50 Years of Cancer Progress: Radiation Oncology

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 --> 00:10Yale Cancer Center, doctor Eric
00:10 --> 00:11Winer.
00:11 --> 00:14Yale Cancer Answers features conversations
00:14 --> 00:15with oncologists and specialists
00:15 --> 00:17who are on the forefront
00:17 --> 00:17of the battle to fight
00:17 --> 00:18cancer.
00:19 --> 00:20This week, it's a conversation
00:20 --> 00:22about radiation oncology with doctor
00:22 --> 00:23Peter Glazer.
00:23 --> 00:25Doctor Glazer is the Robert
00:25 --> 00:26E. Hunter Professor of Therapeutic
00:27 --> 00:27Radiology
00:28 --> 00:30and Professor of Genetics and
00:30 --> 00:31chair of the department of
00:31 --> 00:33therapeutic radiology at the Yale
00:33 --> 00:34School of Medicine.
00:34 --> 00:35Here's doctor Winer.
00:36 --> 00:38Can you just tell us
00:38 --> 00:40a little bit about yourself?
00:40 --> 00:41How is it
00:41 --> 00:43that you came to be
00:43 --> 00:44a radiation oncologist?
00:45 --> 00:46I'm a
00:46 --> 00:48physician scientist with an MD
00:48 --> 00:50and a PhD in genetics,
00:50 --> 00:51and as you mentioned,
00:51 --> 00:53my medical specialty is in
00:53 --> 00:54radiation oncology.
00:56 --> 00:58And my research focuses on fundamental
00:58 --> 00:59cancer biology and
01:00 --> 01:01development of translational
01:02 --> 01:03research opportunities.
01:05 --> 01:06I got started in the
01:06 --> 01:08field because of a strong
01:08 --> 01:09clinical interest in oncology,
01:10 --> 01:11and in taking care of
01:11 --> 01:13cancer patients, and that was
01:13 --> 01:15coupled with a growing research
01:15 --> 01:16interest in the field of
01:16 --> 01:18DNA repair, which is how
01:18 --> 01:19cells fix their DNA.
01:20 --> 01:22And that's an important topic
01:22 --> 01:23in the field of radiation
01:23 --> 01:23oncology.
01:25 --> 01:26Can you just
01:27 --> 01:28tell us a little bit
01:28 --> 01:29about
01:29 --> 01:31radiation as a treatment,
01:32 --> 01:34both in terms of how
01:34 --> 01:35it's delivered, or
01:36 --> 01:38I should say the different
01:38 --> 01:39ways in which it can
01:39 --> 01:40be delivered.
01:41 --> 01:43And then we'll explore
01:43 --> 01:45some other aspects of radiation.
01:45 --> 01:47Sure. Radiation
01:47 --> 01:49oncology is the medical specialty
01:49 --> 01:51that uses focused x rays
01:51 --> 01:52to treat cancer
01:52 --> 01:53because of their ability to
01:53 --> 01:55kill cancer cells.
01:55 --> 01:57And early medical applications of
01:57 --> 01:59radiation were based on radioactive
01:59 --> 02:01materials like radium
02:01 --> 02:02that were discovered by
02:03 --> 02:05Marie Curie, because early on
02:05 --> 02:06it was found that radiation
02:06 --> 02:07causes tumors to shrink.
02:08 --> 02:10Later on, other isotopes like
02:10 --> 02:11cobalt, iridium,
02:12 --> 02:14and others were identified and
02:14 --> 02:14developed,
02:15 --> 02:15and some are used for
02:15 --> 02:17a type of treatment called
02:17 --> 02:19brachytherapy, which involves placement of
02:19 --> 02:19radioactive
02:20 --> 02:20sources
02:21 --> 02:23in close proximity to a
02:23 --> 02:24tumor as is frequently done
02:24 --> 02:26for cancers of
02:27 --> 02:28the gynecologic
02:29 --> 02:30tract in women.
02:31 --> 02:33So a device is actually
02:33 --> 02:34put in and it gives
02:34 --> 02:35off radiation
02:35 --> 02:36while it sits
02:37 --> 02:39essentially near or within somebody.
02:39 --> 02:40It dwells next to the tumor.
02:44 --> 02:46It's put in a
02:46 --> 02:48surgical procedure, and then it's
02:48 --> 02:49removed after a specified time.
02:51 --> 02:52And in some other
02:52 --> 02:54approaches, isotopes are
02:54 --> 02:57injected systemically for special applications
02:57 --> 02:59usually linked to a carrier
02:59 --> 03:00like an antibody.
03:02 --> 03:03When X rays were first
03:03 --> 03:05developed, it was known that
03:05 --> 03:06they could be generated by
03:06 --> 03:07cathode ray tubes, but
03:07 --> 03:08that was low energy and
03:08 --> 03:10had drawbacks. So after World
03:10 --> 03:12War II, a major advance
03:12 --> 03:14was the development of technology
03:14 --> 03:14to
03:15 --> 03:16accelerate electrons
03:17 --> 03:18at high voltage into a
03:18 --> 03:20medical target to
03:20 --> 03:22generate high energy x rays
03:22 --> 03:22or photons.
03:23 --> 03:24And that was the birth
03:24 --> 03:26of the linear accelerator or
03:26 --> 03:26LINAC.
03:27 --> 03:29And this allowed for treatment
03:29 --> 03:30of deep seated tumors in
03:30 --> 03:31the body with sparing of
03:32 --> 03:32superficial
03:32 --> 03:33tissues.
03:35 --> 03:35And it seems to me that
03:35 --> 03:37it was the case many
03:37 --> 03:38years ago
03:38 --> 03:41that radiation oncologists would take
03:41 --> 03:42an x-ray,
03:42 --> 03:44just a standard x-ray that
03:44 --> 03:46might show, for example, in
03:46 --> 03:46the chest
03:47 --> 03:48a lung cancer.
03:48 --> 03:49And
03:49 --> 03:51in what now seems like
03:51 --> 03:53a pretty crude manner,
03:54 --> 03:56they would just draw around
03:56 --> 03:57that tumor and then aim
03:57 --> 03:58the beam
03:59 --> 04:01at the tumor. Is that
04:02 --> 04:03basically right?
04:03 --> 04:04Yes, early on
04:05 --> 04:07the treatment machines were
04:07 --> 04:09were limited in
04:09 --> 04:11their ability to move and
04:11 --> 04:13to deliver shaped beams. So
04:13 --> 04:15most of the treatments were
04:15 --> 04:15from the front or the
04:15 --> 04:17back of the patient in
04:17 --> 04:17a simple
04:18 --> 04:18way.
04:19 --> 04:21And so we were guided
04:21 --> 04:22by what we kind of
04:22 --> 04:23refer to as two dimensional
04:23 --> 04:25imaging, which is those plain
04:25 --> 04:26film x rays.
04:27 --> 04:28But, one of
04:28 --> 04:29the major advances
04:30 --> 04:31in field has
04:31 --> 04:32been the use of advanced
04:33 --> 04:35imaging like CT scans, MRI
04:35 --> 04:36scans, or now even PET
04:36 --> 04:37scanning
04:37 --> 04:39to create three-dimensional images
04:39 --> 04:40of the tumor target.
04:41 --> 04:42And that's coupled with
04:43 --> 04:44many technological
04:44 --> 04:46advances in the linear accelerators
04:46 --> 04:47that allow
04:48 --> 04:50the delivery of very complex,
04:51 --> 04:53beam arrangements that really shape
04:53 --> 04:54the dose distribution in a
04:54 --> 04:55three-dimensional manner.
04:56 --> 04:58And my sense is that
04:58 --> 05:00by using those three-dimensional images
05:00 --> 05:02like CT scans and with
05:02 --> 05:04the changes in some of
05:04 --> 05:04your,
05:05 --> 05:07equipment that delivers radiation,
05:07 --> 05:08two things have happened.
05:08 --> 05:10The treatment is far more
05:10 --> 05:11effective,
05:11 --> 05:13and at the same time,
05:13 --> 05:15you can spare patients a
05:15 --> 05:16lot of the side effects
05:16 --> 05:17that used to be pretty
05:17 --> 05:17commonplace.
05:18 --> 05:20That's right. Because now we
05:20 --> 05:21can shape the dose distribution
05:22 --> 05:23a lot more conformally
05:23 --> 05:24to the tumor itself
05:25 --> 05:27and substantially reduce the dose
05:27 --> 05:28to surrounding tissues.
05:30 --> 05:32That's allowed us to deliver
05:32 --> 05:32the treatments
05:33 --> 05:35much more safely with less
05:35 --> 05:36side effects.
05:36 --> 05:38And in some cases, we
05:38 --> 05:39can give a higher dose
05:39 --> 05:41each day and reduce
05:41 --> 05:42the number of
05:43 --> 05:45days of treatment and that's
05:45 --> 05:45also a
05:45 --> 05:47benefit to patients.
05:47 --> 05:49Before we get into some
05:49 --> 05:50additional advances,
05:50 --> 05:52maybe you could just comment
05:52 --> 05:54on some of the myths
05:54 --> 05:56that people still carry around
05:57 --> 05:58about radiation.
05:59 --> 06:00You know, in
06:00 --> 06:01not such a different way
06:01 --> 06:02than with chemotherapy,
06:03 --> 06:03there are a lot of
06:03 --> 06:05patients who come see us
06:05 --> 06:08and have preconceived notions about
06:08 --> 06:10what these treatments are like
06:10 --> 06:11and will come in saying,
06:11 --> 06:12well, I'm never doing that
06:12 --> 06:13because
06:13 --> 06:15you know, my great aunt received
06:15 --> 06:18that and had some terrible
06:18 --> 06:18problems.
06:19 --> 06:21What are the specific
06:22 --> 06:22misunderstandings
06:23 --> 06:23about radiation?
06:24 --> 06:26Well, I think that
06:27 --> 06:27one is,
06:28 --> 06:29what we're alluding to before
06:29 --> 06:30is, you know,
06:31 --> 06:33historically, some people may remember
06:33 --> 06:33that
06:34 --> 06:35people treated with sort of
06:35 --> 06:37the older fashioned ways of
06:37 --> 06:38giving radiation developed
06:39 --> 06:40skin burns
06:41 --> 06:41that
06:43 --> 06:45were very challenging to treat
06:45 --> 06:46and to heal. But
06:47 --> 06:48the advances that we just
06:48 --> 06:49talked about in
06:50 --> 06:52delivery of radiation more deeply
06:52 --> 06:54into the body and sparing
06:54 --> 06:55the skin with shape beams,
06:57 --> 06:59has allowed us to substantially
06:59 --> 06:59avoid
07:00 --> 07:01the skin damage
07:02 --> 07:02and also
07:03 --> 07:04side effects to other
07:05 --> 07:05tissues.
07:08 --> 07:10And I'm not saying that doesn't sometimes
07:10 --> 07:11happen. There
07:11 --> 07:12can be some
07:13 --> 07:14side effects to the skin,
07:14 --> 07:15but it's much much
07:15 --> 07:17less than it used to be for
07:18 --> 07:19the skin and for
07:19 --> 07:21that matter, other organs too.
07:23 --> 07:24There is some
07:25 --> 07:26effect of radiation as it
07:26 --> 07:28passes through healthy tissue, and
07:28 --> 07:29sometimes that can lead to
07:30 --> 07:32some fatigue and temporary loss
07:32 --> 07:32of energy.
07:33 --> 07:35Sometimes, if patients are treated
07:35 --> 07:37in the area of the
07:37 --> 07:38head and neck, they may
07:38 --> 07:39develop dry mouth,
07:40 --> 07:41or if they're treated in
07:41 --> 07:43the GI tract, they may
07:43 --> 07:44have some symptoms
07:45 --> 07:47associated with that. But, usually
07:47 --> 07:48these symptoms fade over time.
07:49 --> 07:49What are some of the
07:49 --> 07:51most common uses of radiation?
07:52 --> 07:53About sixty percent of all
07:53 --> 07:54cancer patients
07:54 --> 07:56are treated with radiation and
07:57 --> 07:59many different types of tumors
07:59 --> 07:59are treated.
08:03 --> 08:05One very common treatment is for
08:05 --> 08:06cancers of the head and
08:06 --> 08:09neck where radiation is considered
08:09 --> 08:11a curative treatment often in
08:11 --> 08:12combination with chemotherapy.
08:13 --> 08:14We do a lot of
08:14 --> 08:16radiation treatments for breast cancer,
08:16 --> 08:17prostate cancer,
08:18 --> 08:18brain tumors,
08:19 --> 08:21and, tumors of the GI
08:21 --> 08:22tract. I mentioned
08:24 --> 08:25gynecologic
08:25 --> 08:25malignancies
08:26 --> 08:28where radiation is very effective
08:30 --> 08:31and routinely achieves
08:32 --> 08:33curative effect in many of
08:33 --> 08:34those scenarios.
08:34 --> 08:36And in some cases, these are
08:37 --> 08:39a substitute for
08:39 --> 08:41surgery, and in some cases,
08:41 --> 08:42it's done in conjunction with
08:42 --> 08:44surgery.
08:44 --> 08:45Radiation
08:46 --> 08:48is particularly effective for localized
08:48 --> 08:48disease
08:49 --> 08:50and can be an alternative
08:50 --> 08:52to surgery in some cases,
08:52 --> 08:55either because the individual is
08:55 --> 08:56not medically able to undergo an
08:58 --> 08:59operation,
09:00 --> 09:01or because the
09:03 --> 09:04morbidity or side effects
09:04 --> 09:06of getting radiation may actually be
09:07 --> 09:09more favorable than a surgical
09:09 --> 09:10intervention.
09:10 --> 09:12Not so many years ago
09:12 --> 09:14when someone would have cancer
09:14 --> 09:16that unfortunately would spread to
09:16 --> 09:17their brain,
09:18 --> 09:19they very commonly would
09:20 --> 09:20get radiation
09:21 --> 09:23to the entire brain, to
09:23 --> 09:25the whole head essentially.
09:26 --> 09:27And increasingly
09:27 --> 09:29over the years, it seems
09:29 --> 09:30that that's not the case,
09:30 --> 09:32and treatments that are
09:32 --> 09:34referred to as either
09:34 --> 09:35stereotactic
09:36 --> 09:36radiosurgery
09:36 --> 09:38or gamma knife
09:38 --> 09:40have been used and have
09:40 --> 09:41been very effective.
09:42 --> 09:42Can you tell us a
09:42 --> 09:44little bit about those treatments?
09:45 --> 09:47Yes, you're absolutely
09:47 --> 09:47right that
09:48 --> 09:49years ago for
09:50 --> 09:52metastases in the brain,
09:52 --> 09:53treatment would be given to
09:53 --> 09:54what we call the whole
09:54 --> 09:56brain, which is basically the
09:56 --> 09:56upper
09:57 --> 09:58part of the head through
09:58 --> 10:00and through. But the advances
10:00 --> 10:02that I was alluding to
10:02 --> 10:02in terms
10:03 --> 10:05of the technology, the treatment
10:05 --> 10:07machines, and also specialized devices
10:07 --> 10:08like the gamma knife,
10:09 --> 10:11allows very focused treatment of
10:11 --> 10:13individual metastatic lesions,
10:15 --> 10:17with really exquisite precision that
10:17 --> 10:17allow
10:18 --> 10:19a good deal of sparing
10:19 --> 10:22of the surrounding healthy brain.
10:22 --> 10:24So now it's pretty much
10:24 --> 10:25standard of care to
10:26 --> 10:26treat
10:27 --> 10:29the metastatic lesions fairly aggressively,
10:29 --> 10:31but with highly focused treatment.
10:32 --> 10:33And the Gamma Knife actually
10:33 --> 10:34is one of the best
10:34 --> 10:35devices to do that for
10:35 --> 10:37brain lesions because of its
10:37 --> 10:38high precision.
10:38 --> 10:40I mean, this has really
10:41 --> 10:41transformed
10:41 --> 10:43in many ways the treatment
10:43 --> 10:44of cancer that has spread
10:44 --> 10:45to the brain
10:46 --> 10:48and has allowed people to
10:48 --> 10:50live longer and at the
10:50 --> 10:52same time live much better.
10:54 --> 10:56And it's become especially important as systemic
10:56 --> 10:57therapies have improved.
10:58 --> 10:59So now we are taking
11:01 --> 11:02a more aggressive
11:02 --> 11:05approach to trying to
11:06 --> 11:08treat lesions in the brain
11:08 --> 11:10when the systemic disease can
11:10 --> 11:11be controlled by other approaches.
11:12 --> 11:13It seems that there are
11:13 --> 11:16even newer approaches, and you
11:16 --> 11:17have a new machine
11:18 --> 11:19that gives
11:19 --> 11:20guided radiation.
11:21 --> 11:22And maybe you can tell
11:22 --> 11:23us a little bit about
11:23 --> 11:24that, and what
11:25 --> 11:27kind of guidance is used?
11:29 --> 11:30This is along the lines of what
11:30 --> 11:32we call image guided therapy,
11:32 --> 11:34in which the linear
11:34 --> 11:36accelerators have an onboard imaging
11:36 --> 11:37device to help
11:38 --> 11:39us evaluate
11:40 --> 11:42and modify the treatment
11:42 --> 11:44at the time
11:44 --> 11:44the patient
11:46 --> 11:47is in the machine and
11:47 --> 11:49in some cases almost in
11:49 --> 11:50real time.
11:51 --> 11:53This approach started with CT
11:53 --> 11:55scan and MR scan,
11:56 --> 11:58included in Lenox, but this
11:58 --> 12:00new biologically guided therapy incorporates
12:00 --> 12:02a PET scanner or PET
12:02 --> 12:04imager in the device. NOTE Confidence: 0.9444651
12:04 --> 12:05A PET scanner image
12:06 --> 12:09positron emissions from radioactive tracers
12:10 --> 12:10that
12:11 --> 12:12accumulate in the tumor when
12:13 --> 12:13certain
12:13 --> 12:15compounds are given to the
12:15 --> 12:16patient ahead of time. And
12:16 --> 12:18that allows us to account
12:18 --> 12:20for the localization of the
12:20 --> 12:21tumor,
12:22 --> 12:24and also its motion within
12:24 --> 12:25the patient, and in some
12:25 --> 12:27cases depending on the tracer
12:27 --> 12:28we use on its biological
12:28 --> 12:29properties.
12:30 --> 12:31And then we can modify
12:32 --> 12:34the treatment, beamlets,
12:34 --> 12:36in real time based on
12:36 --> 12:38the positron emission pattern.
12:39 --> 12:40How much experience have
12:40 --> 12:41you had with this so far?
12:41 --> 12:43We've had it going
12:43 --> 12:45for about a year, and
12:46 --> 12:47actually, I think we have
12:47 --> 12:49one of the largest experiences
12:49 --> 12:50in the country with this.
12:50 --> 12:52So we're getting more familiar
12:52 --> 12:53with how to best
12:54 --> 12:56incorporate this technology into
12:56 --> 12:58our treatment of patients.
12:58 --> 13:00So it's really
13:01 --> 13:02taking the treatment even
13:03 --> 13:04a step further than you
13:04 --> 13:06would with just a CT
13:06 --> 13:07scan alone
13:07 --> 13:08because with
13:09 --> 13:10the PET part of that
13:10 --> 13:11imaging, you can tell much
13:11 --> 13:12more about what's going on
13:12 --> 13:14in the tumor.
13:14 --> 13:15It has a new dimension.
13:15 --> 13:17Right now, it's primarily
13:17 --> 13:19valuable for accounting for
13:19 --> 13:21motion, especially lesions in the
13:21 --> 13:22lung where you have breathing,
13:23 --> 13:25the breathing cycle that
13:25 --> 13:26causes motion.
13:26 --> 13:28But we think that down
13:28 --> 13:29the road, we will have
13:29 --> 13:31many other applications of the
13:31 --> 13:31technology.
13:32 --> 13:34Well, this is great. We're
13:34 --> 13:35gonna take a break for
13:35 --> 13:36just a minute. And when
13:36 --> 13:37we come back, we're gonna
13:37 --> 13:39talk a little more about
13:39 --> 13:41how radiation works, and then
13:41 --> 13:42we're gonna get into some
13:42 --> 13:44of the research you've done
13:44 --> 13:45related to that.
13:45 --> 13:47Support for Yale Cancer Answers
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13:53 --> 13:55at several convenient locations throughout
13:55 --> 13:55the region.
13:56 --> 13:57To learn more, visit smilowcancer
13:58 --> 13:59hospital dot org.
14:01 --> 14:04The American Cancer Society estimates
14:04 --> 14:05that nearly one hundred and
14:05 --> 14:06fifty thousand people in the
14:06 --> 14:08U. S. will be diagnosed
14:08 --> 14:10with colorectal cancer this year
14:10 --> 14:10alone.
14:11 --> 14:13When detected early, colorectal cancer
14:13 --> 14:14is easily treated and highly
14:14 --> 14:15curable,
14:15 --> 14:16and men and women over
14:16 --> 14:18the age of forty five
14:18 --> 14:19should have regular colonoscopies
14:19 --> 14:21to screen for the disease.
14:21 --> 14:23Patients with colorectal cancer have
14:23 --> 14:25more hope than ever before,
14:25 --> 14:26thanks to increased access to
14:26 --> 14:29advanced therapies and specialized care.
14:30 --> 14:31Clinical trials are currently underway
14:31 --> 14:34at federally designated comprehensive cancer
14:34 --> 14:36centers, such as Yale Cancer
14:36 --> 14:37Center and Smilow Cancer
14:37 --> 14:38Hospital,
14:38 --> 14:40to test innovative new treatments
14:40 --> 14:41for colorectal cancer.
14:42 --> 14:44Tumor gene analysis has helped
14:44 --> 14:46improve management of colorectal cancer
14:46 --> 14:48by identifying the patients most
14:48 --> 14:50likely to benefit from chemotherapy
14:51 --> 14:53and newer targeted agents resulting
14:53 --> 14:55in more patient specific treatment.
14:56 --> 14:57More information is available at
14:57 --> 14:59yale cancer center dot org.
14:59 --> 15:01You're listening to Connecticut Public
15:01 --> 15:02Radio.
15:03 --> 15:04Good evening again. This is
15:04 --> 15:06Eric Winer with Yale Cancer
15:06 --> 15:08Answers, and I'm here tonight
15:08 --> 15:10with my guest,
15:10 --> 15:12doctor Peter Glazer,
15:12 --> 15:14who is a professor of
15:15 --> 15:17therapeutic radiology and a professor
15:17 --> 15:19of genetics here at Yale
15:19 --> 15:20School of Medicine and chair
15:21 --> 15:23of therapeutic radiology.
15:23 --> 15:24Can you tell us a
15:24 --> 15:25little bit
15:26 --> 15:26about
15:27 --> 15:28how it is that radiation
15:29 --> 15:31on a cellular
15:31 --> 15:31level
15:32 --> 15:34kills cancer cells? What does
15:34 --> 15:35it do that makes
15:35 --> 15:36them die?
15:38 --> 15:38The radiation
15:39 --> 15:40that we use
15:40 --> 15:42clinically to treat cancer is
15:42 --> 15:42sometimes
15:43 --> 15:43classified
15:44 --> 15:45as ionizing radiation
15:46 --> 15:48to differentiate it from other
15:48 --> 15:49forms of
15:50 --> 15:52radiation including photons, which is
15:52 --> 15:53visible light.
15:55 --> 15:56And what that means is
15:56 --> 15:59that the radiation, x-ray radiation
15:59 --> 16:01goes into cancer cells
16:02 --> 16:03and causes ionization of the
16:03 --> 16:04molecules
16:04 --> 16:06inside the cell, and that
16:06 --> 16:07leads to a lot of
16:07 --> 16:09chemical reactions that damage the
16:09 --> 16:09DNA.
16:10 --> 16:11So fundamentally,
16:11 --> 16:13radiation causes DNA damage in
16:13 --> 16:14cancer cells
16:15 --> 16:16and if we can provide
16:16 --> 16:18sufficient damage, the cells cannot
16:20 --> 16:22fix themselves well enough to
16:22 --> 16:22recover
16:22 --> 16:24and that leads to a
16:24 --> 16:26destruction of the tumor and
16:26 --> 16:27tumor regression.
16:27 --> 16:29And the DNA is essentially
16:30 --> 16:31the brain of the cancer cell?
16:31 --> 16:33Yes, DNA
16:33 --> 16:35as in all cells, has
16:35 --> 16:36the blueprint for how a
16:36 --> 16:37cell functions,
16:38 --> 16:39and DNA
16:40 --> 16:41leads to the production of
16:41 --> 16:43downstream molecules like RNA and
16:43 --> 16:45proteins. So if you get
16:45 --> 16:46the DNA, then you basically
16:46 --> 16:48block all cellular functions
16:49 --> 16:50and the ability of the
16:50 --> 16:50cell to survive.
16:51 --> 16:52Now one of the things
16:52 --> 16:53that
16:54 --> 16:55one hears as a doctor
16:55 --> 16:57from patients is the question,
16:57 --> 16:59well, doesn't radiation
16:59 --> 17:00cause cancer?
17:01 --> 17:02And I think people are
17:02 --> 17:03often thinking about
17:04 --> 17:06the fact that, you know,
17:06 --> 17:07repeated,
17:08 --> 17:11imaging studies are associated with
17:11 --> 17:12a very small increased risk
17:12 --> 17:14in cancer in certain circumstances.
17:15 --> 17:17Is that a question that
17:17 --> 17:18that all of you get
17:18 --> 17:20asked a fair amount?
17:20 --> 17:21Yes. We sometimes talk about
17:21 --> 17:23that with patients. I
17:23 --> 17:24I think that it, you
17:24 --> 17:26know, it is known that
17:26 --> 17:28there is a link between
17:28 --> 17:29radiation exposure and
17:30 --> 17:31developing malignancies.
17:32 --> 17:33I think this is one
17:33 --> 17:34of the
17:34 --> 17:35key reasons that we've worked
17:35 --> 17:37so hard to develop technologies
17:37 --> 17:39that focus the radiation
17:40 --> 17:41intensively on the tumor and
17:43 --> 17:44work to spare the healthy
17:44 --> 17:44tissue
17:45 --> 17:46as much as we can.
17:47 --> 17:49And, you know, we've studied
17:49 --> 17:50this a lot in the
17:50 --> 17:52field, and the risk of
17:53 --> 17:54secondary malignancies
17:54 --> 17:56is not zero, but it's
17:56 --> 17:57very low, especially for most
17:57 --> 17:58adult patients.
17:59 --> 18:00We worry a little bit
18:00 --> 18:01more about children, which is
18:01 --> 18:03one of the reasons that
18:03 --> 18:04we spend a lot
18:04 --> 18:06of time in developing treatment
18:06 --> 18:08approaches for children that are
18:08 --> 18:10very highly focused. And
18:10 --> 18:12one of the more recent,
18:12 --> 18:14two elements along those lines
18:14 --> 18:15is the use of proton
18:15 --> 18:16beam therapy,
18:16 --> 18:17which is
18:19 --> 18:21especially valuable for treating
18:21 --> 18:21children.
18:22 --> 18:22And,
18:23 --> 18:24there's gonna be a proton
18:24 --> 18:25beam facility
18:26 --> 18:26in Connecticut
18:27 --> 18:29in the not distant future
18:29 --> 18:30that we've been involved with.
18:30 --> 18:32Protons
18:33 --> 18:35are a type of ionizing
18:35 --> 18:36radiation, but instead of x
18:36 --> 18:37rays, they use
18:38 --> 18:40protons, which are a subatomic
18:40 --> 18:40particle,
18:41 --> 18:43which a machine
18:43 --> 18:45called a cyclotron will accelerate.
18:45 --> 18:46And the protons
18:47 --> 18:48also enter into the tissue,
18:48 --> 18:50but they have a special
18:50 --> 18:51property because
18:52 --> 18:53they're a particle with mass
18:53 --> 18:55that they enter tissue and
18:55 --> 18:57they stop suddenly to deposit
18:57 --> 18:58their dose.
18:58 --> 19:00And that lets us tailor the
19:02 --> 19:04delivery of the ionizing radiation
19:05 --> 19:06even better.
19:06 --> 19:07And,
19:07 --> 19:09we think that it has
19:09 --> 19:10some advantages.
19:10 --> 19:13But developing proton beam facilities
19:13 --> 19:14is not a simple endeavor.
19:14 --> 19:16It's much more expensive and
19:16 --> 19:17involved than
19:18 --> 19:19installing a regular LINAC.
19:20 --> 19:22And so there are not
19:22 --> 19:23many in the country,
19:23 --> 19:24and there is
19:24 --> 19:26not one in Connecticut right
19:26 --> 19:27now, but Yale New Haven
19:27 --> 19:29Health System and Hartford HealthCare
19:30 --> 19:30have partnered,
19:31 --> 19:33and we recently did the
19:33 --> 19:33groundbreaking to
19:35 --> 19:37advance a new proton beam
19:37 --> 19:37facility,
19:38 --> 19:39in the center of the
19:39 --> 19:40state that'll be
19:41 --> 19:42a resource for all of
19:42 --> 19:43the people in the region.
19:44 --> 19:45And the price tag for
19:45 --> 19:47these kinds of facilities is
19:47 --> 19:48in the
19:48 --> 19:50tens of millions of dollars.
19:52 --> 19:53You know, this one is
19:53 --> 19:54somewhere in the range of
19:54 --> 19:56seventy million all in with
19:56 --> 19:57all the construction and
19:58 --> 19:58equipment.
20:00 --> 20:01Can you
20:02 --> 20:03talk about some of your
20:03 --> 20:04research?
20:05 --> 20:05And
20:06 --> 20:07I know some of the
20:07 --> 20:08recent research has
20:09 --> 20:10related to the treatment of
20:12 --> 20:13what is
20:14 --> 20:16often thought of as
20:16 --> 20:18inherited breast cancer and other
20:18 --> 20:20cancers that
20:20 --> 20:21arise in the setting of
20:21 --> 20:22of BRCA
20:23 --> 20:23mutations.
20:25 --> 20:27But I know that your
20:27 --> 20:28research career stretches
20:29 --> 20:30pretty far back. And
20:31 --> 20:32what are some of the
20:32 --> 20:33things you've worked on over
20:33 --> 20:34the years? And then maybe
20:34 --> 20:36we can talk more about
20:36 --> 20:36BRCA.
20:37 --> 20:38Yes, I've
20:38 --> 20:40been interested in how
20:41 --> 20:43DNA repair pathways can influence
20:43 --> 20:44the development of cancer and
20:44 --> 20:45how they can be exploited
20:45 --> 20:46for treatment.
20:47 --> 20:48And you mentioned
20:48 --> 20:49the BRCA1
20:49 --> 20:50and BRCA2
20:52 --> 20:53genes which are linked
20:55 --> 20:56to a large extent to
20:56 --> 20:58breast and ovarian cancers.
21:00 --> 21:01And defects in those genes
21:01 --> 21:03lead to a deficiency in
21:03 --> 21:05a pathway of DNA repair
21:05 --> 21:07called homologous recombination.
21:08 --> 21:10We recently discovered that some
21:10 --> 21:12other genes that are seen
21:12 --> 21:13mutated in cancers
21:13 --> 21:15that are linked to abnormal
21:15 --> 21:16metabolism
21:17 --> 21:19also cause a defect in
21:19 --> 21:20the same DNA repair pathway
21:21 --> 21:23and we found unexpectedly
21:23 --> 21:24that they can be exploited
21:25 --> 21:26with
21:27 --> 21:27molecularly
21:28 --> 21:29targeted agents that
21:30 --> 21:31exploit related
21:32 --> 21:33DNA repair pathways.
21:34 --> 21:36And similar to the situation
21:36 --> 21:37with BRCA1 and BRCA2,
21:38 --> 21:39these genes include
21:40 --> 21:42genes with the names IDH1
21:42 --> 21:44and two, SDH and FH
21:44 --> 21:45and they're linked to
21:46 --> 21:49brain tumors, sarcomas, kidney cancers
21:49 --> 21:49and others.
21:51 --> 21:52Some of the strategy that
21:52 --> 21:53we and others have worked
21:53 --> 21:54on, you can think of
21:54 --> 21:56it like a traffic pattern
21:56 --> 21:57since you and I live
21:57 --> 21:58in Southern Connecticut.
21:59 --> 22:00If there's a big
22:00 --> 22:01crash on I-95
22:01 --> 22:02and you can't get where
22:02 --> 22:04you're going, you might think
22:04 --> 22:05of going to the Merritt
22:05 --> 22:05Parkway,
22:06 --> 22:07but we're using an agent
22:07 --> 22:08that blocks the Merritt Parkway,
22:08 --> 22:10so then you have nowhere
22:10 --> 22:10to go.
22:11 --> 22:13And so, we're taking that
22:13 --> 22:14kind of approach for these
22:14 --> 22:16genetically linked cancers.
22:17 --> 22:19And this is by developing
22:19 --> 22:19drugs?
22:20 --> 22:22Yeah. Drugs that target other
22:22 --> 22:23DNA repair pathways. So there's
22:23 --> 22:24a well known class of
22:24 --> 22:26drugs called PARP inhibitors.
22:26 --> 22:27We did not develop them,
22:27 --> 22:29but we're trying to find
22:29 --> 22:31new uses for them.
22:32 --> 22:33Another thing that we did
22:33 --> 22:35was, we found that agents
22:35 --> 22:36that inhibit
22:36 --> 22:37angiogenesis,
22:37 --> 22:39which means the development of
22:39 --> 22:40new blood vessels,
22:41 --> 22:43these can lead to reduced
22:43 --> 22:45oxygen in tumors, a situation
22:45 --> 22:46known as hypoxia.
22:47 --> 22:48And that,
22:48 --> 22:50we found, causes decreased DNA
22:50 --> 22:51repair,
22:51 --> 22:52and we can then exploit
22:53 --> 22:54that situation with some of
22:54 --> 22:55the agents I just talked
22:55 --> 22:56about.
22:56 --> 22:58And is there a role
22:58 --> 22:59for using radiation
22:59 --> 23:00in combination with some of
23:00 --> 23:02these therapies?
23:02 --> 23:03Yes, for sure.
23:03 --> 23:05Some of these DNA repair
23:05 --> 23:06inhibitors like PARP inhibitors,
23:07 --> 23:08and others that are in
23:08 --> 23:10clinical development, there's a number
23:10 --> 23:11of targeted agents,
23:12 --> 23:13that we and others are
23:13 --> 23:14working on to
23:15 --> 23:17inhibit repair pathways that are
23:17 --> 23:17important
23:18 --> 23:20to how the cancer cell
23:20 --> 23:21tries to fix
23:21 --> 23:23the type of DNA damage
23:23 --> 23:24the radiation causes.
23:25 --> 23:26And if I can just
23:26 --> 23:28explore one other combination that's
23:28 --> 23:30been talked about recently. So
23:31 --> 23:31immunotherapy,
23:32 --> 23:33of course, has become,
23:34 --> 23:36the treatment of the past
23:36 --> 23:38decade. It's used in
23:40 --> 23:41well over a dozen different
23:42 --> 23:43tumor types and can be
23:43 --> 23:44highly effective.
23:45 --> 23:47But there's some suggestion that
23:47 --> 23:49radiation could also augment the
23:49 --> 23:50effect of immunotherapy.
23:51 --> 23:53Yes. I think there's
23:53 --> 23:55a lot of intense study,
23:55 --> 23:57both basic science and in
23:57 --> 23:58the clinic, on how to
23:58 --> 24:00best combine radiation and immunotherapy.
24:01 --> 24:02Radiation can
24:03 --> 24:06elicit an inflamed response in
24:06 --> 24:06tumors that
24:08 --> 24:09synergizes
24:09 --> 24:10with the type of immune
24:10 --> 24:11response that
24:12 --> 24:14these immune checkpoint inhibitors will
24:14 --> 24:14provoke.
24:15 --> 24:17It is also thought
24:17 --> 24:19that radiation can cause the
24:19 --> 24:21release of tumor antigens and
24:21 --> 24:22sort of create an in
24:22 --> 24:24situ tumor vaccine, if you
24:24 --> 24:25will.
24:26 --> 24:28So, you know, in general,
24:28 --> 24:29it's thought that
24:30 --> 24:32radiation can enhance the effectiveness
24:32 --> 24:33of tumor
24:33 --> 24:35immune therapy and vice versa,
24:35 --> 24:37that immune therapy or immune
24:37 --> 24:39response will enhance the effect
24:39 --> 24:40of radiation.
24:41 --> 24:42Have you seen a
24:43 --> 24:44change in the
24:45 --> 24:45type of
24:46 --> 24:48medical student who goes into
24:49 --> 24:51radiation oncology today versus
24:52 --> 24:53twenty or thirty years ago?
24:54 --> 24:54It would seem to me
24:54 --> 24:55that a lot of these
24:55 --> 24:57people must be people who
24:57 --> 24:57are
24:59 --> 25:00interested in physics and interested
25:01 --> 25:03in science and
25:03 --> 25:04perhaps interested
25:05 --> 25:07in pursuing careers in research.
25:07 --> 25:08Yes. I think it's always
25:08 --> 25:10been a research friendly
25:11 --> 25:13specialty because there's a lot
25:13 --> 25:15of basic science, and cellular
25:15 --> 25:17biology to explore as well
25:17 --> 25:18as the physics and the
25:18 --> 25:19more technological
25:20 --> 25:20aspects.
25:21 --> 25:22I think that, you know,
25:22 --> 25:24years ago, it
25:24 --> 25:25was felt, well, maybe people
25:25 --> 25:26who had a little bit
25:26 --> 25:28more proclivity for physics might
25:28 --> 25:30go into the field. But
25:30 --> 25:31actually, I think the field
25:31 --> 25:31now
25:32 --> 25:33attracts,
25:33 --> 25:35people that like
25:36 --> 25:37advanced technology that we can
25:37 --> 25:38bring to bear, the image
25:38 --> 25:40guidance, the
25:40 --> 25:42treatment planning that, you know,
25:42 --> 25:43is very computerized and visual,
25:47 --> 25:48so I think it's expanded
25:48 --> 25:50the reach of people that
25:50 --> 25:50are
25:51 --> 25:52interested in the field. And
25:52 --> 25:53the other thing is I
25:53 --> 25:54think people have come to
25:54 --> 25:55know that
25:55 --> 25:57we're a very patient oriented
25:57 --> 25:57specialty,
25:58 --> 26:00just like your specialty medical
26:00 --> 26:02oncology. We're very patient facing,
26:03 --> 26:04and, we have longitudinal
26:05 --> 26:06relationships with our patients, and
26:06 --> 26:08I think that that attracts
26:08 --> 26:10the medical students as well.
26:10 --> 26:12Longitude and relationships with your
26:12 --> 26:13patients
26:13 --> 26:15and, of course, close relationships
26:15 --> 26:17with your colleagues since
26:17 --> 26:19in the care of patients
26:19 --> 26:20with cancer we
26:22 --> 26:24all work together since it
26:24 --> 26:24takes
26:25 --> 26:26far more than any one
26:26 --> 26:27discipline.
26:28 --> 26:29And as we
26:30 --> 26:31wrap up,
26:31 --> 26:32can you
26:33 --> 26:35speculate about where radiation
26:35 --> 26:36oncology
26:36 --> 26:38is going over the course
26:38 --> 26:39of the next
26:39 --> 26:41ten or twenty years?
26:42 --> 26:44What should we be looking for?
26:44 --> 26:45Well, I think that we're
26:45 --> 26:46gonna see a greater
26:46 --> 26:47ability to
26:48 --> 26:49achieve real time adjustments in
26:49 --> 26:50the treatment,
26:50 --> 26:52using some of these onboard
26:52 --> 26:54imaging technologies. And as the
26:55 --> 26:55software
26:56 --> 26:57and hardware improves
26:58 --> 26:59and we can incorporate things
26:59 --> 27:02like artificial intelligence to identify
27:02 --> 27:04the tumor targets, track how
27:04 --> 27:06they move and adjust radiation
27:06 --> 27:07treatments.
27:07 --> 27:09That's going to allow even
27:09 --> 27:10more precise
27:10 --> 27:11and tailored
27:11 --> 27:13radiation therapy for patients.
27:13 --> 27:14I think also we're going
27:14 --> 27:15to see more individualized
27:16 --> 27:17patient treatments based on clinical
27:17 --> 27:19and genetic characteristics
27:20 --> 27:22And, like we were alluding
27:22 --> 27:22to before,
27:23 --> 27:24I see the next five
27:24 --> 27:25or ten years,
27:25 --> 27:26that we will be able
27:26 --> 27:28to deploy new targeted biological
27:29 --> 27:30agents that sensitize tumors to
27:30 --> 27:31radiation
27:32 --> 27:32without
27:33 --> 27:35sensitizing healthy tissues. And,
27:36 --> 27:37for example, we're
27:37 --> 27:38working in the lab to
27:38 --> 27:39develop a class of peptide
27:39 --> 27:41drug conjugates that does just
27:41 --> 27:42that.
27:43 --> 27:44And the preclinical models look
27:44 --> 27:46encouraging, so hopefully that will
27:47 --> 27:48eventually make its way to
27:48 --> 27:50the clinic.
27:50 --> 27:51And not to set up a
27:51 --> 27:52competition with surgery, but do
27:52 --> 27:53you think these changes
27:54 --> 27:56will lead to fewer surgical
27:56 --> 27:56procedures
27:57 --> 27:58and more radiation?
27:59 --> 28:00Well, I think it
28:00 --> 28:02may change the balance for
28:02 --> 28:03certain tumors. I think I've
28:03 --> 28:05seen that the pendulum has
28:05 --> 28:06swung back and forth,
28:08 --> 28:10for different, types of tumors
28:10 --> 28:10where,
28:11 --> 28:13you know, radiation approaches,
28:14 --> 28:15are more favored and then
28:15 --> 28:17surgical. It really
28:17 --> 28:18depends. I mean, the surgeons
28:18 --> 28:19have been very good to
28:19 --> 28:21advance their technology to robotic
28:21 --> 28:24surgeries and minimally invasive surgeries.
28:24 --> 28:25So I think it's all
28:25 --> 28:26to the good for the
28:26 --> 28:27patients, and we'll just have
28:27 --> 28:29more choices for figuring out
28:29 --> 28:30the best treatments.
28:31 --> 28:32Doctor Peter Glazer is the
28:32 --> 28:34Robert E Hunter Professor of
28:34 --> 28:36Therapeutic Radiology and Professor of
28:36 --> 28:37Genetics and Chair of the
28:37 --> 28:39Department of Therapeutic Radiology at
28:39 --> 28:41the Yale School of Medicine.
28:41 --> 28:43If you have questions, the
28:43 --> 28:43address is canceranswers
28:44 --> 28:46at yale dot edu, and
28:46 --> 28:47past editions of the program
28:47 --> 28:48are available in audio and
28:48 --> 28:50written form at yalecancercenter
28:50 --> 28:52dot org. We hope you'll
28:52 --> 28:53join us next time to
28:53 --> 28:54learn more about the fight
28:54 --> 28:54against cancer.
28:55 --> 28:57Funding for Yale Cancer Answers
28:57 --> 28:58is provided by Smilow Cancer
28:58 --> 28:59Hospital.

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50 Years of Cancer Progress: Radiation Oncology with guest Dr. Peter Glazer February 9, 2025

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

call: 203-785-4095

12725

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Dr. Peter Glazer

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