Advances in Cervical Cancer Treatment: Image-Guided Brachytherapy at Yale
January 04, 2023Information
Yale Cancer Center Grand Rounds | January 3, 2023
Presentation by: Dr. Shari Damast
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- 00:00Good afternoon, everybody.
- 00:02Thank you all for coming.
- 00:06It's my really true pleasure to
- 00:10introduce Sherry Dimas today.
- 00:13Sherry is a world's expert on treatment
- 00:18of gynecologic malignancies and you know.
- 00:22We I'm not just throwing
- 00:25that those words around.
- 00:27She really is a leader,
- 00:29and we're so lucky to have
- 00:32her here at Yale University.
- 00:35Sherry trained at Cornell and then
- 00:38did her residency at Memorial Sloan
- 00:41Kettering and joined us 11 years ago.
- 00:46She's now professor of therapeutic radiology,
- 00:50and she.
- 00:51It built our HDR brachytherapy
- 00:55service here at Yale,
- 00:57which is really an incredible accomplishment.
- 01:00So today she's going to be speaking
- 01:02to us about advances in treatment of
- 01:05cervical cancer and welcome Sherry.
- 01:20Thank you so much, Joe,
- 01:21for that very kind introduction and
- 01:23it's really an honor to be here.
- 01:25So as you heard, I direct the
- 01:27gynecologic radiotherapy program here
- 01:29at Yale and today I'm going to be.
- 01:31Talking about brachytherapy and
- 01:32the treatment of cervical cancer,
- 01:34how we approach these patients and
- 01:36specifically the supportive and innovative
- 01:38programs that we have here at Yale
- 01:40for this unique patient population.
- 01:42And they have no financial disclosures.
- 01:45So cervical cancer is a
- 01:46global health problem.
- 01:47Worldwide,
- 01:48there's more than 600,000 new cases per
- 01:50year and more than 340,000 deaths in 2020.
- 01:53And it's particularly a problem in
- 01:55resource limited countries where it's
- 01:57a very common type of cancer and a
- 02:00very common cause of cancer mortality.
- 02:02And in certain regions of
- 02:04Africa and Central America,
- 02:05it's actually the leading cause
- 02:06of cancer related mortality.
- 02:08And unfortunately this is a cancer
- 02:10that disproportionately effects
- 02:12women in low socioeconomic groups
- 02:13and there are complex challenges
- 02:15for these women at every step in
- 02:18the cervical cancer continuum.
- 02:19In the United States,
- 02:20there's more than 14,000 new
- 02:22cases per year and more than
- 02:244000 deaths expected in 2022.
- 02:25The highest incidence is among US Hispanic,
- 02:28black and Native American populations.
- 02:30This is a cancer of young women.
- 02:32It is most frequently diagnosed
- 02:34in women ages 35 to 44.
- 02:36And as we all know,
- 02:37HPV is central to the development
- 02:39of cervical cancer.
- 02:40It causes more than 95% of cases.
- 02:42Risk factors include various
- 02:44sexual behaviors, including young,
- 02:45age at first coitus,
- 02:46multiple sexual partners, history of STI's.
- 02:49It's also more common among those
- 02:51with a compromised immune system.
- 02:53So fortunately,
- 02:54screening cervical cytology and
- 02:55HPV testing has led to reductions
- 02:58in cervical cancer mortality,
- 03:00particularly in resource rich settings.
- 03:02And the incidence of cervical cancer
- 03:04is affected both by epidemiologic
- 03:05risk factors as well as by having
- 03:07access to screening programs.
- 03:09So for those who are screened,
- 03:11cervical cancer may be discovered
- 03:13asymptomatically and very early stages,
- 03:15for example because of an abnormal
- 03:17pap smear or if you know a visible
- 03:20lesion is discovered incidentally
- 03:21on a pelvic examination.
- 03:23But these are not the patients
- 03:24that I see in my practice.
- 03:28So the types of patients that I might
- 03:29see in my practice are typically,
- 03:31let's say, a young woman in her
- 03:3230s or 40s who has a very advanced
- 03:35cancer that's highly symptomatic.
- 03:36And she's probably had bleeding
- 03:37and pain going on for some time.
- 03:39She's perhaps bounced around
- 03:40between different emergency
- 03:41departments and different hospitals,
- 03:43misdiagnosed with fibroids or infection,
- 03:45and she's often from an
- 03:47underserved community.
- 03:48She is often suspicious of the
- 03:50medical student of the medical system
- 03:51and has not had routine screening.
- 03:53She may even be suspicious of a GYN exam,
- 03:56perhaps a history of abuse or
- 03:58trauma in her past and often
- 03:59life hasn't treated her well,
- 04:01and now she's hit with this.
- 04:03What do I mean by this?
- 04:04So this is locally advanced cervical cancer.
- 04:07That's when the tumor has grown to be
- 04:09clinically visible more than 4 centimeters.
- 04:11It invades beyond the cervix
- 04:13into the parametrial tissues.
- 04:14It can extend out to the pelvic sidewall,
- 04:16down into the vagina,
- 04:17can also extend into the surrounding
- 04:20structures of the pelvis,
- 04:21including the bladder or the ******.
- 04:23And for these patients,
- 04:24the primary treatment is not surgery,
- 04:26but rather these patients
- 04:27are treated with chemo,
- 04:28radiation and brachytherapy.
- 04:32The paradigm for treatment is shown here
- 04:34and what I'm showing on the horizontal
- 04:35line is the time frame of treatment.
- 04:37So we try to get all of the
- 04:39treatments done within eight weeks.
- 04:40So for the first five to six
- 04:41weeks of treatment, the treatment
- 04:42consists of external beam radiation,
- 04:44which is what I'm going to show you.
- 04:45These arrows can note weekly
- 04:47cisplatinum chemotherapy,
- 04:48which has been shown in randomized
- 04:49trials to to improve the overall
- 04:51survival in this population.
- 04:52So the first five to six
- 04:54weeks are chemo radiation.
- 04:55That is followed by brachytherapy,
- 04:56which I'm going to talk about today.
- 04:58And again,
- 04:58all these treatments we tried
- 05:00to complete within eight weeks,
- 05:01studies have shown that.
- 05:02Sending treatment beyond eight weeks
- 05:03is associated with a reduction in
- 05:05tumor control and worse outcomes.
- 05:09I think many of you here are familiar
- 05:10with external beam radiation,
- 05:12also called evart.
- 05:13The patient comes every day to our
- 05:15department for five days a week.
- 05:17For five weeks she lies on a
- 05:18table that looks like this.
- 05:19This is called a linear accelerator
- 05:21that delivers high energy X-rays from
- 05:23the outside into a very carefully
- 05:25designed target like what you see here.
- 05:27And this is a target that's
- 05:28designed to incorporate the pelvic
- 05:30tissues that are involved,
- 05:31any lymph nodes that are
- 05:32involved in the pelvis,
- 05:33as well as the periaortic region,
- 05:34which is a common area that's
- 05:36involved with cervical cancer.
- 05:39And specifically with MRT,
- 05:40like in the plan that's shown here,
- 05:42we're able to deliver a very carefully
- 05:44designed field to the areas that
- 05:46are at risk and give much lower
- 05:47dose to any of the surrounding
- 05:49structures in the pelvis through
- 05:50a very carefully modulated beam.
- 05:52Again, we're avoiding the bowel,
- 05:53the, the spine, the kidneys, the,
- 05:56you know, the bone and the muscle.
- 05:58So we're able to deliver this
- 05:59type of treatment with much less
- 06:01toxicity than in the olden days.
- 06:02Another advantage of IRT using the
- 06:04modulated beams is we're able to
- 06:06deliver a high dose to the pelvic
- 06:08lymph node regions and deliver a
- 06:10dose of approximately 60 Gray while
- 06:11giving simultaneously a much lower
- 06:12dose to any of the surrounding
- 06:14tissues in the pelvis.
- 06:17But for cervical cancer,
- 06:18what's unique is that external beam
- 06:20radiation alone is not enough.
- 06:22The second-half of their treatment
- 06:23is delivered with brachytherapy,
- 06:24also called internal radiation,
- 06:26where we have to deliver a much
- 06:28higher dose to the central tumor,
- 06:30really a dose of about 90 Gray.
- 06:32And really the only way to do
- 06:33this is from inside the tumor,
- 06:35not from outside.
- 06:36So brachytherapy involves placing
- 06:37radioactive source and direct contact
- 06:39with the tumor to kill the rapidly
- 06:41dividing cancer cells that are
- 06:43surrounding it and cervical cancer.
- 06:44This is done by placing a rod
- 06:46inside the uterus and a ring
- 06:48type structure in the vagina.
- 06:49And through these applicators,
- 06:50whether they're plastic or metal,
- 06:52we're going to deliver a
- 06:53radioactive source that's going
- 06:55to do well in these applicators.
- 06:56And therefore deliver a much higher
- 06:58dose to the tumor and in doing so
- 07:00with a very steep dose gradient
- 07:01going to give a much lower dose to
- 07:02any of these surrounding tissues.
- 07:04So unlike other types of cancers where
- 07:06brachytherapy is seen as an option,
- 07:08but there are other similar
- 07:10efficacious options like asperity
- 07:11and protons and cervical cancer,
- 07:13that's not the case.
- 07:14There is no substitute for brachytherapy
- 07:16because these other modalities don't
- 07:18allow us to achieve that very high
- 07:20steep dose gradient that I mentioned.
- 07:22But the thing about brachytherapy,
- 07:23it's different than external beam,
- 07:25it's interventional and it requires.
- 07:27Technical skill,
- 07:28but also specialized resources,
- 07:30different equipment,
- 07:30special applicators,
- 07:31and so not everywhere has it.
- 07:36Is this a study from 2013 from
- 07:37this year database which looked at
- 07:39cervical cancer patients with locally
- 07:41advanced disease who were treated
- 07:42with brachytherapy compared to those
- 07:44that did not receive brachytherapy.
- 07:45And you can see that the cause specific
- 07:47survival as well as the overall
- 07:48survival is significantly improved
- 07:50among those that had brachytherapy?
- 07:53This is a similar study from the NCDB
- 07:55in 2014, again more than 7000 locally
- 07:58advanced cervical cancer patients.
- 07:59And specifically asked the question is
- 08:01there how do patients who receive a
- 08:03different form of treatment to escalate
- 08:05those to the cervix such as SPRT,
- 08:07IRT compared to those who have brachytherapy.
- 08:10And again you can see that the
- 08:12women that have brachytherapy have a
- 08:13significantly improved overall survival.
- 08:21So here at Yale, I'm very proud
- 08:22to work with the dedicated team
- 08:24who assure highly coordinated and
- 08:26interdisciplinary care for these women.
- 08:28These pictures are just an illustration
- 08:29of some of the people who might help
- 08:31with any of these cases on a given day.
- 08:33So we work very closely with nurses in the,
- 08:37in the OR in the pacu.
- 08:39We work with the technologists in the
- 08:41MRI suite within our own department.
- 08:42We have dedicated dosimetrist,
- 08:44we have radiation therapists who are
- 08:46intimately involved in our cases,
- 08:48dedicated nursing staff,
- 08:49physics, and we have faculty.
- 08:51Within our own department,
- 08:52as well as faculty within the Joanne Oncology
- 08:54department that we work very closely with,
- 08:56for all of these cases,
- 08:58we work with coordinators,
- 08:59administrative assistance,
- 09:00nurses, residents,
- 09:01fellows from all these different
- 09:04departments listed here.
- 09:05These folks are not only committed to
- 09:07delivering high quality brachytherapy
- 09:08with safety and excellence,
- 09:09but what stands out to me is the
- 09:11compassion that they show and caring
- 09:13for the whole patient and understanding
- 09:14that this is a unique population.
- 09:16A treatment that can be painful,
- 09:18upsetting or even traumatic for patients
- 09:20and requires a recognition of that
- 09:22as well as an interpersonal touch.
- 09:24The good news that I'm going to
- 09:26share with you today is that there
- 09:27has been tremendous technological
- 09:29advances in the field of brachytherapy
- 09:30over the past 10 to 15 years,
- 09:32and I am grateful for the
- 09:33support of my department,
- 09:34the hospital and the Cancer
- 09:35Center for recognizing the
- 09:36benefits that these provide.
- 09:40Today what I'll be talking about
- 09:42is how breakey therapy evolved to
- 09:44modern MRI guided adaptive technique.
- 09:46I'm going to discuss the role of 3D printing
- 09:48and innovation and directions for future.
- 09:50I'm going to discuss training the next
- 09:52generation of brachytherapy providers
- 09:53with simulation based education.
- 09:55And finally, I'll discuss the resources
- 09:56that we have here at Yale to help
- 09:58assure that these women go on to live
- 10:00normal lives after cancer treatment,
- 10:02given the challenges and potential
- 10:03morbidities, sexual and otherwise,
- 10:05that can be associated with such treatments.
- 10:09So how did we get here?
- 10:11So one of the things that drew me
- 10:12to the field of radiotherapy was
- 10:14the technological advancements.
- 10:15And while that's for sure true
- 10:17and well known within our
- 10:18external beam treatments and MRT,
- 10:20it hasn't always been the
- 10:21case with breakey therapy.
- 10:22So there was a period of
- 10:24about four or five decades,
- 10:26I would say between the 1960s and
- 10:27early 2000s were brachytherapy
- 10:28really looked like this.
- 10:30It was kind of the same.
- 10:31This is called an intrauterine tandem
- 10:33that was placed inside the uterus,
- 10:34inside the operating room and
- 10:36this is called a vaginal ovoid.
- 10:37And two of these would be placed
- 10:39on either side of the cervix.
- 10:40Again,
- 10:40we would do this under anesthesia
- 10:41while the patient was in the
- 10:42operating room to surround.
- 10:43These are metal applicators
- 10:44that would surround the cervix.
- 10:46They would get packed into place
- 10:48and we would take an image of
- 10:50these applicators through these.
- 10:52Replicators.
- 10:52We would then load cesium sources
- 10:54to give off a cloud of radiation.
- 10:59So cesium sources came in different
- 11:01strengths and our physicists would
- 11:03figure out how much cesium and where
- 11:05inside these applicators to place them
- 11:06to create a symmetrical pear shaped
- 11:08distribution that looks like this.
- 11:10So we had mathematical formulas and
- 11:11lots of decades of data to know what
- 11:13type of dose we needed to get to
- 11:15these different points in relation
- 11:17to the applicators to achieve good
- 11:19outcomes local control of about 75%.
- 11:24In the mid 2000s things began
- 11:25improving in the planning,
- 11:26optimization and treatment delivery.
- 11:28We had newer applicators that were
- 11:30compatible with an HDR source.
- 11:32So basically the applicators,
- 11:33they were kind of the same idea tandem.
- 11:36This is called a ring
- 11:37which sits in the vagina,
- 11:38but after placing it, packing it,
- 11:41designing radiation plan rather than having
- 11:43a patient have to stay in the hospital.
- 11:45So with cesium the patients
- 11:47would be admitted.
- 11:47In order to give off the dose
- 11:48cloud that was necessary,
- 11:49the patient would have to be admitted
- 11:51to the hospital for 48 to 72 hours.
- 11:53With a decaying radioactive
- 11:54source inside of them.
- 11:56The benefit of an HDR
- 11:57source which is Iridium,
- 11:59is that the same treatment can be
- 12:00delivered in a course of about 10
- 12:02minutes and it can be done in an
- 12:04outpatient setting in a brachytherapy suite.
- 12:05So we could place the applicators,
- 12:07design the radiation plan and treat
- 12:09them in a breakey therapy suite
- 12:10over a period of about 10 minutes.
- 12:12Once the treatment was done
- 12:13they could go home.
- 12:14Another benefit of the applicators
- 12:15is that rather than just
- 12:17imaging them with a plain film,
- 12:19they were CT compatible.
- 12:19So that allowed us to not only see the
- 12:22applicators but actually see the nearby.
- 12:24Organs,
- 12:24the ****** the sigmoid bladder,
- 12:26the bowel,
- 12:26and we were still aiming for that
- 12:28symmetrical pear shaped distribution,
- 12:30but we were able to optimize the dwell
- 12:32times and sort of shrink the dose,
- 12:34cloud a little bit off of the surrounding
- 12:36organs and therefore give much lower
- 12:38dose to the surrounding organs.
- 12:40And it turns out that had a big benefit.
- 12:42This was shown in the stick trial
- 12:44which was a prospective but not
- 12:45randomized trial of about 800 women
- 12:47with locally advanced cervical cancer.
- 12:49And basically compared those that had
- 12:51the film based treatments to those
- 12:52that had CAT scan based treatments,
- 12:54SO3 dimensional seeing the organs.
- 12:56And you can see that local control
- 12:58in both groups was very good,
- 13:00about 75% like I mentioned.
- 13:01But the main advantage of switching
- 13:03to 3/3 dimensional imaging was
- 13:05there was a significant decrease
- 13:06in grade three to four toxicity.
- 13:08So in the film based era
- 13:09the likelihood of having.
- 13:10You know,
- 13:11bowel obstruction and perforation
- 13:12bleeding fistula was about 20 to 25%
- 13:14whereas once you see your organs and you,
- 13:17you know,
- 13:18optimize your your beam accordingly.
- 13:20Now the likelihood of grade 3
- 13:21or 4 toxicities only two to 3%.
- 13:23So that was a big advantage.
- 13:26The next advancement came in the
- 13:28mid 2000 tens, really pioneered in
- 13:29Europe by a group of researchers
- 13:31known as the embraced trialists.
- 13:32And what they sought to do is
- 13:34to incorporate MRI to improve
- 13:36the way we do brachytherapy
- 13:37and to improve local control.
- 13:39And really this group created
- 13:40a renaissance in the cervical
- 13:41brachytherapy community by incorporating
- 13:43MRI into treatment planning.
- 13:47So MRI has always been an
- 13:49important diagnostic imaging
- 13:50modality for cervical cancer.
- 13:52We always get an MRI up front at the
- 13:53time of staging to help determine
- 13:55the local extent of the tumor,
- 13:57if there's any involvement of the vagina,
- 13:59the uterus, the parametrium,
- 14:00the surrounding structures.
- 14:02And even in the LDR era,
- 14:03we would often get a pre brachytherapy
- 14:05MRI after about five weeks of radiation.
- 14:07This is a rapidly growing tumor,
- 14:09so it responds rapidly to radiation.
- 14:11It can shrink by about a centimeter per week.
- 14:13So getting an MRI before brachytherapy
- 14:15would give us information about you know,
- 14:17how much of the tumor is left and
- 14:19also the dimensions of the uterus
- 14:21prior to going to the operating room.
- 14:23But the embrace trial is took it one
- 14:25step further and said we could design
- 14:27applicators that are are MRI compatible.
- 14:29We can do the procedure like we've done
- 14:31place the applicators but now instead
- 14:32of going to CAT scan we can go to MRI
- 14:35and that now we can actually see the
- 14:36cervix in relation to the applicator
- 14:38and see the tumor in relation to the
- 14:40applicator and change the way that
- 14:41we prescribe radiation different
- 14:42from how we've done it for decades.
- 14:44So I mentioned for decades we were
- 14:46looking for this type of pear
- 14:48shaped distribution aiming to get
- 14:49radiation to a certain point from
- 14:51the applicators but with this.
- 14:53Anyway,
- 14:53they through they designed very
- 14:55carefully thought out and develop
- 14:57principles to allow us to deliver
- 14:58dose to the residual cervix and
- 15:00the remaining tumor as seen on MRI.
- 15:05So lots of institutions began adopting
- 15:07this approach and they presented
- 15:10their retrospective outcomes.
- 15:11And you can see here that there was
- 15:14significant improvement in local control
- 15:15when you look at these individual
- 15:17institutional studies looking like local
- 15:19control was now about 90% or higher.
- 15:21So this looked really good
- 15:23and still very low toxicity.
- 15:25The embrace trialists went on to
- 15:27develop a series of prospective
- 15:29studies following over 1000 women and
- 15:32collecting patient reported outcomes
- 15:34and validated toxicity information,
- 15:36looking not only how to optimize the way
- 15:38that we prescribe the dose to the tumor,
- 15:41but also seeking to reduce any treatment
- 15:43related morbidity and how to optimally
- 15:45constrain the dose to the normal tissues.
- 15:47And they put out very high impact
- 15:50papers showing us how we could
- 15:52monitor the dose to the ******
- 15:54to keep the rectal morbidity.
- 15:55Flow, and similarly for the bladder.
- 15:57How to decrease dose of the bladder
- 15:59and keep the bladder morbidity low.
- 16:01And they even put out data for how to
- 16:03limit dose to the vagina to produce less
- 16:06vaginal toxicity for these patients.
- 16:10So with all of this mounting evidence here
- 16:12at Yale, we were able to establish an MRI
- 16:15based program at around 2016 or 2017.
- 16:17And in order to have an MRI based program
- 16:19you need to have access to an MRI.
- 16:21So some radiation departments have an
- 16:23MRI simulator in their department.
- 16:24We do not. So like others we partner
- 16:26with the MRI that's available
- 16:27in our diagnostic imaging suite.
- 16:29You need to invest in MRI safe applicators,
- 16:31you need to meet with our radiology
- 16:33colleagues to develop proper sequences
- 16:35and protocols for imaging and you
- 16:37have to study the concepts,
- 16:38these new concepts.
- 16:39From the get Castro and embrace how
- 16:41to do these target volume delineation,
- 16:43you have to invest in an MRI safe
- 16:44transport system because you're placing
- 16:46applicators in the operating room and
- 16:47now you're taking them to the MRI.
- 16:49You have to have trained staff and
- 16:50you have to have integrated MRI
- 16:52safety procedures,
- 16:52patient questionnaires
- 16:53and procedural checklists.
- 16:55So all of this,
- 16:56this has been our standard way for
- 16:58treating cervical cancer patients
- 16:59for the past six or seven years.
- 17:02And this is what in modern MRI
- 17:04intracavitary tandem and ring
- 17:05plan might look like.
- 17:06You can see that the dose is very
- 17:08concentrated on the cervical tissue
- 17:09due to the physical proximity
- 17:10of the source to the tumor.
- 17:11There's a very steep dose gradient.
- 17:13So none of this high dose is going
- 17:15to any of these surrounding organs.
- 17:16This looks a little bit different
- 17:18than the old fashioned film and
- 17:19point based plans that I showed you.
- 17:21But I will mention here that
- 17:22because of the sort of simplicity
- 17:24of the applicators tandem and ring,
- 17:26you still have a symmetric dose distribution.
- 17:30But the more you start visualizing
- 17:32your tumors on MRI,
- 17:34the more you realize that not
- 17:35every tumor is symmetric and also
- 17:37not every tumor is going to be
- 17:38perfectly covered by one of these
- 17:40symmetric dose distributions.
- 17:41So depicted here in blue is a
- 17:43tumor and in red is the 100% dose
- 17:46that I'm trying to give.
- 17:47And you can see that they're
- 17:49aspects of this tumor in blue that
- 17:51are extending outside of the red.
- 17:53So that is with sort of pushing
- 17:54our dose the best that we can
- 17:56with our intracavitary applicator,
- 17:58whereas an ideal coverage depiction
- 17:59might look like this where the
- 18:01entire tumor is covered in the red.
- 18:05So it turns out that if you take your
- 18:07standard intracavitary applicator
- 18:08tandem and ring and you add what
- 18:10are called interstitial needles that
- 18:12look like this thin plastic needles.
- 18:14If you add a couple of these
- 18:16needles into the tumor to the parts
- 18:17of the tumor that are extending
- 18:19beyond the boundaries of what you
- 18:20would expect to be covered with
- 18:22a standard intracavitary plan,
- 18:23then you could significantly
- 18:25improve the dose coverage.
- 18:28And this is the birth of the
- 18:30so-called hybrid approach,
- 18:31which is basically that it's saying,
- 18:33it's saying that for tumors which you
- 18:35know are larger and might not be well
- 18:37covered with an intracavitary plan,
- 18:38you can add a couple of needles and
- 18:40thereby improve the dose coverage and
- 18:42more and more places started doing this.
- 18:44In fact vendors came up with hybrid
- 18:46applicators that look like this.
- 18:47So again like a tandem and ring,
- 18:49but within the ring applicator
- 18:51there are holes that allow you
- 18:53to thread interstitial needles.
- 18:55So an example of the benefit of
- 18:57this approach is illustrated here.
- 18:59This was a young woman with
- 19:00a very large cervical tumor,
- 19:01stage 3B invading into the
- 19:03left pelvic sidewall.
- 19:04She had a very large tumor that responded
- 19:06well to external beam radiation,
- 19:08but she still had a significant
- 19:10amount of tumor that was present
- 19:11at the time of brachytherapy.
- 19:12If she were to be treated
- 19:14with Intracavitary alone,
- 19:15you would have this circular symmetric
- 19:17dose distribution around the tandem.
- 19:19What you can see here is this is covering
- 19:20the anterior aspect of her tumor,
- 19:22but she still has tumor which
- 19:24is sitting laterally and.
- 19:25Posterior to this dose distribution.
- 19:28So what you could do and probably
- 19:29what you should do would be
- 19:31increase the amount of radiation
- 19:33you're putting in the tantum to
- 19:34better cover the tumor target.
- 19:36Here you can see now we're covering that
- 19:38lateral and posterior aspect of the tumor.
- 19:40But because of the nature of
- 19:42these intracavitary applicators
- 19:43are simultaneously increasing
- 19:44dose anteriorly to the bladder
- 19:47and that's going to result in an
- 19:48increased risk of bladder morbidity.
- 19:50So the benefit of these hybrid applicators
- 19:54is that rather in a case like this,
- 19:56you could thread needles into the lateral
- 19:58and posterior aspect of her tumor,
- 20:00which is what we did.
- 20:01And then you can shape the dose
- 20:03distribution more like this,
- 20:04pull that dose posteriorly to
- 20:05cover the target and actually
- 20:07simultaneously reduce the dose going
- 20:09to the bladder and pull the dose back
- 20:12to create this asymmetric target.
- 20:15So what this graph shows is something that
- 20:18I think a lot of departments have seen,
- 20:20but once you introduce MRI,
- 20:22you suddenly go from IT department where
- 20:24you're doing almost no interstitial
- 20:26procedures to very quickly finding
- 20:27that about 50% of your cases are
- 20:30being done with interstitial needles.
- 20:36So I think these days,
- 20:38customizing dose distributions
- 20:39on a per patient basis,
- 20:41we are doing this more and more.
- 20:43We're no longer aiming for
- 20:44that perfect pear shape,
- 20:45just dosimetry that I showed you earlier
- 20:46and that we did for so many decades.
- 20:48And maybe this seems simple for
- 20:50those of you in the audience,
- 20:51right, we're adding needles,
- 20:53more degrees of freedom.
- 20:54And yet the truth is there's
- 20:55a very steep learning curve
- 20:57within the breakthrough therapy
- 20:58community and it does take time
- 20:59for these new concepts to catch on.
- 21:01And that might be because
- 21:02by training and by nature,
- 21:04many of us in radiation oncology.
- 21:06Not interventionalists,
- 21:07but also sometimes there's
- 21:08inertia and changing the way that
- 21:10you've done things for decades,
- 21:11and also there's training and
- 21:13resources that are required to invest
- 21:15in these types of new procedures.
- 21:17So how common are MRI and interstitial?
- 21:21So this is a American breakey
- 21:23therapy practice survey from 2014.
- 21:25So it's a little bit older,
- 21:27but it showed that between 2007 and 2014,
- 21:29MRI use increased to about 34% of practices.
- 21:33So probably nowadays that would be more.
- 21:35And a 2020 Canadian Practice Survey
- 21:38found that between 2015 and 2020,
- 21:40interstitial use increased.
- 21:41That's the use of needles increased
- 21:43to about 70% of practices.
- 21:45So more and more places are doing this.
- 21:47But not everywhere and currently we
- 21:49are the only place in Connecticut that
- 21:52does MRI guided interstitial brachytherapy.
- 21:54So we do see a lot of referrals
- 21:57from around the state.
- 21:58This is an example of a 73 year
- 22:00old who had a stage 3A cervical
- 22:02cancer with vaginal involvement.
- 22:03So she was treated with pelvic
- 22:04radiation and an outside hospital.
- 22:06But because of the extent of
- 22:07her vaginal involvement,
- 22:08she was not going to be properly
- 22:10treated with intracavitary
- 22:11radiation and so she was sent here
- 22:13for her needle placement,
- 22:14which you can see here in order
- 22:16to better cover this vaginal
- 22:17extent of her disease.
- 22:20This is a 41 year old from an
- 22:22outside hospital who had a very
- 22:24large stage 4A cervical cancer.
- 22:25It was invading into local
- 22:27organs in the pelvis,
- 22:28but it was also extending very laterally.
- 22:30So you can see here what her
- 22:32dose distribution looked like.
- 22:33If she were treated with
- 22:35just tandem and ovoids,
- 22:36her dose distribution would be more narrow.
- 22:38So we added needles to extend
- 22:40her dose out laterally to
- 22:42the side walls of the pelvis.
- 22:44This was a woman who had a very
- 22:46bulky cervical tumor that had a
- 22:47lot of bulk and also intrauterine
- 22:49extent at the time of brachytherapy.
- 22:51So she benefited from this Vienna
- 22:53applicator for dose escalation to her tumor.
- 22:56And this is a young woman that had
- 22:57had a prior early stage cervical
- 22:59cancer treated with a hysterectomy
- 23:01and developed a vaginal recurrence
- 23:02mainly on the left side of her vagina.
- 23:05She would not have benefited from
- 23:07asymmetric dose distribution,
- 23:09but rather she needed needles
- 23:11preferentially in the left 4
- 23:12necks of her vagina.
- 23:13In order to give the proper dose.
- 23:18So as we use more needles,
- 23:20we realize that with MRI,
- 23:22it's helpful not just to sort of
- 23:24place everything in the operating
- 23:25room and then go to MRI post facto
- 23:27and what you get is what you get,
- 23:29but rather to use the MRI,
- 23:31especially for complicated cases
- 23:32to actually help guide the needles.
- 23:34So we do that with iterative to T2 sequences.
- 23:37So we'll bring the patient while
- 23:39they're under anesthesia to the MRI,
- 23:41place our needles the best we can.
- 23:42And if we need to make adjustments,
- 23:44we'll advance further deeper into the pelvis.
- 23:46Take another T2 sequence until we're
- 23:48happy with the needle adjustments.
- 23:52So this is kind of more of an MRI
- 23:54guided approach and in addition
- 23:55to everything that I told you you
- 23:57needed for an MRI based program here,
- 23:59you also need to have access to an MRI,
- 24:01excuse me to an anesthesia team available
- 24:03at the MRI which we are lucky to have here.
- 24:06We need to request extra time in
- 24:07the MRI suite because we're going
- 24:09to be taking multiple scans.
- 24:11We need time to make adjustments
- 24:12and this also requires another
- 24:14level of care coordination between
- 24:16the OR anesthesia imaging, pacu,
- 24:18GYN, oncology etcetera.
- 24:19We reserve these for our most complex.
- 24:22Cases.
- 24:25So that is our current
- 24:27state of MRI at this time.
- 24:29And I'll just mention here
- 24:30in terms of some research,
- 24:32there's research ongoing at Johns
- 24:33Hopkins led by Doctor Akila Viswanathan,
- 24:36to try to improve the efficiency
- 24:38of the MRI procedure by developing
- 24:39kind of MRI tracking devices that
- 24:41allow you to see the needles as
- 24:43you're placing them in real time.
- 24:44So who knows, maybe this will
- 24:45be the state of the field soon.
- 24:49So all of this time and effort and
- 24:51attention to detail is it worth it.
- 24:53So the data shown here would say that it is
- 24:55especially for the larger tumor targets.
- 24:57The larger that your tumor is,
- 24:59the more importance getting that proper
- 25:01dose is in order to achieve local control.
- 25:04So basically giving covering your
- 25:06tumor better is directly correlated
- 25:09with controlling your tumor better.
- 25:11And another advantage by doing these
- 25:13asymmetric dose distributions and,
- 25:15you know, pulling the dose off of
- 25:17the surrounding tissues as you're
- 25:19giving a lower dose to the surrounding
- 25:21organs and causing less morbidity.
- 25:23And now all of this has been shown
- 25:25prospectively in the embrace one trial
- 25:27which was published last year in Lancet
- 25:29Oncology which was the first large scale
- 25:31prospective study testing all these
- 25:33concepts of MRI guided brachytherapy.
- 25:35It accrued patients from
- 25:3624 centers in Europe,
- 25:37Asia and North America more than
- 25:401400 patients between 2008 and
- 25:412015 and results were reported at
- 25:43a median follow-up of 51 months.
- 25:45The main finding was that five year
- 25:47local control was excellent 92%.
- 25:51What was especially impressive about
- 25:52these results is that this 92%
- 25:54local control was not just in the
- 25:56stage one and two smaller tumors,
- 25:58but was true across the board.
- 25:59Even in the stage three and four tumors,
- 26:01these very large and infiltrative tumors
- 26:03still had excellent local control.
- 26:05Especially when we think back to the 75%
- 26:07that we sort of assumed in the olden days.
- 26:11They looked at overall survival
- 26:13at five years which was 74%.
- 26:15There's no direct comparison,
- 26:16but by looking back at it
- 26:18traditional cohorts,
- 26:18that's an improvement by almost 7 to 10%.
- 26:21There was significant reduction
- 26:22in dose to the surrounding organs,
- 26:2450% decrease in major morbidities
- 26:26and five year incidence of a Grade
- 26:283 or higher toxicity on a per organ
- 26:31basis was about 3 to 9%.
- 26:34So these are all very positive
- 26:36outcomes for our patients.
- 26:38So what comes next?
- 26:39So I mentioned that for decades it
- 26:42seemed like the field of breakey
- 26:43therapy was a little bit sleepy and
- 26:46there wasn't much room for change.
- 26:48And yet here we are now in 2023,
- 26:50and I feel like the way we do
- 26:52brachytherapy is ever improving.
- 26:53It's getting more customized.
- 26:54And I think the future looks bright.
- 26:56And part of that is because of 3D printing.
- 26:59As I've shown you,
- 27:00every patient and every tumor is a
- 27:02little bit different and breakey therapy
- 27:04lets us get up close and personal.
- 27:06So the better that you do
- 27:07this on a per patient basis,
- 27:09the better her outcomes will be.
- 27:11But unfortunately,
- 27:11the regulatory system and industry are
- 27:13not always catching up fast enough.
- 27:15And although I showed you some of the
- 27:17modern equipment that we have available,
- 27:19it can take almost a decade for
- 27:20a new device to come to market
- 27:22and to be FDA approved.
- 27:23And it's not particularly
- 27:24profitable for the device companies
- 27:26because at the end of the day,
- 27:27it's just a small group of US specialized
- 27:29users who are doing these treatments.
- 27:31So a lot of the technological
- 27:33advancements nowadays is grassroots
- 27:34and ground up and led by the doctors.
- 27:36And maybe this is fortunate because
- 27:37it's forcing the people who know
- 27:39the field the best to innovate.
- 27:41So we're seeing a rising interest
- 27:42in 3D printing for brachytherapy
- 27:43because it allows customization,
- 27:45low cost and convenience.
- 27:48So this was one of the first published
- 27:50examples of a 3D printed customized
- 27:52ring applicator to guide flexible
- 27:54needles into a complex target.
- 27:56So you can see this is a cervical
- 27:57cancer which is extending to the
- 27:59sidewall and also to the vagina.
- 28:00Looking at this case up front,
- 28:02you kind of know this case is
- 28:03going to need at least you know,
- 28:0510 needles or so to properly cover it.
- 28:07So one way is to go to the operating
- 28:09room and freely place these needles
- 28:10and hope that your needles don't
- 28:12deflect and that they are going to
- 28:14penetrate deep enough into your tissue
- 28:16and land in the exact right spot.
- 28:17But what this group?
- 28:18Did is they said well based on her
- 28:21pre brachytherapy MRI we could design
- 28:22this custom ring cap that's going
- 28:24to go over the existing ring and
- 28:26they drilled holes at pre specified
- 28:28distance and at angles to help guide
- 28:31the needles into the right place.
- 28:33So that going into the procedure of
- 28:35the breakey therapist was able to
- 28:37place these needles at the sort of
- 28:39predetermined spots and better shape
- 28:40the needles and guide them to the tumor.
- 28:43So,
- 28:44you know,
- 28:45I think that there's now been
- 28:46a couple more of these types of
- 28:48published examples in the literature,
- 28:50and it seems like brachytherapy might
- 28:51be a perfect match for 3D printing,
- 28:53given the individualization
- 28:54needed for every application.
- 28:56We're no longer in A1 size fits all era.
- 29:00This is another example of a 3D printed
- 29:02cylinder, similarly to guide needles
- 29:04into a pair of vaginal location.
- 29:06And I will say that when you're in the OR
- 29:08in this very tight space and a very narrow
- 29:11vagina and you're trying to properly,
- 29:13you know, deflect and guide
- 29:14needles at a specific angle,
- 29:15it can be very challenging to do so.
- 29:17Having an applicator which is
- 29:19kind of doing that for you,
- 29:20it's bending and also stabilizing the needle
- 29:22in the right spot makes a lot of sense.
- 29:27This is work from a colleague of
- 29:29mine at Stanford University who
- 29:30worked together with her physicist
- 29:32and engineers at Stanford that they
- 29:35came up with these templates and they
- 29:37basically said rather than 3D customized
- 29:39printing on a per patient basis,
- 29:42rather they developed a repertoire of
- 29:44templates to have in their department to to
- 29:47use for all of their cervical cancer cases.
- 29:50So basically they designed a couple of
- 29:523D printed templates and they choose
- 29:54one of these prior to a procedure.
- 29:56The hitch is on to the tandem.
- 29:58So they'll place a tandem and their ovoids,
- 30:00and then through one of these templates,
- 30:01guide the needles.
- 30:02It's a place and they'll figure out
- 30:04ahead of time which template would
- 30:06be best suited for a given patient.
- 30:08They found this to be a low cost
- 30:10solution and cost about $5 to print
- 30:12this in house and $100 if they.
- 30:14Sent it out to a manufacturer.
- 30:16It removes some of the variability and
- 30:18randomness of the freehand approach and
- 30:20it helps standardize the procedure more,
- 30:22and that way it can make it more
- 30:23accessible to trainees or other
- 30:25practitioners who are looking to get
- 30:26started with a hybrid application process.
- 30:30This was a 3D printed applicator
- 30:32from two of our own brachytherapy,
- 30:35physicist Doctor Christian
- 30:36and Doctor Jay Chen.
- 30:38So this was printed for a patient
- 30:40who had a very narrow vaginal anatomy
- 30:42that wouldn't fit one of our standard
- 30:45applicators and required needles.
- 30:46So 3D printing can be used to rapidly
- 30:49manufacture and implement customized vaginal
- 30:50applicators that could be sterilized,
- 30:52made of biocompatible material and
- 30:54potentially result in high quality
- 30:56brachytherapy for patients whose
- 30:57anatomy is not ideally suited for
- 30:59commercially available applicators.
- 31:01And sometimes we need smaller
- 31:03ones or different shaped ones.
- 31:05This is a different 3D printed vaginal
- 31:07applicator that we're currently testing
- 31:09in a clinical trial here at Yale.
- 31:11It's not for cervical cancer,
- 31:12but for endometrial cancer
- 31:14where vaginal brachytherapy is
- 31:16typically done after hysterectomy.
- 31:18So just to Orient you,
- 31:20this is looking at a patient sideways,
- 31:21this is the bladder, this is the ******.
- 31:23And a typical applicator is this
- 31:25straight vaginal applicator.
- 31:26And through that we aim to give her give
- 31:29a dose of radiation to the vaginal apex.
- 31:32So with this trial is looking at is
- 31:34asking whether if we designed the
- 31:35applicator to look the same at the
- 31:37top where we're giving the radiation,
- 31:38but to taper and narrow as it exits
- 31:40the patient through the lower portion
- 31:42of the vagina and the introitus
- 31:44if that would be more comfortable.
- 31:45For patients and more more well tolerated.
- 31:48So I mentioned the applicator here
- 31:50because of the story which led to
- 31:52its development as a clinician.
- 31:53I had been walking around with this idea
- 31:55in the back of my head for several years.
- 31:57And then one day,
- 31:58completely by chance,
- 31:59I received an e-mail from one of
- 32:00my colleagues who was working
- 32:02with the medical students who had
- 32:03a background in interest in 3D
- 32:05printing and engineering and he
- 32:06just needed a clinical application.
- 32:07So the two of us met and we put our
- 32:10heads together and we designed and 3D
- 32:11printed this one which I mentioned
- 32:13we're currently testing in a trial.
- 32:17So.
- 32:18I think we're still very early on
- 32:20in this journey of 3D printing,
- 32:22but I do know that 3D printing is
- 32:23used in some of the other surgical
- 32:25fields and perhaps there are others
- 32:26here at the Cancer Center or the
- 32:28medical school who have similar
- 32:29programs and developments and would
- 32:30like to collaborate with us.
- 32:32As it stands now,
- 32:33I think potential applications of
- 32:353D printing for cervical cancer
- 32:37brachytherapy include manufacturing
- 32:38personalized guidance templates
- 32:40to optimize needle positions and
- 32:42target dose distributions,
- 32:43also designing individualized
- 32:45applicators to fit patient anatomy.
- 32:47And I do see this as an area of future.
- 32:49Growth and promise.
- 32:53So now I'm going to talk about
- 32:55efforts to improve the way that we
- 32:57teach brachytherapy to our trainees.
- 32:58So I mentioned in the beginning
- 33:00of my talk that without breakey
- 33:02therapy survival outcomes in
- 33:03cervical cancer are not as good.
- 33:06And yet the same research has shown
- 33:08a disturbing high recent decline in
- 33:10the utilization of brachytherapy.
- 33:12So specifically between 1998 and 2009,
- 33:15it was estimated there was a
- 33:17decreased utilization rate of
- 33:19brachytherapy from 83% to 58%.
- 33:21And also data,
- 33:23the research has shown that patients
- 33:25are less likely to receive standard of
- 33:27care treatments at low volume centers.
- 33:30There has been a lot of thought
- 33:31and writing about this particular
- 33:33problem and the potential causes for
- 33:35underutilization of radiotherapy.
- 33:37It could be because of a lack of equipment,
- 33:39because of the intensive workflow.
- 33:41If you're at a smaller practice,
- 33:42you're treating all types of cancers.
- 33:43Maybe you don't have the time
- 33:45and resources for this type of
- 33:46a cervical cancer program.
- 33:47There's also patient access issues.
- 33:49Not everyone can travel
- 33:51for these treatments and.
- 33:52Something that's also come out of
- 33:54numerous surveys is perhaps we aren't
- 33:56properly training our residents,
- 33:58and there was a survey of recent
- 34:00grads and trainees who felt that not
- 34:02seeing a lot of cases during their
- 34:05residency training was a very big
- 34:07barrier to learning breakey therapy.
- 34:09So perhaps people were coming out of
- 34:11training and not feeling comfortable or
- 34:13confident that they could do breakey therapy.
- 34:15So as a field, we've realized that we
- 34:17need to improve the way that we teach it,
- 34:20to make it more accessible and to change
- 34:22its perception from being an advanced,
- 34:24technically challenging technique to one
- 34:26that's a component of routine practice.
- 34:28So it's hard to teach breakey
- 34:30therapy in real time cases.
- 34:32The stakes are high,
- 34:33the patients under anesthesia,
- 34:34things are moving pretty quickly.
- 34:36So to supplement training,
- 34:37there's been a growing interest in
- 34:39doing simulation based education,
- 34:40which basically means using a pelvic
- 34:42mannequin in a setting outside
- 34:43of the OR where you can conduct
- 34:45workshops with residents and they can
- 34:47have the opportunity to place the
- 34:49applicators in a low risk setting.
- 34:52And this has been shown to help trainees
- 34:54remember the steps of the procedure
- 34:56and feel confident in doing the procedure.
- 34:58So that they're more likely to do it
- 35:00when they go out in their own practice.
- 35:01And I've been,
- 35:02I've been able to participate in these
- 35:04workshops at an institutional level,
- 35:06also at national and international meetings,
- 35:08and this picture is taken from work that I
- 35:10did during my sabbatical and in Israel so.
- 35:15I also mentioned earlier in my
- 35:16talk the movement towards more
- 35:18customized applications using needles
- 35:20into the residual cervical tumor.
- 35:22For a long time,
- 35:23the mannequins that were available
- 35:24to us were very kind of hard,
- 35:25durable plastic material that
- 35:27wasn't very stretchy and didn't
- 35:28really permit needle placements.
- 35:30But in 2021,
- 35:31a new prototype Phantom was released.
- 35:34This model was made of this
- 35:36colloidal material that it
- 35:37was stretchy, it had a vagina,
- 35:39cervix, uterus, ****** and bladder,
- 35:41and it also permitted our applicators
- 35:44as well as needle. Placements.
- 35:45So we designed an inaugural workshop
- 35:47here at Yale to validate the model
- 35:49for teaching hybrid needle placements.
- 35:50We presented this work at ABS,
- 35:52the American Brachytherapy Society,
- 35:54last year and recently published our results.
- 35:57This was from the 14 residents
- 35:58in our program who were surveyed
- 36:00and this was their responses to
- 36:02questions pre and post workshop.
- 36:03We asked them questions about
- 36:05their knowledge, preparedness,
- 36:06confidence in performing hybrid
- 36:08brachytherapy procedures.
- 36:09Red meant that they were not
- 36:10at all confident,
- 36:11blue meant that they were very confident.
- 36:13So you can see the shift in responses
- 36:14from pre workshop to post workshop.
- 36:16Obviously we know you can't do this workshop
- 36:18one time and expect everyone to be experts,
- 36:21but there are lots of.
- 36:25Uh, there's lots of programs and
- 36:26development at a national level
- 36:28to improve brachytherapy training,
- 36:29but at least at an institutional level,
- 36:31we hope to continue conducting similar
- 36:33hands-on workshops yearly in our program.
- 36:38So in the last few minutes I'm going to
- 36:40shift gears and talk about quality of life
- 36:43and survivorship and cervical cancer.
- 36:44This is another area at Yale that we
- 36:46have a lot of support with help from our
- 36:48behavioral health and gynecologic colleagues,
- 36:49to make sure that our patients are
- 36:51on board with this information.
- 36:53As I think I've shown,
- 36:54breakey therapy is a very personal treatment,
- 36:56and while going through it can
- 36:58be intense and emotional,
- 36:59for some women it could even be traumatic
- 37:01that we do our best to offer compassion
- 37:03and support every step of the way.
- 37:04Post treatment,
- 37:05even if the cancer is cured and the
- 37:07patient wants to forget about it,
- 37:08put it behind them.
- 37:09The problem is that there can be
- 37:11significant long-term sequelae
- 37:12which take time to develop.
- 37:14These can be sexual or other effects
- 37:16that can negatively and permanently
- 37:17impact the lives of our patients
- 37:19if they're not properly addressed.
- 37:20But many of these issues can be addressed,
- 37:22treated or even prevented.
- 37:23So we have to follow our patients
- 37:25very closely.
- 37:26So in my opinion,
- 37:27post treatment care of women who've
- 37:29been through breaking therapy is a
- 37:30critical aspect of caring for the
- 37:32whole patient because we don't want
- 37:33to save one part of their lives and
- 37:35then accidentally ruin another part.
- 37:39So this is just an example of what
- 37:42happens to vaginal tissue after radiation.
- 37:45Now we all know that whatever your treatment
- 37:47modality is, whether it's surgery,
- 37:48chemotherapy or radiation, the name of
- 37:50the game is to minimize side effects.
- 37:52So here's what happens after radiation.
- 37:55This is a biopsy from a healthy,
- 37:56normal vagina.
- 37:57This is looking in the in the basil
- 38:00layer and you can see this is elastin,
- 38:03which is imaged with autofluorescence
- 38:05and it looks nice and linear.
- 38:07This is biopsy.
- 38:08From the vagina of a cervical cancer patient
- 38:10three to five years after radiation.
- 38:12So again it takes time,
- 38:13but what you can see is proliferation and
- 38:16elastosis and this can lead to progressive
- 38:18thickening and stiffening of the vagina.
- 38:20This can take months to years to
- 38:22develop after radiation and its
- 38:23effects can be permanent,
- 38:24results in difficulty with
- 38:25exam or pain with intercourse.
- 38:27So vaginal morbidity to some extent,
- 38:30whether it's mucosal adhesions or
- 38:32bleeding after radiation is pretty common.
- 38:34And you know,
- 38:35even if it's mild that can have
- 38:37a significant impact.
- 38:38On sexual function and the impact goes
- 38:41beyond the physical manifestations.
- 38:43Studies have shown that one to four,
- 38:44one to five cervical cancer patients
- 38:46have vaginal issues causing dyspareunia,
- 38:49and a significant proportion of these
- 38:51women stay sexually active despite pain
- 38:53to maintain their partner satisfaction
- 38:55and avoid marital marital problems.
- 38:57So this is a pretty complex problem.
- 39:00Physical symptoms can lead
- 39:01to all of these issues here,
- 39:03whether it's distress, fear of pain,
- 39:05cancer, loss of femininity,
- 39:07decreased body image,
- 39:08difficulty with partner.
- 39:09Communication.
- 39:09A very simplified example of this
- 39:11would be a young cervical cancer
- 39:13patient is treated with radiation.
- 39:14She has pelvic issues that result
- 39:16in problems with dyspareunia.
- 39:17She doesn't bring it up with her doctors.
- 39:19She remains sexually active,
- 39:20albeit with tremendous pain and suffering.
- 39:22She has relationship issues that result.
- 39:24Her partner leaves her,
- 39:25she has low self esteem and she
- 39:27thinks something's wrong with her.
- 39:28I'm not saying that we as radiation
- 39:30oncologists can help with all
- 39:31of those issues,
- 39:32but we could do a lot simply by
- 39:33raising and normalizing sexual
- 39:35concerns with our patients,
- 39:36asking them about what they're
- 39:38experiencing and making appropriate.
- 39:39Girls when needed.
- 39:40So one simple thing that we can
- 39:42do is really just ask our patients
- 39:44about their symptoms.
- 39:45So this is guidelines that
- 39:47were written by ASCO,
- 39:50so I'd encourage you all to take
- 39:51a look at this if you haven't seen
- 39:52it was put out in 2018 looking at
- 39:54interventions to address sexual
- 39:55problems in people with cancer.
- 39:57The number one recommendation is that
- 39:58it's the provider's responsibility
- 40:00to initiate this conversation and to
- 40:02ask patients. About their symptoms.
- 40:06So how are we doing radiation oncology?
- 40:08This is a abstract that was presented
- 40:10at Astro in 2022 looking at
- 40:12disparities in physician assessment
- 40:14of sexual dysfunction in women
- 40:16versus men receiving brachytherapy.
- 40:17Men population was prostate cancer,
- 40:19women population with cervical cancer.
- 40:21Among the prostate cancer patients
- 40:2390% had sexual function assessed.
- 40:25Among cervical cancer patients about 10%.
- 40:28So I think that unwittingly a lot
- 40:29of providers are in addressing
- 40:31sexual health with their patients,
- 40:33especially with their female patients.
- 40:35It's probably not on the.
- 40:36Providers, radar,
- 40:36it's not really part of our culture.
- 40:38I remember seeing this first hand
- 40:40as a resident understanding that
- 40:42patients are having these issues,
- 40:44but not really knowing how to address it,
- 40:46not being trained how to address it.
- 40:48So there's a lot of barriers
- 40:50to discussion and you can see
- 40:52here there's physician barriers,
- 40:54there's barriers on the patient side as well.
- 40:56And when you add these up,
- 40:57it's very, you know,
- 40:58becomes very difficult to talk
- 41:00about these issues in the clinic.
- 41:01And I think it's especially amplified
- 41:03in the female cancer population.
- 41:05But I think that one of the main
- 41:07reasons why doctors might not ask is
- 41:09because they might not know how to
- 41:11address the problems they might uncover.
- 41:13But the tragedy of that really
- 41:14is that there's a lot of very,
- 41:16very simple low tech tools that can
- 41:18really be available to everyone.
- 41:20So these are strategies to improve
- 41:22vaginal and sexual health and I
- 41:24would say they could be effective for
- 41:26probably about 80% of the types of
- 41:27symptoms that we see after radiation.
- 41:29So just some examples would be
- 41:31educating patients and giving them
- 41:33dilators to improve elasticity
- 41:35and present prevent adhesions.
- 41:37A lot of our patients have atrophy
- 41:40after radiating the pelvis,
- 41:41that hypo, estrogen and.
- 41:42Also fragility of the mucosa
- 41:44as a result of the radiation,
- 41:45the brachytherapy vaginal estrogen
- 41:47is very helpful,
- 41:48improving soreness and friction.
- 41:50Lots of education about lubricants
- 41:52and moisturizers or improving,
- 41:54you know,
- 41:55genito urinary symptoms of menopause
- 41:56or climacteric symptoms.
- 41:57A lot of our patients benefit from hormones.
- 42:01So in our practice,
- 42:02we recommend a comprehensive approach
- 42:04where the conversation starts before
- 42:05any treatments been given up front.
- 42:07We counsel patients about potential
- 42:09vaginal and sexual morbidity,
- 42:10quote incidence rates,
- 42:11discussed mitigation strategies
- 42:13and normalize the concern.
- 42:14During the radiation planning,
- 42:15we try to limit the vaginal dose
- 42:17as much as we can.
- 42:18Now we have guidelines from the embrace
- 42:20and others as to how to do this effectively.
- 42:22And then in terms of secondary prevention,
- 42:24a lot of the strategies that I showed
- 42:26you earlier recommending dilators,
- 42:27lubricants, moisturizers,
- 42:28screening patients for sexual concerns.
- 42:30Assessing vaginal and vulvar tissue quality,
- 42:33screening patients for menopausal symptoms,
- 42:35and referring our patients for
- 42:36further counseling and intervention,
- 42:37if warranted.
- 42:40So I'll mention here that education
- 42:42on this topic is an interest of mine,
- 42:44and I am a board member for an
- 42:45organization called the Scientific Network
- 42:47on female sexual health and cancer.
- 42:49So for those of you who are interested,
- 42:50the website is shown here.
- 42:52It has a lot of links to valuable resources,
- 42:54both for patients as well As for providers,
- 42:56so I'd encourage you all to take a look.
- 42:58And back in November,
- 42:59I hosted here at Yale the 8th
- 43:01annual scientific meeting,
- 43:02which drew almost 100 researchers
- 43:05from around the country.
- 43:06We are very lucky at Yale to
- 43:08have The Sims Clinic.
- 43:09So we realize that physical symptoms
- 43:11aren't the full picture and that
- 43:12sexual dysfunction can be a complex
- 43:14problem that has psychological,
- 43:15relational and cultural components.
- 43:16And the symptoms caused by radiation
- 43:18can compound already existing
- 43:20emotional and interpersonal issues.
- 43:21So one of this resource is The Sims Clinic,
- 43:24which was developed by Doctor
- 43:26Ratner and Doctor Minkin and has
- 43:28representation from Julianne,
- 43:30oncology,
- 43:30gynecology with specialization and menopause,
- 43:33as well as psychiatry and psychology,
- 43:34and they do a comprehensive evaluation.
- 43:36For our patients,
- 43:37we refer many of our patients
- 43:38there for their sexuality,
- 43:40menopausal and intimacy
- 43:41needs after brachytherapy.
- 43:42So I'm making a major plug
- 43:43for this wonderful program.
- 43:44And actually at the meeting
- 43:45that we hosted here in November,
- 43:47it was a pleasure to have a
- 43:48presentation from The Sims Clinic.
- 43:49I should mention that's also run by
- 43:52Johanna Diario and it's really one
- 43:55of the oldest programs in the world
- 43:57like this and has served as a model
- 43:59for many of the others to emulate.
- 44:01So with that, I'll end.
- 44:04We should be proud at Yale to have
- 44:06the resources that we need to treat
- 44:08our cervical cancer patients the
- 44:09best way that we can and to also
- 44:10help them live their lives the best
- 44:12way they can when treatment is done.
- 44:13So thank you for your attention and
- 44:15I'd be happy to take any questions.
- 44:25OK. Joe. So great, fantastic structure.
- 44:33So the the amount of
- 44:35personalization of therapy is.
- 44:39Unlike any other site for the treatment.
- 44:44And so I was just, I was just curious
- 44:46just to hear a little bit more about.
- 44:49How you work with the community?
- 44:52Because obviously we have
- 44:53all of these resources here,
- 44:54we have you here, you know, and you're
- 44:57instrumenting some of your patients,
- 44:58get treated a little bit in the
- 45:01Community and then come here.
- 45:03How do you negotiate that and
- 45:05how do you work with the with
- 45:09the outside referring Dr.
- 45:10to get that done?
- 45:11Yeah, I think that's a I
- 45:12think that's a great question.
- 45:13So, so I don't see myself as like
- 45:16a technician like philosophically
- 45:17I care for the whole patient.
- 45:20But I I also want to say that the
- 45:22good news is there are breaky
- 45:24therapists in Connecticut.
- 45:25I'm not the only breaky therapist in
- 45:26Connecticut and they do a wonderful job.
- 45:28So many patients are treated outside
- 45:30hospitals, but they also know these.
- 45:32Are referring doctors know that for
- 45:34patients that need a lot of needles,
- 45:36if it's a particularly big tumor
- 45:37or you know a vaginal that has
- 45:39a lot of vaginal involvement,
- 45:41they will send them up front to see
- 45:42me and I'll partner with them because.
- 45:44So I don't think I need to be treating
- 45:46all of the cases in Connecticut.
- 45:47But there are some cases that will
- 45:49really clearly benefit from needles
- 45:51and in general we don't want to
- 45:52split care between teams.
- 45:53So I think you know if there's one doctor
- 45:55that can do the whole thing start to finish,
- 45:57that's going to be better.
- 45:58There will be less delays and you'll get
- 46:00through that treatment time a lot quicker.
- 46:02And Umm, you know,
- 46:04so I think that when there's
- 46:05really no other effective way,
- 46:07I'm always happy to see the patient.
- 46:09I meet them up front and this
- 46:10is kind of our policy here.
- 46:11We always review their pathology here.
- 46:13We are part of the decision making up front.
- 46:15We do our own baseline exam and you know,
- 46:18because of resources and whatnot,
- 46:19I have to set up the OR times in advance.
- 46:21So I guess I see myself as a referral
- 46:23for the most complicated cases,
- 46:26but not for all the cases.
- 46:27Does that answer your question?
- 46:31Yes.
- 46:37Especially.
- 46:40You mentioned about it, you just,
- 46:43you know, place much under the R,
- 46:46so you place the Middle Ages or transcript.
- 46:53Oh, that's a great question.
- 46:54So, right. So the question is about
- 46:56real time image guidance of needles.
- 46:58So you're right.
- 46:59There are several, not a lot,
- 47:01but there are some institutions that
- 47:02have an expertise doing transrectal
- 47:03ultrasound and that is a very
- 47:05good modality to see where you're
- 47:06placing your needles in real time.
- 47:09And others do MRI's kind of
- 47:12like how we've been doing it.
- 47:13I think there's a, there's also a,
- 47:16what do you call it,
- 47:17like a learning curve with
- 47:18the transrectal ultrasound.
- 47:19So I tried it a couple of times,
- 47:22but I found that sort of placing
- 47:23the needles and going to MRI.
- 47:24Is effective for me,
- 47:26but there are practices that
- 47:27do the transrectal ultrasound
- 47:29with excellent results.
- 47:30Yeah, it's a good question.
- 47:33Yes.
- 47:46Yeah, they can do it pretty quickly.
- 47:48I don't recall in that particular case,
- 47:49but I think it's faster.
- 47:52So I would like to grow
- 47:53our 3D printing program.
- 47:54I think that's really an area for
- 47:57future development and a lot of promise.
- 47:59So, so like the like I mentioned at Stanford,
- 48:02they have an in House 3D printer
- 48:03within their own department.
- 48:04So they can do that very rapidly.
- 48:06I don't think it takes too much time to
- 48:09do but but we needed a couple of weeks.
- 48:11Just do it for sure.
- 48:15Yes.
- 48:18Yeah.
- 48:35So I don't see Chris in the audience.
- 48:37I think he he's done some
- 48:39research into that question.
- 48:41So the Mr. Lennox,
- 48:42I think you can use to image your,
- 48:44I think it is the right,
- 48:46it is the right amount of magnetism
- 48:50that you can image your implants well,
- 48:52but I don't and I know one of our
- 48:55physicists has sort of looked into that
- 48:57but because we don't have an MRI linac,
- 48:59so I haven't examined that too
- 49:01extensively but I I think that
- 49:03it would be compatible with
- 49:05the majority of the MRI.
- 49:06Safe applicators.
- 49:10Yes, look, look. Move forward
- 49:13to to new innovations and and
- 49:16new therapies as you know proton therapy.
- 49:21Do you think that that's another
- 49:24modality that you'll be able to?
- 49:26Used to produce side effects.
- 49:31Are there? Other sites that are using.
- 49:38So it's not not that common.
- 49:40I know that Doctor Lily Lynn at MD
- 49:42Anderson has the most experience using
- 49:45protons for gynecologic malignancies.
- 49:47But apart from that,
- 49:48I don't think it's been used that often.
- 49:51I don't think it'll replace brachytherapy,
- 49:54but in terms of whether it would be
- 49:56useful for for pelvic radiation,
- 49:57there's really not a lot of
- 49:58data about that at this point.
- 49:59I feel like when we start our program,
- 50:01we're going to be focused more on
- 50:03some of the more CNS type of and
- 50:06pediatric type of cases, but maybe.
- 50:08With with more research,
- 50:10we'll see if if that's helpful.
- 50:14So to be determined.
- 50:15But probably for reradiation cases I
- 50:17can imagine that would be very helpful.
- 50:22OK.