April 14, 2025 • 52 mins
Dr. Ashley Aaroe joins us today to talk all about Neuro-oncology, from brain tumor classification, to complications of chemotherapy and immunotherapy, to the importance of patient advocacy.
- Check out our website at www.theneurotransmitters.com to sign up for emails, classes, and quizzes!
- Would you like to be a guest or suggest a topic? Email us at contact@theneurotransmitters.com
- Follow our podcast channel on 𝕏 @neuro_podcast for future news!
- Find me on 𝕏 @DrKentris
The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Michael Kentris (00:03):
Hello and welcome back to the
Neurotransmitters.
I'm your host, dr MichaelKentris, and today we're going
to be talking about a prettycomplicated field, at least
that's how I feel about it.
We're going to be talking aboutsome neuro-oncology and to help
me out with that, I'm veryfortunate to have Dr Ashley
Aaroe, neuro-oncologist at MDGod.
(00:23):
I've already messed up at MDAnderson, where she is currently
in attending also did herfellowship in neuro-oncology
there after completing neurologyresidency at Cornell.
So thank you so much forjoining us.
Dr. Ashley Aaroe (00:36):
Thank you so much.
I'm really excited to join youtoday.
Dr. Michael Kentris (00:39):
So first of all, tell me a little bit about
for those who might be a littleunfamiliar.
First of all tell me a littlebit about for those you know who
might be a little unfamiliar.
Obviously we know what oncologyis, generally speaking, but
what's?
Dr. Ashley Aaroe (00:52):
different about neuro-oncology other than
just being brains?
Yeah, no, I really love to talkabout it.
I think even within neurologyresidency, you know, not all
residents are exposed toneuro-oncology or have an idea
of what it means, and soincreasing awareness is how we
get people interested in goinginto the field.
What a neuro-oncologist does isit can be a little bit
different depending on where youpractice.
So there are someneuro-oncologists that are
(01:15):
really focused on prescribingchemotherapy for primary brain
tumors like glioblastoma, forexample, and there are other
neuro-oncologists who are morefocused on treating patients
with neurological complicationsof systemic cancer and cancer
therapy.
What really drew me to thisfield is that you can do a
little bit of everything, soneuro-oncology is very much at
(01:38):
the center of all the thingsthat I really love about
neurology.
So you treat cerebrovascularpathology, because patients with
cancer have a higher incidenceof stroke.
You also see tumor-associatedepilepsy.
You see neuromuscularcomplications of checkpoint
inhibitor immunotherapy.
Those are just a few examples,but even you know headache and
(02:02):
autoimmune neurology get foldedinto neuro-oncology.
I think as a neuro-oncologisttoo again, depending on where
you practice you have theopportunity also to be in some
ways like a primary care doc foryour patients.
For example, my glioblastomapatients aren't following with
their, your PMD as frequentlyand I see them every one or two
months for chemotherapyclearance.
(02:23):
So you take over a little bitof family practice.
You have to know a little bitof internal medicine as well,
and so it's kind of you get todabble in a lot of different
things.
It used to be thatneuro-oncologists really came
from the medical oncologytraining pathway, so people who
go into internal medicine do amedical oncology fellowship and
(02:44):
then are drawn into a moreneuro-based practice again for
brain tumor cancer treatment.
But then the neurologist feltthat we should be able to bridge
this gap and so more and morepatients are I keep saying,
patients.
I don't know why it's on mymind, um, but um, but more and
more people are going through aneurology pathway.
Dr. Michael Kentris (03:06):
Excellent.
Yeah, it is something that Iknow.
I didn't graduate residencythat long ago, but it was one of
those things where I didn'treally consider it much unless
you were going to be at one ofthose bigger academic
institutions as necessarilybeing like a viable career
pathway.
Are we seeing moreneuro-oncology, more neurology
(03:29):
residents, I should say,entering the field of
neuro-oncology in general, youthink?
Dr. Ashley Aaroe (03:33):
I do.
I think we are doing a good jobof getting neurology residents
interested in and exposed to thefield.
I would say that you know, forme I thought I was going to be a
movement disorders neurologistwhen I matched into neurology
residency and that's when someof my background in medical
school and research had been.
But I just really got suckedinto neuro-oncology and when I
(03:55):
rotated at Memorial SloanKettering as a resident, those
were the patients that Icouldn't stop thinking about in
the cases that I couldn't stoptalking about.
So really that exposure made ahuge difference in my career
trajectory.
There's very much a need forneuro-oncologists.
There's a shortage ofneurologists in general and
(04:16):
neuro-oncology too.
I feel like our patients oftenhave cognitive or mobility
concerns.
They may not be able to make itto a large center like Sloan
Kettering or MD Anderson, and soa lot of places are recruiting
neuro-oncologists and you couldbe, you know, a neuro-oncologist
(04:36):
in an academic medical center,but even so be only one of one
or one of two, or, you know,there's also a role for
neuro-oncologists in thecommunity as well, outside
academia, and so it's very mucha growing field, but one that
still has a shortage ofpractitioners compared to the
patient volume and need.
Dr. Michael Kentris (04:55):
No, I think that's an excellent point and
definitely some goodconsiderations for people who
might be considering it as acareer trajectory.
So you talked a little bitabout some of the common
conditions that you're dealingwith and how you are almost a
stand-in primary care physicianfor a lot of these patients.
I feel that is kind of anunder-recognized aspect of
(05:16):
neurology care in general.
For a lot of our chronicconditions is that you sort of
become the touchpoint for a lotof that person's medical care.
What does a day in the life ofa neuro-oncologist tend to look
like?
Dr. Ashley Aaroe (05:27):
That's a great question and I think that
that's extremely variable tooFor me.
In my practice I probably, Iwould say I'm about 50-50 in
terms of taking care of primarybrain tumor patients and taking
care of neurology consultationsin patients with systemic cancer
, and so I have, you know, twodays of clinic a week and then I
(05:49):
spend a varying amount of timeon our inpatient services.
So it really is, you know, kindof a week-to-week thing, but a
lot of folks are strictlyoutpatient in terms of their
practice.
So I have a pretty, you know,robust mix in clinic of patients
, you know, with example ofglioblastoma or medulloblastoma
(06:11):
rare tumor types I am reviewingtheir imaging treatment planning
.
I also have a very high numberof patients who, for example,
have peripheral neuropathy fromtheir taxal chemotherapy, and so
I'm managing that too.
I happen to really like thatmix and really like that
variability.
I find also that something thatI perhaps didn't know I would
(06:35):
be seeing as much of when I wasa resident, you know, applying
into neuro-oncology fellowshipthere's a lot of neuroimmunology
, and so I don't think Iappreciated how much I would be
haunted by misbehaving immunecells in my practice as a
neuro-oncologist, but a lot ofperineoplastic disorders,
complications of immunotherapy,which has very much
(06:55):
revolutionized the care of anumber of different cancers.
You know, I think melanoma is areally great example of that,
but there are many others.
And then also there are somediagnostic conundrums.
So you see an undiagnosed brainmass.
Is it a glioma?
Is it something else?
So I've stumbled acrossneurosarcoidosis and, you know,
amyloid related angiitis andvery other rare birds.
(07:19):
That way, just by virtue ofundiagnosed brain mass coming
into clinic, so it's a, just byvirtue of undiagnosed brain mass
coming into clinic, so it's a.
I think you can very muchtailor your practice to what
your specific area of interestis, but for me I really like the
variability.
Dr. Michael Kentris (07:32):
No, that's great, and I imagine
neuro-oncology kind of by itsnature is very much a
multidisciplinary type of fieldwhere you're working very
closely with both medicaloncologists as well as
neurosurgeons and probablygeneral surgeons of other
stripes as well.
Dr. Ashley Aaroe (07:49):
Yeah, absolutely, and that's something
I really love about the field.
I kind of in some ways, youknow, every week at least once,
I see myself as a bridge betweenneurology and another specialty
.
For example, if there's apatient with lymphoma that's
involving the brain, I'm goingto be, you know, working with a
medical oncologist who's aspecialist in lymphoma
(08:10):
neurosurgeon to figure outshould be biopsy, you know, and
everybody has slightly differentperspectives just based on
their experience of how totackle a problem, and so I
really enjoy sort of being inthat liaison role.
Sort of being in that liaisonrole.
I would say, as aneuro-oncologist, I definitely
work the most closely with theneurosurgeons, the radiation
oncologists and theneuroradiologists and
(08:31):
neuropathologists.
I would say, as aneuro-oncologist, your best
friend is going to be someone indiagnostic medicine, because
the classification of braintumors in particular changed a
lot in 2021 with the new WHOguidelines.
There's so many intricaciesabout how these tumors are
classified and they havesignificant ramifications for
(08:55):
their treatment and prognosis,and some of these things are
very much hot off the press evensince the 2021 classifications
came out.
I would mention, too, thatthere are some brain tumors
where they have a characteristicappearance on imaging and that
is stuff that's really an activearea of study, and new things
are being discovered every daytoo.
Definitely, befriending yourneuroradiologist and your
(09:17):
neuropathologist is important inmy field.
Dr. Michael Kentris (09:20):
No, that makes a ton of sense and I
remember reading some of thoseguidelines just this last year,
and even from the time again youknow I graduated in 2017, it's
been such a shift where we'rekind of moving away from a lot
of the kind of traditional, likemicroscope based diagnosis to
these molecular markers andgenetic markers and it is
(09:44):
rapidly multiplying to kind ofjust a very labyrinthine amount
of knowledge.
Dr. Ashley Aaroe (09:49):
Yeah, I think the difficulty is that every
time we have a newclassification, our
understanding of these tumorschanges and then we have to look
through the previous literaturein a slightly different light.
But I was actually listening tothe continuum recently about
the cephalalgias, the autonomiccephalalgias, and talking about
how they have, you know, a veryrobust classification scheme and
it makes it much easier tostudy these disorders and
(10:10):
develop, you know, interventionsfor them and I think we're
getting there with my field too,but it is very nuanced and it
you know not to oversimplify toomuch, but it used to be.
You look under a microscope,you see a glial neoplasm,
microvascular proliferation.
You look under a microscope,you see a glial neoplasm,
microvascular proliferation, andnecrosis is GBM.
But now there are so manylittle things that have come
down the pipeline that you knowa patient that goes to the OR
(10:32):
gets a resection, they may ormay not have an integrated WHO
2021 classification by the timethey're discharged from the
hospital, because it may be thatthere's next generation
sequencing required of the tumortissue to know with certainty
what it is, or even methylationprofiling, which not all centers
can do.
So you might, you know yourneuropathology friend may say,
(10:52):
hey, I've sent the tissue to theNIH and once we get their
result we'll know what kind ofbrain tumor this is.
And so that can be really hard,I think, for patients, because
they're waiting, you know, foran answer.
I've heard also of severalsituations where a patient is
given a prelim diagnosis andthen the actual diagnosis
changes very radically whenthose specialized tests come
(11:13):
back.
So, for example, oh, it lookslike a low-grade glioma under
the microscope.
You know it's not veryproliferative, the KI-67 isn't
that high, but oh, by the way,it meets these molecular
features of a glioblastoma.
Now we have to treat it like aglioblastoma.
The prognosis is like aglioblastoma.
That can be really jarring forfolks.
And I think the other thing toois that you know the
(11:34):
availability of some of thesespecialized tests is not, it's a
bit limited.
And so for patients who alreadyhave, you know, barriers to
accessing medical care or seeinga subspecialist, you know they
may miss out on some of thesethings.
And you know, to give an example, when I first started working
(11:55):
as an attending, I had a patientwith a glioma that had an Ntrek
fusion, and Ntrek fusions areonly in 1% or 2% of primary
brain tumors.
It's quite rare.
But we identified it when hecame to us and you know we
started an N-TREK inhibitor andthat can actually shrink these
kinds of tumors and inneuro-oncology we have better
treatments than we used to butwe still don't have a whole lot
(12:15):
that will shrink or make a tumorgo away.
And unfortunately we startedthis, you know, too late for
this patient and he ultimatelysuccumbed to his disease
relatively quickly, especiallybecause there was a period of
time where we were fighting withinsurance with a prior
authorization, but when I sawhim it was about eight months
after his initial diagnosis.
It's just that he was at a placethat was not able to identify,
(12:38):
not able to perform the fusiontesting to identify that NTRK
fusion, and so I do veryfrequently wonder, you know, he
would have had a very differentoutlook and in clinical course
had he been at a place thatcould order and perform that
testing expediently right fromthe get go, and that kind of
inequity bothers me and so youknow I think the field is is
(13:02):
racing forward, but we got tomake sure everybody you know is
able to benefit from that, and Ikind of went in a weird little
tangent on that.
But I think those are a coupleof elements about my field that
I think are really interestingproblems.
Dr. Michael Kentris (13:15):
No, I really appreciate the
perspective.
That kind of dovetails wellinto my next question was and
you hinted at this a bit some ofthe challenges that are more
unique to a neuro-oncologypractice.
Dr. Ashley Aaroe (13:28):
Yeah, I would say definitely.
Access to things like clinicaltrials and to advanced tumor
testing is something that isvery much.
They're buzzworthy topics in myfield as we try to tackle these
issues for our patients.
I think that disparities inneuro-oncology are, you know,
(13:49):
it's an emerging field but notfully studied yet.
I think it's thought of, youknow by a lot of folks that, for
example, glioblastoma is adisease of elderly white males,
and you know definitely that isthe demographic that we see most
commonly.
But it's still important toaddress, you know, populations
(14:11):
of patients that are not, youknow, that demographic and try
to some things where there's no100%.
This is the answer to how we dothings and, to give an example,
(14:32):
there's a type of low-gradeglioma called an
oligodendroglioma, or an oligofor short, and these are tumors
that are relatively slow-growing, indolent.
Patients tend to live with themfor a long time before they
progress or ultimately limittheir life expectancy.
And so, because of how rarethey are compared to things like
(14:53):
lung cancer, because they'rerelatively indolent to begin
with, you know, recruitingpatients into a clinical trial,
then waiting for that data tomature takes a lot of time, and
so there's still some equipoiseabout you know, two different
chemotherapy regimens.
There's camp temozolomide andthere's camp PCV, which is a
three drug regimen.
We should have answers to that,you know, pretty soon.
(15:15):
But even now, when you go toone center for another, it's
very practice dependent becausewe still don't have that final
answer.
And so there's a lot of gray.
There's a lot of you know I dothis because I was trained this
way, but I think there's a lotleft to be explored.
I guess my other thought about aunique thing in neuro-oncology
and it's certainly somethingthat's not surprising or strange
(15:39):
to neurologists who treat anumber of rare and serious
conditions is just the access tonew drugs and to clinical
trials and then alsocompassionate use.
It's something that patients arevery interested in and it's
sometimes really hard to getthem these therapies, and if you
can't get someone, you know thenew drug that's on the market.
(16:01):
I think there are also a lot ofpeople who you know are filling
in the gaps with other thingsand so, for example, trying to,
there's a lot in theneuro-oncology community about
things like CBD or ivermectinand the, you know, fibendazole,
and those are things that Idon't prescribe in my practice,
(16:22):
but I think, because you know,we don't have the cure for
glioblastoma.
You know there's such a seriousand horrifying condition to be
diagnosed with, you know, for apatient.
But I think people are justlooking for every possible thing
that they can do to fight thesetumors.
And so I think it's toughbecause as a neuro-oncologist I
feel like my job is to have, youknow, conversations where I can
(16:44):
really help people vet what'sout there.
But the truth is people arelooking to complementary and
alternative approaches justbecause, you know, we don't have
very good chemos yet, we don'thave the cure for GBM quite yet.
So I think handlingmisinformation and we all know
that that's proliferating in thesocial media age is another
element to what makes practiceneuro-oncology a little bit
(17:05):
challenging sometimes.
Dr. Michael Kentris (17:07):
No, that's great, and I mean not great, but
it's great thoughts on it.
One of the things you mentionedearlier you had this patient
who you were trying to get adrug approved and the prior
authorization process heldthings up and, as you said, with
many rare conditions, notnecessarily unique to
(17:27):
neuro-oncology or even neurologyat large, is that we have these
pathophysiologic theories ofhow things may work and a
medication that theoreticallyshould have an effect on a
pathway which we know it doesn'talways work that way.
But when we don't havenecessarily an quote-unquote
FDA-approved option, I find thatwe often are reaching for some
(17:49):
of these options.
How often do you find that theinsurance issue is a blockage
for trying treatments inhospitals what may otherwise be
appropriately selected patients?
Dr. Ashley Aaroe (18:02):
So I would say I'm pretty privileged,
practicing where I do, that Ifeel like there are several
small armies that will help menavigate insurance issues, and a
lot of oncologists don't haveaccess to that kind of support.
I would say that there areemerging sort of tumor agnostic
indications.
So, for example, if my patientwith a glioma that glioma has
(18:26):
the BRAF V600E alteration, whichis more classically known to be
associated with melanoma, it isincreasingly easier for me to
borrow a melanoma drug or atargeted therapy and use it to
treat my patient with glioma,especially because some of the
basket trials that have beendone, which are it's, you know
all comers, solid tumor typeswith this alteration, I think so
(18:50):
it's getting easier.
I would say that it's still aprocess and it's not infrequent
that in my mind, as I decide youknow what therapy should a
patient be receiving next, andas I decide you know what
therapy should a patient bereceiving next, that one factor
in my mind is well, how quicklycan I get something that's off
label or, you know,compassionate use?
(19:10):
You end up working prettyclosely with some of these
pharmaceutical companies andreally in some ways relying on
their medical liaisons to sayyou know, hey, can you help me
get this paperwork processed assoon as possible, or is there
any way that you can help us out?
It's definitely getting easier,but still tough.
Dr. Michael Kentris (19:31):
No, that makes sense.
In neuro-oncology, obviouslywe're dealing with people who
have usually very serious, oftendisabling types of diseases.
There's the medical piece of it.
But in terms of working withtherapists, whether speech
therapists, physical therapists,other types of assistive device
type programs, is that a commonpart of your practice and, if
(19:56):
so, what are the unique hurdlesthat you might have to jump
through there?
Dr. Ashley Aaroe (20:00):
Absolutely, I would say.
The majority of my patientswith brain tumors are actively
participating in physical,occupational, speech or
cognitive therapy.
It's also part of ourinstitutional guidelines that
folks with brain tumors that youconsider getting a baseline
neurocognitive assessment andalso repeating that assessment
at certain intervals followingtreatments like radiation, most
(20:23):
classically, that you'remonitoring for cognitive
disability.
So it really does becomemultidisciplinary, and we are
lucky to have a greatneuropsychology team and I think
their input is really valuableas well.
I would say that there's anemerging understanding of the
importance of neuropalliativecare in brain tumors and so
(20:47):
often involving a supportivecare team or a multidisciplinary
palliative care team early on,you know, not only improves
quality of life but can actuallyhelp folks with brain tumors
live longer too, and so I thinkvery much continuing to
destigmatize palliative care andreally emphasizing, you know,
(21:07):
we need to take care of you as aperson and not just try to, you
know, kill as many tumor cellsas possible that too, but you
know it should be a kind ofintegrated thing.
I think all of those elementsare really important.
Sometimes patients, you know,will have issues related to
chronic pain as well, and so,you know, will have issues
related to chronic pain as well,and so you know, for example,
I've had patients who had, youknow, an extensive spinal
(21:30):
surgery for their spinal cordependymoma and they have no
evidence of disease, but they dostill follow frequently with me
with supportive care, you know,with pain management, as
they're on surveillance, and forphysical therapy, rehab,
getting Botox, you know, forspasticity.
All of those are really crucialpieces of the care.
Dr. Michael Kentris (21:48):
Gotcha and that's a great point that you
bring up is that even if we have, let's say, surgical, or
someone goes into remission,that doesn't necessarily mean
that they're going to besymptom-free.
Dr. Ashley Aaroe (21:59):
Yeah, I think that's very true, and I think we
also have to be very cognizantof what we can do iatrogenically
with the treatments that wehave.
You know, for example, a lot offolks with low-grade glioma are
diagnosed when they're in theiryoung adulthood, and you know,
if you treat them with radiationand granted, there are new
(22:21):
radiation techniques, likeprotons specifically, that may
have a lower risk of delayedmemory or neurocognitive
sequelae but that's stillsomething that you have to think
about, where you know, if youjump to radiation for a patient
with a low-grade glioma, youknow chances are that they are
going to have some memorytrouble after that, and so you
(22:41):
know that plays into selectingpatients for different treatment
options and also knowing whenis the right time to initiate
treatment, and so for somepatients with a low-grade glioma
, you might reasonably observethem after resection before
going to radiation, just due tothat concern.
A lot of patients also are, youknow, glioblastoma patients.
(23:03):
Again, classically are oldermales, but we do see
glioblastoma and otherhigh-grade gliomas affect
younger folks too, and so youhave to think about will you be
impairing someone's fertility bygiving them alkylating
chemotherapy?
So you know, fertilitypreservation is something that
we have to talk about and thereare even more.
You know specific preservationis something that we have to
(23:23):
talk about, and and there areeven more, you know specific
considerations for adolescentand young adult patients too.
So those are all things thatthat are also in the back of my
mind, you know, when I see apatient with a new diagnosis of
a brain or spine tumor.
Dr. Michael Kentris (23:35):
No, that's her.
Yeah, I, I always forget aboutthe fertility aspect, you know,
even for you know, young men aswell as women.
So do you work pretty closelywith like a certain are there.
I guess this is a bit of astrange word.
Are there specialists withinreproductive medicine who
specifically work with like kindof those pre-treatment oncology
(23:55):
patients?
Dr. Ashley Aaroe (23:56):
Yeah, oncofertility is also a very
growing field For us at mycenter.
Growing field For us at mycenter it's housed within the
adolescent and young adultmedicine practice.
So those patients for example,if I refer a brain tumor patient
to their practice, they'reassessing them for physical
(24:16):
occupational therapy needs.
How are they doing with ifthey're still in school or if
they're working?
How are they navigating thatwith their brain tumor?
There's emotional supportsupport groups and then also
there will be someone fromgynecologic oncology or urologic
oncology that's helping withfertility preservation.
Those folks also get genetictesting.
I really love the practice ofthat group because I do think
(24:38):
that it sort of it highlightshow many resources are needed to
take the best care of patientswith cancer.
And I think also they remind meof survivorship considerations,
like we were just talking about.
Because I think you know, ofcourse, when you're dealing with
a brain tumor, especially anincurable brain tumor, you want
(24:59):
to be aggressive, you want tokeep that from recurring for as
long as possible, but I thinkthat you can't forget about the
survivorship piece too.
Dr. Michael Kentris (25:07):
No, that's a great point To switch gears.
Just a little bit about thesystemic toxicities of cancer
treatment.
So you mentioned obviously alot of times we have patients
with chemotherapy-inducedneuropathy and does your
practice you know obviously alot of us in medicine we know
(25:28):
about gabapentin, pregabalin,kind of the usual neuropathy
meds.
Does your practice differ inany particular way or do you
have any special tricks forthese types of patients?
Dr. Ashley Aaroe (25:38):
Yeah, so that's a great question.
There are many, many differentways to delve into that.
I would say there's forchemotherapy-induced peripheral
neuropathy specifically, there'sa lot of benefit at least in
the literature and in mypractice to things like Cymbalta
or the TCAs.
I think the other thing that'simportant to know is that in
(26:02):
order to get a benefit fromthings like gabapentin or Lyrica
, you may actually have to uptitrate to a pretty hefty dose.
Too often I've seen folks thatget started on like 300 of
gabapentin at night and then itdoesn't do anything and then we
just stop it saying it didn'twork, so really giving it a
little bit of time.
This is purely anecdotal, but Ido like some compounding creams
(26:26):
with like amitriptyline andketamine that can be applied
topically.
I think in general we havebetter interventions for
paresthesia and pain than we doto restore a lack of sensation
from chemotherapy relatedneuropathy, and you see patients
that are really debilitated dueto gait instability because
they can't feel the ground.
I've seen, actually, a coupleof patients get into motor
(26:50):
vehicle accidents because theyhave issues with gauging the
pressure on the gas or the brakepedals, and so it's, I think,
something that is important tohone in on One area specifically
with neuropathy that I'minterested in is how do you
identify patients that are atparticular risk?
So we know certain drugs areassociated more highly with
(27:14):
neuropathy, like taxols,platinum-based chemotherapies
notorious culprits but how do weidentify patients who are at
particularly high risk?
So I would say, maybe once ortwice I've seen a patient that
had really high arches and hadspecific sort of leg and foot
anatomy.
(27:34):
That made me think, oh, maybethey have charcomeree tooth,
which is an underlying heritableneuropathy, and we did actually
diagnose it.
And then we are neuropathy andwe did actually diagnose it, and
then we are out.
We should probably try to think, you know, of other non
platinum based chemotherapies,and so that was like a really
nice you know being able to talkto the oncologist about hey,
I'm really worried that this isa high risk patient, even though
(27:57):
he doesn't subjectively have alot of symptoms from it.
He probably will if we give himsomething very neurotoxic.
So I think you know, aside fromthat very specific kind of
situation, we need to do abetter job of realizing who's at
risk.
I think my major takeaways wouldbe that there are certain
chemotherapy-associatedneurotoxicities that are really
(28:21):
well described in the literature.
For example, cytarabine causescerebellar dysfunction,
Methotrexate causesleukoencephalopathy, among other
things, and so for aneuro-oncologist, those
associations get kind of bakedinto us and so we can help folks
, you know, understand, you know, is the patient developing this
(28:42):
neurological symptom due totheir therapy or due to
something else?
And I think that that's a wayin which we can advise our
medical oncology colleagues.
I would say.
Also, with regards toimmunotherapy, I would say that
immunotherapy associatedtoxicities that mimic idiopathic
(29:03):
neurological conditions aredifferent animals.
So, for example, you can have aGuillain-Barre-like syndrome
from checkpoint inhibitors.
In many ways that's similar toan idiopathic Guillain-Barre.
That happens after somebody hasa diarrheal illness, but it can
behave differently too.
So, for example, I have seensome cases, certainly less
(29:25):
common, where they can havemultiple sort of relapses
instead of being a monophysicillness like it would be
obviously for regularGuillain-Barre, if you will.
I think it's also reallyimportant to know oh gosh, I'm
going off on another tangenthere, so feel free to stop me.
Dr. Michael Kentris (29:44):
No, no, I'm loving it.
Dr. Ashley Aaroe (29:48):
For my field it's really important to know
the history of treatmentsomebody has received and the
sequence, and also to know themechanisms of action.
So my first question foranybody who is on a clinical
trial is that a bispecificT-cell engager that I might
expect to have a risk ofdeveloping encephalopathy?
Or, you know, is it somethingconjugated to a taxol that might
(30:12):
also produce neuropathy, eventhough that hasn't been
described in the literature?
Because this is the first, youknow, phase one study that this
is being used for.
So stuff like that, I think, iskind of unique to my field too.
Dr. Michael Kentris (30:25):
No, that's super important to know.
I know.
I've know at least even where Iam at a non-academic community
hospital, probably at least twoor three times a year I'll see
someone who has somecomplication of immunotherapy,
like all the CAR T-cell typestuff, and I've seen a myositis,
a myasthenia type and, as yousaid, a GBS type presentation
(30:48):
all within just the last year.
And, as we know, sometimes wehave our traditional treatments
for these disorders andsometimes we don't see the same
kind of responses to treatmentthat we would normally expect.
So I guess what I would say isso, let's say I have a lot of
times where I would be doingsteroids or IVIG or plasma
exchange.
Is there any evidence for goingkind of beyond that to like we
(31:11):
would in some of thoserefractory cases where we're
using, like rituximab or evencyclophosphamide or you know,
ironically treating chemotherapyinduced problems with more
chemotherapy?
Dr. Ashley Aaroe (31:20):
Yeah.
So I would say we see thatpretty frequently here.
So for here you know and Ithink a lot of institutions are
similar you know that they use agrading system for
neurotoxicity and if it's a highenough grade or severity you
will treat it very aggressively.
So I've seen patients withRituxan and Fliximab like pretty
early on, just jump straight toPlex, you know, hit it with
(31:43):
everything, just because thesetoxicities can be so severe.
I would say that in terms ofimmunotherapy related toxicities
, you also have to balance yourinterventions with the risk of
interfering with the treatmentefficacy.
So I would say, as a generalphenomenon, a lot of the
(32:06):
patients who developneurotoxicities will also be the
ones that develop a response, apositive therapeutic response
from a cancer perspective.
So, for example, there are someCAR T therapies that have an off
switch, if you will like.
If you develop a severe enoughtoxicity from it, you can give
something that will effectivelyshut the CAR T cells down.
(32:27):
And the decision about when todo that is, I think, obviously a
very high stakes one, not justfrom the neurological
perspective but from theoncologic one too, and that's
something that I've observedalso.
I've been fortunate to be, youknow, asked by some of my
medical oncology colleagues whoare working to develop new
therapies.
You know we see X symptom, thatyou know neurological symptom
(32:49):
develop, but we also notice thatthat's happening more in the
patients who are also havingtheir tumor shrink.
So how do we layer out, youknow, what doses or what
interventions are appropriate sothat someone can get the
maximal benefit but also not,you know, accrue more
neurological injury at the sametime?
And that's a very finebalancing act too.
Dr. Michael Kentris (33:08):
Those are great considerations.
I know it's easy for us asspecialists to sometimes get our
blinders on and just like wehave to stop the neurologic
process.
And then what about the cancer?
It does definitely become verytricky in those situations, and
this was something I just becamefamiliar with.
I think you had mentioned itjust briefly.
Was some of these likeinfliximab, which, if I remember
(33:30):
correctly, is IL-6.
Correct me if I'm wrong there.
Dr. Ashley Aaroe (33:35):
For infliximab TNF-alpha.
Dr. Michael Kentris (33:37):
Oh, okay, Now is this one of those new
protocols that is sort of likefor these CAR-T immunotherapy
type adverse reactions.
Dr. Ashley Aaroe (33:47):
So it is something that's in the
therapeutic armamentarium.
But what I would say is so ifwe're talking about CAR-T
neurotoxicity, there's a coupleof.
I think you may have beenthinking of tocilizumab, which
is anti-IL-6.
Yes, yes, so with regards tohow CAR-T cell neurotoxicity is
usually managed, so I can go ona whole separate thing about
(34:08):
that.
So we know that these patientsare at risk for developing
encephalopathy and also seizuresand also cerebral edema, which
can cause attendant ICP issuesif it's severe enough.
But typically what we'll see isthat patient receives CAR T
cells.
Then they might develop what'scalled cytokine release syndrome
.
A few days later, with fever,hypoxia, some systemic
(34:33):
manifestations, you'll see theircytokine levels in the serum
and then, a few days after that,you may start to see them
develop encephalopathy, and sotypically these patients become
inattentive and have difficultywith language first, and so
there's actually a gradingsystem, now called the ICE score
(34:53):
, where it's a score out of 10and you take away a point for
everything that the patient isnot able to do For example,
listing days of the weekbackwards, naming things,
writing a sentence, becausethese are all thought to be sort
of sensitive indicators ofneurotoxicity, and those
patients will receive steroids.
Now the cytokine releasesyndrome that often is
(35:15):
associated with and precedes thedevelopment of neurotoxicity
can be managed with an anti-IL-6agent like tocilizumab.
But tocilizumab does not treatneurotoxicity, and so the
mainstay of intervention isdexamethasone.
For the neurotoxicity piece Ihave read, and every single time
(35:36):
, I have to be honest, I forgetthe mechanism.
I learn it because I think it'sfascinating, and then I
immediately forget it.
But there is a mechanism bywhich tocilizumab may
paradoxically increase theamount of circulating IL-6
within the CNS because itdoesn't cross the blood-brain
barrier, and so just thetakeaway would be that
tocilizumab does not fix CAR-Tneurotoxicity it's really
(35:58):
steroids and if severe enoughthen you may consider other
agents like infliximab orrituxan or you know if the CAR T
product has sort of one ofthese off switches, if you will.
But I think it's, the story ofCAR T neurotoxicity is a really
fascinating one because you know, obviously this drug, this
(36:19):
treatment, comes down thepipeline.
That is, you know we're seeingamazing therapeutic responses.
But when we first started tosee neurotoxicity we didn't know
how to identify it quickly,grade it, and so if you look at
the literature, the incidence ofneurotoxicity in the early
studies for CAR T is all overthe place.
(36:41):
It's a very wide range and themorbidity and mortality from
neurotoxicity was also quitehigh.
So I think it's kind of forneurologists in general, you are
sort of at the forefront of,you know, as these drugs come
down the pipeline, trying tofigure out what is the
(37:03):
neurological piece of things andhow can we manage toxicity.
Dr. Michael Kentris (37:11):
No, yeah, that's very challenging.
I would be remiss if I didn'task a subject that's very much
on the mind of many neurologistswhen we encounter patients with
weird symptoms who have ahistory of cancer, whether
systemic or neurology, isperineoplastic syndrome, which I
know is.
You know, there's been aproliferation of antibody
(37:31):
markers over the last decade andthere seems to be no end in
sight.
One of the things I always readabout in the guidelines is that
we need to be looking forclinical signs and symptoms that
map onto a perineoplasticsyndrome and not just sending
antibodies willy-nilly.
But I would be curious to getyour perspective as someone
(37:52):
who's more in the weeds of it.
Dr. Ashley Aaroe (37:54):
Yeah, I think it's definitely hard to know
when to order the panel.
Do we do serum, Do we do CSF,Do we do both?
It's always a difficultdecision.
Classically, perineoplasticsyndromes are those that the
neurological symptoms are beforethe diagnosis of cancer and so
(38:15):
leading up to a diagnosis-known,well-documented, longstanding
history of cancer after theyreceive immunotherapy, if they
develop neurotoxicity.
It's very situation dependent.
(38:36):
But I think one thing aboutneurology in general that I find
myself constantly sort oftrying to explain to folks in
medicine or neurosurgery is thatit really isn't just the lab
test, and I think that'sparticularly true of
perineoplastic disorders.
So you might get something thathas a low or moderate positive
(38:59):
titer, but it may not fit theclinical syndrome and it may not
fit the underlying cancer too,and so then you really have to
question does that result meansomething or not?
And I think that's the beautyand pain of neurology is that it
really is everything togetherthe history, the exam and also
(39:19):
the data points.
So using those panels in acircumspect way is challenging,
I have to admit.
There are cases where I lookback and I think to myself why
did I order the panels?
It was just we did not have asatisfactory other explanation,
but it was my suspicion for aparaneoplastic disorder really
(39:41):
high enough to justify doing it.
I've had situations where Ithought the exact opposite.
So it's all that to say thatit's tough, but I think that you
touched upon or alluded to thatit really has to be in the
appropriate clinical setting.
Dr. Michael Kentris (39:56):
Yeah, I've definitely been in that same
boat where I've had this likeyeah, this is a strange
constellation of symptoms and Iorder a perineoplastic panel and
I get a weak positive back on.
Something like this doesn't fitat all.
But now I have to spend allthis time explaining to the
patient.
You know all the things thatyou just said and you know
sometimes it goes over well,sometimes I'm referring for a
(40:17):
second opinion.
But yeah, it can be achallenging situation when you
open that Pandora's box.
Dr. Ashley Aaroe (40:23):
For sure.
Dr. Michael Kentris (40:24):
One other thing I was curious to ask you
when I was reading through yourprofile is that you've done a
lot of work with advocacy, withpublic policy, with the American
Academy of Neurology as well asthe National Brain Tumor
Society, and for those of ourlisteners who work in healthcare
, whether they're nursingphysicians et cetera what does
that look like?
How does one become involved,and what kind of career personal
(40:48):
satisfaction have you gottenfrom your work there?
Dr. Ashley Aaroe (40:51):
Yeah.
So I first got into advocacythrough the American Academy of
Neurology with their eventNeurology on the Hill, and that
was really eyeopening.
So at the time that Iparticipated I was in residency
and I think a lot of folks willhave the residency clinic
experience in which there arelimited resources to help your
(41:12):
patients.
You're kind of like a safetynet sort of, and there are so
many things about the practiceof medicine that you wish you
could change but you feelhelpless to, especially when
you're still a trainee.
And so I felt like by gettingto go to one of these events
where they have folks that willtrain you in how to be an
effective advocate, how toconvey something about your very
(41:35):
, very specialized field and thething that you really care
about, how do you explain thatto somebody that has no
background in what it is thatyou're talking about and how do
you get them as passionate aboutit as you?
I think that was a reallyexciting experience, and so I
continued some of the workthrough Head to the Hill with
the National Brain Tumor Societyas well.
So there are a variety ofevents through medical societies
(41:56):
and patient advocacy groupsthat you will be able to either
go to Capitol Hill to meet withlawmakers and their staff, or
even locally, you know havingmeetings with your local
legislators, or even locally,you know, having meetings with
your local legislators.
Something that stays with meabout these experiences is that
(42:18):
I think when I was at aneurology on the Hill you know
these little cafes undergroundas you go from one building to
another in DC and there was arepresentative from a group for
rare genetic disorders,mitochondrial disorders, and
they had been doing theiradvocacy work for a really long
time and they said you know, thething about it is that
everybody can generally agreethat we should help people who
(42:39):
are sick and that we should tryto advance science and medicine,
but nobody's really againstthat.
But where that falls in termsof somebody's priority list, as
they're also jugglingconsiderations about education
and infrastructure and otherthings, it's easy for for things
to get lost in the wayside, um,especially if, if they're more
(43:02):
rare conditions, um, and soreally, I think being an
effective advocate is being agood teacher and a good
storyteller of hey.
This is why you should spare amoment to think about this
specific issue and how do wemake this better?
Advocacy for me reallymitigated a lot of symptoms of
(43:31):
burnout that I was experiencingas a resident, because I felt
empowered to have a voice andaddress some of the systemic
things that I didn't think Icould do anything about
otherwise, and I really enjoyedmeeting with other like-minded.
You know neurologists and otherhealthcare providers, but also
you know patients and familymembers, who are the most
important.
You know pieces of of advocacywork.
(43:51):
It just it's very modifying,motivating and satisfying.
That was modifying, that's anew word for today, so I'm
really passionate about it and,again, I think it's something
that we're starting to talkabout in neuro-oncology as a
field and a lot of folks aredoing great work, like Joshua
Boudou up at Memorial SloanKetter.
Dr. Michael Kentris (44:13):
Awesome, that's great, and I'd just like
to get your final thoughts.
This is a very fast-movingfield, lots of developments in
the pipeline.
What do you hope to see in thenext five years or so?
Dr. Ashley Aaroe (44:30):
And again, I think we're doing better at
exposing residents to it,getting residents excited about
it.
I think also, you know, from atherapeutic perspective for the
primary brain tumors, I'm reallyhopeful about unlocking things
like targeted therapy.
(44:50):
For example, the IDH inhibitorvoracidinib is getting a lot of
buzz based on a trial calledIndigo out of Sloan-Kettering
last year.
I think we'll start to see moretargeted therapies.
I think we'll start to be ableto integrate them into how we
treat patients.
So it's not just having thedrug available but knowing when
and how to use it.
I think that we need to learnmore about, but I'm hopeful
(45:12):
about that.
I'm also hopeful aboutunlocking the potential of
immunotherapy for brain tumors.
So, historically, you knowthings like CAR-T for gliomas,
you know vaccines, you know havebeen less promising but less
effective, you know in oldstudies.
But there's more and morestrategies that are coming down
(45:34):
the pipeline that I do thinkwe're on the brink of
incorporating immunotherapiesand targeted therapies into our
day-to-day practice.
So I'm hopeful about that.
I'm hopeful for helpingpatients with brain tumors live
longer and live better andultimately, you know, the thing
we're all shooting for is a curefor brain tumors and gliomas,
(45:54):
and you know so I have hope forthat too.
With regards to cancerneurology, I think that again,
we need to do a better job ofidentifying the populations of
patients most at risk fordeveloping things like
chemotherapy, associatedcognitive impairment and
neuropathy.
I think we'll do a better jobof identifying biomarkers of
(46:18):
patients who are developingthose issues, hopefully while
they're still mild or evenpotentially preclinical.
It could be someday that we seea lab value that tells us ah,
this is increasing.
I don't know if that's going tobe something like a change in
BDNF or a neurofilament linechain, but maybe, oh, we should
watch this patient a little bitmore closely for the emergence
(46:39):
of some neurological processrelated therapy.
I think those are the thingsthat I look forward to
Ultimately.
I mean, I'm super biased, but Ithink my field is an extremely
exciting one.
I feel like you know thefeeling I get when I come to
work is is what it must have.
(46:59):
I imagine okay, I'm being alittle melodramatic here, but I
can't stop myself I imagine it'ssimilar to what it would have
been like working at NASA in thein the sixties, because there's
just stuff happening.
There's a lot of passionate,interested, motivated you know
people from differentbackgrounds across medicine and
science that are doing amazingwork, and the field is changing
(47:21):
every day.
So that's that's what I what Ithink is is exciting about my
field and I am quite certainthat five years from now, sure
there'll be things that areadvanced in immunotherapy,
targeted therapy, stratifyingpatients.
I'm sure something's going tohappen that I have no faint idea
(47:41):
what that is and it's justgoing to come out of nowhere and
it's going to revolutionize howwe approach patients with
cancer and brain tumors.
That I think is awesome.
So, anyway, I'll stop myselfreigning in a little bit there.
Dr. Michael Kentris (47:53):
But yeah, no, the enthusiasm is infectious
.
This is making me excited, youknow, if someone who's normally
I'm not going to say superenthused about neuro-oncology,
this is very exciting to me aswell, and you know, obviously
practicing in a more generalneurology setting it's.
I think it behooves us to beaware of these advancements and
(48:14):
how we can further treat ourpatients who may, as you said,
not have ready access to thesemore tertiary or even quaternary
academic centers where thereare these other things available
.
What can we still do in theseother settings to improve
quality of life and outcomes.
Dr. Ashley Aaroe (48:32):
If I can say, one final soapbox that I have is
keep an open mind, because careof patients with cancer is
changing so quickly.
For example, it used to bethought of that, you know, a
patient with cancer that has alarge vessel occlusion for
stroke is not going to benefitfrom a thrombectomy because they
have cancer right.
(48:53):
So challenging those kinds ofstigmas I think is important.
There were some studies thatcame out that showed, even
though there is a higher risk ofsymptomatic ICH in patients
with large vessel occlusionstroke that undergo thrombectomy
, who have cancer, that they canhave comparable functional
outcomes and benefits and thatthere are patients with cancer
that you know, even stage fourcancer that can live for a long
(49:17):
time.
You know, even stage fourcancer that can live for a long
time, you know.
So I think it's just aboutkeeping an open mind.
You know, for the generalneurologists that are out there,
that you know having cancer andwhat that means really looks
very different than it did acouple decades ago, and so I
(49:37):
think, again, keeping an openmind is super important.
Dr. Michael Kentris (49:43):
That's very well said and, to borrow a
phrase or a concept from ourneuro ICU colleagues, we have to
make sure that we avoid medicalnihilism, right?
This belief that everything'sgoing to be bad and then we do
nothing and it is bad and wewere right the whole time.
It's very much aself-fulfilling prophecy if we
just let it be that way.
Dr. Ashley Aaroe (50:02):
I think that's a great point and it's funny
that you mentioned that.
I feel like there's a very oddthread that links neuro-oncology
and neuro-critical care andit's something that I would have
never appreciated as a resident, because neuro-ICU was not my
thing and any of my faculty whotrained me could probably tell
you that.
But my husband's a neurointensivist and he says neuro
oncology is neuro critical carein slow motion and I think
(50:25):
there's something to that.
But I think that it's kind of anice little phrase that he came
up with.
I think it rings true and Ithink that you're exactly right
about one of those kind ofconnections being that how you
approach a patient and how youapproach a situation can have
(50:45):
significant bearing on theoutcome, and avoiding
therapeutic nihilism is reallyimportant much for coming on and
talking with us today.
Dr. Michael Kentris (51:01):
I certainly feel uplifted by your
enthusiastic outlook on thefuture and I appreciate you
sharing all of your insights.
If people want to find some ofthe work you've done or find you
online, where should they look?
How should they reach out?
Dr. Ashley Aaroe (51:09):
I do.
I'm not great at X, but I am onX, if you find me, which I
still want to call it Twitteranyway, but I am always happy to
connect about neuro-oncology,and thanks for letting me ramble
at you.
It was just about the thingthat I love talking about.
Dr. Michael Kentris (51:28):
No, I appreciate it.
That's why I love being able tohave folks like yourself on
here is to hear about theirpassions and hear like the good
things that are coming in thefuture.
So thank you very much again.
If people want to find me, I'malso on x slash Twitter at Dr
Kentris D-R-K-E-N-T-R-I-S, andyou can also find our past work
(51:51):
on the website attheneurotransmitterscom.
Thank you so much again forcoming on and I really
appreciate it.
Thank you.
Hello and welcome back to the
Neurotransmitters.
I'm your host, dr MichaelKentris, and today we're going
to be talking about a prettycomplicated field, at least
that's how I feel about it.
We're going to be talking aboutsome neuro-oncology and to help
me out with that, I'm veryfortunate to have Dr Ashley
Aaroe, neuro-oncologist at MDGod.
(00:23):
I've already messed up at MDAnderson, where she is currently
in attending also did herfellowship in neuro-oncology
there after completing neurologyresidency at Cornell.
So thank you so much forjoining us.
Dr. Ashley Aaroe (00:36):
Thank you so much.
I'm really excited to join youtoday.
Dr. Michael Kentris (00:39):
So first of all, tell me a little bit about
for those who might be a littleunfamiliar.
First of all tell me a littlebit about for those you know who
might be a little unfamiliar.
Obviously we know what oncologyis, generally speaking, but
what's?
Dr. Ashley Aaroe (00:52):
different about neuro-oncology other than
just being brains?
Yeah, no, I really love to talkabout it.
I think even within neurologyresidency, you know, not all
residents are exposed toneuro-oncology or have an idea
of what it means, and soincreasing awareness is how we
get people interested in goinginto the field.
What a neuro-oncologist does isit can be a little bit
different depending on where youpractice.
So there are someneuro-oncologists that are
(01:15):
really focused on prescribingchemotherapy for primary brain
tumors like glioblastoma, forexample, and there are other
neuro-oncologists who are morefocused on treating patients
with neurological complicationsof systemic cancer and cancer
therapy.
What really drew me to thisfield is that you can do a
little bit of everything, soneuro-oncology is very much at
(01:38):
the center of all the thingsthat I really love about
neurology.
So you treat cerebrovascularpathology, because patients with
cancer have a higher incidenceof stroke.
You also see tumor-associatedepilepsy.
You see neuromuscularcomplications of checkpoint
inhibitor immunotherapy.
Those are just a few examples,but even you know headache and
(02:02):
autoimmune neurology get foldedinto neuro-oncology.
I think as a neuro-oncologisttoo again, depending on where
you practice you have theopportunity also to be in some
ways like a primary care doc foryour patients.
For example, my glioblastomapatients aren't following with
their, your PMD as frequentlyand I see them every one or two
months for chemotherapyclearance.
(02:23):
So you take over a little bitof family practice.
You have to know a little bitof internal medicine as well,
and so it's kind of you get todabble in a lot of different
things.
It used to be thatneuro-oncologists really came
from the medical oncologytraining pathway, so people who
go into internal medicine do amedical oncology fellowship and
(02:44):
then are drawn into a moreneuro-based practice again for
brain tumor cancer treatment.
But then the neurologist feltthat we should be able to bridge
this gap and so more and morepatients are I keep saying,
patients.
I don't know why it's on mymind, um, but um, but more and
more people are going through aneurology pathway.
Dr. Michael Kentris (03:06):
Excellent.
Yeah, it is something that Iknow.
I didn't graduate residencythat long ago, but it was one of
those things where I didn'treally consider it much unless
you were going to be at one ofthose bigger academic
institutions as necessarilybeing like a viable career
pathway.
Are we seeing moreneuro-oncology, more neurology
(03:29):
residents, I should say,entering the field of
neuro-oncology in general, youthink?
Dr. Ashley Aaroe (03:33):
I do.
I think we are doing a good jobof getting neurology residents
interested in and exposed to thefield.
I would say that you know, forme I thought I was going to be a
movement disorders neurologistwhen I matched into neurology
residency and that's when someof my background in medical
school and research had been.
But I just really got suckedinto neuro-oncology and when I
(03:55):
rotated at Memorial SloanKettering as a resident, those
were the patients that Icouldn't stop thinking about in
the cases that I couldn't stoptalking about.
So really that exposure made ahuge difference in my career
trajectory.
There's very much a need forneuro-oncologists.
There's a shortage ofneurologists in general and
(04:16):
neuro-oncology too.
I feel like our patients oftenhave cognitive or mobility
concerns.
They may not be able to make itto a large center like Sloan
Kettering or MD Anderson, and soa lot of places are recruiting
neuro-oncologists and you couldbe, you know, a neuro-oncologist
(04:36):
in an academic medical center,but even so be only one of one
or one of two, or, you know,there's also a role for
neuro-oncologists in thecommunity as well, outside
academia, and so it's very mucha growing field, but one that
still has a shortage ofpractitioners compared to the
patient volume and need.
Dr. Michael Kentris (04:55):
No, I think that's an excellent point and
definitely some goodconsiderations for people who
might be considering it as acareer trajectory.
So you talked a little bitabout some of the common
conditions that you're dealingwith and how you are almost a
stand-in primary care physicianfor a lot of these patients.
I feel that is kind of anunder-recognized aspect of
(05:16):
neurology care in general.
For a lot of our chronicconditions is that you sort of
become the touchpoint for a lotof that person's medical care.
What does a day in the life ofa neuro-oncologist tend to look
like?
Dr. Ashley Aaroe (05:27):
That's a great question and I think that
that's extremely variable tooFor me.
In my practice I probably, Iwould say I'm about 50-50 in
terms of taking care of primarybrain tumor patients and taking
care of neurology consultationsin patients with systemic cancer
, and so I have, you know, twodays of clinic a week and then I
(05:49):
spend a varying amount of timeon our inpatient services.
So it really is, you know, kindof a week-to-week thing, but a
lot of folks are strictlyoutpatient in terms of their
practice.
So I have a pretty, you know,robust mix in clinic of patients
, you know, with example ofglioblastoma or medulloblastoma
(06:11):
rare tumor types I am reviewingtheir imaging treatment planning
.
I also have a very high numberof patients who, for example,
have peripheral neuropathy fromtheir taxal chemotherapy, and so
I'm managing that too.
I happen to really like thatmix and really like that
variability.
I find also that something thatI perhaps didn't know I would
(06:35):
be seeing as much of when I wasa resident, you know, applying
into neuro-oncology fellowshipthere's a lot of neuroimmunology
, and so I don't think Iappreciated how much I would be
haunted by misbehaving immunecells in my practice as a
neuro-oncologist, but a lot ofperineoplastic disorders,
complications of immunotherapy,which has very much
(06:55):
revolutionized the care of anumber of different cancers.
You know, I think melanoma is areally great example of that,
but there are many others.
And then also there are somediagnostic conundrums.
So you see an undiagnosed brainmass.
Is it a glioma?
Is it something else?
So I've stumbled acrossneurosarcoidosis and, you know,
amyloid related angiitis andvery other rare birds.
(07:19):
That way, just by virtue ofundiagnosed brain mass coming
into clinic, so it's a, just byvirtue of undiagnosed brain mass
coming into clinic, so it's a.
I think you can very muchtailor your practice to what
your specific area of interestis, but for me I really like the
variability.
Dr. Michael Kentris (07:32):
No, that's great, and I imagine
neuro-oncology kind of by itsnature is very much a
multidisciplinary type of fieldwhere you're working very
closely with both medicaloncologists as well as
neurosurgeons and probablygeneral surgeons of other
stripes as well.
Dr. Ashley Aaroe (07:49):
Yeah, absolutely, and that's something
I really love about the field.
I kind of in some ways, youknow, every week at least once,
I see myself as a bridge betweenneurology and another specialty
.
For example, if there's apatient with lymphoma that's
involving the brain, I'm goingto be, you know, working with a
medical oncologist who's aspecialist in lymphoma
(08:10):
neurosurgeon to figure outshould be biopsy, you know, and
everybody has slightly differentperspectives just based on
their experience of how totackle a problem, and so I
really enjoy sort of being inthat liaison role.
Sort of being in that liaisonrole.
I would say, as aneuro-oncologist, I definitely
work the most closely with theneurosurgeons, the radiation
oncologists and theneuroradiologists and
(08:31):
neuropathologists.
I would say, as aneuro-oncologist, your best
friend is going to be someone indiagnostic medicine, because
the classification of braintumors in particular changed a
lot in 2021 with the new WHOguidelines.
There's so many intricaciesabout how these tumors are
classified and they havesignificant ramifications for
(08:55):
their treatment and prognosis,and some of these things are
very much hot off the press evensince the 2021 classifications
came out.
I would mention, too, thatthere are some brain tumors
where they have a characteristicappearance on imaging and that
is stuff that's really an activearea of study, and new things
are being discovered every daytoo.
Definitely, befriending yourneuroradiologist and your
(09:17):
neuropathologist is important inmy field.
Dr. Michael Kentris (09:20):
No, that makes a ton of sense and I
remember reading some of thoseguidelines just this last year,
and even from the time again youknow I graduated in 2017, it's
been such a shift where we'rekind of moving away from a lot
of the kind of traditional, likemicroscope based diagnosis to
these molecular markers andgenetic markers and it is
(09:44):
rapidly multiplying to kind ofjust a very labyrinthine amount
of knowledge.
Dr. Ashley Aaroe (09:49):
Yeah, I think the difficulty is that every
time we have a newclassification, our
understanding of these tumorschanges and then we have to look
through the previous literaturein a slightly different light.
But I was actually listening tothe continuum recently about
the cephalalgias, the autonomiccephalalgias, and talking about
how they have, you know, a veryrobust classification scheme and
it makes it much easier tostudy these disorders and
(10:10):
develop, you know, interventionsfor them and I think we're
getting there with my field too,but it is very nuanced and it
you know not to oversimplify toomuch, but it used to be.
You look under a microscope,you see a glial neoplasm,
microvascular proliferation.
You look under a microscope,you see a glial neoplasm,
microvascular proliferation, andnecrosis is GBM.
But now there are so manylittle things that have come
down the pipeline that you knowa patient that goes to the OR
(10:32):
gets a resection, they may ormay not have an integrated WHO
2021 classification by the timethey're discharged from the
hospital, because it may be thatthere's next generation
sequencing required of the tumortissue to know with certainty
what it is, or even methylationprofiling, which not all centers
can do.
So you might, you know yourneuropathology friend may say,
(10:52):
hey, I've sent the tissue to theNIH and once we get their
result we'll know what kind ofbrain tumor this is.
And so that can be really hard,I think, for patients, because
they're waiting, you know, foran answer.
I've heard also of severalsituations where a patient is
given a prelim diagnosis andthen the actual diagnosis
changes very radically whenthose specialized tests come
(11:13):
back.
So, for example, oh, it lookslike a low-grade glioma under
the microscope.
You know it's not veryproliferative, the KI-67 isn't
that high, but oh, by the way,it meets these molecular
features of a glioblastoma.
Now we have to treat it like aglioblastoma.
The prognosis is like aglioblastoma.
That can be really jarring forfolks.
And I think the other thing toois that you know the
(11:34):
availability of some of thesespecialized tests is not, it's a
bit limited.
And so for patients who alreadyhave, you know, barriers to
accessing medical care or seeinga subspecialist, you know they
may miss out on some of thesethings.
And you know, to give an example, when I first started working
(11:55):
as an attending, I had a patientwith a glioma that had an Ntrek
fusion, and Ntrek fusions areonly in 1% or 2% of primary
brain tumors.
It's quite rare.
But we identified it when hecame to us and you know we
started an N-TREK inhibitor andthat can actually shrink these
kinds of tumors and inneuro-oncology we have better
treatments than we used to butwe still don't have a whole lot
(12:15):
that will shrink or make a tumorgo away.
And unfortunately we startedthis, you know, too late for
this patient and he ultimatelysuccumbed to his disease
relatively quickly, especiallybecause there was a period of
time where we were fighting withinsurance with a prior
authorization, but when I sawhim it was about eight months
after his initial diagnosis.
It's just that he was at a placethat was not able to identify,
(12:38):
not able to perform the fusiontesting to identify that NTRK
fusion, and so I do veryfrequently wonder, you know, he
would have had a very differentoutlook and in clinical course
had he been at a place thatcould order and perform that
testing expediently right fromthe get go, and that kind of
inequity bothers me and so youknow I think the field is is
(13:02):
racing forward, but we got tomake sure everybody you know is
able to benefit from that, and Ikind of went in a weird little
tangent on that.
But I think those are a coupleof elements about my field that
I think are really interestingproblems.
Dr. Michael Kentris (13:15):
No, I really appreciate the
perspective.
That kind of dovetails wellinto my next question was and
you hinted at this a bit some ofthe challenges that are more
unique to a neuro-oncologypractice.
Dr. Ashley Aaroe (13:28):
Yeah, I would say definitely.
Access to things like clinicaltrials and to advanced tumor
testing is something that isvery much.
They're buzzworthy topics in myfield as we try to tackle these
issues for our patients.
I think that disparities inneuro-oncology are, you know,
(13:49):
it's an emerging field but notfully studied yet.
I think it's thought of, youknow by a lot of folks that, for
example, glioblastoma is adisease of elderly white males,
and you know definitely that isthe demographic that we see most
commonly.
But it's still important toaddress, you know, populations
(14:11):
of patients that are not, youknow, that demographic and try
to some things where there's no100%.
This is the answer to how we dothings and, to give an example,
(14:32):
there's a type of low-gradeglioma called an
oligodendroglioma, or an oligofor short, and these are tumors
that are relatively slow-growing, indolent.
Patients tend to live with themfor a long time before they
progress or ultimately limittheir life expectancy.
And so, because of how rarethey are compared to things like
(14:53):
lung cancer, because they'rerelatively indolent to begin
with, you know, recruitingpatients into a clinical trial,
then waiting for that data tomature takes a lot of time, and
so there's still some equipoiseabout you know, two different
chemotherapy regimens.
There's camp temozolomide andthere's camp PCV, which is a
three drug regimen.
We should have answers to that,you know, pretty soon.
(15:15):
But even now, when you go toone center for another, it's
very practice dependent becausewe still don't have that final
answer.
And so there's a lot of gray.
There's a lot of you know I dothis because I was trained this
way, but I think there's a lotleft to be explored.
I guess my other thought about aunique thing in neuro-oncology
and it's certainly somethingthat's not surprising or strange
(15:39):
to neurologists who treat anumber of rare and serious
conditions is just the access tonew drugs and to clinical
trials and then alsocompassionate use.
It's something that patients arevery interested in and it's
sometimes really hard to getthem these therapies, and if you
can't get someone, you know thenew drug that's on the market.
(16:01):
I think there are also a lot ofpeople who you know are filling
in the gaps with other thingsand so, for example, trying to,
there's a lot in theneuro-oncology community about
things like CBD or ivermectinand the, you know, fibendazole,
and those are things that Idon't prescribe in my practice,
(16:22):
but I think, because you know,we don't have the cure for
glioblastoma.
You know there's such a seriousand horrifying condition to be
diagnosed with, you know, for apatient.
But I think people are justlooking for every possible thing
that they can do to fight thesetumors.
And so I think it's toughbecause as a neuro-oncologist I
feel like my job is to have, youknow, conversations where I can
(16:44):
really help people vet what'sout there.
But the truth is people arelooking to complementary and
alternative approaches justbecause, you know, we don't have
very good chemos yet, we don'thave the cure for GBM quite yet.
So I think handlingmisinformation and we all know
that that's proliferating in thesocial media age is another
element to what makes practiceneuro-oncology a little bit
(17:05):
challenging sometimes.
Dr. Michael Kentris (17:07):
No, that's great, and I mean not great, but
it's great thoughts on it.
One of the things you mentionedearlier you had this patient
who you were trying to get adrug approved and the prior
authorization process heldthings up and, as you said, with
many rare conditions, notnecessarily unique to
(17:27):
neuro-oncology or even neurologyat large, is that we have these
pathophysiologic theories ofhow things may work and a
medication that theoreticallyshould have an effect on a
pathway which we know it doesn'talways work that way.
But when we don't havenecessarily an quote-unquote
FDA-approved option, I find thatwe often are reaching for some
(17:49):
of these options.
How often do you find that theinsurance issue is a blockage
for trying treatments inhospitals what may otherwise be
appropriately selected patients?
Dr. Ashley Aaroe (18:02):
So I would say I'm pretty privileged,
practicing where I do, that Ifeel like there are several
small armies that will help menavigate insurance issues, and a
lot of oncologists don't haveaccess to that kind of support.
I would say that there areemerging sort of tumor agnostic
indications.
So, for example, if my patientwith a glioma that glioma has
(18:26):
the BRAF V600E alteration, whichis more classically known to be
associated with melanoma, it isincreasingly easier for me to
borrow a melanoma drug or atargeted therapy and use it to
treat my patient with glioma,especially because some of the
basket trials that have beendone, which are it's, you know
all comers, solid tumor typeswith this alteration, I think so
(18:50):
it's getting easier.
I would say that it's still aprocess and it's not infrequent
that in my mind, as I decide youknow what therapy should a
patient be receiving next, andas I decide you know what
therapy should a patient bereceiving next, that one factor
in my mind is well, how quicklycan I get something that's off
label or, you know,compassionate use?
(19:10):
You end up working prettyclosely with some of these
pharmaceutical companies andreally in some ways relying on
their medical liaisons to sayyou know, hey, can you help me
get this paperwork processed assoon as possible, or is there
any way that you can help us out?
It's definitely getting easier,but still tough.
Dr. Michael Kentris (19:31):
No, that makes sense.
In neuro-oncology, obviouslywe're dealing with people who
have usually very serious, oftendisabling types of diseases.
There's the medical piece of it.
But in terms of working withtherapists, whether speech
therapists, physical therapists,other types of assistive device
type programs, is that a commonpart of your practice and, if
(19:56):
so, what are the unique hurdlesthat you might have to jump
through there?
Dr. Ashley Aaroe (20:00):
Absolutely, I would say.
The majority of my patientswith brain tumors are actively
participating in physical,occupational, speech or
cognitive therapy.
It's also part of ourinstitutional guidelines that
folks with brain tumors that youconsider getting a baseline
neurocognitive assessment andalso repeating that assessment
at certain intervals followingtreatments like radiation, most
(20:23):
classically, that you'remonitoring for cognitive
disability.
So it really does becomemultidisciplinary, and we are
lucky to have a greatneuropsychology team and I think
their input is really valuableas well.
I would say that there's anemerging understanding of the
importance of neuropalliativecare in brain tumors and so
(20:47):
often involving a supportivecare team or a multidisciplinary
palliative care team early on,you know, not only improves
quality of life but can actuallyhelp folks with brain tumors
live longer too, and so I thinkvery much continuing to
destigmatize palliative care andreally emphasizing, you know,
(21:07):
we need to take care of you as aperson and not just try to, you
know, kill as many tumor cellsas possible that too, but you
know it should be a kind ofintegrated thing.
I think all of those elementsare really important.
Sometimes patients, you know,will have issues related to
chronic pain as well, and so,you know, will have issues
related to chronic pain as well,and so you know, for example,
I've had patients who had, youknow, an extensive spinal
(21:30):
surgery for their spinal cordependymoma and they have no
evidence of disease, but they dostill follow frequently with me
with supportive care, you know,with pain management, as
they're on surveillance, and forphysical therapy, rehab,
getting Botox, you know, forspasticity.
All of those are really crucialpieces of the care.
Dr. Michael Kentris (21:48):
Gotcha and that's a great point that you
bring up is that even if we have, let's say, surgical, or
someone goes into remission,that doesn't necessarily mean
that they're going to besymptom-free.
Dr. Ashley Aaroe (21:59):
Yeah, I think that's very true, and I think we
also have to be very cognizantof what we can do iatrogenically
with the treatments that wehave.
You know, for example, a lot offolks with low-grade glioma are
diagnosed when they're in theiryoung adulthood, and you know,
if you treat them with radiationand granted, there are new
(22:21):
radiation techniques, likeprotons specifically, that may
have a lower risk of delayedmemory or neurocognitive
sequelae but that's stillsomething that you have to think
about, where you know, if youjump to radiation for a patient
with a low-grade glioma, youknow chances are that they are
going to have some memorytrouble after that, and so you
(22:41):
know that plays into selectingpatients for different treatment
options and also knowing whenis the right time to initiate
treatment, and so for somepatients with a low-grade glioma
, you might reasonably observethem after resection before
going to radiation, just due tothat concern.
A lot of patients also are, youknow, glioblastoma patients.
(23:03):
Again, classically are oldermales, but we do see
glioblastoma and otherhigh-grade gliomas affect
younger folks too, and so youhave to think about will you be
impairing someone's fertility bygiving them alkylating
chemotherapy?
So you know, fertilitypreservation is something that
we have to talk about and thereare even more.
You know specific preservationis something that we have to
(23:23):
talk about, and and there areeven more, you know specific
considerations for adolescentand young adult patients too.
So those are all things thatthat are also in the back of my
mind, you know, when I see apatient with a new diagnosis of
a brain or spine tumor.
Dr. Michael Kentris (23:35):
No, that's her.
Yeah, I, I always forget aboutthe fertility aspect, you know,
even for you know, young men aswell as women.
So do you work pretty closelywith like a certain are there.
I guess this is a bit of astrange word.
Are there specialists withinreproductive medicine who
specifically work with like kindof those pre-treatment oncology
(23:55):
patients?
Dr. Ashley Aaroe (23:56):
Yeah, oncofertility is also a very
growing field For us at mycenter.
Growing field For us at mycenter it's housed within the
adolescent and young adultmedicine practice.
So those patients for example,if I refer a brain tumor patient
to their practice, they'reassessing them for physical
(24:16):
occupational therapy needs.
How are they doing with ifthey're still in school or if
they're working?
How are they navigating thatwith their brain tumor?
There's emotional supportsupport groups and then also
there will be someone fromgynecologic oncology or urologic
oncology that's helping withfertility preservation.
Those folks also get genetictesting.
I really love the practice ofthat group because I do think
(24:38):
that it sort of it highlightshow many resources are needed to
take the best care of patientswith cancer.
And I think also they remind meof survivorship considerations,
like we were just talking about.
Because I think you know, ofcourse, when you're dealing with
a brain tumor, especially anincurable brain tumor, you want
(24:59):
to be aggressive, you want tokeep that from recurring for as
long as possible, but I thinkthat you can't forget about the
survivorship piece too.
Dr. Michael Kentris (25:07):
No, that's a great point To switch gears.
Just a little bit about thesystemic toxicities of cancer
treatment.
So you mentioned obviously alot of times we have patients
with chemotherapy-inducedneuropathy and does your
practice you know obviously alot of us in medicine we know
(25:28):
about gabapentin, pregabalin,kind of the usual neuropathy
meds.
Does your practice differ inany particular way or do you
have any special tricks forthese types of patients?
Dr. Ashley Aaroe (25:38):
Yeah, so that's a great question.
There are many, many differentways to delve into that.
I would say there's forchemotherapy-induced peripheral
neuropathy specifically, there'sa lot of benefit at least in
the literature and in mypractice to things like Cymbalta
or the TCAs.
I think the other thing that'simportant to know is that in
(26:02):
order to get a benefit fromthings like gabapentin or Lyrica
, you may actually have to uptitrate to a pretty hefty dose.
Too often I've seen folks thatget started on like 300 of
gabapentin at night and then itdoesn't do anything and then we
just stop it saying it didn'twork, so really giving it a
little bit of time.
This is purely anecdotal, but Ido like some compounding creams
(26:26):
with like amitriptyline andketamine that can be applied
topically.
I think in general we havebetter interventions for
paresthesia and pain than we doto restore a lack of sensation
from chemotherapy relatedneuropathy, and you see patients
that are really debilitated dueto gait instability because
they can't feel the ground.
I've seen, actually, a coupleof patients get into motor
(26:50):
vehicle accidents because theyhave issues with gauging the
pressure on the gas or the brakepedals, and so it's, I think,
something that is important tohone in on One area specifically
with neuropathy that I'minterested in is how do you
identify patients that are atparticular risk?
So we know certain drugs areassociated more highly with
(27:14):
neuropathy, like taxols,platinum-based chemotherapies
notorious culprits but how do weidentify patients who are at
particularly high risk?
So I would say, maybe once ortwice I've seen a patient that
had really high arches and hadspecific sort of leg and foot
anatomy.
(27:34):
That made me think, oh, maybethey have charcomeree tooth,
which is an underlying heritableneuropathy, and we did actually
diagnose it.
And then we are neuropathy andwe did actually diagnose it, and
then we are out.
We should probably try to think, you know, of other non
platinum based chemotherapies,and so that was like a really
nice you know being able to talkto the oncologist about hey,
I'm really worried that this isa high risk patient, even though
(27:57):
he doesn't subjectively have alot of symptoms from it.
He probably will if we give himsomething very neurotoxic.
So I think you know, aside fromthat very specific kind of
situation, we need to do abetter job of realizing who's at
risk.
I think my major takeaways wouldbe that there are certain
chemotherapy-associatedneurotoxicities that are really
(28:21):
well described in the literature.
For example, cytarabine causescerebellar dysfunction,
Methotrexate causesleukoencephalopathy, among other
things, and so for aneuro-oncologist, those
associations get kind of bakedinto us and so we can help folks
, you know, understand, you know, is the patient developing this
(28:42):
neurological symptom due totheir therapy or due to
something else?
And I think that that's a wayin which we can advise our
medical oncology colleagues.
I would say.
Also, with regards toimmunotherapy, I would say that
immunotherapy associatedtoxicities that mimic idiopathic
(29:03):
neurological conditions aredifferent animals.
So, for example, you can have aGuillain-Barre-like syndrome
from checkpoint inhibitors.
In many ways that's similar toan idiopathic Guillain-Barre.
That happens after somebody hasa diarrheal illness, but it can
behave differently too.
So, for example, I have seensome cases, certainly less
(29:25):
common, where they can havemultiple sort of relapses
instead of being a monophysicillness like it would be
obviously for regularGuillain-Barre, if you will.
I think it's also reallyimportant to know oh gosh, I'm
going off on another tangenthere, so feel free to stop me.
Dr. Michael Kentris (29:44):
No, no, I'm loving it.
Dr. Ashley Aaroe (29:48):
For my field it's really important to know
the history of treatmentsomebody has received and the
sequence, and also to know themechanisms of action.
So my first question foranybody who is on a clinical
trial is that a bispecificT-cell engager that I might
expect to have a risk ofdeveloping encephalopathy?
Or, you know, is it somethingconjugated to a taxol that might
(30:12):
also produce neuropathy, eventhough that hasn't been
described in the literature?
Because this is the first, youknow, phase one study that this
is being used for.
So stuff like that, I think, iskind of unique to my field too.
Dr. Michael Kentris (30:25):
No, that's super important to know.
I know.
I've know at least even where Iam at a non-academic community
hospital, probably at least twoor three times a year I'll see
someone who has somecomplication of immunotherapy,
like all the CAR T-cell typestuff, and I've seen a myositis,
a myasthenia type and, as yousaid, a GBS type presentation
(30:48):
all within just the last year.
And, as we know, sometimes wehave our traditional treatments
for these disorders andsometimes we don't see the same
kind of responses to treatmentthat we would normally expect.
So I guess what I would say isso, let's say I have a lot of
times where I would be doingsteroids or IVIG or plasma
exchange.
Is there any evidence for goingkind of beyond that to like we
(31:11):
would in some of thoserefractory cases where we're
using, like rituximab or evencyclophosphamide or you know,
ironically treating chemotherapyinduced problems with more
chemotherapy?
Dr. Ashley Aaroe (31:20):
Yeah.
So I would say we see thatpretty frequently here.
So for here you know and Ithink a lot of institutions are
similar you know that they use agrading system for
neurotoxicity and if it's a highenough grade or severity you
will treat it very aggressively.
So I've seen patients withRituxan and Fliximab like pretty
early on, just jump straight toPlex, you know, hit it with
(31:43):
everything, just because thesetoxicities can be so severe.
I would say that in terms ofimmunotherapy related toxicities
, you also have to balance yourinterventions with the risk of
interfering with the treatmentefficacy.
So I would say, as a generalphenomenon, a lot of the
(32:06):
patients who developneurotoxicities will also be the
ones that develop a response, apositive therapeutic response
from a cancer perspective.
So, for example, there are someCAR T therapies that have an off
switch, if you will like.
If you develop a severe enoughtoxicity from it, you can give
something that will effectivelyshut the CAR T cells down.
(32:27):
And the decision about when todo that is, I think, obviously a
very high stakes one, not justfrom the neurological
perspective but from theoncologic one too, and that's
something that I've observedalso.
I've been fortunate to be, youknow, asked by some of my
medical oncology colleagues whoare working to develop new
therapies.
You know we see X symptom, thatyou know neurological symptom
(32:49):
develop, but we also notice thatthat's happening more in the
patients who are also havingtheir tumor shrink.
So how do we layer out, youknow, what doses or what
interventions are appropriate sothat someone can get the
maximal benefit but also not,you know, accrue more
neurological injury at the sametime?
And that's a very finebalancing act too.
Dr. Michael Kentris (33:08):
Those are great considerations.
I know it's easy for us asspecialists to sometimes get our
blinders on and just like wehave to stop the neurologic
process.
And then what about the cancer?
It does definitely become verytricky in those situations, and
this was something I just becamefamiliar with.
I think you had mentioned itjust briefly.
Was some of these likeinfliximab, which, if I remember
(33:30):
correctly, is IL-6.
Correct me if I'm wrong there.
Dr. Ashley Aaroe (33:35):
For infliximab TNF-alpha.
Dr. Michael Kentris (33:37):
Oh, okay, Now is this one of those new
protocols that is sort of likefor these CAR-T immunotherapy
type adverse reactions.
Dr. Ashley Aaroe (33:47):
So it is something that's in the
therapeutic armamentarium.
But what I would say is so ifwe're talking about CAR-T
neurotoxicity, there's a coupleof.
I think you may have beenthinking of tocilizumab, which
is anti-IL-6.
Yes, yes, so with regards tohow CAR-T cell neurotoxicity is
usually managed, so I can go ona whole separate thing about
(34:08):
that.
So we know that these patientsare at risk for developing
encephalopathy and also seizuresand also cerebral edema, which
can cause attendant ICP issuesif it's severe enough.
But typically what we'll see isthat patient receives CAR T
cells.
Then they might develop what'scalled cytokine release syndrome
.
A few days later, with fever,hypoxia, some systemic
(34:33):
manifestations, you'll see theircytokine levels in the serum
and then, a few days after that,you may start to see them
develop encephalopathy, and sotypically these patients become
inattentive and have difficultywith language first, and so
there's actually a gradingsystem, now called the ICE score
(34:53):
, where it's a score out of 10and you take away a point for
everything that the patient isnot able to do For example,
listing days of the weekbackwards, naming things,
writing a sentence, becausethese are all thought to be sort
of sensitive indicators ofneurotoxicity, and those
patients will receive steroids.
Now the cytokine releasesyndrome that often is
(35:15):
associated with and precedes thedevelopment of neurotoxicity
can be managed with an anti-IL-6agent like tocilizumab.
But tocilizumab does not treatneurotoxicity, and so the
mainstay of intervention isdexamethasone.
For the neurotoxicity piece Ihave read, and every single time
(35:36):
, I have to be honest, I forgetthe mechanism.
I learn it because I think it'sfascinating, and then I
immediately forget it.
But there is a mechanism bywhich tocilizumab may
paradoxically increase theamount of circulating IL-6
within the CNS because itdoesn't cross the blood-brain
barrier, and so just thetakeaway would be that
tocilizumab does not fix CAR-Tneurotoxicity it's really
(35:58):
steroids and if severe enoughthen you may consider other
agents like infliximab orrituxan or you know if the CAR T
product has sort of one ofthese off switches, if you will.
But I think it's, the story ofCAR T neurotoxicity is a really
fascinating one because you know, obviously this drug, this
(36:19):
treatment, comes down thepipeline.
That is, you know we're seeingamazing therapeutic responses.
But when we first started tosee neurotoxicity we didn't know
how to identify it quickly,grade it, and so if you look at
the literature, the incidence ofneurotoxicity in the early
studies for CAR T is all overthe place.
(36:41):
It's a very wide range and themorbidity and mortality from
neurotoxicity was also quitehigh.
So I think it's kind of forneurologists in general, you are
sort of at the forefront of,you know, as these drugs come
down the pipeline, trying tofigure out what is the
(37:03):
neurological piece of things andhow can we manage toxicity.
Dr. Michael Kentris (37:11):
No, yeah, that's very challenging.
I would be remiss if I didn'task a subject that's very much
on the mind of many neurologistswhen we encounter patients with
weird symptoms who have ahistory of cancer, whether
systemic or neurology, isperineoplastic syndrome, which I
know is.
You know, there's been aproliferation of antibody
(37:31):
markers over the last decade andthere seems to be no end in
sight.
One of the things I always readabout in the guidelines is that
we need to be looking forclinical signs and symptoms that
map onto a perineoplasticsyndrome and not just sending
antibodies willy-nilly.
But I would be curious to getyour perspective as someone
(37:52):
who's more in the weeds of it.
Dr. Ashley Aaroe (37:54):
Yeah, I think it's definitely hard to know
when to order the panel.
Do we do serum, Do we do CSF,Do we do both?
It's always a difficultdecision.
Classically, perineoplasticsyndromes are those that the
neurological symptoms are beforethe diagnosis of cancer and so
(38:15):
leading up to a diagnosis-known,well-documented, longstanding
history of cancer after theyreceive immunotherapy, if they
develop neurotoxicity.
It's very situation dependent.
(38:36):
But I think one thing aboutneurology in general that I find
myself constantly sort oftrying to explain to folks in
medicine or neurosurgery is thatit really isn't just the lab
test, and I think that'sparticularly true of
perineoplastic disorders.
So you might get something thathas a low or moderate positive
(38:59):
titer, but it may not fit theclinical syndrome and it may not
fit the underlying cancer too,and so then you really have to
question does that result meansomething or not?
And I think that's the beautyand pain of neurology is that it
really is everything togetherthe history, the exam and also
(39:19):
the data points.
So using those panels in acircumspect way is challenging,
I have to admit.
There are cases where I lookback and I think to myself why
did I order the panels?
It was just we did not have asatisfactory other explanation,
but it was my suspicion for aparaneoplastic disorder really
(39:41):
high enough to justify doing it.
I've had situations where Ithought the exact opposite.
So it's all that to say thatit's tough, but I think that you
touched upon or alluded to thatit really has to be in the
appropriate clinical setting.
Dr. Michael Kentris (39:56):
Yeah, I've definitely been in that same
boat where I've had this likeyeah, this is a strange
constellation of symptoms and Iorder a perineoplastic panel and
I get a weak positive back on.
Something like this doesn't fitat all.
But now I have to spend allthis time explaining to the
patient.
You know all the things thatyou just said and you know
sometimes it goes over well,sometimes I'm referring for a
(40:17):
second opinion.
But yeah, it can be achallenging situation when you
open that Pandora's box.
Dr. Ashley Aaroe (40:23):
For sure.
Dr. Michael Kentris (40:24):
One other thing I was curious to ask you
when I was reading through yourprofile is that you've done a
lot of work with advocacy, withpublic policy, with the American
Academy of Neurology as well asthe National Brain Tumor
Society, and for those of ourlisteners who work in healthcare
, whether they're nursingphysicians et cetera what does
that look like?
How does one become involved,and what kind of career personal
(40:48):
satisfaction have you gottenfrom your work there?
Dr. Ashley Aaroe (40:51):
Yeah.
So I first got into advocacythrough the American Academy of
Neurology with their eventNeurology on the Hill, and that
was really eyeopening.
So at the time that Iparticipated I was in residency
and I think a lot of folks willhave the residency clinic
experience in which there arelimited resources to help your
(41:12):
patients.
You're kind of like a safetynet sort of, and there are so
many things about the practiceof medicine that you wish you
could change but you feelhelpless to, especially when
you're still a trainee.
And so I felt like by gettingto go to one of these events
where they have folks that willtrain you in how to be an
effective advocate, how toconvey something about your very
(41:35):
, very specialized field and thething that you really care
about, how do you explain thatto somebody that has no
background in what it is thatyou're talking about and how do
you get them as passionate aboutit as you?
I think that was a reallyexciting experience, and so I
continued some of the workthrough Head to the Hill with
the National Brain Tumor Societyas well.
So there are a variety ofevents through medical societies
(41:56):
and patient advocacy groupsthat you will be able to either
go to Capitol Hill to meet withlawmakers and their staff, or
even locally, you know havingmeetings with your local
legislators, or even locally,you know, having meetings with
your local legislators.
Something that stays with meabout these experiences is that
(42:18):
I think when I was at aneurology on the Hill you know
these little cafes undergroundas you go from one building to
another in DC and there was arepresentative from a group for
rare genetic disorders,mitochondrial disorders, and
they had been doing theiradvocacy work for a really long
time and they said you know, thething about it is that
everybody can generally agreethat we should help people who
(42:39):
are sick and that we should tryto advance science and medicine,
but nobody's really againstthat.
But where that falls in termsof somebody's priority list, as
they're also jugglingconsiderations about education
and infrastructure and otherthings, it's easy for for things
to get lost in the wayside, um,especially if, if they're more
(43:02):
rare conditions, um, and soreally, I think being an
effective advocate is being agood teacher and a good
storyteller of hey.
This is why you should spare amoment to think about this
specific issue and how do wemake this better?
Advocacy for me reallymitigated a lot of symptoms of
(43:31):
burnout that I was experiencingas a resident, because I felt
empowered to have a voice andaddress some of the systemic
things that I didn't think Icould do anything about
otherwise, and I really enjoyedmeeting with other like-minded.
You know neurologists and otherhealthcare providers, but also
you know patients and familymembers, who are the most
important.
You know pieces of of advocacywork.
(43:51):
It just it's very modifying,motivating and satisfying.
That was modifying, that's anew word for today, so I'm
really passionate about it and,again, I think it's something
that we're starting to talkabout in neuro-oncology as a
field and a lot of folks aredoing great work, like Joshua
Boudou up at Memorial SloanKetter.
Dr. Michael Kentris (44:13):
Awesome, that's great, and I'd just like
to get your final thoughts.
This is a very fast-movingfield, lots of developments in
the pipeline.
What do you hope to see in thenext five years or so?
Dr. Ashley Aaroe (44:30):
And again, I think we're doing better at
exposing residents to it,getting residents excited about
it.
I think also, you know, from atherapeutic perspective for the
primary brain tumors, I'm reallyhopeful about unlocking things
like targeted therapy.
(44:50):
For example, the IDH inhibitorvoracidinib is getting a lot of
buzz based on a trial calledIndigo out of Sloan-Kettering
last year.
I think we'll start to see moretargeted therapies.
I think we'll start to be ableto integrate them into how we
treat patients.
So it's not just having thedrug available but knowing when
and how to use it.
I think that we need to learnmore about, but I'm hopeful
(45:12):
about that.
I'm also hopeful aboutunlocking the potential of
immunotherapy for brain tumors.
So, historically, you knowthings like CAR-T for gliomas,
you know vaccines, you know havebeen less promising but less
effective, you know in oldstudies.
But there's more and morestrategies that are coming down
(45:34):
the pipeline that I do thinkwe're on the brink of
incorporating immunotherapiesand targeted therapies into our
day-to-day practice.
So I'm hopeful about that.
I'm hopeful for helpingpatients with brain tumors live
longer and live better andultimately, you know, the thing
we're all shooting for is a curefor brain tumors and gliomas,
(45:54):
and you know so I have hope forthat too.
With regards to cancerneurology, I think that again,
we need to do a better job ofidentifying the populations of
patients most at risk fordeveloping things like
chemotherapy, associatedcognitive impairment and
neuropathy.
I think we'll do a better jobof identifying biomarkers of
(46:18):
patients who are developingthose issues, hopefully while
they're still mild or evenpotentially preclinical.
It could be someday that we seea lab value that tells us ah,
this is increasing.
I don't know if that's going tobe something like a change in
BDNF or a neurofilament linechain, but maybe, oh, we should
watch this patient a little bitmore closely for the emergence
(46:39):
of some neurological processrelated therapy.
I think those are the thingsthat I look forward to
Ultimately.
I mean, I'm super biased, but Ithink my field is an extremely
exciting one.
I feel like you know thefeeling I get when I come to
work is is what it must have.
(46:59):
I imagine okay, I'm being alittle melodramatic here, but I
can't stop myself I imagine it'ssimilar to what it would have
been like working at NASA in thein the sixties, because there's
just stuff happening.
There's a lot of passionate,interested, motivated you know
people from differentbackgrounds across medicine and
science that are doing amazingwork, and the field is changing
(47:21):
every day.
So that's that's what I what Ithink is is exciting about my
field and I am quite certainthat five years from now, sure
there'll be things that areadvanced in immunotherapy,
targeted therapy, stratifyingpatients.
I'm sure something's going tohappen that I have no faint idea
(47:41):
what that is and it's justgoing to come out of nowhere and
it's going to revolutionize howwe approach patients with
cancer and brain tumors.
That I think is awesome.
So, anyway, I'll stop myselfreigning in a little bit there.
Dr. Michael Kentris (47:53):
But yeah, no, the enthusiasm is infectious
.
This is making me excited, youknow, if someone who's normally
I'm not going to say superenthused about neuro-oncology,
this is very exciting to me aswell, and you know, obviously
practicing in a more generalneurology setting it's.
I think it behooves us to beaware of these advancements and
(48:14):
how we can further treat ourpatients who may, as you said,
not have ready access to thesemore tertiary or even quaternary
academic centers where thereare these other things available
.
What can we still do in theseother settings to improve
quality of life and outcomes.
Dr. Ashley Aaroe (48:32):
If I can say, one final soapbox that I have is
keep an open mind, because careof patients with cancer is
changing so quickly.
For example, it used to bethought of that, you know, a
patient with cancer that has alarge vessel occlusion for
stroke is not going to benefitfrom a thrombectomy because they
have cancer right.
(48:53):
So challenging those kinds ofstigmas I think is important.
There were some studies thatcame out that showed, even
though there is a higher risk ofsymptomatic ICH in patients
with large vessel occlusionstroke that undergo thrombectomy
, who have cancer, that they canhave comparable functional
outcomes and benefits and thatthere are patients with cancer
that you know, even stage fourcancer that can live for a long
(49:17):
time.
You know, even stage fourcancer that can live for a long
time, you know.
So I think it's just aboutkeeping an open mind.
You know, for the generalneurologists that are out there,
that you know having cancer andwhat that means really looks
very different than it did acouple decades ago, and so I
(49:37):
think, again, keeping an openmind is super important.
Dr. Michael Kentris (49:43):
That's very well said and, to borrow a
phrase or a concept from ourneuro ICU colleagues, we have to
make sure that we avoid medicalnihilism, right?
This belief that everything'sgoing to be bad and then we do
nothing and it is bad and wewere right the whole time.
It's very much aself-fulfilling prophecy if we
just let it be that way.
Dr. Ashley Aaroe (50:02):
I think that's a great point and it's funny
that you mentioned that.
I feel like there's a very oddthread that links neuro-oncology
and neuro-critical care andit's something that I would have
never appreciated as a resident, because neuro-ICU was not my
thing and any of my faculty whotrained me could probably tell
you that.
But my husband's a neurointensivist and he says neuro
oncology is neuro critical carein slow motion and I think
(50:25):
there's something to that.
But I think that it's kind of anice little phrase that he came
up with.
I think it rings true and Ithink that you're exactly right
about one of those kind ofconnections being that how you
approach a patient and how youapproach a situation can have
(50:45):
significant bearing on theoutcome, and avoiding
therapeutic nihilism is reallyimportant much for coming on and
talking with us today.
Dr. Michael Kentris (51:01):
I certainly feel uplifted by your
enthusiastic outlook on thefuture and I appreciate you
sharing all of your insights.
If people want to find some ofthe work you've done or find you
online, where should they look?
How should they reach out?
Dr. Ashley Aaroe (51:09):
I do.
I'm not great at X, but I am onX, if you find me, which I
still want to call it Twitteranyway, but I am always happy to
connect about neuro-oncology,and thanks for letting me ramble
at you.
It was just about the thingthat I love talking about.
Dr. Michael Kentris (51:28):
No, I appreciate it.
That's why I love being able tohave folks like yourself on
here is to hear about theirpassions and hear like the good
things that are coming in thefuture.
So thank you very much again.
If people want to find me, I'malso on x slash Twitter at Dr
Kentris D-R-K-E-N-T-R-I-S, andyou can also find our past work
(51:51):
on the website attheneurotransmitterscom.
Thank you so much again forcoming on and I really
appreciate it.
Thank you.
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com
On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!