Melanoma and Brain Metastases
October 04, 2021Information
October 3, 2021
Yale Cancer Center
visit: http://www.yalecancercenter.org
email: canceranswers@yale.edu
call: 203-785-4095
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- 00:00Funding for Yale Cancer Answers
- 00:03is provided by Smilow Cancer
- 00:05Hospital and AstraZeneca.
- 00:08Welcome to Yale Cancer Answers
- 00:10with host Dr Anees Chagpar.
- 00:12Yale Cancer Answers features the
- 00:14latest information on cancer care by
- 00:16welcoming oncologists and specialists
- 00:18who are on the forefront of the
- 00:20battle to fight cancer. This week,
- 00:22it's a conversation about Melanoma and
- 00:25brain metastases with Doctor Thuy Tran.
- 00:27Dr Tran is an instructor of
- 00:29medicine in medical oncology at
- 00:31the Yale School of Medicine,
- 00:32where Dr Chagpar is a
- 00:34professor of surgical oncology.
- 00:37Doctor Tran, maybe we can start off
- 00:39by you telling us a little bit
- 00:40about yourself and what you do.
- 00:42Absolutely, I am a translational
- 00:45researcher at Yale Cancer Center.
- 00:48I did my residency and fellowship
- 00:50in heme/onc here and I'm happy to
- 00:53be involved in the Melanoma team
- 00:55treating patients with advanced
- 00:57malignancies and skin cancers.
- 00:59I do a lot of translational research,
- 01:01which means that I am working at the
- 01:03bench but also take what we find out
- 01:05at the bench straight to the clinic
- 01:07so that we can effect real change
- 01:09in how we treat this disease.
- 01:11So tell us a little bit
- 01:13more about your research.
- 01:14I mean you work in the Melanoma team,
- 01:18how exactly does the translational
- 01:20research part fit in and what
- 01:22specifically are you looking at?
- 01:25I've been spending the past couple
- 01:27years really looking at innate
- 01:29immunity in the brain and how we
- 01:31can really capitalize on stimulating
- 01:33those cells and in conjunction with
- 01:35our currently available
- 01:37therapies to try to improve
- 01:39disease outcomes for our patients.
- 01:41So just to give you an example.
- 01:43One of the projects that I'm
- 01:45highly involved with is trying to
- 01:47target the blood brain barrier.
- 01:49The blood brain barrier
- 01:51has been a really understudied but
- 01:54very clinically relevant and highly
- 01:56impactful way for cancers to really
- 01:58gain an advantage and to metastasize
- 02:01and grow in the brain and so really
- 02:03trying to focus on the blood brain
- 02:06barrier and try to get these drugs
- 02:08into the brain has been an
- 02:10area of ongoing interest.
- 02:12Just to give you an example.
- 02:13So one of our currently active
- 02:16projects is looking at targeting Veg F,
- 02:19which stands for vascular
- 02:21endothelial growth factor.
- 02:22It's a subtle kind that really
- 02:24stimulates blood vessel development,
- 02:26and sometimes these tumors and the
- 02:28immune cells surrounding them will
- 02:30secrete this cytokine to help stimulate
- 02:33tumor growth and so how can we
- 02:35target this protein as well as maybe
- 02:38target the endothelial cells themselves to
- 02:40help decrease tumor growth in the brain.
- 02:43And so we have a couple of
- 02:45interesting targets,
- 02:45one of which is currently an active
- 02:48clinical trial within our Melanoma group
- 02:50looking at Melanoma and lung cancer
- 02:52patients who have brain metastases.
- 02:55And so this clinical trial is
- 02:57a phase two study looking at
- 02:59the combination of bevacizumab,
- 03:01which is our anti veg F drug
- 03:02to help minimize blood vessel
- 03:05development in combination with
- 03:07an immune stimulating agent,
- 03:09the checkpoint inhibitor pembrolizumab,
- 03:11which targets another pathway
- 03:13to help stimulate our own bodies
- 03:15immune system to help fight cancer.
- 03:18We're also going to be developing a
- 03:21second clinical trial of pembrolizumab
- 03:24or immune stimulating agent in
- 03:26combination with Lenvatinib,
- 03:28which instead of targeting the
- 03:29cytokine itself,
- 03:30targets the veg F receptors on the
- 03:33endothelial cells and hopefully we
- 03:35can get even a more dramatic immune response.
- 03:39So today I want to take a step back
- 03:41here and just kind of talk a little bit
- 03:43about the blood brain barrier itself.
- 03:46What exactly is it and how
- 03:50does it affect cancer cells?
- 03:52As we're always learning more
- 03:54and more about the blood brain barrier,
- 03:56it's not as simple as we first thought
- 03:58where it's just comprised of the
- 04:00blood vessel and death elial cells,
- 04:02the blood brain barrier is
- 04:04actually much more complicated.
- 04:05It's composed of not only
- 04:07the endothelial cells,
- 04:07but all these supportive cells
- 04:10adjacent to them,
- 04:11and so this includes parasites
- 04:13which control vasoconstriction
- 04:14or the ability of these blood
- 04:17vessels to contract and dilate.
- 04:19It also includes all the supportive
- 04:22astrocytes which have their
- 04:24little processes in and feet
- 04:26on the endothelial cells.
- 04:28It includes interneurons,
- 04:30it includes microglia,
- 04:32microglia are considered,
- 04:33sort of the innate immune cells
- 04:35that reside within the brain.
- 04:37How come the cancer cells can get
- 04:39into the brain but the drugs can't?
- 04:42You know the blood brain barrier
- 04:44in normal states without any
- 04:47pressure related to metastasis is
- 04:50a very intact endothelial layer,
- 04:52meaning that there are these specific
- 04:55interconnections within or
- 04:57between the endothelial cells
- 04:59that prevent any other molecules,
- 05:01such as drugs such as immune cells from
- 05:05infiltrating or getting beyond them.
- 05:08They typically are described
- 05:09as the soldiers.
- 05:11Remember the Roman soldiers
- 05:13if you ever watch one of those
- 05:15movies with all their Shields up
- 05:18so they form an impenetrable
- 05:20barrier to help prevent things
- 05:22from getting past that layer.
- 05:25And that's what's really
- 05:26caused a lot of issues.
- 05:28For example,
- 05:29in breast cancer therapy where
- 05:31chemotherapies that traditionally
- 05:33work in breast cancers can't
- 05:34penetrate into the brain,
- 05:36and so we're seeing a lot more of late
- 05:39relapses in the brain because these
- 05:41cancer effective therapies are not
- 05:43able to penetrate and circulate there.
- 05:46So why can the cancer cells get
- 05:48through those those Roman Shields?
- 05:50I mean, it sounds like that should really be,
- 05:53as you say, an impenetrable barrier.
- 05:55And yet, cancer cells can seem to
- 05:57sneak their way through.
- 05:59Cancer cells when they metastasize,
- 06:04they go through a very complex process,
- 06:08basically giving them the ability to
- 06:10invade through normal tissue and during
- 06:13that process they adopt a different shape,
- 06:16a different morphology.
- 06:17They become migratory.
- 06:19They get enter the bloodstream,
- 06:21and when they circulate,
- 06:23they essentially get into the brain.
- 06:25And either lodge at Branch points
- 06:28within those blood vessels in the
- 06:30brain and cancer cells have all
- 06:32sorts of different proteins and
- 06:34things that they up regulate or
- 06:37express to help them survive and
- 06:40proliferate during this process,
- 06:42and a few of those proteins include
- 06:45things like matrix metalloproteases
- 06:47where they can break apart different
- 06:50elements of the tumor stroma,
- 06:52or the tumor microenvironment,
- 06:54and this allows them
- 06:56essentially to break apart those tight
- 06:58junctions within this endothelial cells.
- 07:01Wedge themselves in between these
- 07:05cells and eventually be able to set up
- 07:08shop and grow there.
- 07:09So I guess just to
- 07:11press the point further,
- 07:14my question is if the tumor cells can kind
- 07:17of finagle their way through this barrier,
- 07:20either they make holes in the barrier,
- 07:23they kind of distort and try to get through,
- 07:26then are those changes to
- 07:29the blood brain barrier that allow
- 07:32the cancer cells to get through,
- 07:35those don't seem to be permanent enough
- 07:37to allow our drugs to get through.
- 07:39Or is there another thing at play?
- 07:41Are the drugs too large?
- 07:44Is it that they can't squish
- 07:46through the little spaces?
- 07:48Or is this more than simply
- 07:50a mechanical problem?
- 07:52I think the answer is actually a little
- 07:55complicated to address and we don't
- 07:57really at this point fully understand
- 07:59how our current effective therapies
- 08:01really penetrate to get into the brain.
- 08:04So one hypothesis
- 08:05is that actually when we give immune
- 08:07therapy these immune stimulating
- 08:09drugs that help educate our own
- 08:12immune system to fight the cancer,
- 08:14we're doing that below the
- 08:17neck so peripherally,
- 08:18so these educated immune cells can
- 08:21then subsequently migrate through
- 08:24the circulation into the brain.
- 08:27They have a much easier ability
- 08:29to transmigrate through the
- 08:31endothelial layer and get into
- 08:33the tumor to where they can have
- 08:36antitumor effect,
- 08:37the other component of this is maybe
- 08:40the defects that lead to
- 08:43forming a tumor in the brain caused
- 08:45vessel leakiness and vessel damage,
- 08:47and such that you have this
- 08:51chronic adima or loss of vessel
- 08:54integrity and that therefore
- 08:56allows these large monoclonal
- 08:59antibodies which are essentially
- 09:01our immune checkpoint drugs,
- 09:03to actually access
- 09:06into the tumor
- 09:07ecause these vessels are already so leaky.
- 09:09That's really great
- 09:11news on the immunotherapy front,
- 09:14knowing that these therapies
- 09:16can get into the brain,
- 09:18I guess the next question is, well,
- 09:20how come chemotherapy drugs can't do that?
- 09:23I mean, we give them
- 09:25peripherally into a vein below the neck,
- 09:28right into a hand,
- 09:29they get into a blood vessel.
- 09:31How come they can't follow the same
- 09:34kinds of path?
- 09:38Yeah, so our blood brain barrier
- 09:40through our development
- 09:42has upregulated a lot
- 09:45of drug efflux pumps and so these
- 09:48endothelial cells that constitute
- 09:50the blood brain barrier they have
- 09:53these specialized pumps that whenever
- 09:56drug does penetrate into the cells,
- 09:58they pump them right back out
- 10:00into the circulation.
- 10:01And so that's what limits the effectiveness
- 10:05of standard chemotherapy and
- 10:07it's really not a very good treatment
- 10:10option for patients with brain metastases.
- 10:14OK, I get all of that.
- 10:16So now let's talk a little
- 10:18bit more about this.
- 10:20Veg F that you were
- 10:21mentioning just a moment ago,
- 10:23this vascular endothelial
- 10:24growth factor is that something
- 10:26that is present on particular
- 10:29cancer cells that these
- 10:30therapies now are attacking?
- 10:33Veg F is upregulated in a lot
- 10:36of different cell types, and
- 10:38one of those being Melanoma,
- 10:39where we have found that circulating
- 10:42veg F is actually a poor prognostic
- 10:45marker in patients, so they
- 10:47say essentially they have worse
- 10:49outcomes when they have elevated
- 10:50circulating levels of this protein.
- 10:53So the protein is in the circulation.
- 10:55It's not necessarily on the
- 10:57tumor cells, or is it on both?
- 10:58It's very ubiquitously expressed.
- 11:02It can be expressed by the tumor cells
- 11:05themselves and have a local effect in that
- 11:08increased regulation or increased
- 11:11expression of VEGF can also
- 11:14appear as circulating levels.
- 11:17Tumor cells, in addition to immune cells,
- 11:21can also increase veg F levels too.
- 11:23So, for example,
- 11:24a specific type of immune cell
- 11:27which essentially gobble up a lot
- 11:30of tumor cells or cell debris.
- 11:33One of those is macrophages.
- 11:35So macrophages are able to secrete
- 11:37high levels of veg F as well.
- 11:40And so that makes me think that
- 11:43these anti VEGF therapies that you're
- 11:46looking at in clinical trials,
- 11:48they might be
- 11:50something not specific
- 11:53for particular patients that they might
- 11:55be more ubiquitously used rather than
- 11:57some of the therapies that come out
- 12:00where you really need to check the
- 12:02tumor cells to make sure that
- 12:05particular protein or that particular
- 12:06receptor is on the tumor cell.
- 12:08It sounds like this is something that
- 12:11could be used for most patients.
- 12:13Is that right?
- 12:14That's correct. So actually,
- 12:16even recently within the past couple
- 12:18weeks we've had another FDA approval
- 12:21for the combination of pembrolizumab
- 12:22and lenvatinib,
- 12:25being one of our veg F receptor
- 12:27targeting drugs in addition to other
- 12:30receptors that it does block as well.
- 12:33So that was actually just in
- 12:36advanced renal cell carcinoma.
- 12:38The combination is already
- 12:40been also approved in
- 12:41advanced endometrial cancer,
- 12:43and then actually Merck,
- 12:46the company that produces pembrolizumab
- 12:51is currently investigating this combination
- 12:55in the first line and second line
- 12:58setting for Melanoma patients as well.
- 13:01Wow, all really interesting
- 13:02developments which we will need
- 13:04to investigate more when we take
- 13:07a brief break for medical minute.
- 13:09Please stay tuned to learn
- 13:10more about Melanoma
- 13:11and brain metastases with
- 13:13my guest doctor Thuy Tran.
- 13:15Funding for Yale Cancer Answers
- 13:17comes from AstraZeneca, dedicated
- 13:19to advancing options and providing
- 13:21hope for people living with cancer.
- 13:24More information at AstraZeneca Dash us.com.
- 13:30The American Cancer Society
- 13:32estimates that more than 65,000
- 13:34Americans will be diagnosed with
- 13:36head and neck cancer this year,
- 13:38making up about 4% of all cancers
- 13:41diagnosed. When detected early,
- 13:43however, head and neck cancers are
- 13:45easily treated and highly curable.
- 13:47Clinical trials are currently
- 13:49underway at federally designated
- 13:51Comprehensive cancer centers such
- 13:53as Yale Cancer Center and at Smilow
- 13:55Cancer Hospital to test innovative new
- 13:57treatments for head and neck cancers.
- 14:00Yale Cancer Center was recently awarded
- 14:02grants from the National Institutes
- 14:05of Health to fund the Yale Head
- 14:07and neck Cancer Specialized program
- 14:10of Research Excellence or SPORE to
- 14:12address critical barriers to treatment
- 14:14of head and neck squamous cell
- 14:17carcinoma due to resistance to immune
- 14:19DNA damaging and targeted therapy.
- 14:22More information is available at
- 14:25yalecancercenter.org you're listening
- 14:26to Connecticut Public Radio.
- 14:29Welcome back to Yale Cancer Answers.
- 14:32This is doctor Anees Chagpar and I'm
- 14:34joined tonight by my guest Doctor Thuy Tran.
- 14:37We're talking about the care of patients
- 14:39with Melanoma and brain metastases,
- 14:42and right before the break we were
- 14:45talking about some of the techniques,
- 14:48some of the new trials that are ongoing,
- 14:51especially looking at use of anti
- 14:54veg F therapies and immunotherapy
- 14:56for patients with Melanoma,
- 14:59who had brain metastases.
- 15:01So I thought we'd take a step back and talk a
- 15:04little bit more about patients with Melanoma
- 15:07who have brain metastases.
- 15:08So I think all of us know that Melanoma
- 15:11is one of the deadliest skin cancers.
- 15:14But how common is Melanoma?
- 15:19Many patients get Melanoma.
- 15:21What proportion of them will
- 15:23actually develop brain metastases?
- 15:26Melanoma over the past couple decades
- 15:29it's actually the incidence
- 15:32that's increasing more recently about 75,000
- 15:35new cases are diagnosed each year and
- 15:38it's a malignancy that is driven by both
- 15:42genetic as well as environmental causes,
- 15:45some of which are related to non
- 15:49UV exposure and so really a lot of
- 15:52Melanoma develops as we grow older in
- 15:56our fifth generation or fifth decade.
- 15:59And so it does have a higher
- 16:02dominance in men,
- 16:03and there are certain mutations
- 16:06associated with it.
- 16:0850% of melanomas will contain
- 16:11a BRAF mutation that we can actually
- 16:14target with effective BRAF inhibiting
- 16:16drugs as well as MEC inhibiting drugs
- 16:19that also help boost that response.
- 16:22So just to pick up on
- 16:24the genetic element for a second
- 16:26one of the things that you said,
- 16:28which I found really interesting
- 16:30and I think our listeners will be
- 16:33interested to learn about as well is
- 16:35that there are a lot of melanomas
- 16:38that are not related to UV exposure.
- 16:40That may be genetic,
- 16:42so by that do you mean that we should
- 16:45know about our family history in terms
- 16:47of our risk of developing Melanoma?
- 16:50And when you talk about BRAF mutations,
- 16:53are you talking about germline
- 16:55mutations or are these more
- 16:57somatic mutations that you'll find in a tumor?
- 17:01The BRAF mutations are new mutations.
- 17:05Sometimes we actually see
- 17:07these mutations present but not
- 17:09associated with any malignancy.
- 17:11But when they do appear associated
- 17:15with advanced Melanoma,
- 17:16it is something that we can actually target.
- 17:19Now these BRAF mutations
- 17:20are not unique to Melanoma.
- 17:21They're actually present in
- 17:24certain types of colon cancers.
- 17:27And as well as lung cancers.
- 17:28And so the same drugs apply they're
- 17:31as effective in those other types
- 17:33of cancers as they are in Melanoma.
- 17:36And so some people, even if they wear
- 17:39sunscreen and they make sure
- 17:41that they're not getting a lot of
- 17:43UV exposure and so on and so forth.
- 17:45They can still get Melanoma because of
- 17:47these genetic mutations. Is that right?
- 17:49Yes, in terms of the non sun
- 17:52exposed related melanomas, we typically
- 17:55think of those as a acreal melanomas.
- 17:57Meaning they form between the hands,
- 17:59the webs of the hands and
- 18:01the feet on her extremities,
- 18:04and so these are typically places
- 18:05that you know aren't basking
- 18:06in the Sun and other places
- 18:10that melanomas can evolve from,
- 18:12is the mucosal lining of
- 18:16our upper oral pharanx
- 18:18as well as the anal rectal region.
- 18:21Vulvar melanomas from the reproductive tract,
- 18:25as well as uveal melanoma's also
- 18:27from the pigmented layers of the eyes.
- 18:29So Melanoma, in essence,
- 18:31is a cancer of the melanocytes.
- 18:34These pigmented cells and so anywhere
- 18:36where we have pigment there are
- 18:40melanocytes associated with them.
- 18:42When you think
- 18:44about these genetic mutations,
- 18:46now that we know more and more about them,
- 18:48certainly you know people who have a
- 18:53genetic mutation who are at increased risk,
- 18:56they may want to take additional precautions.
- 18:59You know making sure that
- 19:00they're really getting
- 19:02a good dermatologic exam,
- 19:04and staying out of the sun,
- 19:05and so on and so forth.
- 19:07But one of the questions that I
- 19:09have is for some genetic mutation,
- 19:11for example for the RET proto oncogene,
- 19:15which predisposes to thyroid cancers,
- 19:18these are things that newborn
- 19:21babies have tested,
- 19:22whereas other mutations like
- 19:24BRCA for example is something
- 19:26that we don't generally test
- 19:29until you know somebody comes
- 19:30up to us and says,
- 19:31you know I have a family history of
- 19:34breast cancer and so should I get tested.
- 19:36Where does BRAF kind of
- 19:38fit into the grand scheme of things?
- 19:41It's less clear whether having
- 19:44a pre-existing BRAF mutation
- 19:46ultimately will induce cancer.
- 19:49A lot of the times it doesn't,
- 19:51and it's just something that we
- 19:54pick up that's not prognostic or
- 19:58indicative of any future malignancy.
- 20:01It's really something that we
- 20:03find later on once the cancer is
- 20:05developed that we can potentially
- 20:06target as an effective therapy.
- 20:08And you mentioned, BRCA mutations
- 20:11in a very small
- 20:13subset of patients can
- 20:16contribute to increased risk of
- 20:18Melanoma as well as pancreatic cancer.
- 20:20So really it depends on family
- 20:23history and it really depends
- 20:25on your personal history too.
- 20:26If you have a patient with multiple
- 20:29melanomas with a strong family
- 20:32history of multiple immediate
- 20:34kin with Melanoma cancers,
- 20:36that's when we typically
- 20:39flag and refer
- 20:41these patients to genetic counseling
- 20:43to see if there are indeed these
- 20:45generalized mutations that predispose
- 20:47these patients to developing Melanoma
- 20:50as well as other malignancies.
- 20:52And so it really has an
- 20:54impact on family members,
- 20:55particularly children.
- 20:56When we see patients in the clinic,
- 20:59we always counseled them about preventive
- 21:02measures that they can do to limit
- 21:06additional UV damage and sun exposure risk,
- 21:08but also,
- 21:12seeing the dermatologist regularly,
- 21:14making sure that they have full
- 21:16body skin exams and making sure
- 21:18that their family and their next
- 21:20of kin are also screened with
- 21:22full body skin exams as well.
- 21:25Sadly there isn't anything that we can
- 21:28do that will kind of reverse that,
- 21:32but certainly taking additional precautions
- 21:34like all of us should be in terms of
- 21:37avoiding sun exposure and wearing
- 21:38sunscreen and avoiding tanning salons and
- 21:40things like that are really good ideas.
- 21:43I wanted to take us back to the
- 21:46whole concept of brain metastases so
- 21:48we know that Melanoma, as you said,
- 21:52the incidence is increasing.
- 21:53People are getting this as they get older.
- 21:55But what proportion of patients with
- 21:58Melanoma actually will get brain metastases?
- 22:02So about 40% of patients with
- 22:04advanced Melanoma at some
- 22:06point get a brain metastasis.
- 22:08Now, as we're using a lot of
- 22:11better imaging modalities,
- 22:13mainly MRI of the brain,
- 22:15we're catching a lot of
- 22:17asymptomatic brain metastases,
- 22:19so these are very small
- 22:20metastases that are not associated with
- 22:22significant edema around them,
- 22:24and so we're able to treat
- 22:26these smaller metastases earlier so that
- 22:29they don't later become a larger issue.
- 22:33There's a lot of toxicity
- 22:36related to symptomatic brain metastases
- 22:38because the brain itself is,
- 22:40you know, encased in a very thick
- 22:44structural support system,
- 22:46which is the skull,
- 22:47and so there's not a lot of
- 22:49room for any lesions to expand
- 22:52or any swelling to occur,
- 22:53and so you have a very finite
- 22:56window to address growing
- 22:58lesions in the brain and so that's why
- 23:01we've come up with alternative and
- 23:03adjunctive therapies to help achieve
- 23:05local control in the brain better.
- 23:07And that includes not in
- 23:09addition to immune therapy,
- 23:11but also adding radiation to that
- 23:13plan to help boost that immune response.
- 23:17I want to get to the
- 23:19treatments and what we can do
- 23:21about brain metastases in a minute.
- 23:24But that 40% number,
- 23:26that seemed high to me.
- 23:28So is that 40% of people who present
- 23:31with advanced Melanoma or any Melanoma? NOTE Confidence: 0.928736929523809
- 23:34For example,
- 23:35let's suppose you were going
- 23:37to your dermatologist and you
- 23:39know they happen to find a small
- 23:41Melanoma on the back of your hand.
- 23:44Would you automatically get a brain MRI and
- 23:47is your risk still 40% of
- 23:50getting a brain metastases?
- 23:52No, just to correct that
- 23:55number really only applies to
- 23:57those with advanced Melanoma,
- 23:59so Melanoma that has metastasized
- 24:02to other areas of the body,
- 24:05typically, for staging for Melanoma
- 24:07we really rely on tumor thickness and
- 24:10whether or not it's gone to lymph nodes.
- 24:12When it's gone to the lymph nodes,
- 24:14that makes you a stage three Melanoma
- 24:17and at the initial visit we usually
- 24:19scan the brain to just make
- 24:21sure that it isn't a stage four
- 24:23Melanoma that we aren't catching,
- 24:25and under diagnosing what would
- 24:28have been metastatic disease.
- 24:30So that 40% really reflects those with
- 24:33advanced disease that spread beyond
- 24:36the lymph nodes to other distant sites.
- 24:39Got it and so if you do have a brain
- 24:42met it could be asymptomatic.
- 24:45It could be picked up on an MRI or it
- 24:48could be symptomatic at presentation.
- 24:50Tell us a little bit more about how exactly
- 24:55you treat these patients?
- 25:00So if you presented with symptoms are
- 25:04you likely to resolve those symptoms?
- 25:06How good are our treatments?
- 25:10The treatments themselves over the past
- 25:13five years have just magically improved.
- 25:16Not only do we have better systemic therapies
- 25:19that we know are effective in the brain,
- 25:22but we also are better at timing in terms
- 25:25of when to go in and resect symptomatic
- 25:29brain metastases or radiate them in
- 25:32conjunction with her systemic therapies.
- 25:35So, for example,
- 25:36if a patient presents to the emergency room
- 25:40with nausea, vomiting,
- 25:41some dizziness and balance issues,
- 25:44they get a brain scan in the emergency room
- 25:47are found to have new lesions in the brain,
- 25:50if those lesions are large and associated
- 25:53with significant edema, and that is
- 25:55what's contributing to the symptoms,
- 25:57oftentimes we have to get our
- 26:00neurosurgery colleagues involved to
- 26:02rapidly address that lesion and
- 26:04the most rapid way is via surgery.
- 26:07You know, it's a morbid procedure,
- 26:08but the outcomes are typically
- 26:10very good and people have
- 26:12a very fast recovery.
- 26:13If, for example,
- 26:15the lesion is amenable to what we
- 26:19call stereotactic radiosurgery,
- 26:21which is very high radiation but
- 26:24very focused radiation to try to
- 26:26spare the normal surrounding brain
- 26:28tissue and therefore limit the side
- 26:31effects of radiation in the brain,
- 26:33that itself is also a very effective therapy.
- 26:36It's considered definitive, however,
- 26:38it can only really be treated
- 26:41for lesions that are less than 3 centimeters,
- 26:44if you have a lesion greater
- 26:46than 3 centimeters,
- 26:46surgery is the best option.
- 26:49If you have multiple lesions,
- 26:51basically multiple small lesions,
- 26:53too many to be individually treated
- 26:56with what we call stereotactic
- 26:59radiosurgery or gamma knife,
- 27:01then the next option is whole
- 27:04brain radiation which used to be very
- 27:07neurotoxic long term because these patients
- 27:10would develop cognitive decline later on.
- 27:13Memory issues very similar to dementia.
- 27:17Nowadays we have additional options
- 27:19where we can spare the hippocampus.
- 27:21This learning and memory center
- 27:23in our brain and so we can try to
- 27:26avoid some of these late chronic
- 27:29sequella of radiation therapy.
- 27:31Other options are to actually use some
- 27:33of the drugs that have been known to be
- 27:36effective in treating Alzheimer's patients
- 27:38while they get whole brain radiation to try
- 27:41to have a neuroprotective effect to spare
- 27:44the normal brain from receiving
- 27:46some of the detrimental long
- 27:49term side effects of radiation.
- 27:51I mean it sounds like there's
- 27:53a lot of potential for
- 27:55therapies for brain metastases,
- 27:57but just in our last 30 seconds.
- 28:00So if you have a brain
- 28:02metastasis and it's been treated,
- 28:04what's your overall prognosis?
- 28:06So we're finding with the combination
- 28:09of radiation and immune therapies,
- 28:11prognosis can be actually very good.
- 28:14Before it was three to six months
- 28:16for anyone with brain metastases.
- 28:18Now we're talking years out.
- 28:21If you have a tumor that
- 28:23responds to these treatments,
- 28:24and so the overall survival,
- 28:26the prognosis is much more bright
- 28:28than what it was ten years ago.
- 28:31Doctor Thuy Tran is an instructor
- 28:33of medicine in medical oncology
- 28:35at the Yale School of Medicine.
- 28:37If you have questions,
- 28:38the address is cancer answers at
- 28:41yale.edu and past editions of the
- 28:43program are available in audio and
- 28:46written form at yalecancercenter.org.
- 28:47We hope you'll join us next week to
- 28:50learn more about the fight against
- 28:52cancer here on Connecticut Public
- 28:54radio funding for Yale Cancer
- 28:55Answers is provided by Smilow
- 28:57Cancer Hospital and AstraZeneca.