Breaking Barriers in the Future of Brain Tumor Treatment

Transcript

00:00 --> 00:01Funding for Yale Cancer Answers
00:01 --> 00:03is provided by Smilow Cancer
00:03 --> 00:04Hospital.
00:06 --> 00:08Welcome to Yale Cancer Answers
00:08 --> 00:09with the director of the
00:09 --> 00:11Yale Cancer Center, doctor Eric
00:11 --> 00:11Winer.
00:12 --> 00:14Yale Cancer Answers features conversations
00:14 --> 00:15with oncologists
00:15 --> 00:16and specialists who are on
00:16 --> 00:18the forefront of the battle
00:18 --> 00:18to fight cancer.
00:19 --> 00:20This week, it's a conversation
00:21 --> 00:22about the care of patients
00:22 --> 00:23with brain tumors with doctor
00:23 --> 00:24James Hansen.
00:25 --> 00:26Doctor Hansen is an associate
00:26 --> 00:28professor of therapeutic radiology at
00:28 --> 00:30the Yale School of Medicine.
00:30 --> 00:31Here's doctor Winer.
00:33 --> 00:34How did you get interested
00:34 --> 00:35in radiation oncology?
00:36 --> 00:38That goes back
00:38 --> 00:40way back to when I
00:40 --> 00:41was a kid growing up,
00:42 --> 00:42and I was a big
00:42 --> 00:44fan of Marvel comic books.
00:44 --> 00:46And if anybody remembers those,
00:46 --> 00:48all those superheroes got their
00:48 --> 00:50powers from radiation. Spiderman
00:50 --> 00:51was bitten by a
00:51 --> 00:52radioactive spider.
00:53 --> 00:54The Incredible Hulk was bombarded
00:54 --> 00:55with gamma rays.
00:56 --> 00:57I figured, who wouldn't want
00:57 --> 00:58to have a career in
00:58 --> 00:59radiation?
01:00 --> 01:01So, unfortunately,
01:01 --> 01:02I've been a radiation doctor
01:02 --> 01:04for years now, and I'm
01:04 --> 01:05here to tell you, those
01:05 --> 01:07comics are actually fiction. I've
01:07 --> 01:08not yet seen anybody
01:08 --> 01:10exposed to radiation get superpowers.
01:11 --> 01:12But I have witnessed some
01:12 --> 01:14incredible courage in our patients.
01:14 --> 01:15And I would say those
01:15 --> 01:16are the real superheroes for
01:16 --> 01:17sure.
01:17 --> 01:18Why don't you tell us
01:18 --> 01:19a little bit
01:20 --> 01:20about
01:21 --> 01:23gamma knife? What is this?
01:23 --> 01:25It's a form of radiation.
01:25 --> 01:26I think a lot of
01:26 --> 01:27people know that, but they
01:27 --> 01:28don't know much in the
01:28 --> 01:30way of specifics and
01:30 --> 01:32where we might use it
01:32 --> 01:33and where we wouldn't use it.
01:34 --> 01:36I absolutely
01:37 --> 01:38love the Gamma Knife. I
01:38 --> 01:39think it's a fantastic machine.
01:40 --> 01:41I have just one
01:41 --> 01:43problem with it, and that
01:43 --> 01:45is its name. I wish
01:45 --> 01:45for all the world it
01:45 --> 01:46would not have included the
01:46 --> 01:48word knife because that scares
01:48 --> 01:50all of our patients. There
01:50 --> 01:51is no knife involved. It's
01:51 --> 01:52just a machine
01:52 --> 01:54that is designed to give
01:54 --> 01:54radiation
01:54 --> 01:56extremely accurately and, specifically,
01:57 --> 01:59extremely accurately in the brain.
01:59 --> 02:00And when we're talking about
02:00 --> 02:02the brain, accuracy is literally
02:02 --> 02:04everything because we're using radiation
02:04 --> 02:06to kill things, which is
02:06 --> 02:07good for tumors, but not
02:07 --> 02:09great for normal tissue cells.
02:09 --> 02:10A gamma knife can get
02:10 --> 02:11us to less than a
02:11 --> 02:12tenth of a millimeter of
02:12 --> 02:14error in our targeting.
02:14 --> 02:15We can leave
02:15 --> 02:15the rest of the normal
02:15 --> 02:16brain alone.
02:17 --> 02:18We do that with a
02:18 --> 02:19combination of a 3D
02:19 --> 02:20targeting box that goes on
02:20 --> 02:21the patient's head,
02:22 --> 02:24some complex MRI imaging, and
02:24 --> 02:26then some very sophisticated arrangements
02:26 --> 02:27of some actual
02:27 --> 02:29radioactive sources that give a
02:29 --> 02:30hundred and ninety two beams
02:30 --> 02:32to one little tiny dot
02:32 --> 02:32in space.
02:33 --> 02:34And so we can position
02:34 --> 02:35the patient so that one
02:35 --> 02:36little dot is right where
02:36 --> 02:37we want it. It's kinda
02:37 --> 02:39like painting by pointillism, where
02:39 --> 02:41you just dot dot dot
02:41 --> 02:42dot dot to cover your
02:42 --> 02:43target, and you leave the
02:43 --> 02:44rest of the brain alone.
02:44 --> 02:46We call those shots.
02:46 --> 02:48So you can target very
02:48 --> 02:49small tumors.
02:50 --> 02:51The smaller, the
02:51 --> 02:53better. We love small. Yes.
02:53 --> 02:53And
02:54 --> 02:55what's the largest tumor you
02:55 --> 02:57can target with a gamma
02:57 --> 02:57knife?
02:58 --> 02:59There's no limit,
03:00 --> 03:01but the larger the tumor,
03:02 --> 03:03the greater the volume of
03:03 --> 03:04normal brain around it that
03:04 --> 03:05is getting hit by some
03:05 --> 03:06degree of radiation. So we
03:06 --> 03:07have to be a little
03:07 --> 03:08bit careful. We've got ways
03:08 --> 03:09that we can deal with
03:09 --> 03:10that by adjusting our dose
03:10 --> 03:11or maybe having the patient
03:11 --> 03:13come back for a couple
03:13 --> 03:14treatments instead of doing it
03:14 --> 03:15all in one day. So
03:15 --> 03:17there's no real limit,
03:17 --> 03:17truthfully.
03:18 --> 03:21But, practically, when
03:21 --> 03:22would you stop thinking about
03:22 --> 03:23doing gamma knife
03:24 --> 03:25and start thinking about doing
03:25 --> 03:27something different in terms of
03:27 --> 03:27size?
03:28 --> 03:29Well, it depends very much
03:29 --> 03:30on
03:30 --> 03:31what kind of a cancer
03:31 --> 03:33we are dealing with, because
03:33 --> 03:34as you know, it's an
03:34 --> 03:36entirely new world now with
03:36 --> 03:37targeted therapies and such.
03:38 --> 03:38If
03:39 --> 03:40we are worried that a
03:40 --> 03:41cancer is spread widely throughout
03:41 --> 03:43the brain, it's not just
03:43 --> 03:44in the one area, then
03:45 --> 03:46we'll need to have conversations
03:46 --> 03:47about perhaps we might need
03:47 --> 03:48to revert to the standard
03:48 --> 03:50technique of the whole brain
03:50 --> 03:50radiation.
03:51 --> 03:52But we try to avoid
03:52 --> 03:53that for as long as
03:53 --> 03:54we can because we do
03:54 --> 03:56have this gamma knife technology.
03:57 --> 03:58And
03:58 --> 03:59with this technology,
03:59 --> 04:01you can give much higher
04:01 --> 04:02doses of radiation than with
04:02 --> 04:03standard radiation?
04:05 --> 04:06That's basically true. Yeah. It's
04:06 --> 04:07it comes down
04:08 --> 04:09to the biology of radiation,
04:09 --> 04:10and we didn't need to
04:10 --> 04:11get too far into the
04:11 --> 04:13woods on that. But there's
04:13 --> 04:14a difference between giving radiation
04:15 --> 04:16all in one big dose
04:16 --> 04:18versus a bunch of small
04:18 --> 04:19doses. And what the gamma
04:19 --> 04:20knife can do, because it's
04:20 --> 04:21so accurate,
04:21 --> 04:22we can really hit the
04:22 --> 04:23target hard
04:24 --> 04:24once
04:24 --> 04:26compared to having to treat
04:26 --> 04:27the entire brain over multiple
04:27 --> 04:29fractions with a tinier dose
04:29 --> 04:30to let the brain recover.
04:31 --> 04:33And when you do those
04:33 --> 04:35multiple fractions, say over two
04:35 --> 04:37weeks or even longer sometimes,
04:38 --> 04:40the total dose has to
04:40 --> 04:42be increased.
04:43 --> 04:43It's
04:44 --> 04:45a little bit of hand
04:45 --> 04:46waving in terms of how we
04:47 --> 04:48say which dose is equivalent
04:48 --> 04:49to the other, and not
04:49 --> 04:50all of us believe those
04:50 --> 04:51equations.
04:52 --> 04:53But theoretically, yes, we might
04:53 --> 04:55treat in a single fraction,
04:55 --> 04:56for example, to a dose
04:56 --> 04:57of twenty gray,
04:57 --> 04:58whereas the total dose of
04:58 --> 05:00a whole brain treatment is
05:00 --> 05:00typically
05:00 --> 05:01thirty gray.
05:02 --> 05:03But it's not a perfect
05:03 --> 05:04correlation at all.
05:06 --> 05:08And when you're treating cancer
05:08 --> 05:09in the brain,
05:10 --> 05:12this is both cancers that
05:12 --> 05:13start in the brain as
05:13 --> 05:14well as cancers that spread
05:14 --> 05:15to the brain?
05:16 --> 05:17That's right. It does
05:18 --> 05:19depend very much on exactly
05:19 --> 05:21what we are treating.
05:21 --> 05:22By far and away, the
05:22 --> 05:23most common
05:24 --> 05:25tumors that we are treating
05:25 --> 05:26are cancers that have spread
05:26 --> 05:27to the brain, which are
05:27 --> 05:28things that we call brain
05:28 --> 05:29metastases.
05:30 --> 05:31There are other forms of
05:31 --> 05:32tumors that we treat as
05:32 --> 05:33well that start in the
05:33 --> 05:34brain, meningiomas,
05:34 --> 05:36pituitary adenomas, and such.
05:37 --> 05:37But far and away, the
05:37 --> 05:39metastases are our number one
05:39 --> 05:40that we treat.
05:41 --> 05:42And
05:42 --> 05:43metastases
05:43 --> 05:45happen in patients who have
05:45 --> 05:46an initial cancer
05:46 --> 05:48and then develop a recurrence
05:48 --> 05:50of that cancer. And sometimes
05:51 --> 05:52it spreads to the brain.
05:52 --> 05:54Recently, there's been talk that
05:54 --> 05:56brain metastases seem to be
05:56 --> 05:57increasing.
05:58 --> 05:59Do you have thoughts about
05:59 --> 05:59that?
06:00 --> 06:02I think that's in large
06:02 --> 06:05part credit to oncologists like
06:05 --> 06:08yourself, that are getting better
06:08 --> 06:09and better at treating disease
06:09 --> 06:11everywhere else in the body.
06:11 --> 06:13The brain, unfortunately,
06:13 --> 06:14is a little bit tougher
06:14 --> 06:16to get those medicines into.
06:16 --> 06:17As we know, there's
06:17 --> 06:18something called the blood brain
06:18 --> 06:20barrier that keeps those drugs
06:20 --> 06:21out. So while we're doing
06:21 --> 06:23better at controlling disease outside
06:23 --> 06:23the brain,
06:24 --> 06:25we still need better ways
06:25 --> 06:26to control disease in the
06:26 --> 06:28brain. And that's getting
06:28 --> 06:30better and better. So we're
06:30 --> 06:32relying less and less on
06:32 --> 06:33the whole brain radiation,
06:33 --> 06:34more on the gamma knife
06:34 --> 06:36as these better targeted therapies
06:36 --> 06:37come along to help us.
06:38 --> 06:40And there have been studies
06:40 --> 06:41that have shown that
06:41 --> 06:43patients actually do better when
06:43 --> 06:45treated with gamma knife
06:45 --> 06:46or related technologies
06:47 --> 06:49than getting whole brain.
06:50 --> 06:52Sure. Absolutely. The normal
06:52 --> 06:53brain doesn't wanna get exposed
06:53 --> 06:55to that radiation. It can
06:55 --> 06:56have an effect on things
06:56 --> 06:56like
06:57 --> 06:58short term memory and
06:58 --> 06:59just overall
06:59 --> 07:01energy levels. So if we
07:01 --> 07:03can avoid it, we should
07:03 --> 07:04when we can. That's not
07:04 --> 07:05to say that there isn't
07:05 --> 07:06a time and a place
07:06 --> 07:08for the whole brain radiation.
07:08 --> 07:09It's we just have to
07:09 --> 07:10pick and choose our battles,
07:10 --> 07:11for sure.
07:11 --> 07:12And
07:12 --> 07:14when would you give whole
07:14 --> 07:14brain radiation?
07:16 --> 07:16So
07:16 --> 07:18it's very much dependent on
07:18 --> 07:19the patient and the situation.
07:20 --> 07:21If we don't have
07:21 --> 07:23a good targeted therapy to
07:23 --> 07:24back us up and we
07:24 --> 07:25have
07:25 --> 07:27many, many spots to go
07:27 --> 07:29after, you know, thirty, forty,
07:29 --> 07:29fifty,
07:30 --> 07:31then we know if we
07:31 --> 07:33see fifty spots, there's probably
07:33 --> 07:34another ten or twenty that
07:34 --> 07:35we can't see, and it
07:35 --> 07:36makes more sense for the
07:36 --> 07:36patient
07:36 --> 07:37to treat everything.
07:39 --> 07:40Other types of disease, for
07:40 --> 07:41example, small cell lung cancer
07:41 --> 07:43is a type that tends
07:44 --> 07:45to very commonly go to
07:45 --> 07:46the brain, and we tend
07:46 --> 07:47to have a lower threshold
07:47 --> 07:48for activating that whole brain
07:48 --> 07:50decision in that case. But
07:50 --> 07:51even that, we're trying to
07:51 --> 07:52back off on nowadays.
07:55 --> 07:56I have to say as
07:56 --> 07:58a medical oncologist
07:59 --> 08:00taking care of mostly women
08:00 --> 08:01with breast cancer,
08:03 --> 08:05that the advances in radiation
08:06 --> 08:07largely through techniques like the
08:07 --> 08:09gamma knife, have been incredible
08:09 --> 08:10over the years.
08:10 --> 08:10And
08:11 --> 08:14radiation oncologists have been able
08:14 --> 08:15to treat
08:15 --> 08:17more and more with
08:17 --> 08:19really less and less toxic
08:19 --> 08:19approaches.
08:21 --> 08:23Yeah. And I'm particularly excited
08:23 --> 08:24about what we're seeing with
08:24 --> 08:26these new antibody drug conjugates
08:26 --> 08:28like HER2 that are really
08:29 --> 08:31helping us delay that need
08:31 --> 08:32to activate the whole brain
08:32 --> 08:34protocol. So we can help
08:34 --> 08:34you
08:34 --> 08:36target just the most important
08:36 --> 08:37tumors, and the drugs can
08:37 --> 08:38perhaps take care of the
08:38 --> 08:40smaller ones, which is a
08:40 --> 08:41big change from
08:41 --> 08:42even just a few years
08:42 --> 08:43ago.
08:44 --> 08:45Yeah. Which is,
08:46 --> 08:47of course, among the many
08:47 --> 08:48reasons why having
08:49 --> 08:51people participate in multidisciplinary
08:52 --> 08:53teams is so important.
08:54 --> 08:54Absolutely.
08:55 --> 08:56We wouldn't have nowhere near
08:56 --> 08:58the confidence to do what
08:58 --> 08:59we do if we didn't
08:59 --> 09:00know we had the backup
09:00 --> 09:03of people like Veronica Chiang,
09:03 --> 09:04who's one of our neurosurgeons,
09:04 --> 09:06who can operate when we
09:06 --> 09:07need help or operate the
09:07 --> 09:09the laser technology when there's
09:09 --> 09:10some radiation treatment effect that
09:10 --> 09:11we need to fix.
09:12 --> 09:14I always need someone to
09:14 --> 09:15call when I say, you
09:15 --> 09:16know, I'm this is close
09:16 --> 09:17to needing whole brain, but
09:18 --> 09:19can you back me up?
09:19 --> 09:20Do you have any targeted
09:20 --> 09:21therapy that I can argue
09:21 --> 09:22will take care of the
09:22 --> 09:23smaller spots, and I can
09:23 --> 09:24just go after the
09:24 --> 09:25important ones right now?
09:26 --> 09:27You can't do this
09:27 --> 09:29by any one specialty anymore.
09:29 --> 09:30Not sure maybe you ever
09:30 --> 09:31could, truthfully.
09:33 --> 09:35It's absolutely the case.
09:35 --> 09:36And what about
09:37 --> 09:39patients who have primary brain
09:39 --> 09:40tumors where
09:40 --> 09:41the cancer starts in the
09:41 --> 09:43brain? Cancers like glioblastoma
09:44 --> 09:46and other forms of
09:46 --> 09:47brain cancer?
09:48 --> 09:49Are there times when you
09:49 --> 09:51use Gamma Knife after someone
09:51 --> 09:52has had surgery?
09:52 --> 09:53Very rare,
09:54 --> 09:55especially here in our own
09:55 --> 09:56institution.
09:57 --> 09:58For example, the
09:58 --> 09:58glioblastomas,
09:59 --> 10:00we tend to think
10:01 --> 10:02because of their infiltrative nature
10:03 --> 10:04and the larger volume that
10:04 --> 10:05you need to cover to
10:05 --> 10:06get all
10:06 --> 10:07the hands of the cells
10:07 --> 10:08that are extending,
10:09 --> 10:10it's better to go with
10:10 --> 10:12that longer, what we call
10:12 --> 10:14fractionated course and in combination
10:14 --> 10:15with the chemotherapy.
10:16 --> 10:17The Gamma Knife for other
10:17 --> 10:19radiosurgery techniques might come into
10:19 --> 10:20play
10:20 --> 10:22after that. So if later
10:22 --> 10:23down the road there was
10:23 --> 10:24just one little spot that
10:24 --> 10:25came back, then I might
10:25 --> 10:26get a call from, for
10:26 --> 10:28example, doctor Contessa or doctor
10:28 --> 10:29Bindra to say,
10:30 --> 10:30do you think you
10:30 --> 10:31could gamma knife that one
10:31 --> 10:33little spot? I've already given
10:33 --> 10:33what I can do from
10:33 --> 10:34the Linac side, which is
10:34 --> 10:36called a linear accelerator, the
10:36 --> 10:37normal radiation.
10:38 --> 10:39It's a fairly
10:39 --> 10:40rare occurrence that we would
10:40 --> 10:40do that.
10:41 --> 10:42Yeah.
10:45 --> 10:46I think that,
10:47 --> 10:48you know, all of this
10:48 --> 10:49shows that these decisions
10:49 --> 10:52are really very, very complicated.
10:53 --> 10:54And then what about other
10:55 --> 10:56cancers in other parts of
10:56 --> 10:58the body other than the
10:58 --> 10:59brain? Do you use gamma
10:59 --> 11:01knife in those situations too?
11:02 --> 11:03Not the gamma knife. The
11:03 --> 11:04gamma knife is specifically
11:05 --> 11:07built around that head
11:07 --> 11:08frame and such so that
11:08 --> 11:09we can have a 3D
11:09 --> 11:10targeting specifically
11:11 --> 11:12in the brain. But the
11:12 --> 11:13concept
11:13 --> 11:14of radiosurgery,
11:14 --> 11:15meaning giving radiation
11:16 --> 11:19extremely accurately in one dose
11:19 --> 11:19or a couple of
11:19 --> 11:20doses,
11:20 --> 11:22absolutely applies elsewhere in the
11:22 --> 11:23body.
11:23 --> 11:24We just call it something
11:24 --> 11:26else. We call it stereotactic
11:27 --> 11:28body radiotherapy,
11:28 --> 11:29or SBRT.
11:29 --> 11:30For example,
11:31 --> 11:33doctor Johung tends to use
11:33 --> 11:34this for our pancreatic cancers.
11:34 --> 11:36Doctor Park uses this for
11:36 --> 11:37our lung cancers.
11:38 --> 11:39Absolutely, the field of radiation
11:39 --> 11:41has exploded in terms
11:41 --> 11:42of new,
11:42 --> 11:44faster, better ways to use
11:44 --> 11:45radiation to treat cancer. And
11:45 --> 11:46so what is it that
11:46 --> 11:48led to this bifurcation
11:48 --> 11:51between Gamma Knife and stereotactic
11:51 --> 11:52radiosurgery?
11:54 --> 11:56Well, the concept of stereotactic
11:56 --> 11:57radiosurgery just means we're treating
11:57 --> 11:59something super accurately with a
11:59 --> 12:01high dose in a few
12:01 --> 12:01fractions.
12:02 --> 12:04The gamma knife is entirely
12:04 --> 12:06based on basically a brand
12:06 --> 12:07and the use of that
12:07 --> 12:09specific head frame. So you
12:09 --> 12:10may have heard of things
12:10 --> 12:11like the CyberKnife.
12:12 --> 12:13Again, they decided to use
12:13 --> 12:14the word knife. I think
12:14 --> 12:15that was a mistake.
12:16 --> 12:17So that's just
12:17 --> 12:19a different brand?
12:19 --> 12:20Yeah. It does not use the
12:22 --> 12:24cobalt sources like the
12:24 --> 12:25gamma knife does, but it's
12:25 --> 12:26the same idea of giving
12:26 --> 12:28radiation hyper accurately just to
12:28 --> 12:29the problem areas.
12:30 --> 12:30And
12:31 --> 12:32just back to gamma knife
12:32 --> 12:33for a second. So a
12:33 --> 12:35a patient has a gamma
12:35 --> 12:36knife treatment.
12:36 --> 12:37Do they need to be
12:37 --> 12:39in the hospital? Can they
12:39 --> 12:40go home that same day?
12:40 --> 12:41What are the
12:42 --> 12:43consequences a day or two
12:43 --> 12:44later?
12:44 --> 12:46It's remarkably well tolerated.
12:47 --> 12:48Almost all of our patients
12:48 --> 12:49go home the very same
12:49 --> 12:49day.
12:50 --> 12:51They're a little tired for
12:51 --> 12:52a couple days and a
12:52 --> 12:54little sore where the frame
12:54 --> 12:55has been attached.
12:55 --> 12:56But other than that, it's
12:56 --> 12:58a very well tolerated treatment.
12:58 --> 12:59And that is a huge
12:59 --> 12:59benefit
12:59 --> 13:01because it's so much faster
13:01 --> 13:02than other forms of radiation.
13:03 --> 13:04We can get them on
13:04 --> 13:05to the next phase of
13:05 --> 13:06either chemotherapy
13:06 --> 13:08or targeted therapy or clinical
13:08 --> 13:09trial without any delay.
13:12 --> 13:13Even beyond that, who wants
13:13 --> 13:15to feel badly from a
13:15 --> 13:16treatment? The
13:17 --> 13:18easier a treatment
13:18 --> 13:20is, the more you can
13:20 --> 13:21think about getting it.
13:23 --> 13:24Well, we're gonna take a
13:24 --> 13:27very brief break. And when
13:27 --> 13:28we come back, we'll continue
13:28 --> 13:29talking to
13:30 --> 13:32James Hansen, associate professor of
13:32 --> 13:33therapeutic radiology,
13:33 --> 13:35and we'll move on to
13:35 --> 13:36talk about
13:36 --> 13:38some of his own research,
13:39 --> 13:40focused on a very different
13:40 --> 13:41area.
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13:55 --> 13:55Smilowcancer
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13:59 --> 14:01Genetic testing can be useful
14:01 --> 14:02for people with certain types
14:02 --> 14:03of cancer that seem to
14:03 --> 14:04run-in their families.
14:05 --> 14:06Genetic counseling is a process
14:06 --> 14:08that includes collecting a detailed
14:08 --> 14:10personal and family history,
14:10 --> 14:11a risk assessment,
14:12 --> 14:13and a discussion of genetic
14:13 --> 14:14testing options.
14:15 --> 14:16Only about five to ten
14:16 --> 14:17percent of all cancers are
14:17 --> 14:19inherited and genetic testing is
14:19 --> 14:21not recommended for everyone.
14:21 --> 14:23Individuals who have a personal
14:23 --> 14:25and or family history that
14:25 --> 14:27includes cancer at unusually early
14:27 --> 14:28ages,
14:28 --> 14:30multiple relatives on the same
14:30 --> 14:31side of the family with
14:31 --> 14:32the same cancer,
14:33 --> 14:34more than one diagnosis of
14:34 --> 14:36cancer in the same individual,
14:37 --> 14:37rare cancers,
14:38 --> 14:39or family history of a
14:39 --> 14:41known altered cancer predisposing
14:41 --> 14:43gene could be candidates for
14:43 --> 14:44genetic testing.
14:45 --> 14:46Resources for genetic counseling and
14:46 --> 14:48testing are available at federally
14:48 --> 14:50designated comprehensive cancer centers,
14:51 --> 14:52such as Yale Cancer Center
14:52 --> 14:54and Smilow Cancer Hospital.
14:54 --> 14:56More information is available at
14:56 --> 14:58yale cancer center dot org.
14:58 --> 15:00You're listening to Connecticut Public
15:00 --> 15:00Radio.
15:01 --> 15:03Hello again. This is Eric
15:03 --> 15:05Winer with Yale Cancer Answers,
15:05 --> 15:06and I'm here again
15:07 --> 15:09with our guest, doctor James
15:09 --> 15:10Hansen,
15:10 --> 15:12a radiation oncologist
15:12 --> 15:14who focuses on
15:14 --> 15:16gamma knife treatment
15:16 --> 15:17in his clinical work.
15:18 --> 15:20But beyond that, like many,
15:20 --> 15:21many physicians,
15:23 --> 15:25is involved in research as
15:25 --> 15:25well,
15:26 --> 15:27involved in research to try
15:28 --> 15:29to make
15:29 --> 15:31treatment better for patients in
15:31 --> 15:32the future.
15:32 --> 15:34Some of that research involves
15:34 --> 15:35clinical trials. Some of it
15:35 --> 15:37involves more basic work to
15:37 --> 15:38try to
15:38 --> 15:39come up
15:40 --> 15:41with new approaches
15:43 --> 15:44that could lead to clinical
15:44 --> 15:45trials in the future.
15:46 --> 15:47So I wanna talk to
15:47 --> 15:48you about
15:50 --> 15:51lupus related antibodies
15:52 --> 15:54and how this might
15:54 --> 15:55ultimately improve
15:56 --> 15:58care for individuals who have
15:58 --> 15:58glioblastoma.
15:59 --> 16:01And maybe before you talk
16:01 --> 16:03about lupus related antibodies,
16:04 --> 16:05maybe you could just talk
16:05 --> 16:05for
16:06 --> 16:08a minute or two about
16:08 --> 16:08glioblastoma
16:09 --> 16:10and
16:10 --> 16:12where we stand with that
16:12 --> 16:13very difficult to treat cancer.
16:14 --> 16:15Did you say you wanted
16:15 --> 16:16me to talk about lupus
16:16 --> 16:19related antibodies in cancer?
16:19 --> 16:20That sounds a little off
16:20 --> 16:21the norm here.
16:23 --> 16:24It is, it's your work.
16:24 --> 16:26Oh, how about that?
16:26 --> 16:27Alright. Yes. Happy to talk
16:27 --> 16:28about that.
16:28 --> 16:29So
16:29 --> 16:30glioblastoma
16:31 --> 16:32is one of the most
16:32 --> 16:32aggressive
16:33 --> 16:34primary brain tumors that we
16:34 --> 16:35encounter.
16:36 --> 16:37And one of the reasons
16:37 --> 16:38that it's so tough to
16:38 --> 16:39beat is
16:39 --> 16:41that it has figured out
16:41 --> 16:42ways to sort of cloak
16:42 --> 16:43itself so that it kind
16:43 --> 16:45of, I like to say, it runs
16:46 --> 16:47silent, meaning that our own
16:47 --> 16:49immune system can't see it,
16:49 --> 16:50can't fight it off. So
16:50 --> 16:52we try to be
16:52 --> 16:54aggressive with surgery and radiation
16:54 --> 16:56and chemotherapy, but we really
16:56 --> 16:57need backup from the immune
16:57 --> 16:58system to get after it.
16:58 --> 16:59And, unfortunately,
17:00 --> 17:01the T cells and such
17:01 --> 17:02just don't tend to find
17:02 --> 17:04it. And that's why glioblastoma
17:05 --> 17:06is called immunologically,
17:07 --> 17:07quote, unquote,
17:08 --> 17:08cold.
17:09 --> 17:10So we figured
17:10 --> 17:11if there was a way
17:11 --> 17:12to heat up those tumors,
17:12 --> 17:13maybe we could get better
17:13 --> 17:14outcomes.
17:14 --> 17:16And by cold, you mean
17:16 --> 17:16that
17:17 --> 17:18immunotherapy
17:18 --> 17:19as we give it today
17:20 --> 17:21doesn't seem to have any
17:21 --> 17:22impact on glioblastomas.
17:23 --> 17:24You got it. So all
17:24 --> 17:25those antibody things we see
17:25 --> 17:27advertised on TV that are
17:27 --> 17:29really making a huge difference
17:29 --> 17:30in other kinds of cancers,
17:31 --> 17:32they're not touching glioblastoma.
17:33 --> 17:33So we need a way
17:33 --> 17:35to figure out why
17:35 --> 17:36or how to break that
17:36 --> 17:37cycle.
17:37 --> 17:39So where would we
17:39 --> 17:40look to find a hyperactive
17:40 --> 17:42immune system?
17:42 --> 17:44How about autoimmunity,
17:45 --> 17:46like lupus?
17:46 --> 17:47So in lupus,
17:48 --> 17:50a patient's own immune system
17:50 --> 17:52goes a little crazy and
17:52 --> 17:54starts attacking its own cells
17:54 --> 17:54and tissues.
17:55 --> 17:56So we figured, well, if
17:56 --> 17:57we could figure out what
17:57 --> 17:58are the mechanisms
17:59 --> 18:00driving that
18:00 --> 18:01and just isolate a few
18:01 --> 18:02of them, maybe we could
18:02 --> 18:03use some of those
18:03 --> 18:05to awaken the immune system
18:05 --> 18:06in glioblastoma.
18:07 --> 18:08And that's what my lab
18:08 --> 18:10focuses on, is understanding mechanisms
18:10 --> 18:11of autoimmunity
18:12 --> 18:12with the goal of using
18:12 --> 18:14them against cancer.
18:14 --> 18:15And let me just ask
18:15 --> 18:17you. Lupus, if I remember
18:17 --> 18:18right, from
18:19 --> 18:20days when I
18:20 --> 18:22trained in internal medicine,
18:22 --> 18:24is actually a disease that
18:24 --> 18:26occasionally affects the brain as well?
18:26 --> 18:28Absolutely. And patients,
18:29 --> 18:31at times, unfortunately, get what's
18:31 --> 18:32called lupus cerebritis,
18:33 --> 18:35where those antibodies seem
18:35 --> 18:37to attack the brain.
18:38 --> 18:39That's exactly right.
18:39 --> 18:40But how in the world
18:40 --> 18:42are they doing that? Antibodies
18:42 --> 18:43aren't supposed to be able
18:43 --> 18:45to cross the blood brain
18:45 --> 18:45barrier.
18:46 --> 18:47Antibodies aren't even supposed to
18:47 --> 18:48be able to penetrate
18:49 --> 18:50into live cells. So that's
18:50 --> 18:52a good segue. Thank you.
18:54 --> 18:56Antibody therapy, as we know
18:56 --> 18:58it currently, is focused on
18:58 --> 18:59binding things
18:59 --> 19:00on the outside of cells,
19:00 --> 19:02things circulating in the blood
19:02 --> 19:03or on the surface of
19:03 --> 19:03cells.
19:04 --> 19:05Now this is where a
19:05 --> 19:06lot of critics might say,
19:06 --> 19:08well, no. Some antibodies get
19:08 --> 19:09eaten by cells.
19:09 --> 19:10But I say that those
19:10 --> 19:11don't count because they then
19:11 --> 19:13get destroyed inside the cell
19:13 --> 19:14by endosomes and lysosomes.
19:15 --> 19:16What's remarkable
19:17 --> 19:18about lupus antibodies we have
19:18 --> 19:19found
19:19 --> 19:20is that a subset of
19:20 --> 19:21them
19:21 --> 19:23are reactive against a patient's
19:23 --> 19:24own DNA.
19:25 --> 19:25And so sort of a
19:25 --> 19:27hallmark of lupus is these
19:27 --> 19:28anti DNA antibodies.
19:30 --> 19:31And so they look for
19:31 --> 19:33DNA, and they find DNA
19:33 --> 19:34where it is
19:35 --> 19:36concentrated. So it's kind of
19:36 --> 19:36like
19:37 --> 19:39if anybody who's listening has
19:39 --> 19:40seen the movie Star Trek
19:40 --> 19:41there is a part
19:41 --> 19:42of that movie wherein
19:43 --> 19:45the Enterprise is facing a
19:45 --> 19:45cloaked
19:46 --> 19:47bad guy ship, and they
19:47 --> 19:48can't figure out how to
19:48 --> 19:49find it. Until suddenly, they
19:49 --> 19:50realize
19:51 --> 19:52the thing has to have
19:52 --> 19:53a tailpipe. And so they
19:53 --> 19:54figure out a way to
19:54 --> 19:55fire off a photon torpedo
19:56 --> 19:57to track its exhaust back
19:57 --> 19:58to its source.
19:59 --> 20:01Tumor exhaust is DNA,
20:01 --> 20:03nucleic acids, as the tumor
20:03 --> 20:04cells are cycling and releasing
20:04 --> 20:05them. So we thought, well,
20:05 --> 20:07maybe these anti DNA antibodies
20:07 --> 20:09will find tumors by tracking
20:09 --> 20:10their exhaust back to the
20:10 --> 20:11source. And, indeed, they do.
20:11 --> 20:13And what's even more remarkable
20:13 --> 20:14is when they get there,
20:14 --> 20:16they're sticking to the nucleoside
20:16 --> 20:17components of DNA,
20:17 --> 20:19and then the live tumor
20:19 --> 20:21cells and other environmental
20:21 --> 20:21cells
20:22 --> 20:24are pulling those nucleosides in
20:24 --> 20:25through this thing called a
20:25 --> 20:27nucleoside salvage pathway.
20:27 --> 20:28And so it pulls the
20:28 --> 20:30antibody in. And the antibody
20:30 --> 20:32then gets into those cells,
20:32 --> 20:34skips all the security guys.
20:34 --> 20:35It skips the lysosomes and
20:35 --> 20:36the endosomes, and it has
20:36 --> 20:38free rein inside that cell.
20:39 --> 20:40Some of them go to
20:40 --> 20:40the nucleus.
20:41 --> 20:42Some go to the cytoplasm.
20:43 --> 20:44What we just found, and
20:44 --> 20:45we just published in Science
20:45 --> 20:47Signaling and is getting quite
20:47 --> 20:48a lot of attention and
20:48 --> 20:49very excited about,
20:49 --> 20:50is that one of these
20:50 --> 20:52antibodies, when it gets into
20:52 --> 20:54that cytoplasm, the liquid part
20:54 --> 20:55of the cell, not the
20:55 --> 20:55nucleus,
20:56 --> 20:58it's sticking to RNA,
20:58 --> 20:59a specific type of nucleic
20:59 --> 21:00acid.
21:00 --> 21:01And then finally,
21:02 --> 21:03something inside the cell called
21:03 --> 21:05a pattern recognition receptor
21:06 --> 21:07sees that and says,
21:08 --> 21:09that's not supposed to be
21:09 --> 21:11here. I don't know what's
21:11 --> 21:12going on, but something bad
21:12 --> 21:14has happened. And it triggers
21:14 --> 21:15off an immune reaction. And
21:15 --> 21:17it finally says, oh my
21:17 --> 21:18goodness.
21:18 --> 21:19There's a tumor here this
21:19 --> 21:21whole time. We've been sitting
21:21 --> 21:22amongst this. We didn't realize.
21:22 --> 21:24And then it recruits T
21:24 --> 21:25cells, and we do see
21:25 --> 21:26an improved response.
21:26 --> 21:27So we figured out a
21:27 --> 21:29way, we believe, to use
21:29 --> 21:30a lupus antibody that can
21:30 --> 21:32cross the blood brain barrier,
21:32 --> 21:34penetrate into live cells, and
21:35 --> 21:36tumor cells and non tumor
21:36 --> 21:37cells fire up the immune
21:37 --> 21:38system
21:38 --> 21:39and improve outcomes. It does
21:39 --> 21:40it by itself.
21:41 --> 21:42And if you throw in
21:42 --> 21:43an immune checkpoint blockade antibody,
21:44 --> 21:45like those classic anti PD
21:45 --> 21:46ones,
21:46 --> 21:48it works even better. So
21:48 --> 21:49we're pretty thrilled by
21:49 --> 21:50this, and we we hope
21:50 --> 21:51that we can get this
21:52 --> 21:53to the clinical trials as
21:53 --> 21:54soon as we possibly can.
21:55 --> 21:57Now if it
21:57 --> 21:59also goes to normal cells
21:59 --> 22:00in the brain, is there
22:00 --> 22:02some chance it would
22:02 --> 22:03increase the
22:04 --> 22:05side effects from immunotherapy
22:06 --> 22:07in those normal cells in
22:07 --> 22:08the brain?
22:08 --> 22:10That's the real trick. Right?
22:10 --> 22:10Is doing this in a
22:10 --> 22:12way that we don't cause
22:12 --> 22:12harm.
22:13 --> 22:14And this is where it's
22:14 --> 22:15all about
22:15 --> 22:17where is the antibody gonna
22:17 --> 22:18go. And and the beauty
22:18 --> 22:19of this, and I wish
22:19 --> 22:20I could take credit for
22:20 --> 22:21it. I didn't design this.
22:21 --> 22:23This is a natural antibody,
22:23 --> 22:25a natural lupus antibody.
22:25 --> 22:27It will only penetrate cells
22:27 --> 22:29in areas that are super
22:29 --> 22:30highly concentrated
22:31 --> 22:32in the DNA that's released
22:32 --> 22:34by the tumor because that's
22:34 --> 22:35its path into the cell.
22:35 --> 22:37So when it if it
22:37 --> 22:38finds other areas in the
22:38 --> 22:39normal brain that are not
22:39 --> 22:41soaked in DNA, it will
22:41 --> 22:42not penetrate. And that's the
22:42 --> 22:43first thing that we looked
22:43 --> 22:44for. Where does the
22:44 --> 22:46antibody go? And it just
22:46 --> 22:47goes into the area of
22:47 --> 22:48the tumor and the surrounding
22:48 --> 22:49area, not into the normal
22:49 --> 22:50brain.
22:51 --> 22:52So it preferentially
22:52 --> 22:54goes into the tumor on its own.
22:54 --> 22:56Correct. Based on
22:56 --> 22:57targeting
22:57 --> 22:59the DNA. And if you
22:59 --> 23:01follow that reasoning further
23:02 --> 23:03in noncancer applications,
23:04 --> 23:06these antibodies will also find
23:06 --> 23:08areas of damage. So for
23:08 --> 23:08example,
23:08 --> 23:10my colleagues and my
23:10 --> 23:12team have found as well,
23:12 --> 23:14these antibodies will find areas
23:14 --> 23:14of a stroke
23:15 --> 23:15in the brain
23:16 --> 23:17or a heart attack
23:18 --> 23:19Because DNA is being released
23:19 --> 23:21by the damaged cells.
23:21 --> 23:22Exactly.
23:22 --> 23:24So all this excitement about
23:24 --> 23:26this antibody by itself as
23:26 --> 23:27engaging the immune system,
23:28 --> 23:29I think, is great.
23:29 --> 23:31There's one more dimension to it.
23:32 --> 23:33Wait a second. If this
23:33 --> 23:35antibody can get into cells
23:35 --> 23:36and it can avoid all
23:36 --> 23:37the security,
23:37 --> 23:38skip the lysosomes,
23:40 --> 23:41will it carry other things
23:41 --> 23:42with it in?
23:42 --> 23:43And indeed,
23:44 --> 23:45we haven't published this yet,
23:45 --> 23:45but I mean, this
23:45 --> 23:46is just between you and me, right?
23:46 --> 23:47No one's listening
23:47 --> 23:48to this. I hope, oh,
23:48 --> 23:49wait. There's this radio.
23:50 --> 23:51I'll still be able to
23:51 --> 23:51say it.
23:52 --> 23:55Absolutely. These antibodies can carry
23:55 --> 23:56cargos in with them, whether
23:56 --> 23:58they are nucleic acids or
23:58 --> 23:59linked other antibodies.
23:59 --> 24:00So we can use these
24:00 --> 24:02antibodies to deliver things to
24:02 --> 24:03either increase the effect on
24:03 --> 24:05tumors or perhaps to treat
24:05 --> 24:07heart attacks, perhaps to improve
24:07 --> 24:09improve treatment of stroke. The
24:09 --> 24:10sky's the limit in my
24:10 --> 24:11opinion.
24:12 --> 24:12So
24:13 --> 24:15almost like what we now
24:15 --> 24:17call drug antibody conjugates, you
24:17 --> 24:18could
24:18 --> 24:20theoretically link
24:20 --> 24:21a little bit of some
24:21 --> 24:23drug that would be toxic
24:23 --> 24:24to the cancer to the
24:24 --> 24:25antibody.
24:26 --> 24:28Absolutely. In fact, that was
24:29 --> 24:30a paper from
24:30 --> 24:31last year, and I'm
24:31 --> 24:32really, really glad you gave
24:32 --> 24:33me that segue.
24:33 --> 24:35I was in, ACS Central
24:35 --> 24:37Science. So everyone has asked
24:37 --> 24:38me along the way,
24:39 --> 24:39why don't you use these
24:39 --> 24:41antibodies to deliver
24:41 --> 24:42drugs? And I said, well,
24:42 --> 24:44it doesn't make sense because
24:44 --> 24:45the whole idea of an
24:45 --> 24:47antibody drug conjugate
24:47 --> 24:48is it gets eaten up,
24:49 --> 24:50and then the lysosome
24:50 --> 24:51breaks it down, and that's
24:51 --> 24:52how the drug gets released.
24:53 --> 24:54What's gonna release the drug
24:54 --> 24:55for these antibodies? They don't
24:55 --> 24:56go to the lysosome.
24:57 --> 24:57But finally,
24:58 --> 25:00a great postdoc by the
25:00 --> 25:00name of Faye Kao in
25:00 --> 25:03my lab figured out when
25:03 --> 25:04one of these antibodies goes
25:04 --> 25:05zipping on into the cell,
25:06 --> 25:07this one goes into the
25:07 --> 25:07nucleus,
25:08 --> 25:10something happens and it triggers
25:10 --> 25:11a specific
25:12 --> 25:12protease,
25:12 --> 25:14a protein that cuts
25:14 --> 25:15other things apart from a
25:15 --> 25:16lysosome
25:16 --> 25:17to chase it into the
25:17 --> 25:18nucleus.
25:19 --> 25:20And that's what breaks it
25:20 --> 25:21down in the nucleus. And
25:21 --> 25:22then we realized,
25:23 --> 25:24if we use a linker
25:24 --> 25:26that that protease will cut,
25:26 --> 25:27now we can deliver things
25:27 --> 25:28into the nucleus,
25:29 --> 25:30and the drug will be
25:30 --> 25:31released. And so you've heard
25:31 --> 25:32of ADCs,
25:33 --> 25:34antibody drug conjugates.
25:35 --> 25:36We have now coined the
25:36 --> 25:36phrase
25:37 --> 25:37ANADCs
25:38 --> 25:40for anti nuclear antibody drug
25:40 --> 25:41conjugates. And I'm really trying
25:41 --> 25:42to get that to stick.
25:42 --> 25:44So, hopefully, people that are
25:44 --> 25:45listening will use that too.
25:46 --> 25:47Well, I mean, of course,
25:47 --> 25:48we're gonna have to see
25:48 --> 25:50if this works in people,
25:50 --> 25:50but,
25:51 --> 25:53the whole idea sounds pretty
25:53 --> 25:55cool to me.
25:55 --> 25:56I think so too.
25:57 --> 25:58And so
25:58 --> 25:59in using these
26:00 --> 26:02lupus antibodies, is there any
26:02 --> 26:03risk that a patient
26:03 --> 26:05is gonna develop some symptoms
26:05 --> 26:06of lupus?
26:07 --> 26:08Sure. That's the first question
26:08 --> 26:09on our minds and on
26:09 --> 26:10everybody's mind.
26:12 --> 26:13When it comes to an
26:13 --> 26:14anti DNA antibody,
26:15 --> 26:16one of the dangers we've
26:16 --> 26:17seen associated with lupus is
26:17 --> 26:19that they can get stuck
26:19 --> 26:20in the kidneys, and then
26:20 --> 26:21they can trigger an immune
26:21 --> 26:22response against the kidney to
26:22 --> 26:23cause this thing called
26:24 --> 26:26lupus nephritis, just inflammation
26:26 --> 26:27of the kidney.
26:27 --> 26:28The good news is
26:29 --> 26:30most of that is caused
26:30 --> 26:32by what we call the
26:32 --> 26:33constant regions of the antibody,
26:33 --> 26:35the FC tail for
26:35 --> 26:36those that know any antibody
26:36 --> 26:36structure.
26:37 --> 26:38And the magic of these
26:38 --> 26:40antibodies that allows them to
26:40 --> 26:41do their thing to bind
26:41 --> 26:43DNA, bind RNA,
26:43 --> 26:44penetrate
26:44 --> 26:45cells, has nothing to do
26:45 --> 26:47with the FC or any
26:47 --> 26:48of their constants, all in
26:48 --> 26:49the variable regions. So we've
26:49 --> 26:51created what we call fragments,
26:52 --> 26:53single chain variable fragments and
26:53 --> 26:55such that don't have any
26:55 --> 26:56of the dangerous lupus causing
26:56 --> 26:58parts, but still preserve the
26:58 --> 26:59cell penetrating activity,
27:00 --> 27:01the delivery aspects,
27:01 --> 27:03and the engagement of all
27:03 --> 27:04those factors that we want
27:04 --> 27:05to try to fight off
27:05 --> 27:05these diseases.
27:06 --> 27:07Well, it sounds to me
27:07 --> 27:08like we wanna try to
27:08 --> 27:09encourage you to do this
27:09 --> 27:10work as quickly as you
27:10 --> 27:13can because it sounds pretty
27:13 --> 27:13promising.
27:13 --> 27:14Thank you. Yeah.
27:15 --> 27:15I can take all the
27:15 --> 27:17encouragement I can get.
27:21 --> 27:22The truth is
27:23 --> 27:24that if we didn't have
27:24 --> 27:26research, if we didn't have
27:26 --> 27:26both
27:26 --> 27:28research in laboratories
27:28 --> 27:30and research in the clinic,
27:31 --> 27:33cancer treatment wouldn't change. And
27:33 --> 27:35what has led to really
27:35 --> 27:36a revolution in cancer therapeutics
27:37 --> 27:38over the last
27:39 --> 27:39twenty,
27:39 --> 27:41twenty five years
27:41 --> 27:43has been all the research
27:43 --> 27:44that has gone on, and
27:44 --> 27:46it's really quite remarkable.
27:47 --> 27:47No question.
27:49 --> 27:50You know, and it's just
27:50 --> 27:52so very important.
27:52 --> 27:53So in our last
27:54 --> 27:55minute or so,
27:55 --> 27:56maybe you could,
27:57 --> 27:58look into the future
27:59 --> 28:01and tell us what you
28:01 --> 28:03think are gonna be the
28:04 --> 28:06new directions for radiation oncology
28:07 --> 28:08in the years ahead.
28:09 --> 28:10Yeah. So I I'm very
28:10 --> 28:11excited about
28:12 --> 28:13immunotherapy
28:13 --> 28:14and the combination
28:15 --> 28:15with radiation.
28:17 --> 28:18And we have so much
28:18 --> 28:19to learn about
28:20 --> 28:20how the radiation
28:21 --> 28:22triggers and talks to the
28:22 --> 28:23immune system.
28:23 --> 28:24But when we can figure
28:24 --> 28:25that out, I think we'll
28:25 --> 28:27have even more ways to
28:27 --> 28:28activate
28:28 --> 28:30those, quote, unquote, cold tumors
28:30 --> 28:31by giving radiation to the
28:31 --> 28:33right area at the right time.
28:33 --> 28:35Doctor James Hansen is
28:35 --> 28:37an associate professor of therapeutic
28:37 --> 28:38radiology at the Yale School
28:38 --> 28:39of Medicine.
28:40 --> 28:41If you have questions, the
28:41 --> 28:42address is canceranswersyale
28:43 --> 28:44dot edu,
28:44 --> 28:45and past editions of the
28:45 --> 28:47program are available in audio
28:47 --> 28:49and written form at yale
28:49 --> 28:50cancer center dot org.
28:50 --> 28:52We hope you'll join us
28:52 --> 28:53next time to learn more
28:53 --> 28:54about the fight against cancer.
28:55 --> 28:56Funding for Yale Cancer Answers
28:56 --> 28:58is provided by Smilow Cancer
28:58 --> 28:59Hospital.

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Breaking Barriers in the Future of Brain Tumor Treatment with guest Dr. James Hansen April 21, 2025

Yale Cancer Center

visit: https://www.yalecancercenter.org

email: canceranswers@yale.edu

call: 203-785-4095

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Dr. James Hansen

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