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

January 04, 2023

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.