50 Years of Cancer Progress: Radiation Oncology
February 10, 2025ID12725
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- 00:00Funding for Yale Cancer Answers
- 00:02is provided by Smilow Cancer
- 00:04Hospital.
- 00:06Welcome to Yale Cancer Answers
- 00:08with the director of the
- 00:09Yale Cancer Center, doctor Eric
- 00:11Winer.
- 00:12Yale Cancer Answers features conversations
- 00:14with oncologists and specialists
- 00:16who are on the forefront
- 00:17of the battle to fight
- 00:18cancer.
- 00:19This week, it's a conversation
- 00:20about radiation oncology with doctor
- 00:23Peter Glazer.
- 00:24Doctor Glazer is the Robert
- 00:25E. Hunter Professor of Therapeutic
- 00:27Radiology
- 00:28and Professor of Genetics and
- 00:30chair of the department of
- 00:31therapeutic radiology at the Yale
- 00:33School of Medicine.
- 00:35Here's doctor Winer.
- 00:37Can you just tell us
- 00:38a little bit about yourself?
- 00:40How is it
- 00:42that you came to be
- 00:43a radiation oncologist?
- 00:45I'm a
- 00:47physician scientist with an MD
- 00:49and a PhD in genetics,
- 00:51and as you mentioned,
- 00:52my medical specialty is in
- 00:53radiation oncology.
- 00:56And my research focuses on fundamental
- 00:58cancer biology and
- 01:01development of translational
- 01:02research opportunities.
- 01:05I got started in the
- 01:07field because of a strong
- 01:08clinical interest in oncology,
- 01:11and in taking care of
- 01:12cancer patients, and that was
- 01:13coupled with a growing research
- 01:15interest in the field of
- 01:17DNA repair, which is how
- 01:18cells fix their DNA.
- 01:21And that's an important topic
- 01:22in the field of radiation
- 01:23oncology.
- 01:25Can you just
- 01:27tell us a little bit
- 01:29about
- 01:30radiation as a treatment,
- 01:33both in terms of how
- 01:34it's delivered, or
- 01:37I should say the different
- 01:39ways in which it can
- 01:40be delivered.
- 01:42And then we'll explore
- 01:44some other aspects of radiation.
- 01:46Sure. Radiation
- 01:47oncology is the medical specialty
- 01:50that uses focused x rays
- 01:51to treat cancer
- 01:53because of their ability to
- 01:54kill cancer cells.
- 01:56And early medical applications of
- 01:58radiation were based on radioactive
- 02:00materials like radium
- 02:01that were discovered by
- 02:03Marie Curie, because early on
- 02:05it was found that radiation
- 02:06causes tumors to shrink.
- 02:09Later on, other isotopes like
- 02:10cobalt, iridium,
- 02:12and others were identified and
- 02:14developed,
- 02:15and some are used for
- 02:16a type of treatment called
- 02:17brachytherapy, which involves placement of
- 02:19radioactive
- 02:20sources
- 02:22in close proximity to a
- 02:23tumor as is frequently done
- 02:25for cancers of
- 02:28the gynecologic
- 02:30tract in women.
- 02:31So a device is actually
- 02:33put in and it gives
- 02:34off radiation
- 02:35while it sits
- 02:37essentially near or within somebody.
- 02:39It dwells next to the tumor.
- 02:45It's put in a
- 02:46surgical procedure, and then it's
- 02:48removed after a specified time.
- 02:51And in some other
- 02:53approaches, isotopes are
- 02:55injected systemically for special applications
- 02:58usually linked to a carrier
- 02:59like an antibody.
- 03:02When X rays were first
- 03:04developed, it was known that
- 03:05they could be generated by
- 03:06cathode ray tubes, but
- 03:08that was low energy and
- 03:09had drawbacks. So after World
- 03:11War II, a major advance
- 03:12was the development of technology
- 03:14to
- 03:15accelerate electrons
- 03:18at high voltage into a
- 03:19medical target to
- 03:21generate high energy x rays
- 03:22or photons.
- 03:23And that was the birth
- 03:24of the linear accelerator or
- 03:26LINAC.
- 03:28And this allowed for treatment
- 03:29of deep seated tumors in
- 03:30the body with sparing of
- 03:32superficial
- 03:33tissues.
- 03:35And it seems to me that
- 03:36it was the case many
- 03:37years ago
- 03:39that radiation oncologists would take
- 03:41an x-ray,
- 03:43just a standard x-ray that
- 03:45might show, for example, in
- 03:46the chest
- 03:47a lung cancer.
- 03:49And
- 03:50in what now seems like
- 03:52a pretty crude manner,
- 03:54they would just draw around
- 03:56that tumor and then aim
- 03:58the beam
- 04:00at the tumor. Is that
- 04:02basically right?
- 04:04Yes, early on
- 04:05the treatment machines were
- 04:08were limited in
- 04:10their ability to move and
- 04:11to deliver shaped beams. So
- 04:14most of the treatments were
- 04:15from the front or the
- 04:16back of the patient in
- 04:17a simple
- 04:18way.
- 04:20And so we were guided
- 04:21by what we kind of
- 04:22refer to as two dimensional
- 04:24imaging, which is those plain
- 04:25film x rays.
- 04:27But, one of
- 04:28the major advances
- 04:30in field has
- 04:32been the use of advanced
- 04:33imaging like CT scans, MRI
- 04:35scans, or now even PET
- 04:37scanning
- 04:38to create three-dimensional images
- 04:40of the tumor target.
- 04:41And that's coupled with
- 04:43many technological
- 04:45advances in the linear accelerators
- 04:47that allow
- 04:48the delivery of very complex,
- 04:51beam arrangements that really shape
- 04:53the dose distribution in a
- 04:55three-dimensional manner.
- 04:57And my sense is that
- 04:58by using those three-dimensional images
- 05:00like CT scans and with
- 05:02the changes in some of
- 05:04your,
- 05:05equipment that delivers radiation,
- 05:08two things have happened.
- 05:09The treatment is far more
- 05:11effective,
- 05:12and at the same time,
- 05:13you can spare patients a
- 05:15lot of the side effects
- 05:16that used to be pretty
- 05:17commonplace.
- 05:19That's right. Because now we
- 05:20can shape the dose distribution
- 05:22a lot more conformally
- 05:24to the tumor itself
- 05:26and substantially reduce the dose
- 05:27to surrounding tissues.
- 05:30That's allowed us to deliver
- 05:32the treatments
- 05:33much more safely with less
- 05:35side effects.
- 05:37And in some cases, we
- 05:38can give a higher dose
- 05:40each day and reduce
- 05:42the number of
- 05:43days of treatment and that's
- 05:45also a
- 05:46benefit to patients.
- 05:48Before we get into some
- 05:49additional advances,
- 05:51maybe you could just comment
- 05:53on some of the myths
- 05:55that people still carry around
- 05:57about radiation.
- 05:59You know, in
- 06:01not such a different way
- 06:02than with chemotherapy,
- 06:03there are a lot of
- 06:04patients who come see us
- 06:06and have preconceived notions about
- 06:09what these treatments are like
- 06:10and will come in saying,
- 06:11well, I'm never doing that
- 06:13because
- 06:14you know, my great aunt received
- 06:16that and had some terrible
- 06:18problems.
- 06:20What are the specific
- 06:22misunderstandings
- 06:23about radiation?
- 06:25Well, I think that
- 06:27one is,
- 06:28what we're alluding to before
- 06:30is, you know,
- 06:31historically, some people may remember
- 06:33that
- 06:34people treated with sort of
- 06:36the older fashioned ways of
- 06:37giving radiation developed
- 06:39skin burns
- 06:41that
- 06:43were very challenging to treat
- 06:45and to heal. But
- 06:47the advances that we just
- 06:48talked about in
- 06:50delivery of radiation more deeply
- 06:53into the body and sparing
- 06:54the skin with shape beams,
- 06:57has allowed us to substantially
- 06:59avoid
- 07:01the skin damage
- 07:02and also
- 07:03side effects to other
- 07:05tissues.
- 07:08And I'm not saying that doesn't sometimes
- 07:10happen. There
- 07:12can be some
- 07:13side effects to the skin,
- 07:14but it's much much
- 07:16less than it used to be for
- 07:18the skin and for
- 07:19that matter, other organs too.
- 07:23There is some
- 07:25effect of radiation as it
- 07:27passes through healthy tissue, and
- 07:29sometimes that can lead to
- 07:30some fatigue and temporary loss
- 07:32of energy.
- 07:34Sometimes, if patients are treated
- 07:36in the area of the
- 07:37head and neck, they may
- 07:38develop dry mouth,
- 07:41or if they're treated in
- 07:42the GI tract, they may
- 07:43have some symptoms
- 07:45associated with that. But, usually
- 07:47these symptoms fade over time.
- 07:49What are some of the
- 07:50most common uses of radiation?
- 07:52About sixty percent of all
- 07:53cancer patients
- 07:55are treated with radiation and
- 07:58many different types of tumors
- 07:59are treated.
- 08:04One very common treatment is for
- 08:05cancers of the head and
- 08:06neck where radiation is considered
- 08:09a curative treatment often in
- 08:11combination with chemotherapy.
- 08:13We do a lot of
- 08:14radiation treatments for breast cancer,
- 08:16prostate cancer,
- 08:18brain tumors,
- 08:20and, tumors of the GI
- 08:22tract. I mentioned
- 08:25gynecologic
- 08:25malignancies
- 08:26where radiation is very effective
- 08:30and routinely achieves
- 08:32curative effect in many of
- 08:33those scenarios.
- 08:35And in some cases, these are
- 08:37a substitute for
- 08:39surgery, and in some cases,
- 08:41it's done in conjunction with
- 08:43surgery.
- 08:44Radiation
- 08:46is particularly effective for localized
- 08:48disease
- 08:49and can be an alternative
- 08:51to surgery in some cases,
- 08:53either because the individual is
- 08:55not medically able to undergo an
- 08:59operation,
- 09:00or because the
- 09:03morbidity or side effects
- 09:05of getting radiation may actually be
- 09:08more favorable than a surgical
- 09:10intervention.
- 09:11Not so many years ago
- 09:12when someone would have cancer
- 09:14that unfortunately would spread to
- 09:16their brain,
- 09:18they very commonly would
- 09:20get radiation
- 09:22to the entire brain, to
- 09:24the whole head essentially.
- 09:26And increasingly
- 09:28over the years, it seems
- 09:30that that's not the case,
- 09:31and treatments that are
- 09:33referred to as either
- 09:34stereotactic
- 09:36radiosurgery
- 09:37or gamma knife
- 09:39have been used and have
- 09:41been very effective.
- 09:42Can you tell us a
- 09:43little bit about those treatments?
- 09:45Yes, you're absolutely
- 09:47right that
- 09:48years ago for
- 09:50metastases in the brain,
- 09:53treatment would be given to
- 09:54what we call the whole
- 09:55brain, which is basically the
- 09:56upper
- 09:57part of the head through
- 09:59and through. But the advances
- 10:01that I was alluding to
- 10:02in terms
- 10:04of the technology, the treatment
- 10:05machines, and also specialized devices
- 10:07like the gamma knife,
- 10:09allows very focused treatment of
- 10:12individual metastatic lesions,
- 10:15with really exquisite precision that
- 10:17allow
- 10:18a good deal of sparing
- 10:20of the surrounding healthy brain.
- 10:23So now it's pretty much
- 10:24standard of care to
- 10:26treat
- 10:27the metastatic lesions fairly aggressively,
- 10:30but with highly focused treatment.
- 10:32And the Gamma Knife actually
- 10:33is one of the best
- 10:34devices to do that for
- 10:35brain lesions because of its
- 10:37high precision.
- 10:39I mean, this has really
- 10:41transformed
- 10:42in many ways the treatment
- 10:44of cancer that has spread
- 10:45to the brain
- 10:46and has allowed people to
- 10:49live longer and at the
- 10:50same time live much better.
- 10:54And it's become especially important as systemic
- 10:56therapies have improved.
- 10:59So now we are taking
- 11:02a more aggressive
- 11:03approach to trying to
- 11:06treat lesions in the brain
- 11:08when the systemic disease can
- 11:10be controlled by other approaches.
- 11:12It seems that there are
- 11:14even newer approaches, and you
- 11:17have a new machine
- 11:18that gives
- 11:20guided radiation.
- 11:21And maybe you can tell
- 11:23us a little bit about
- 11:24that, and what
- 11:26kind of guidance is used?
- 11:29This is along the lines of what
- 11:31we call image guided therapy,
- 11:33in which the linear
- 11:34accelerators have an onboard imaging
- 11:36device to help
- 11:39us evaluate
- 11:41and modify the treatment
- 11:43at the time
- 11:44the patient
- 11:46is in the machine and
- 11:48in some cases almost in
- 11:49real time.
- 11:51This approach started with CT
- 11:53scan and MR scan,
- 11:56included in Lenox, but this
- 11:58new biologically guided therapy incorporates
- 12:01a PET scanner or PET
- 12:02imager in the device. NOTE Confidence: 0.9444651
- 12:04A PET scanner image
- 12:07positron emissions from radioactive tracers
- 12:10that
- 12:11accumulate in the tumor when
- 12:13certain
- 12:14compounds are given to the
- 12:15patient ahead of time. And
- 12:17that allows us to account
- 12:19for the localization of the
- 12:21tumor,
- 12:22and also its motion within
- 12:24the patient, and in some
- 12:26cases depending on the tracer
- 12:28we use on its biological
- 12:29properties.
- 12:30And then we can modify
- 12:33the treatment, beamlets,
- 12:35in real time based on
- 12:36the positron emission pattern.
- 12:39How much experience have
- 12:41you had with this so far?
- 12:42We've had it going
- 12:44for about a year, and
- 12:46actually, I think we have
- 12:48one of the largest experiences
- 12:49in the country with this.
- 12:50So we're getting more familiar
- 12:52with how to best
- 12:54incorporate this technology into
- 12:57our treatment of patients.
- 12:59So it's really
- 13:01taking the treatment even
- 13:03a step further than you
- 13:05would with just a CT
- 13:06scan alone
- 13:08because with
- 13:09the PET part of that
- 13:10imaging, you can tell much
- 13:12more about what's going on
- 13:13in the tumor.
- 13:14It has a new dimension.
- 13:15Right now, it's primarily
- 13:17valuable for accounting for
- 13:19motion, especially lesions in the
- 13:21lung where you have breathing,
- 13:24the breathing cycle that
- 13:25causes motion.
- 13:27But we think that down
- 13:29the road, we will have
- 13:30many other applications of the
- 13:31technology.
- 13:33Well, this is great. We're
- 13:34gonna take a break for
- 13:35just a minute. And when
- 13:37we come back, we're gonna
- 13:38talk a little more about
- 13:40how radiation works, and then
- 13:41we're gonna get into some
- 13:43of the research you've done
- 13:44related to that.
- 13:46Support for Yale Cancer Answers
- 13:48comes from Smilow Cancer Hospital,
- 13:50where all patients have access
- 13:52to cutting edge clinical trials
- 13:53at several convenient locations throughout
- 13:55the region.
- 13:56To learn more, visit smilowcancer
- 13:58hospital dot org.
- 14:02The American Cancer Society estimates
- 14:04that nearly one hundred and
- 14:05fifty thousand people in the
- 14:07U. S. will be diagnosed
- 14:08with colorectal cancer this year
- 14:10alone.
- 14:11When detected early, colorectal cancer
- 14:13is easily treated and highly
- 14:15curable,
- 14:16and men and women over
- 14:17the age of forty five
- 14:18should have regular colonoscopies
- 14:20to screen for the disease.
- 14:22Patients with colorectal cancer have
- 14:24more hope than ever before,
- 14:25thanks to increased access to
- 14:27advanced therapies and specialized care.
- 14:30Clinical trials are currently underway
- 14:32at federally designated comprehensive cancer
- 14:34centers, such as Yale Cancer
- 14:36Center and Smilow Cancer
- 14:38Hospital,
- 14:39to test innovative new treatments
- 14:40for colorectal cancer.
- 14:42Tumor gene analysis has helped
- 14:44improve management of colorectal cancer
- 14:47by identifying the patients most
- 14:49likely to benefit from chemotherapy
- 14:51and newer targeted agents resulting
- 14:54in more patient specific treatment.
- 14:56More information is available at
- 14:58yale cancer center dot org.
- 15:00You're listening to Connecticut Public
- 15:02Radio.
- 15:03Good evening again. This is
- 15:04Eric Winer with Yale Cancer
- 15:06Answers, and I'm here tonight
- 15:09with my guest,
- 15:11doctor Peter Glazer,
- 15:13who is a professor of
- 15:16therapeutic radiology and a professor
- 15:18of genetics here at Yale
- 15:19School of Medicine and chair
- 15:22of therapeutic radiology.
- 15:24Can you tell us a
- 15:25little bit
- 15:26about
- 15:27how it is that radiation
- 15:29on a cellular
- 15:31level
- 15:32kills cancer cells? What does
- 15:34it do that makes
- 15:36them die?
- 15:38The radiation
- 15:39that we use
- 15:41clinically to treat cancer is
- 15:42sometimes
- 15:43classified
- 15:44as ionizing radiation
- 15:46to differentiate it from other
- 15:48forms of
- 15:51radiation including photons, which is
- 15:53visible light.
- 15:56And what that means is
- 15:57that the radiation, x-ray radiation
- 15:59goes into cancer cells
- 16:02and causes ionization of the
- 16:04molecules
- 16:05inside the cell, and that
- 16:07leads to a lot of
- 16:08chemical reactions that damage the
- 16:09DNA.
- 16:11So fundamentally,
- 16:12radiation causes DNA damage in
- 16:14cancer cells
- 16:15and if we can provide
- 16:17sufficient damage, the cells cannot
- 16:20fix themselves well enough to
- 16:22recover
- 16:23and that leads to a
- 16:24destruction of the tumor and
- 16:26tumor regression.
- 16:28And the DNA is essentially
- 16:30the brain of the cancer cell?
- 16:32Yes, DNA
- 16:33as in all cells, has
- 16:35the blueprint for how a
- 16:37cell functions,
- 16:38and DNA
- 16:40leads to the production of
- 16:42downstream molecules like RNA and
- 16:44proteins. So if you get
- 16:45the DNA, then you basically
- 16:47block all cellular functions
- 16:49and the ability of the
- 16:50cell to survive.
- 16:51Now one of the things
- 16:53that
- 16:54one hears as a doctor
- 16:56from patients is the question,
- 16:58well, doesn't radiation
- 16:59cause cancer?
- 17:01And I think people are
- 17:03often thinking about
- 17:05the fact that, you know,
- 17:07repeated,
- 17:09imaging studies are associated with
- 17:11a very small increased risk
- 17:13in cancer in certain circumstances.
- 17:16Is that a question that
- 17:17that all of you get
- 17:19asked a fair amount?
- 17:20Yes. We sometimes talk about
- 17:22that with patients. I
- 17:23I think that it, you
- 17:25know, it is known that
- 17:27there is a link between
- 17:28radiation exposure and
- 17:31developing malignancies.
- 17:32I think this is one
- 17:33of the
- 17:35key reasons that we've worked
- 17:36so hard to develop technologies
- 17:38that focus the radiation
- 17:40intensively on the tumor and
- 17:43work to spare the healthy
- 17:44tissue
- 17:45as much as we can.
- 17:48And, you know, we've studied
- 17:49this a lot in the
- 17:50field, and the risk of
- 17:54secondary malignancies
- 17:55is not zero, but it's
- 17:56very low, especially for most
- 17:58adult patients.
- 17:59We worry a little bit
- 18:00more about children, which is
- 18:02one of the reasons that
- 18:03we spend a lot
- 18:05of time in developing treatment
- 18:07approaches for children that are
- 18:09very highly focused. And
- 18:11one of the more recent,
- 18:13two elements along those lines
- 18:14is the use of proton
- 18:16beam therapy,
- 18:17which is
- 18:19especially valuable for treating
- 18:21children.
- 18:22And,
- 18:23there's gonna be a proton
- 18:25beam facility
- 18:26in Connecticut
- 18:27in the not distant future
- 18:29that we've been involved with.
- 18:31Protons
- 18:34are a type of ionizing
- 18:35radiation, but instead of x
- 18:37rays, they use
- 18:38protons, which are a subatomic
- 18:40particle,
- 18:42which a machine
- 18:44called a cyclotron will accelerate.
- 18:46And the protons
- 18:47also enter into the tissue,
- 18:49but they have a special
- 18:51property because
- 18:52they're a particle with mass
- 18:54that they enter tissue and
- 18:55they stop suddenly to deposit
- 18:57their dose.
- 18:59And that lets us tailor the
- 19:03delivery of the ionizing radiation
- 19:05even better.
- 19:07And,
- 19:08we think that it has
- 19:09some advantages.
- 19:11But developing proton beam facilities
- 19:13is not a simple endeavor.
- 19:15It's much more expensive and
- 19:16involved than
- 19:18installing a regular LINAC.
- 19:20And so there are not
- 19:22many in the country,
- 19:24and there is
- 19:25not one in Connecticut right
- 19:26now, but Yale New Haven
- 19:28Health System and Hartford HealthCare
- 19:30have partnered,
- 19:32and we recently did the
- 19:33groundbreaking to
- 19:36advance a new proton beam
- 19:37facility,
- 19:39in the center of the
- 19:40state that'll be
- 19:42a resource for all of
- 19:43the people in the region.
- 19:44And the price tag for
- 19:46these kinds of facilities is
- 19:48in the
- 19:49tens of millions of dollars.
- 19:52You know, this one is
- 19:53somewhere in the range of
- 19:54seventy million all in with
- 19:56all the construction and
- 19:58equipment.
- 20:01Can you
- 20:02talk about some of your
- 20:04research?
- 20:05And
- 20:06I know some of the
- 20:07recent research has
- 20:09related to the treatment of
- 20:13what is
- 20:15often thought of as
- 20:17inherited breast cancer and other
- 20:19cancers that
- 20:20arise in the setting of
- 20:22of BRCA
- 20:23mutations.
- 20:25But I know that your
- 20:27research career stretches
- 20:29pretty far back. And
- 20:31what are some of the
- 20:32things you've worked on over
- 20:33the years? And then maybe
- 20:34we can talk more about
- 20:36BRCA.
- 20:37Yes, I've
- 20:39been interested in how
- 20:41DNA repair pathways can influence
- 20:43the development of cancer and
- 20:45how they can be exploited
- 20:46for treatment.
- 20:47And you mentioned
- 20:49the BRCA1
- 20:50and BRCA2
- 20:52genes which are linked
- 20:56to a large extent to
- 20:57breast and ovarian cancers.
- 21:00And defects in those genes
- 21:01lead to a deficiency in
- 21:04a pathway of DNA repair
- 21:06called homologous recombination.
- 21:08We recently discovered that some
- 21:10other genes that are seen
- 21:12mutated in cancers
- 21:14that are linked to abnormal
- 21:16metabolism
- 21:18also cause a defect in
- 21:19the same DNA repair pathway
- 21:22and we found unexpectedly
- 21:24that they can be exploited
- 21:26with
- 21:27molecularly
- 21:28targeted agents that
- 21:31exploit related
- 21:32DNA repair pathways.
- 21:35And similar to the situation
- 21:36with BRCA1 and BRCA2,
- 21:38these genes include
- 21:41genes with the names IDH1
- 21:42and two, SDH and FH
- 21:45and they're linked to
- 21:47brain tumors, sarcomas, kidney cancers
- 21:49and others.
- 21:51Some of the strategy that
- 21:52we and others have worked
- 21:54on, you can think of
- 21:55it like a traffic pattern
- 21:56since you and I live
- 21:57in Southern Connecticut.
- 21:59If there's a big
- 22:00crash on I-95
- 22:02and you can't get where
- 22:03you're going, you might think
- 22:04of going to the Merritt
- 22:05Parkway,
- 22:06but we're using an agent
- 22:08that blocks the Merritt Parkway,
- 22:09so then you have nowhere
- 22:10to go.
- 22:11And so, we're taking that
- 22:13kind of approach for these
- 22:15genetically linked cancers.
- 22:17And this is by developing
- 22:19drugs?
- 22:20Yeah. Drugs that target other
- 22:22DNA repair pathways. So there's
- 22:24a well known class of
- 22:25drugs called PARP inhibitors.
- 22:27We did not develop them,
- 22:28but we're trying to find
- 22:30new uses for them.
- 22:32Another thing that we did
- 22:33was, we found that agents
- 22:35that inhibit
- 22:37angiogenesis,
- 22:38which means the development of
- 22:40new blood vessels,
- 22:42these can lead to reduced
- 22:44oxygen in tumors, a situation
- 22:46known as hypoxia.
- 22:47And that,
- 22:49we found, causes decreased DNA
- 22:51repair,
- 22:51and we can then exploit
- 22:53that situation with some of
- 22:54the agents I just talked
- 22:56about.
- 22:57And is there a role
- 22:58for using radiation
- 23:00in combination with some of
- 23:01these therapies?
- 23:03Yes, for sure.
- 23:04Some of these DNA repair
- 23:05inhibitors like PARP inhibitors,
- 23:08and others that are in
- 23:09clinical development, there's a number
- 23:10of targeted agents,
- 23:12that we and others are
- 23:14working on to
- 23:15inhibit repair pathways that are
- 23:17important
- 23:19to how the cancer cell
- 23:20tries to fix
- 23:22the type of DNA damage
- 23:23the radiation causes.
- 23:25And if I can just
- 23:26explore one other combination that's
- 23:29been talked about recently. So
- 23:31immunotherapy,
- 23:32of course, has become,
- 23:35the treatment of the past
- 23:37decade. It's used in
- 23:40well over a dozen different
- 23:42tumor types and can be
- 23:44highly effective.
- 23:45But there's some suggestion that
- 23:47radiation could also augment the
- 23:50effect of immunotherapy.
- 23:52Yes. I think there's
- 23:54a lot of intense study,
- 23:56both basic science and in
- 23:57the clinic, on how to
- 23:58best combine radiation and immunotherapy.
- 24:02Radiation can
- 24:04elicit an inflamed response in
- 24:06tumors that
- 24:09synergizes
- 24:10with the type of immune
- 24:11response that
- 24:12these immune checkpoint inhibitors will
- 24:14provoke.
- 24:16It is also thought
- 24:17that radiation can cause the
- 24:19release of tumor antigens and
- 24:22sort of create an in
- 24:23situ tumor vaccine, if you
- 24:25will.
- 24:27So, you know, in general,
- 24:29it's thought that
- 24:30radiation can enhance the effectiveness
- 24:33of tumor
- 24:34immune therapy and vice versa,
- 24:36that immune therapy or immune
- 24:38response will enhance the effect
- 24:39of radiation.
- 24:42Have you seen a
- 24:43change in the
- 24:45type of
- 24:47medical student who goes into
- 24:50radiation oncology today versus
- 24:52twenty or thirty years ago?
- 24:54It would seem to me
- 24:55that a lot of these
- 24:56people must be people who
- 24:57are
- 24:59interested in physics and interested
- 25:01in science and
- 25:04perhaps interested
- 25:05in pursuing careers in research.
- 25:08Yes. I think it's always
- 25:09been a research friendly
- 25:12specialty because there's a lot
- 25:13of basic science, and cellular
- 25:16biology to explore as well
- 25:17as the physics and the
- 25:18more technological
- 25:21aspects.
- 25:21I think that, you know,
- 25:23years ago, it
- 25:25was felt, well, maybe people
- 25:26who had a little bit
- 25:27more proclivity for physics might
- 25:29go into the field. But
- 25:30actually, I think the field
- 25:31now
- 25:33attracts,
- 25:34people that like
- 25:36advanced technology that we can
- 25:38bring to bear, the image
- 25:39guidance, the
- 25:41treatment planning that, you know,
- 25:42is very computerized and visual,
- 25:47so I think it's expanded
- 25:49the reach of people that
- 25:50are
- 25:51interested in the field. And
- 25:52the other thing is I
- 25:53think people have come to
- 25:54know that
- 25:55we're a very patient oriented
- 25:57specialty,
- 25:59just like your specialty medical
- 26:01oncology. We're very patient facing,
- 26:03and, we have longitudinal
- 26:05relationships with our patients, and
- 26:07I think that that attracts
- 26:09the medical students as well.
- 26:11Longitude and relationships with your
- 26:12patients
- 26:14and, of course, close relationships
- 26:16with your colleagues since
- 26:18in the care of patients
- 26:19with cancer we
- 26:22all work together since it
- 26:24takes
- 26:25far more than any one
- 26:27discipline.
- 26:28And as we
- 26:30wrap up,
- 26:32can you
- 26:33speculate about where radiation
- 26:36oncology
- 26:37is going over the course
- 26:38of the next
- 26:40ten or twenty years?
- 26:43What should we be looking for?
- 26:44Well, I think that we're
- 26:45gonna see a greater
- 26:47ability to
- 26:48achieve real time adjustments in
- 26:50the treatment,
- 26:51using some of these onboard
- 26:52imaging technologies. And as the
- 26:55software
- 26:56and hardware improves
- 26:58and we can incorporate things
- 27:00like artificial intelligence to identify
- 27:03the tumor targets, track how
- 27:04they move and adjust radiation
- 27:07treatments.
- 27:08That's going to allow even
- 27:09more precise
- 27:10and tailored
- 27:12radiation therapy for patients.
- 27:14I think also we're going
- 27:15to see more individualized
- 27:16patient treatments based on clinical
- 27:18and genetic characteristics
- 27:20And, like we were alluding
- 27:22to before,
- 27:23I see the next five
- 27:24or ten years,
- 27:26that we will be able
- 27:27to deploy new targeted biological
- 27:29agents that sensitize tumors to
- 27:31radiation
- 27:32without
- 27:34sensitizing healthy tissues. And,
- 27:36for example, we're
- 27:37working in the lab to
- 27:38develop a class of peptide
- 27:40drug conjugates that does just
- 27:42that.
- 27:43And the preclinical models look
- 27:45encouraging, so hopefully that will
- 27:47eventually make its way to
- 27:48the clinic.
- 27:50And not to set up a
- 27:51competition with surgery, but do
- 27:53you think these changes
- 27:54will lead to fewer surgical
- 27:56procedures
- 27:57and more radiation?
- 27:59Well, I think it
- 28:00may change the balance for
- 28:02certain tumors. I think I've
- 28:04seen that the pendulum has
- 28:06swung back and forth,
- 28:08for different, types of tumors
- 28:10where,
- 28:12you know, radiation approaches,
- 28:14are more favored and then
- 28:16surgical. It really
- 28:17depends. I mean, the surgeons
- 28:19have been very good to
- 28:20advance their technology to robotic
- 28:22surgeries and minimally invasive surgeries.
- 28:24So I think it's all
- 28:25to the good for the
- 28:26patients, and we'll just have
- 28:28more choices for figuring out
- 28:30the best treatments.
- 28:31Doctor Peter Glazer is the
- 28:33Robert E Hunter Professor of
- 28:34Therapeutic Radiology and Professor of
- 28:36Genetics and Chair of the
- 28:38Department of Therapeutic Radiology at
- 28:40the Yale School of Medicine.
- 28:42If you have questions, the
- 28:43address is canceranswers
- 28:44at yale dot edu, and
- 28:46past editions of the program
- 28:47are available in audio and
- 28:49written form at yalecancercenter
- 28:51dot org. We hope you'll
- 28:52join us next time to
- 28:53learn more about the fight
- 28:54against cancer.
- 28:55Funding for Yale Cancer Answers
- 28:57is provided by Smilow Cancer
- 28:59Hospital.