Advances in Cervical Cancer Treatment: Image-Guided Brachytherapy at Yale

Transcript

• 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.