptomeningeal disease?”, that’ll help guide us to what the symptoms are. So if you’re talking about the fluid that surrounds the brain and the spinal cord, what lives in that fluid are various nerves that control functions around your face and head. So those are called the cranial nerves.
And then through your spine, the coming out of your spine, are spinal nerves that float in that fluid, that live in that fluid. So they can be impacted by cancer cells in that space. So, you see a lot of, what we call cranial nerve symptoms. So that’s things like numbness on your face, on your chin, you know, difficulty chewing, swallowing, facial weakness, double vision. So a lot of – and hearing changes – so a lot of things dealing with your cranial nerves, because those nerves are affected because they’re in that space.
And then spinal nerves. So that can control things like neuropathic pain. So numbness, tingling, you know, pain that you can get from spinal nerves. And then your lower down spinal nerves that control really critical functions with your bowel and bladder. So you can see some changes there as well.
Additionally, because it’s the fluid that this is living in, sometimes with these patients, we can get a fluid buildup. So we get this pressure, if you think of it. Pressure increase. And with that, we can see things like headaches, nausea, and vomiting. So there are a variety of symptoms that leptomeningeal disease can bring upon. But those are kind of the basics 101 of symptomatology.
Christine Hodgdon:
I love that visual that you provided, because I think I always just kept thinking of it in the brain, but we have to remember that lepto really affects the brain and the spinal cord and it’s that fluid. So I really liked the way that you described the cranial nerves, you’re going to have some different symptoms, versus if the lepto is around your spinal cord.
Cause I’ve worked with lepto patients who have trouble walking. So I thought that that was the main symptom, but it really does seem to kind of run the gamut. So thank you for that explanation.
Video #4
Christine Hodgdon:
How is lepto typically diagnosed? I had trouble finding this. I just tried to do some quick internet searches and it just seems like everybody does something different. So I’m curious to hear, you know, how you are able to diagnose this.
Dr. Kumthekar:
So there are three, basically, three methodologies that we use to diagnose. The gold standard, sort of, standard of care, is CSF cytology. So, as I mentioned, lepto is cancer cells in that fluid. So we sample that fluid via, typically a lumbar puncture. You sample that fluid, and you look at it under a microscope to see, are there cancer cells present? So that’s CSF cerebrospinal fluid cytology. That is the sort of textbook answer.
But ancillary to that, providing support are things like imaging. So MRI of your brain and your spinal cord, as well as clinical symptoms. So it’s all three together right now that are guiding our diagnostics. CSF cytology being sort of number one, and then MRIs, and clinical symptoms. And that, three, kind of trilogy together is what we use for the diagnostics.
I will say that, as a field, we know that there are shortcomings to those diagnostics and we are trying to look at the next generation. And beyond just improving upon treatments, we really want to improve upon diagnostics. That’ll help us so many fold, right? It will help us, of course, diagnose sooner, better, earlier. It will help us follow patients along their treatment courses better. And, you know, it really can revolutionize how we design and plan clinical trials, if we have a better foundational understanding of our diagnostics.
So there is how we currently do it, which is important to know, but also how we plan to improve upon those diagnostics. Because there are challenges to our current diagnostic paradigm.
Christine Hodgdon:
Absolutely. I really, I like that there’s three different modalities by which you can really make a diagnosis. And I wanted to ask this, because I think I’ve heard this from other doctors. Do you only need one lumbar puncture to prove, like if you get a negative result, do you recommend doing more than one lumbar puncture, or is one really sufficient?
Dr. Kumthekar:
So it’s a great question. And the answer would be dependent on the situation. So the reason why people say that is because the sensitivity of a lumbar puncture and CSF cytology is not that great with one lumbar puncture. So depending again, on what you read, it could be 50 to 60, 66%. So that means that a third of the time, plus, we might be missing a positive result. So we might have a false negative. That sensitivity increases with subsequent lumbar punctures.
So after a lumbar puncture number two, you might be up to like 70, 80%. And then maybe with three, maybe 85, 90, depending on which paper you’re reading. But we never really get past that 90% even after three lumbar punctures.
But the reason why my answer to you isn’t yes, do a second one, is because it’s very situationally dependent. If I have a patient who is – I have a negative CSF cytology, but I have clear symptoms and clear MRI imaging, I might sit down with that patient and decide, you know, it’s not going to impact how we manage your care and I don’t need to necessarily, you know, have you go through another lumbar puncture, let’s go this way.
Versus if there was nothing on the MRI and, you know, we were really still on the fence and it was going to impact further care. Then I might suggest in that situation that, hey, you know, we need more data to stand on solid footing with our treatment decisions. Then I might say, yes, let’s proceed with another lumbar puncture. So it’s really, you know, the whole patient, keeping kind of the whole patient in mind.
Christine Hodgdon:
Yeah. And that I think as metastatic patients, we’re kind of used to this. It’s a, “it depends” answer, you know, it’s like, it really does depend on the situation. It depends on many different factors, but I just wanted to ask if there was a straightforward answer. And I think what we’re learning with leptomeningeal disease is that there really aren’t a lot of straightforward answers and we’re going to get to the research that’s been ongoing.
Video #5
Christine Hodgdon:
How is leptomeningeal disease treated, then? We know how it’s diagnosed. How do you manage this disease in patients?
Dr. Kumthekar:
Yeah, and I laugh only because this is another, “it depends” answer. But there are multiple modalities that can be used to treat leptomeningeal disease. Historically, the primary modality has been radiation-based.
If you think about leptomeningeal disease, again, going back to that very first question. Anatomically, is something that surrounds the brain and spinal cord. You can imagine that some of our fields for radiation can be quite large. And so we often do radiation if we need to palliate symptoms, if we need to make symptoms better quickly, I like to lean on radiation for that primarily.
Other modalities that we might utilize either instead of, or after, could be things like intrathecal therapy. And this might be something I’m not sure if the listeners are familiar with it. But essentially, with intrathecal therapy, there are two ways to administer it. You can either do it via a lumbar puncture where you’re in that fluid space and then you can inject chemotherapies.
And more commonly what we use, is basically a port that we surgically place, similar to like a port that you would have chemotherapy go into, into your bloodstream. This is a port that communicates directly with your ventricular system, or that CSF fluid system, where we’re able to directly administer drugs to the CSF.
So we’ve talked about radiation, intrathecal therapy, and a third modality is systemic therapy. So that’s just chemotherapy, or medical therapy, directed therapy, that can be orally administrated, can be orally given, can be given via IV, so in different manners. Just like traditional chemotherapy that you think of for breast cancer.
Christine Hodgdon:
Got it. And I just wanted to mention the intrathecal delivery, when you were talking about that port. That’s called an Ommaya port. Is that correct?
Dr. Kumthekar:
Correct. Yeah.
Christine Hodgdon:
Okay. I just wanted to make sure I had that right. I’m curious, just for myself. How often do you use whole brain radiation? I think again, you’re going to tell me it depends on where the lepto is located. Cause I know I’ve definitely seen patients get radiation to the spine cause they’re having trouble walking. But do you use whole brain radiation often?
Dr. Kumthekar:
We do. And I can’t quote you a number because it’s kind of different site to site, patient to patient, you know? In terms of across the board, across the world or the country. I couldn’t tell you a percentage, but absolutely we do. We use whole brain radiation. We might use skull-based radiation where a lot of those cranial nerves are.
You know, leptomeningeal disease can look very different from patient to patient. It could have more bulky or nodular disease, or it could be diffuse and quite thin. And those are situations and various factors that we use in mind to decide treatment. So I think what I might sort of mold this question into is, what are the different factors that influence what we decide to do for our lepto patients?
So that includes things like the symptomatology of patients. So, what are the symptoms that that specific patient has, and is the treatment that we give going to alleviate or help those symptoms? It really is going to depend also on what’s happening throughout the rest of the body. Because we might be able to come up with a treatment regimen that can ideally kill two birds with one stone that addresses the systemic disease and the brain disease.
Proximity to when radiation was, is very important in deciding intrathecal therapy or what kind of chemos we might use. And the functional status of a patient – how well a patient’s doing, how are they functioning day to day and what sorts of treatments can they endure? So there’s a lot of different factors that go into that “it depends” answer.
Christine Hodgdon:
Yeah. And it sounds like you can actually use a combination of some of these different treatments as well. Is that right?
Dr. Kumthekar:
Yeah, absolutely.
Video #6
Christine Hodgdon:
Now I want to get to – this is the juicy stuff. I think this is what people want to know about. What is the emerging research in leptomeningeal disease? And I would love for you to comment on clinical trials. I know you lead many, and I would like to hear if there’s any lepto trials ongoing right now. That would be wonderful.
Dr. Kumthekar:
Yeah.
Christine Hodgdon:
Please let us know.
Dr. Kumthekar:
Absolutely. So that in and of itself is a long talk, but I’ll mention a few that I think are kind of nice to keep on the horizon. And what I also want to say is that the clinical trial portfolio that we have on clinicaltrials.gov, across the country, across the world, changes on a daily, weekly, monthly basis because these things open and close.
So, I could mention things now and the status of them could be really different by the time this recording happens, or by the time you watch this recording. So please take it with a grain of salt, depending on the time that you’re seeing this. And I would encourage everyone to go to clinicaltrials.gov and you can type in leptomeningeal disease and find out everything that’s open at that given moment. So…
Christine Hodgdon:
And we’ll also have a trial search on our website that, you know, you can actually input the data of your subtype, all of that information. It’s just a little bit easier to manage than the clinicaltrials.gov website. But I’ve definitely used it and leptomeningeal is such a distinct term that you can definitely find some trials.
Dr. Kumthekar:
No, absolutely. So then I guess to answer your question, there are many trials ongoing right now. There are a few dozen in the US that are going on. And some include novel administrations of intrathecal therapies. So, for example, there’s an intrathecal nivolumab study, ongoing. There’s an intrathecal combination of trastuzumab and pertuzumab ongoing.
Christine Hodgdon:
Okay. So that would be for HER2+ patients?
Dr. Kumthekar:
That one’s HER2+ disease. There’s also an ongoing study with pembrolizumab for all solid tumor patients. There’s a novel compound that had very positive phase two results that was published last year. And so there’s going to be actually the first planned registration study, phase three, randomized registration study, in leptomeningeal disease with the drug called ANG1005. It’s called the ANGLeD study. That’s planned to open early next year.
So there’s a lot of forward movement and many, many more that I’m leaving out. And so there’s an ongoing one, actually with tucatinib. Which I know you were talking about earlier with the HER2+ study.
Christine Hodgdon:
Yeah.
Dr. Kumthekar:
So there are, I feel bad for the many studies that I’m leaving out right now. But it’s just to say, you know, we’re encouraged and we’re moving forward. And there are more studies now than there were a few years ago, more than there were a year ago. And we do need to just keep that momentum going and keep adding more and more to lepto and brain metastasis studies.
Christine Hodgdon:
Absolutely. We just need more trials in general. And I think that’s the other piece of this whole initiative, is that we want to advance research for patients living with central nervous system disease.
So, all these trials will be listed in our website. So don’t worry if you’re forgetting any. I just wanted to comment though, that you had mentioned, a few of the drugs you mentioned were actually immunotherapy drugs. And so in some of them, some of what you talked about would be administered through that Ommaya port that we talked about before. So that’s one type of trial. But I was very interested in the – I’m not sure how you said it – ANG 1005. Is that –
Dr. Kumthekar:
Uh-huh, yeah.
Christine Hodgdon:
And, is that actually chemotherapy? That’s a chemotherapy drug, right?
Dr. Kumthekar:
It’s an antibody drug conjugate. So what that means –
Christine Hodgdon:
Ohh, okay.
Dr. Kumthekar:
Yeah. So it’s an antibody that’s basically meant to help cross blood brain barrier and blood CSF barrier.
Christine Hodgdon:
Yeah.
Dr. Kumthekar:
And then it’s an antibody that’s bonded to three compounds of paclitaxel, which is a chemotherapy. So it actually gets the chemotherapy to the location that it’s intended to get to.
Video #7 – Note: This video is posted under the Advice Section on the website
Christine Hodgdon:
Do you have any recommendations for patients newly diagnosed with leptomeningeal disease?
Dr. Kumthekar:
Yeah, absolutely. I would say a few things. So, I think, listen to your doctors. They have treated this before, they’ll guide you properly. Listen to the facts. You know, I know that we all are comforted by facts and science and reading.
But what I always tell my patients is, I give them statistics that they might want, the facts that they might want, and then I graciously tell them to crumple it all up and toss it in the wastebasket because we’re all our own statistic. And so, my advice to you would be, take in all the information, science is what moves us forward, and then gently push it aside and continue, you know, continue that hope because I believe in that.
And then I would also say lean on others. And that can look really different to different people, cause we all lean on others differently. That could look like online support groups, that can look like one-on-one support, that can look on online support.
There’s just so many different ways that we each need that. So do what feels right to you, but know that there are multiple avenues of that support. I think this website itself is fantastic. So there’s a lot of different, great resources out there. And I think that if you’re in a situation where you want to meet with a neuro-oncologist, there are many different ways to do that as well. I’m sure if you talked to your doctor that they could help facilitate that as well. If you didn’t have someone in your own institution.
