2022 Susan Beris, MD, Brain Tumor Symposium: Optimizing Brain Tumor Care in the Community

May 19, 2022

May 18, 2022

Presentations by: Jennifer Moliterno, MD, FAANS, Zachary Corbin, MD, MHS, Bruce McGibbon, MD, and Brian Jin, LCSW

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00:00All right, so again, welcome this evening.
00:03It's really a pleasure to have everybody
00:05here and thank you for being here.
00:08So first I have one disclosure
00:10which is not relevant to what
00:12we're going to be talking about.
00:15And actually I had my slides backwards,
00:17so I apologize.
00:18So first I want to start by
00:20thanking Connecticut brain tumor
00:22alliance and the national brain
00:24tumor society who have partnered
00:25with us in support of this seminar.
00:28They are wonderful organizations who.
00:30Really help and support patients with
00:32brain tumors and we are grateful for
00:35their support and their partnership.
00:37I want to talk a little bit and
00:39introduce Susie Barris to all of you.
00:41So she is become my dear friend.
00:44She was my patient and she was practicing
00:48as a pediatrician in Connecticut.
00:52Very beloved pediatrician and one
00:54day she had a seizure in her office.
00:57She was then diagnosed with a glioblastoma
01:00in her motor strip and so she was
01:03transferred to a local hospital and was
01:06told that her tumor was inoperable.
01:08Because of its location in the motor
01:10strip and that a biopsy was offered,
01:13Susie,
01:13being a physician,
01:14thought to to see if maybe there
01:17were some options or alternatives,
01:19or she sought opinions throughout
01:21the Northeast Corridor.
01:22I was thankful and privileged enough to
01:24be the one to end up caring for her.
01:27I performed in awake craniotomy on her.
01:29We removed all of the tumor safely and
01:31this is a picture of her and I at the
01:34Connecticut brain tumor lions path of hope.
01:37Two weeks after her surgery.
01:39They have, uh,
01:40their annual 5K.
01:41She ran it twice and I walked it
01:44once so she is an amazing person.
01:47And in gratitude for her success
01:50she is now about almost about
01:53four years after her surgery.
01:56In her gratitude,
01:58she has been incredibly generous
02:01to us and to our program,
02:03and so we recently named our
02:05Nurse Surgical Oncology program
02:06in her honor and her fund support.
02:09The seminar,
02:09as well as other efforts to try
02:11to educate the community patients
02:13and providers about the importance
02:15of of brain tumor care and and
02:18brain tumor management,
02:20so very grateful to her
02:22and to her friendship.
02:24So tonight,
02:24my portion of the talk is going
02:26to be talking about surgical
02:28strategies for primary brain tumors.
02:30We have Zach Corbin who's going
02:32to follow me talking about neural
02:34oncology approaches.
02:35Bruce Mcgibbons talking about
02:37radiation oncology approaches,
02:39and then the probably the most
02:41important aspect of the talk.
02:43Brian Jin talking about from social work,
02:46talking about the management and
02:48support of patients and their families.
02:50So again, one disclosure that's not relevant,
02:53so we are fortunate to perform the
02:55most number of brain tumor surgeries
02:57each year in Connecticut and care
02:59for the highest volume of patients.
03:01We do try to partner with the Community
03:04in that a lot of the Community,
03:05neurosurgeons and other providers,
03:07will refer patients to us for
03:09more complex cases, and I'll show some
03:11examples of where and how we can.
03:14We can be helpful.
03:15All of the tumors that we operate on
03:17undergo what we call whole exome sequencing,
03:20which is a really.
03:21Next generation sequencing technique
03:23that allows us to understand the tumor
03:26from a molecular standpoint and that
03:28enables us to to treat people from a
03:30very precise and personalized manner.
03:33And we discussed every patient in
03:35our multidisciplinary tumor board,
03:36which I direct and everybody here attends,
03:39as well as our precision
03:40brain tumor board each week.
03:42These are just an example of some cases.
03:44I always show my patients
03:46the preop and POSTOP scans.
03:48I don't know if you're seeing
03:49my my mouse or not,
03:51but preop is on the left post OP is on
03:54the right and you can see for instance,
03:56the glioblastoma Mirren and in
03:58the motor strip that was gross,
04:01totally resected,
04:02some more aggressive meningiomas
04:04that we manage,
04:05and take care of again
04:07vestibular schwannomas,
04:08which we'll talk a little bit
04:10about interventricular tumors,
04:11and again, pre and postop.
04:13With the comparisons with showing
04:15the extent of resection and we'll
04:17talk about how removing as much tumor
04:20as safely as possible is really the
04:22goal to any type of of neurosurgical
04:24care for brain tumor patients.
04:26So the goal of primary brain
04:28tumor surgery of course,
04:29to establish a diagnosis and and to
04:33establish sorry and to establish
04:35an accurate diagnosis to maintain,
04:38improve quality and quantity of life.
04:41And by what I.
04:41What I mean by that is that there's
04:43great evidence that shows the more tumor.
04:46We're able to remove safely.
04:48The better the patient does,
04:50this really has shown effect
04:52across all tumor types.
04:54Maybe without the the
04:55exception of of lymphomas.
04:57In small cell lung cancer,
04:59but otherwise brain tumors
05:01benefit from being gross,
05:02totally resected,
05:03and patients benefit from the resection while
05:06maintaining their neurological function,
05:08or even improving their
05:10neurological function.
05:11How do we do that?
05:13And so similar to Susie's tumor
05:14patients can be told that they have
05:17an inoperable tumor because it's in
05:19in an eloquent part of the brain,
05:21an eloquent meaning a highly
05:22functioning part of the brain,
05:24and So what are the secrets to
05:26the success we have all the the
05:28gadgets and and gazebos that that
05:30that gadgets and gizmos that that
05:32we need in our state of the art
05:34operating rooms with GPS systems and
05:36ultrasounds were the only center in
05:38the state to have an intraoperative MRI,
05:41which I'll show the benefit of.
05:43But really,
05:43I think a lot of it comes down
05:46to expertise and experience,
05:48and in fact that has a lot to do with
05:51more sophisticated microsurgical techniques,
05:53and especially when we're talking
05:56about preserving function.
05:57And really the gold standard for
05:59that is is neuromonitoring or use of
06:02neuromonitoring and functional mapping,
06:04as well as a weak surgery,
06:05which I'll show some examples of.
06:08This was a slide that was given
06:09to me by
06:10the Chair of mass general Neurosurgery,
06:12and I I really like it because I think it.
06:14It speaks volumes.
06:16This is as you can see,
06:18as the case volume increases and this is
06:22the percentage of of cranial specialization.
06:24What this shows is that surgeons who do
06:27higher volume and are more specialized
06:29in a particular area of neurosurgery,
06:32cranial versus spine,
06:33that would even argue tumor versus
06:36other aspects of neurosurgery.
06:38Have better outcomes in terms of
06:40their patients, and that's certainly
06:42something that we see here.
06:44I have a short video which I
06:47hope you don't mind me sharing.
06:48Unfortunately I have to pull it up elsewhere,
06:51but this is a great example and
06:53I've I've shown this before,
06:55so forgive me if you've seen my talks
06:57before and have seen the video,
06:59but I think it's a real great
07:01example of what we're able to do.
07:06205 Sixty one can you hear it OK?
07:09Surgery, waking up in the middle of the
07:11procedure and knowing what's going on.
07:13But in some cases that can be a lifesaver,
07:15lifesaver and necessary.
07:16We're going to explain that in a moment,
07:18but first we do want to introduce you
07:20to a man named Andy Andy is a husband
07:22and father of two kids and a nurse.
07:24Another interesting fact about him,
07:26he's also a professionally trained singer.
07:29He's even performed with his
07:30church choir at Carnegie Hall,
07:32but Andy felt his entire life come to a halt
07:35when he was diagnosed with brain cancer.
07:37He needed surgery to remove
07:38as much of a tumor.
07:40It's possible that tumor in the part
07:42of his brain that controls speech and,
07:44yes, singing.
07:45That's where a special surgery comes in.
07:47Surgeons at Yale,
07:48New Haven Smilow Cancer Hospital
07:50have perfected a procedure
07:51called in a weight craniotomy.
07:53They invited us into the operating
07:55room and we did not hesitate to see
07:57this incredible procedure first hand.
08:02In an operating room at Yale,
08:04New Haven Hospital.
08:07Doctors are working to remove
08:08the tumor from the brain of
08:10a 31 year old man named Andy.
08:12He is a singer.
08:15A husband and father of two for most
08:19surgeries waking up in the middle of
08:21the operation would be a disaster.
08:26And anesthesiologist doing his best
08:29to make sure Andy does just that.
08:33They still surgeons have drilled
08:35through his skull and have already
08:37begun to remove part of the tumor.
08:39Located on the left side
08:41of his temporal lobe.
08:42The area which controls language.
08:46Medical staff puts a microphone on him.
08:49It's not for our cameras,
08:50it's so the entire room,
08:53including the operating surgeon,
08:54can hear what Andy has to say.
08:59The procedure is called an awake craniotomy.
09:03I was telling you earlier I I don't know
09:05if it's from the brain surgery or the fact
09:08that I have to have a couple of copies
09:11for neurophysiologist. Brook Callahan
09:13sits next to him and begins her work. I
09:16am going to say a sentence and I
09:18want you to repeat it after me.
09:20The seashore smells like salt.
09:23It's like. Action can be heard
09:26on a speaker throughout the room.
09:28Neurosurgeon Doctor Jennifer moliterno.
09:33Has mastered multitasking,
09:35operating and listening.
09:38Great Doctor Moliterno and her
09:40team worked diligently to remove
09:42as much of the tumor as possible.
09:44What she can't see are critical
09:46microscopic language fibers which
09:48are splayed over the tumor.
09:49The best way to try to remove
09:51as much tumor and preserve his
09:53language is to do it with him away.
09:55Get too close to those critical fibers.
09:58You'll know it. What can you do in a chair?
10:05I don't know. Yeah,
10:07a little bit of confusion, so that's
10:09a great way to me to tell me to stop.
10:13And so even though there might
10:14be a little bit of tumor there,
10:16the risk and benefit of removing
10:18that tumor and having him not
10:19speak for the rest of his life.
10:21Tells you exactly what the right decision is.
10:24If he was asleep,
10:25I would have had no idea.
10:26As Doctor Moliterno continues
10:28operating at a safer spot and he
10:31surprises us when this happens.
10:39He does in the middle of surgery.
10:42Andy's a classically trained
10:43singer, shares his talent.
10:502 1/2 hours into the procedure,
10:52doctor Moliterno decides
10:53it's time to wrap up.
10:55The surgeons are done with the
10:56first part of the surgery.
10:57So what's happening now is they're
10:59bringing in an MRI machine and
11:00they're going to look at the work
11:02that they did and see how much of
11:04the tumor they were able to remove.
11:08We go into another room that
11:10are able to sit with Doctor
11:11Moliterno as she analyzes her work.
11:14The before kierans think tumor and after.
11:21You don't have to go back in and feel
11:24satisfied pending a week allowed us to get
11:27that outcome and preserve this function.
11:30Now Andy was back home with his
11:32family two days after surgery,
11:34five days after the surgery,
11:36he was able to sing at his son's baptism.
11:38He's also saying again with his
11:41church choir and the Yale Camerata,
11:43which is a professional choir.
11:45Just a couple of weeks ago, Andy is
11:47undergoing chemotherapy and radiation,
11:48but he does say he's feeling good.
11:51And, of course, warm wishes to him.
11:53He is just.
11:56So that is a great example in my
11:58mind as to why we do what we do
12:01and how we can really push the
12:03limits from a surgical perspective.
12:09OK, another example of a patient of
12:12mine who underwent 10 away craniotomy
12:14and so this was an in another man
12:17who presented with language trouble.
12:20He was at a different hospital
12:23and outside hospital and you can
12:25see here was his initial scan.
12:27He had a glioblastoma just around
12:29his his language area and that
12:31was prohibiting him from speaking.
12:33You can see that he underwent a
12:36postop MRI just a short time.
12:38After and really there was not much tumor,
12:41if any that was removed,
12:42and so they had achieved a diagnosis
12:45of glioblastoma,
12:46but he was then referred to
12:48me because as you can imagine,
12:50which Zach and Bruce will will
12:52get to it can be quite hard to
12:54to radiate an area such as this,
12:56or to get patients through through
12:58chemotherapy when there's that much
13:00mass and and Mass Effect and and edema,
13:02especially near critical language structures.
13:05So we ended up getting a functional
13:07MRI similar to Andy. We kept him.
13:10Awake during surgery and we were
13:11able to remove the tumor and his
13:14language improved considerably.
13:15Not all patients need to be awake
13:18during surgery in order for us
13:20to safely remove and and get the
13:22the maximal extent of resection.
13:24This is one of my favorite stories
13:26and I have a lot that are similar,
13:29but I think this one really highlights
13:32the multidisciplinary effort that
13:34that we provide on every patient.
13:36So this is a gentleman in 2013.
13:38As you can see.
13:39He presented to another hospital.
13:42And and underwent a biopsy for this tumor.
13:46That's located here,
13:47turned out to be a glioblastoma.
13:49He was told that the mass was
13:51too risky to remove.
13:52He then was referred to me for
13:54consideration of another opinion.
13:56I thought that this could be safely removed,
13:59and so we did, and even for someone like me,
14:02who does brain tumor surgery every day,
14:05you can still get fooled and
14:06you can still miss some tumor.
14:08And so this is an example of
14:09our interoperative MRI,
14:10which you can see here.
14:12That's housed in our operating
14:14room and a little bit of tumor I
14:16left behind that got tucked and
14:17hidden underneath the brain.
14:19So while he was asleep on the table
14:21after I removed most of the mass,
14:23we got the intraoperative MRI saw that
14:25and I went back and was able to resect it.
14:28This pathology was confirmed as GPM,
14:31showing an unmethylated MGMT status,
14:34which is usually a poor prognostic factor.
14:37His care was then provided by
14:39Yocom bearing our neuro oncologist,
14:41as well as Renji.
14:43Who had the patient on our standard
14:46of of care?
14:47Stoop radiation and temozolomide and
14:50one of our fantastic homegrown Yale
14:54clinical trials that Ranjeet was Pi
14:57and and directed and and and really found it.
15:01He was enrolled on.
15:02He then was enrolled on other clinical
15:04trials that we offer and then switched
15:06on various chemotherapies until he
15:08progressed and when he did he welcome
15:11sent him back to me with this recurrence.
15:13So I operated on him again and here
15:16you can see we did a wider resection
15:18and of course pathology was the same
15:20but the whole exome sequencing that
15:22we performed that really helps us
15:25understand the tumors better showed
15:27he had what we call a hyper mutated
15:29phenotype and the significance of
15:31this is that we know based on the
15:33literature that these tumors tend to be
15:36more susceptible to immune checkpoint
15:38inhibitors and so he was then started on
15:41nivolumab and then also with Avastin.
15:43Intermittently,
15:44and he is currently about 8 1/2 years
15:47from his initial time of diagnosis and
15:50I love this story and when I presented
15:52I always say that this is in no way
15:55and I had rejected him one other time.
15:57Sorry I forgot to mention that I in
15:59no way I'm saying that all of our GBM
16:02patients will survive 8 1/2 years or longer.
16:04I really do wish that was the case,
16:07but he is a great example of how
16:09I believe if he had stopped it.
16:11Just biopsy, there's no way in my mind.
16:14That he would still be alive 8
16:171/2 years after a biopsy.
16:18And so this is a great example of how when
16:20we work together with aggressive surgery,
16:23maximal safe resection even a few times,
16:26we can really push the limits of
16:28what we can do with with the other
16:31clinical trials and other adjuvants.
16:33This is a more recent example
16:35of of a patient who was seen at
16:38another hospital in Connecticut.
16:40He had this large tumor that you can
16:42see here in his fourth ventricle.
16:44This actually caused some obstruction
16:46of of fluid,
16:47so at the outside hospital he underwent
16:49a placement of a shunt to address the
16:52management and build up of the fluid and
16:55also underwent a biopsy of the mass.
16:57The biopsy showed that it
16:58was a malignant tumor,
17:00but unfortunately it wasn't
17:02able to to characterize.
17:03What type of the tumor it was?
17:06And so this patient was followed
17:08with a serial scan a few months later
17:10that showed increase in size of the
17:13tumor and further backup of fluid.
17:15Despite the shunt he was referred
17:17to me for surgical resection.
17:19We were able to remove all of the tumor
17:21and now we can target his treatment better.
17:24Now knowing exactly what type of
17:26tumor it is and also the shunt was
17:28removed because he doesn't need it.
17:30Given the fact that the tumor was removed
17:32and the backup of fluid was alleviated.
17:34So again,
17:35another great example for diagnosis how it
17:38can really be helpful in guiding management.
17:41The maximal set extent of resection doesn't
17:45necessarily apply just to malignant tumors,
17:48and so this is an example of a
17:50vestibular schwannoma patient
17:51and acoustic neuroma patient,
17:53and these tumors are are 99.9% benign,
17:57and so they're not malignant,
17:58but they're tricky and that they
18:00occur next to the brain stem,
18:02and they have a very intimate
18:04association and relationship with
18:06the facial nerve,
18:07and so this patient presents it elsewhere.
18:09He underwent a surgery by another.
18:12Surgeon and this is his preoperative scan.
18:14This is his post operative scan.
18:16Three months later in 2012 and you can see
18:18not much of a difference between the two.
18:21Not much tumor had been removed.
18:23They continued to monitor this and in 2017
18:27in conjunction with another radiation
18:30oncologist ended up giving focused
18:33radiation or gamma knife radiosurgery.
18:35She went on about a year later
18:38to start experiencing this,
18:40which is pretty bad.
18:42Swelling in her brainstem.
18:43As a result,
18:45she became pretty debilitated by this tumor,
18:48so much so that she required very,
18:50very high dose steroids,
18:51which led to a steroid myopathy which led
18:54to significant muscle wasting and weakness.
18:57She was confined to a wheelchair,
18:59and Zach was actually became involved
19:00with her care at that point,
19:02and and kindly referred
19:04her to me when he did this.
19:06Was her preoperative scan and that was
19:08when he had become involved with her care?
19:10You can still see the swelling in the
19:12brain stem over here and we took her
19:15to surgery and got a nice resection.
19:17So another example where working
19:20with people and and providing the
19:23best possible surgical outcome
19:26really does impact people's lives.
19:29Another type of brain tumor that
19:32everyone usually thinks of as being
19:35benign as meningioma and we at Yale
19:37have really done a lot of work to
19:39understand these tumors and the
19:41biology of these tumors and why
19:43sometimes they don't behave as
19:45benign as as one would think.
19:47So this is another patient who
19:49in 2015 underwent a resection.
19:52I don't have those films,
19:54but he had what we call a convexity
19:57meningioma and so another.
19:58Hospital in 2015 underwent resection.
20:01Was told it was a grade one meningioma,
20:03not to be worried about it.
20:05It was removed and he can go about his life.
20:08He ended up having some weakness
20:10due to as you can see,
20:11some swelling in 2017 that was
20:15associated with regrowth of the
20:17tumor and so he got this scan.
20:19He saw a few other surgeons not me at
20:21the time and the decision was to to
20:24do gamma knife radiosurgery targeted.
20:26Then two years after.
20:28The radio surgery he progressively worsened.
20:31He was confined to a wheelchair
20:34with weakness.
20:35The tumor had grown more and he had
20:38intractable seizures at that point.
20:39In 2019, he was sent to me.
20:41This was a pretty straightforward surgery,
20:43despite the radiation,
20:44and we were able to roast, totally remove it.
20:48His weakness improved,
20:49and his seizures went away.
20:50But the question that that I have and
20:52that we've been asking here at Yale,
20:54from a research perspective is,
20:56could this have been better
20:57predicted or manage the first time?
20:59And the answer is yes,
21:00and I'll show you briefly why.
21:02So the general lab,
21:03as well as others has really
21:06understood the genomics underlying
21:08sporadic meningiomas and we now know
21:11about 80 or 85% of sporadic
21:13meningiomas are caused by mutation.
21:16Somatic mutations in these genes,
21:19and so the most common and in the
21:21interest of time I won't get into
21:23everything but the most common
21:25mutation underlying sporadic
21:26meningiomas is somatic mutation.
21:29Involving NF2 with or without
21:31chromosome 22 loss.
21:32These this, this abnormality has been
21:35seen as part of the pathway to more
21:39aggressive meningioma formation,
21:41and I'll talk about that in a
21:42few minutes and so when we think
21:44of grade one meningiomas,
21:46there's also grade 2 meningiomas
21:48and grade 2 meningiomas can either
21:50arise as grade 2 meningiomas,
21:52which we call denova with
21:55certain genomic characteristics,
21:56or they can progress from low grade.
21:59High grade, very similar to gliomas.
22:03Part of the work that I have focused
22:05on is the clinical correlations and so
22:08initially and and we've revised this
22:10even even more so to be more inclusive.
22:12More recently is localizing the
22:15meningioma subgroups based on genomic
22:18mutation with intracranial location,
22:21and so I use this all the time in the
22:23sense that when patients come to my
22:25clinic based on where their tumor where,
22:27their meningeal might is located
22:29in their head,
22:30I can predict with a pretty
22:32good degree of certainty.
22:33And the underlying genomic mutation.
22:36And so why is that relevant?
22:38Because we've gone on with thanks in
22:40part to the Connecticut brain tumor
22:42alliance and their support of our work
22:44to understand the clinical relevance.
22:47And so these genomic subgroups
22:48we have found to be linked to
22:52various clinical manifestations,
22:53whether that's seizure.
22:55Whether that's also to do
22:57with histological subtypes,
22:58or Bony involvement, etcetera,
23:00we have been able to uncover that
23:03one area I wanted to touch upon,
23:05and I apologize for the.
23:06This slide it was.
23:07We were the first to publish
23:09on recurrence being related to
23:12meningioma molecular subgroup,
23:14and so again very busy slide,
23:16but the take home message is that we
23:19identified for the genomic subgroups
23:21with more aggressive clinical
23:23behavior in terms of recurrence,
23:26and so specifically those
23:27tumors with an NF2 mutation,
23:30those with an A KT1 mutation or
23:32other molecules involving the Pi 3
23:35kinase signaling pathway, hedgehog.
23:36Familiar pathway or trap?
23:38Seven or more likely to record an
23:40average 22 times higher than others,
23:43and this held true at 17 times
23:46higher amongst grade ones.
23:47And So what type of mutation is
23:50underlying or driving the meningioma
23:52biology is associated with whether
23:54or not the tumor will occur and
23:57even when it will occur in that
23:59some of these tumors with a KT1
24:02mutations in the PI3 kinase signaling
24:04pathway typically recurs sooner.
24:07And this is 1 aspect of of the answer
24:09to the puzzle as to why some grade one
24:13meningioma is behave more aggressively,
24:16and so here going back to our patient,
24:18how could how could this have been
24:20predicted in managed differently
24:21the first time?
24:22This is how and so this is an example
24:24of our molecular analysis report
24:26that we receive on every patient
24:29we operate on at Yale.
24:30And here the histological diagnosis of this
24:33patient was actually a Grade 2 meningioma,
24:36not a grade. And Angioma,
24:38which was initially diagnosed in 2015.
24:40So you might say, well,
24:42maybe I transitioned from
24:43a low grade to high grade.
24:44The answer is no.
24:46Looking at the molecular information,
24:48there's an NF2 mutation and then based
24:52on the chromosomal abnormalities
24:54in the copy number alterations,
24:57we can tell that this was one that
25:00was denovo and had been a typical
25:03meningioma but was misdiagnosed
25:05histologically back in 2015.
25:07And so, in our hands we would have
25:09respected that tumor and likely
25:11radiated the tumor up front after,
25:13or at least kept a very close follow up.
25:16Another patient with another one
25:18of these grade one meningiomas.
25:20This was a patient that was
25:22operated on by someone else.
25:24Had this large tumor surgeon
25:25left a small residual to preserve
25:27endocrine function and just six
25:29months later you can see the growth.
25:32That's not growth that you would
25:34expect with a Grade 1 meningioma,
25:36and so then the patient underwent radiation
25:38and then continued to have growth.
25:41This is actually not the most
25:42recent follow up.
25:43I'm sorry for that error.
25:44She's had more growth, more recurrence.
25:48I've operated on her a couple of times.
25:49Since then she's had more radiation
25:51and has been enrolled in clinical trials.
25:54And here's her Histology
25:56and molecular report,
25:58so it still remains a grade one meningioma,
26:01but you can see that a KT1 missense
26:03mutation and based on our findings in
26:06the neural oncology paper and here,
26:07you see that these tumors
26:09tend to occur earlier.
26:11And the last patient example,
26:14very complicated, patient with another grade,
26:16one meningioma who underwent
26:19surgery elsewhere a few times.
26:21Radiation elsewhere a few times,
26:24was enrolled in a clinical trial
26:26with Priscilla Brosterhous at MGH.
26:28She recurred.
26:29This was her recurrence,
26:31highly vascular tumor.
26:32As you can see,
26:33Priscilla center down here
26:35to me for surgical resection.
26:37We got a nice surgical resection,
26:39and here's her genomics again that.
26:41Act one mutation and so the point
26:43being is that maximizing the surgical
26:46resection is of course a huge part in
26:49survival and progression free survival.
26:52Getting a good tissue diagnosis
26:54is incredibly important,
26:55but really managing patients as
26:57we do in most academic centers do
27:00based on the molecular diagnosis and
27:02not just not relying on Histology,
27:04is incredibly important.
27:07We hope that our patients find it
27:09easy to navigate through the system
27:11through our multi disciplines and
27:13of course through our health system
27:15including Bruce and and others who
27:17are located in Greenwich and other
27:19satellite places throughout the state.
27:21We're so thankful to the Lovemark
27:23Foundation and the Connecticut
27:25brain tumor alliance to provide
27:26support to our patients,
27:27and I am incredibly thankful to these
27:30ladies and men who I work with every day.
27:32Jillian and Marcy,
27:33who are nurse practitioners in
27:35our brain tumor surgery program.
27:37Kelly and Marsala,
27:38who are nurse coordinators
27:40Larry and the other staff who work in the
27:43operating room who assist me every day,
27:45my clinical research fellow Sagar
27:46Shari and and a bunch of other people,
27:49who unfortunately aren't on this
27:51in this picture, and Neil and Mary
27:53and I them my clinical fellow,
27:55so thank you once again for listening.
27:57Thank you to Doctor Barris for
28:00her generosity and her friendship.
28:03I will turn this over to Zach and
28:05I guess we'll take questions at
28:08the end and I'll stop sharing.
28:10So Zach Corbin. A friend, a colleague.
28:16A wonderful neuro oncologist,
28:18and I'm really exciting.
28:19Because excited,
28:20because he's going to speak to you now
28:22about emerging therapies for brain tumors.
28:24And he's also going to talk about
28:25some of his exciting research and and
28:27work that he's doing with imaging.
28:33Perfect thank you so much for
28:36that wonderful introduction and
28:38talk and what a lovely dovetail.
28:40I wish if I had actually
28:42been able to modify my title,
28:44I would say emerging classifications
28:46and therapies of brain tumors
28:47because a lot of what I'm going
28:49to talk about is exactly that.
28:51The really we have changed recently.
28:53The way we're thinking
28:55about primary brain tumors.
28:56So yeah, so I'm Zachary Corbin.
28:58I'm one of the neuro oncologists
29:00based at Smilo and I look forward to
29:02talking to you for a few minutes.
29:03Today and thank you for having me so.
29:07I'd like to start by saying that I
29:09do have a a disclosure that I will be
29:12discussing off label use of procarbazine,
29:14otherwise no relevant disclosures.
29:16I'm going to talk about my
29:18the structure of my talk.
29:20We talk about glioma and meningioma
29:23very similarly to doctor Moliterno
29:25talk about the classification that
29:27we have begun to use very recently.
29:30Based on the 2021 WHO and then
29:33standards of care,
29:35including some relatively new ASCO
29:38snow guidelines that can help
29:41clinicians make the decision about
29:42patients who are not able to or choose
29:45not to enroll in clinical trials.
29:47And then,
29:48of course,
29:48I want to discuss about clinical trials.
29:50That we have available at Yale,
29:52and the approaches that they may offer.
29:55Then I'll switch to meningioma and
29:56doctor Moliterno has covered a lot of the
29:59standard of care have been in GMs already,
30:00but I'll summarize,
30:01and then I'll discuss a couple of
30:04clinical trials we have available.
30:06And absolutely at the end.
30:07I look forward to.
30:08Sharing some research that I'm
30:11doing and some observational studies
30:12that are available to patients
30:14who are seen at her Cancer Center.
30:16So without further ado,
30:17I'd like to talk a little bit about glioma,
30:21and I'm sure most people watching this
30:25talk are familiar with the disease,
30:27but some I think underappreciated
30:30facts include that it is the second
30:32most common type of primary brain tumor.
30:34It has a higher burden than I
30:36think most realized that 19,000.
30:38New diagnosis in the US.
30:40The most recent count annually and over
30:4412,000 of these patients have glioblastomas,
30:47and despite even even more than what
30:50doctor Moliterno has had a chance to cover.
30:54What we do clinically and research.
30:56Despite all of this and for decades.
30:59Less than excuse me,
31:00just a little bit over one in 20
31:03patients at five years remain alive.
31:05The most recent count is 7.2% and
31:07I'm going to end by saying the silver
31:09lining is that count is going up
31:11and so we are making gains and we
31:14are continuing on our quest as I'm
31:16sure most watching this talk are.
31:20Pathologically or histopathologically,
31:21and hopefully you guys can see my point here,
31:24feel blastoma appears like this.
31:25You can see lots of areas in the
31:28tumor microscopically that have
31:29different shapes and nuclei.
31:31You can see necrosis.
31:32You can see pseudo palisading areas,
31:34which is what this call where you
31:36can see the
31:37sheets kind of dive into the necrosis and
31:40you can see areas of vascular proliferation.
31:43Another thing that I always like
31:45to talk about is how important
31:47publicly this disease is.
31:49So these three men all died of glioblastoma
31:52or high grade glioma and for those of you
31:56who don't know who one of these people are,
31:59I'm sure that most people know all of them.
32:01This is Ted Kennedy,
32:03he was President John F.
32:05Kennedy's brother.
32:05This is Beau Biden,
32:07President Biden son and this is John
32:10McCain's most recent example of this picture,
32:12but I think.
32:13That this really goes to show how,
32:15although a rare disease,
32:17officially an extremely important
32:19disease in many other ways
32:21than we might initially think.
32:23So as I said,
32:24I'm going to talk about the way we
32:26classify gliomas in the context of the 2021,
32:29WHO classification of tumors
32:31of the central nervous system.
32:33This is actually very recent,
32:35and last time I checked,
32:36we still didn't have the because
32:38of COVID related printing delays.
32:40We still didn't have the actual
32:42final results to review ourselves,
32:44but we have this preview and I'm
32:46going to summarize it for you today.
32:48So the preview I think is
32:50best summarized in a diagram,
32:52and you can see starting here that.
32:54Really,
32:55we start where we used to be
32:57with histopathology and then as
32:59doctor Moliterno was discussing.
33:01The answer is largely now related
33:04to molecular findings and the
33:06first dichotomy is the IDH
33:09isocitrate dehydrogenase genes.
33:12So a tumor that expresses an IDH mutation
33:15is a tumor for which we understand
33:18the patient who has that tumor.
33:20Their outcomes are better and the
33:23tumor grows less and then a dichotomy.
33:25After Idhe mutation is whether or not that
33:28tumor expresses another genetic change,
33:30it's called 1P19.
33:31Q code deletion and so an IDH mutant
33:341P19 Q code deleted tumor almost
33:37no matter what it appears under.
33:39The microscope isn't all the good enough,
33:41Ryoma and I'll get into gliomas
33:44are actually graded histologically,
33:46as are the other tumors.
33:47So that is where we can use
33:50Histology and molecular features
33:51so WHO grade two and WHO grade 3
33:53all the good and agree on this.
33:56And then if actually there is no one P.
33:5819 Q code deletion,
34:00you can see that there are
34:02astrocytomas which are IH mutant.
34:05These are kind of cousins of the stoma,
34:08but actually even a Grade 4
34:11astrocytoma that is an NIH mutant
34:14is in this classification,
34:16not considered a glioblastoma.
34:17That is a big change we used to call
34:20patients who had tumors that were WHO
34:23grade for histologically a glioblastoma.
34:25If they were astrocytic,
34:27whether or not they had ID communications.
34:30So you can see that this whole
34:32category of tumors is quite different
34:34because it has different molecular
34:36features and also different clinical
34:38outcomes and so moving right.
34:40Unfortunately these tumors grow more
34:42aggressively in patients who have
34:44them have generally shorter outcomes,
34:46although with aggressive treatments,
34:47we're hoping that that also will
34:49change. So if the patient does
34:51not have an ID quotation we refer
34:53to that as an IH wild type tumor.
34:56And you can see that those characteristics
34:58under the microscope I described before
35:00can help describe a glioblastoma
35:01which is also called glioblastoma idh,
35:04wildtype CCNS, WHO grade four.
35:07And then you can see that there are other
35:10similar Leo Blastomas or similar gliomas.
35:13Sorry that have a Grade 4 characteristic
35:15and in general these are considered diffuse,
35:18midline and diffuse hemispheric
35:20gliomas with the midline glioma has
35:23an H3K27 alteration so moving on.
35:27The standard of care for glioblastoma
35:30is still based on a study that was
35:33actually old when I was a fellow,
35:36which is the study protocol.
35:37And you'll hear us discuss the study
35:39protocol when we discuss management and
35:41a couple things I want to highlight
35:43on this slide is that the curves
35:46despite aggressive treatment,
35:47continue to go down,
35:49but this is actually continues to be
35:51the basis for which we treat many
35:54patients and maybe motivation to
35:56keep these curves.
35:57Up for pursuing more clinical trials
35:59and then the other thing I'd like to
36:01show once again is that it's 2005.
36:03So now 17 years old and we do
36:06have additional advancements.
36:09I'm not trying to say that we
36:10have been frozen since 2005,
36:11but it is remarkable to think
36:14about how long we've been.
36:16We've had these results so as I was saying,
36:19I'd like to move forward just
36:20because guidelines not just
36:21have the tree clear blastoma,
36:23but all gliomas and so this is
36:25the American Society for clinical.
36:27Ecology ASCO and the Society
36:30for Neuro Oncology.
36:312 American organizations to manage
36:33Neuro ONC and they issued combined
36:35recommendations for the different
36:36categories of tumor and so I
36:39thought I would just go through the
36:41different categories one by one.
36:43I mentioned all of these in the diagram
36:46that I discussed before all go into gliomas,
36:49Deputy O grade one.
36:51I should I should say,
36:53but you guys already know.
36:55The maximum safe for section and when
36:58possible is the start to management
37:00of almost all of these tumors.
37:02But once we get to maximum safer section
37:05and have the best pathologic evidence,
37:08observation is possible,
37:10which means we monitor closely with
37:12scans and these patients low risk
37:15disease has specific features,
37:16but if a patient is over 40 or
37:19a patient has remaining tumor,
37:21they are not considered low risk,
37:23and so we proceed with radiation
37:25combined with.
37:26Either procarbazine Lomustine
37:27and Chris Vincristine,
37:28which you'll hear me discuss for
37:31here on as PCV or team ITAR or TMZ.
37:36Temodar is emphasized as an option if
37:40there's concerns for someone tolerating PCV.
37:44However,
37:45I would say that there are also
37:48oncologists that actually favor temodar
37:51because the evidence is also strong
37:54for temodar in that the stoop protocol,
37:58for example,
37:58is a more treated and more
38:00aggressive tumor with team donor,
38:02and this is an open question
38:04which we are actually
38:05trying to address at Yale.
38:07Olive good good inglima
38:08is Newton grade three.
38:10We do not have any ability to monitor these,
38:13whether or not the tumor is entirely
38:15or we would not recommend.
38:16I should say, monitoring these.
38:17Whether or not the tumor is entirely removed,
38:19we would proceed with radiation
38:22combined with PCV or possibly all
38:25using team radar as an alternative.
38:28I astrocytomas IH mutants
38:30that are WHO grade 2.
38:33For those of you who are familiar
38:34with the old classification,
38:35these used to be called diffuse astrocytomas.
38:38These are possible to observe,
38:40once again with good characteristics.
38:43Some some would argue that they
38:45should be treated with radiation
38:47followed by adjuvant chemotherapy,
38:49and in this case,
38:50I think the field generally
38:52prefers temodar over PCV,
38:54but the guidelines offer
38:55a choice between both.
38:57In case it's not clear why one
38:59would prefer team at our over PCV,
39:01PCV is a is a.
39:03Is a chemotherapy regimen that
39:06involves multiple chemotherapies that
39:08each involve different side effects
39:10that can be difficult to tolerate,
39:11and they can also limit the ability for
39:15the patient to take the whole regimen.
39:17Temodar is less prone to those limitations.
39:22So moving forward,
39:24astrocytoma ID student debt charade 3.
39:27This is a tumor that there is
39:29some debate about how to treat,
39:30but radiation with adjuvant temodar
39:33is the recommended method and the
39:35guidelines and then maybe there's more
39:38debate with IDH mutant tumors WHO grade 4.
39:41Once again,
39:41these tumors used to be called gliomas,
39:43tumors that we now refer
39:45to them as astrocytoma,
39:46IDH, Newton.
39:47So radiation with adjuvant temodar is
39:51is offered or treatment for the study
39:56protocol as a glioblastoma is treated.
39:59So moving forward glioblastoma.
40:01Sorry IH wild type tumors.
40:04Astrocytoma IH well typed either
40:06grades two or three are generally
40:08recommended to be treated as the oldest.
40:11Thomas Glioblastoma is our idea 12
40:15type who grade 4 so those tumors.
40:18We recommend treating either with the
40:21study protocol or possibly additional
40:23changes in a subset of patients,
40:26so the study protocol,
40:27which I've now mentioned
40:28probably 8 times by name,
40:29but haven't actually told you what it is.
40:31This is where you do radiation
40:33combined with Team Adar.
40:34At the same time,
40:36that's called Chemoradiotherapy
40:37with temodar and then patients
40:39receive 6 cycles or six months
40:41of team that are thereafter.
40:43You patients are certainly are physicians
40:46and patients together are certainly
40:48allowed to receive more chemotherapy.
40:50Up to 12 is is still standard,
40:52but most of the field is considering
40:55moving back to six cycles at this point.
40:58Certainly in some patients.
41:00And alternating electric fields are delivered
41:03by a device called the Optune device,
41:06and this may be added either
41:08actually at diagnosis,
41:10which is what this recommendation is about,
41:12or have recurrence actually
41:13in a subset of patients.
41:15These patients are patients who may
41:17be elderly or may have some reasons
41:19why we don't think they could
41:20tolerate what it ends up being.
41:22Quite an intense therapy we can proceed
41:25with hypofractionated radiation with
41:27concurrent and adjuvant Thermidor
41:28hypofractionated is only three weeks long.
41:31As opposed to six weeks long,
41:33but I'm not going to get into
41:34any more details about radiation
41:36because Doctor Mcgibbon is the
41:37expert and we'll be speaking later.
41:39And then alternatively,
41:40if we think that team radar may
41:42not be useful because of other
41:43molecular features which are
41:45outside of the scope of this talk,
41:46you could you could do
41:48hypofractionated radiation alone.
41:49You could do team at our monotherapy
41:51alone and then of course there are
41:53some patients that either choose
41:54or may not tolerate any treatment
41:56and supportive care is an option
41:59to proceed with with glioblastoma.
42:01So on a brighter note,
42:02I'd like to talk about clinical
42:04trials that we offer.
42:05So one thing to talk about clinical
42:07trials is that these trials often
42:09don't replace the standard of
42:11care we get that question a lot.
42:13Often they will augment the standard of care,
42:15or they ask questions about the
42:17standard of care and the other thing
42:19to note about clinical trials is
42:20that a clinical trial that I would
42:22recommend to a patient is going
42:24to be one that exhibits equipoise.
42:26This is a true experiment where
42:28we're trying to answer something we
42:29don't know the answer to, and so.
42:32I mentioned the the question that this
42:34trial is trying to address already,
42:37so we have a trial for patients who
42:40have oligodendrogliomas WHO grade
42:41two who have high risk disease.
42:43Once again,
42:44they're over 40 or they have a
42:47residual tumor or grade three.
42:49They can enroll in a trial where
42:51we are actually proceeding with
42:52adjuvant radiation that's either
42:53combined with temodar or they proceed
42:55with radiation followed by PCP.
42:57Because once again we have this
42:58question where we don't know what
43:00is better and all the good and.
43:01Family and patients who have
43:02all the good nucleonics.
43:04We have more trials in patients
43:06who have leonas demo.
43:07So we have a Phase 01 trial which
43:09is an early phase trial where we're
43:12testing an immunotherapy regimen that
43:14targets a type of checkpoint that's
43:17called TIGIT that is used in addition
43:20to or possibly alternating with,
43:22the PD1 checkpoint,
43:23which is a more famous checkpoint
43:25that others may have heard of.
43:26Drugs like pembrolizumab and nivolumab
43:29target the PD one checkpoint,
43:31we have a phase one trial of
43:33a drug called FB PMT,
43:35which is targeting cancer cell signaling.
43:38And that is for patients who have
43:40glioblastoma appearance or when the
43:42tumor is growing back as doctor
43:44Moliterno showed in multiple of the cases.
43:46And then we have a trial that's really
43:48complex and really kind of marvelous.
43:50That's called the GBM agile trial.
43:52In this trial was designed to exist
43:54for a long time at a brain tumor
43:56center like Yale and allow us to
43:58sub installed agile because we're
44:00able to sub in drugs that may be
44:02exciting without having to close
44:03the trial and open a
44:05new trial. And so we have multiple
44:07arms in this trial, so patients can
44:09receive multiple types of therapies.
44:11And also the trial allows
44:13for enrollment of patients in
44:14different phases of their disease.
44:16So there are GBM agile arms where
44:18patients can enroll at diagnosis and
44:21where patients can enroll at recurrence.
44:23So it's complex to describe,
44:26but really an amazing thing
44:28and pretty advanced.
44:29A pretty remarkable advance.
44:30I think in clinical trial design
44:32and it's a privilege to be able to
44:35offer patients the agents that are
44:37being tested in GBM agile and they
44:39will continue to change over time.
44:41We also have a phase three,
44:42double blind placebo controlled
44:44trial where we are adding.
44:46As I said,
44:48we often add adding a experimental agent
44:51called Enza Star in to the street protocol.
44:54So to shift gears now.
44:57So I'm going to talk about meningioma
44:59briefly and then some trials.
45:00We have.
45:01Meningioma meningioma is actually the
45:03most common type of primary brain tumor.
45:06This annual incidence is around 35,000,
45:09which I also think is remarkable and
45:11as doctor Moliterno covered many
45:13patients who have meningioma are
45:15patients who have benign meningiomas,
45:18although I prefer to call them
45:20meningioma dibujo grade one.
45:21This will be labeled them pathologically.
45:24That's about 80%,
45:25and the overall survival of these
45:27tumors is difficult to categorize
45:29and has been reported in different
45:31ways over multiple sources.
45:32But I'm giving you summaries here so
45:35patients who have who Grade 1 tumors.
45:37Certainly live over 10 years
45:38and they may live longer.
45:40Patients often don't even need
45:42surgery with these tumors,
45:43and so we don't actually really know the
45:45true burden of WHO grade one minute GMs.
45:48But about.
45:5018% or about 1/5 of patients have more
45:52aggressive tumors that Doctor Mall
45:54Turner has lots of experience with
45:56called atypical meningiomas Debuchy
45:57grade two and there's variable reports
46:00about how long patients in general
46:02live at this point with these tumors.
46:04But we think about 80 to 100% of
46:06patients remain alive at five years,
46:08which is good.
46:10Unfortunately, WHO grade 3 tumors,
46:12also called in plastic and angiomas I guess.
46:15Fortunately,
46:15they're quite rare.
46:17Approximately 2% or so patients have
46:19these tumors who have meningioma,
46:21but the median overall survival is
46:23much more dramatically lower that
46:25measured in a couple years two to three.
46:28So standard of care with meningioma,
46:30so we have to discuss something
46:32that we don't generally talk about
46:34in gliomas which is presumed
46:36meningioma is a whole category
46:37of patients who have a scan.
46:39I think some of the times they get
46:40very scared they come to see either
46:42in their surgeon neurologist and we
46:43may tell them this tumor may not
46:45cause you difficulty with it looks
46:46to us like it may be a WHO Grade 1
46:50meningioma and we can monitor it.
46:51So we call those presumed meningioma.
46:53They're often asymptomatic,
46:54and imaging surveillance may be appropriate,
46:57but once it becomes.
46:58Medical jobs than they do,
46:59and then I might prefer that
47:01patient to doctor Moliterno.
47:02Then we proceed with maximum
47:04security just the same way,
47:05with glioma and surgery or radiation.
47:09If surgery is not possible or
47:11the options for these presumed
47:13or asymptomatic managements.
47:14And really as I was saying
47:16with with all grades one,
47:17two and three we start otherwise
47:20with maximal surgical resection.
47:21Meningioma,
47:22WHO grade one specifically if it has
47:24recurrent disease we consider radiation
47:27and then we get into controversy.
47:29Which we are having also a
47:31clinical trial at Yale to address.
47:33So the controversy is what to do with
47:35someone who has an atypical meningioma.
47:36W2 grade two that has had a gross total
47:39resection as doctor Moliterno showed.
47:41In a case.
47:42These do recur, but not all the time,
47:45and sometimes we think that
47:46the radiation may not actually
47:48benefit as much as it put causes.
47:50Some patients harm,
47:52so we we then proceed to more specific cases
47:56where there is residual disease on the scan.
47:59After a surgery and for those patients,
48:02we often we do recommend radiation for
48:05patients who have anaplastic meningioma,
48:07or there's even less controversy
48:08for those patients,
48:09resection or otherwise.
48:11We recommend radiation.
48:13So the clinical trials that are
48:15available in Ninja for WHO Grade
48:172 after gross total receptions.
48:19This controversy is addressed
48:21by a phase three trial.
48:23Whether it's randomized patients either
48:25go on surveillance or we proceed with
48:28radiation and we continue to monitor.
48:31For patients who have either WHO grades one,
48:34two, or three,
48:35any of those grades,
48:37if they have a specific target,
48:40they are offered enrollment in what
48:44is a multi arm trial as well that
48:47currently has an AKT inhibitor
48:49that's called Kappa Vasser tip,
48:51where CDK inhibitor that's called
48:54abemaciclib Bemis cycling is actually
48:56currently an approved medication,
48:58so it's interesting to be able
49:00to to offer it in this trial.
49:03So now I'm going to switch
49:05gears and talk about.
49:07One of my true loves which is measuring.
49:11Metabolic disease and also metabolic
49:13processes in primary brain tumors,
49:15and I'd like to talk briefly about
49:17what target you would do or what
49:19metabolic change you would target.
49:21You would measure,
49:22so that is called the Warburg effect.
49:25The Warburg effect is really a
49:28biochemical principle, and really briefly.
49:29When any cell which is this is the,
49:33this is the outside of the
49:34cell in my diagram.
49:34This is the inside of the cell,
49:36cause glucose,
49:36which most people are familiar with.
49:38The each you get glucose,
49:39glucose comes in and becomes a
49:41certain molecule called pyruvate,
49:43and then the body may process it either
49:45through a process called oxidative
49:47phosphorylation through a part of
49:49the cell called the mitochondria,
49:51which is the Semitic cartoon,
49:53and then it may either and.
49:55Then it evolves CO2 which
49:57might be bicarbonate,
49:58because bicarbonate and CO2 exist in water.
50:00Which most of the inside of the cell is.
50:02Alternatively,
50:03pyruvate may become lactate,
50:05but it actually does not
50:07use oxygen in this case,
50:08and that's called lysis.
50:09So the Warburg effect defines the
50:12fact that even in normal oxygen,
50:15a tumor cell or tumor process
50:18favors lactate and glycolysis,
50:20and so that Warburg effect shifts tumor
50:23Physiology in this diagram to the right.
50:26And so to measure this difference
50:28might help us with lots of
50:30insights about how tumors work,
50:32and I have two ways that I've
50:35opened observational studies.
50:36These are not trials,
50:37we're actually just trying to
50:39measure characteristics of the
50:40tumors and not affect anyone's care.
50:42But two ways we might measure
50:44the Warburg effect.
50:45This is called the Warburg index.
50:47We take patients and offer
50:49them a what's called an FDG or
50:52floor deoxy glucose PET scan.
50:54So FDG is a small dose of radioactivity
50:56that also comes via the blood
50:58comes into the cell and it's it's
51:00phosphorylated or phosphorus is
51:02added to FDG and it stays there
51:04and we can actually observe it in
51:06something called the scintillator.
51:08Now the very observant ones would
51:10say that we're only watching
51:11one part of metabolism.
51:13That's right,
51:14so this is actually basically
51:15total glucose metabolism.
51:16This is a rough estimate of
51:18oxidative phosphorylation,
51:19so we use a different technique in
51:21these patients as well, called Mrs.
51:23Petrosky or spectroscopic imaging,
51:25and we can detect the lactate,
51:26and so we have the both sides,
51:28lactate and FDG.
51:29We give us the Warburg index.
51:32This is a clinically available tool
51:34and we're very excited to be able to
51:36offer it to patients who are otherwise.
51:38It's even care or brain tumor center.
51:41And earlier,
51:41but also very exciting and its
51:44development process is called
51:45deuterium metabolic imaging.
51:47Deuterium metabolic imaging.
51:48We use deuterated glucose that
51:50patients can just drink the same
51:51way you drink a soda or Gatorade,
51:53and the glucose comes in and
51:55becomes pyruvate.
51:56It becomes lactate and it becomes
51:59molecules called glutamate and glutamine.
52:01The point is that in a marvelous way,
52:03in this specific MRI scanner,
52:05we can actually see lactate,
52:08and we can see glutamine,
52:09glutamine representing these two.
52:12Processes directly,
52:13and so we can see the Warburg index
52:15shifting to the right and we call
52:17this the Warburg effect once again.
52:19And so here's a great example that
52:21we were able to publish of a patient
52:23of mine who had a brain tumor.
52:25And this is actually an IDH wild type wheel.
52:28Best drama and you can see that they
52:30have a very large forberg effect,
52:32so there's there's lots of
52:34possibilities here about what we
52:36might use this for patients who
52:38have higher warburger effects.
52:39We have a theory that and it
52:41has been shown there.
52:41Tumors are more aggressive and
52:43can we actually walk the way the
52:45Warburg effect might change over
52:46the course of their treatment year,
52:48either in radiation or chemotherapy?
52:50Can we predict whether or not
52:52someone might survive the way
52:54the the patient with the tumor?
52:55That doctor Moliterno showed,
52:57we predict better survival or poorer
53:00survival based on metabolic signatures.
53:03So thank you guys so much for listening.
53:05I want to acknowledge all of my current and
53:09prior lab mates and they have done so well.
53:13Two of them are already in medical
53:15school and also my funding.
53:16I received the Yci scholar word
53:18as well as my collaborators R1,
53:21and this is really a process both
53:23clinical care for brain tumors as well
53:25as clinical research for brain tumors
53:28takes a village and not only doctor
53:30Moliterno and the other neurosurgeons,
53:32not only doctors bearing and Amuro
53:35and Hafler and the other neurologists.
53:38Of course my mentors from before the YCI,
53:40my colleagues at MRC the Pet Center.
53:43And of course, radiation oncology,
53:45including Doctor Mcgibbon.
53:46So thanks so much everyone,
53:49and I will now stop sharing
53:51so that everyone can.
53:52Move forward,
53:53I guess we'll take questions at the end.
53:56Yeah, people can just throw questions
53:58into question and answer or into the chat,
54:01but that was really an excellent talk.
54:02Zach. Thank you so much.
54:04So next I just want to introduce
54:06Doctor Bruce Mcgibbon who
54:08is from Greenwich Hospital.
54:09He is the medical director
54:11there for radiation oncology.
54:13Thank you so much.
54:15Great talk so far.
54:16I'm really pleased to be
54:18invited to give this this talk.
54:21Like Jim was mentioning,
54:22I'm down at the Greenwich site,
54:23previously at the Trumbull site and
54:25it's just really great to be able
54:28to collaborate with our experts
54:30in New Haven and and extend care
54:32down the state to really have
54:34a broader outreach to to what
54:36we can help patients with with
54:38this type of collaborative care.
54:40Let me share my screen here.
54:46OK.
54:51No.
54:56Go back OK, so I'll be talking about the
54:58role of radiation therapy in the treatment
55:01of brain tumors and with a particular
55:03focus on glioblastoma and meningioma,
55:05I have no disclosures.
55:09So where does radiation therapy fit in?
55:11Uh, you've heard about it a little
55:14bit this evening, but just briefly.
55:16I would say for benign tumors,
55:19sometimes radiation is given
55:20in place of surgery.
55:22If it's something quite small and
55:24and really doesn't require surgery,
55:25but more often given sometimes
55:27as postoperative treatment
55:28if the tumor is left behind,
55:30or were some extra worried that it will
55:34progress and then for malignant tumors.
55:37That, like, uh,
55:38we talk about glioblastoma and
55:39the anaplastic tumors, and so on.
55:41That doctor Cogan was doing such
55:43a nice job of going through.
55:45Sometimes we'll offer radiation
55:46when there's only been a biopsy,
55:48but more commonly as we heard a lot about.
55:51We really love when a maximum safe
55:53for section that can be done and
55:55and the outcomes are so much better.
55:57And, you know,
55:58we really are hand in glove with all
56:01the other experts from neurology,
56:03you know,
56:04surgery and the other folks
56:05being mentioned on this on this.
56:07Talk series.
56:09The radiation most of the treatments are
56:12done in what's called a linear accelerator,
56:15which is what you see in the top left
56:17corner here, and that is the cursor.
56:19So the patient would lie on
56:21the table like this.
56:23Kind of zooming in.
56:24There's usually a mask that's done
56:25to help hold people.
56:26Still,
56:26it's not painful in any way you
56:28can see and breathe through it,
56:30but it helps to hold the head still.
56:31So when we're delivering radiation with,
56:34you know millimeter something,
56:35submillimeter accuracy,
56:36we're really delivering
56:37exactly where we want,
56:38and not a little to one side or the other.
56:41The radiation comes out of
56:42the head of the machine here,
56:44and this this portion of machine can
56:47rotate around so we can come at the
56:50at the tumor from different angles.
56:52In the head of the Machine is a really
56:55nifty device called a multi leaf
56:57collimator which is represented here.
56:59Each is ignacy, their own like little slats,
57:02and these are very thin leaves.
57:03They're very tall,
57:05but they're made of a tungsten alloy,
57:08which is a really heavy metal.
57:09And when patients often ask,
57:11you know when I go to the dentist.
57:12I I have a lead apron,
57:14what do I get here and say,
57:15well,
57:15the lead apron is not going to
57:16cut it for therapeutic radiation
57:17or go straight through it,
57:19but if you have a the equivalent
57:20of lead apron which is several.
57:22Inches thick in the head of the gene.
57:24That's what's really giving the
57:26protection and doing the shaping
57:28of the radiation.
57:29We also have something that's
57:31been developed over the last.
57:34I'd say 10 to 15 years and was
57:35really hitting its stride now called
57:37image guided radiation therapy.
57:39So we do some planning scans
57:41before radiation,
57:42including a CAT scan and overlay
57:44that as I'll show later and talk
57:46with MRI studies and other studies
57:48will help us to show where we want
57:50to treat what we want to avoid,
57:52and then when the patients come
57:53for these daily treatments so
57:55we can do imaging on the table.
57:56So if you look here on the right,
57:57the head of the machine here again
57:59is where the ration comes out.
58:00But these panels on the sides can do imaging,
58:03so we can look in the head and say OK,
58:04how does the skull align today
58:07compared to yesterday compared to
58:08when we did the planning scan and
58:10so these images in the in the left
58:12in the middle are representing
58:14really a fusion or overlay between
58:16a daily scan and a planning scan.
58:21Just give one example here of a
58:24glioblastoma this the patient presented
58:26with headaches and some difficulties
58:27with concentrating and the image showed
58:30this large tumor on the left side.
58:35I'll just go briefly through this.
58:37It's already been discussed.
58:38Very nice doctor Corbin, but you know,
58:39for glioblastoma we're always looking
58:40for that maximum safe resection.
58:42We usually allow about 3:00 to 5:00 or
58:44up to three to six weeks between surgery
58:47and when we start the chemotherapy and
58:50radiation and then to be followed by more
58:53chemo and sometimes the Optune device.
58:55When we're making decision about
58:57what style of radiation uh, to use,
58:59uh, we're looking at the the age,
59:02the overall performance status,
59:04other features like MGMT that was
59:06mentioned a little bit before we're
59:07looking to see if there any clinical
59:10trials that are available to really try
59:12to advance the field in that way as well,
59:13and give patients you know the
59:15best that's possible.
59:16So we put all the together and see
59:18which style reason we're going to do.
59:19I would say the majority of the
59:21time will use that stoop protocol
59:23with 30 treatments that actually.
59:25These are done Monday to Friday,
59:27so it's a six week course.
59:29It actually has two phases.
59:30The 1st 23 treatments in the final seven
59:32were the 1st 23 a little bit broader and
59:34the final seven are a little bit smaller.
59:36They called it a come down idea and that's
59:39the most the most common one by far.
59:42But we have what's called hypofractionated
59:46treatments and those could be offered
59:48in someone who is elderly and and
59:51has some other performance issues
59:53or there's a travel concern or.
59:56You know things of that nature.
59:57We're trying to to be creative,
59:59and how we're going to deliver
01:00:00the treatment and and you know
01:00:03balance side effects with with
01:00:05treatment intensity and intent.
01:00:07So in the hyperfractionated realm,
01:00:08the one that we use the most
01:00:10is a 15 treatment course.
01:00:12But we have actually data for
01:00:15five and and 10 treatments.
01:00:17Usually for going all the way down to five.
01:00:19Those are pretty intensive,
01:00:20so that's usually somewhere
01:00:21we're not doing a chemotherapy.
01:00:23And I would say probably the same
01:00:24with the 10, but 15 can be done.
01:00:26Throughout chemo
01:00:30so going back to to the case,
01:00:31we have the square button where
01:00:33now things have been removed.
01:00:35We get a postoperative MRI to assess
01:00:38what that looks like now and and
01:00:40then we get into the planning phase.
01:00:42So what we'll do is we'll take
01:00:46where things were before surgery,
01:00:47where they are after surgery and do
01:00:50some drawings which are represented
01:00:51by this kind of teal color,
01:00:53cyan color and the purplish pink color,
01:00:56and we're trying to to really dial in.
01:00:59What we need to treat and this could involve,
01:01:01uh, you know,
01:01:02collaboration with the surgeon as well.
01:01:04If we're not sure about you know an
01:01:06area talking to the radiologists
01:01:07we're really dialing in what?
01:01:09What's at risk here and creating
01:01:11a margin around that to account
01:01:13for any microscopic extension
01:01:15that could have happened?
01:01:16There's a very intensive design process
01:01:19where we work with our physics crew,
01:01:21typically between the time that we got
01:01:23our planning caps going to make that mask,
01:01:24and when we start treatments about one week,
01:01:27sometimes up to a week and a
01:01:28half and some more complicated.
01:01:29Days and these images on the left are
01:01:32representing kind of vaguely make
01:01:35out that there's also a person's
01:01:37head that's represented in this
01:01:39treatment planning software.
01:01:40And then again that this kind of
01:01:42pink and bluish colors are present.
01:01:43We're trying to treat and usually
01:01:45these things are done in arcs,
01:01:47so this picture on on the bottom is
01:01:49trying to represent how the machine
01:01:51is going to move around the head.
01:01:52So at each we can play with different things.
01:01:55We can move the angle of the table to
01:01:57create a different angle of attack.
01:01:58We can.
01:01:59Move the gantry or the head of the
01:02:01machine around and at every position.
01:02:03We can vary the intensity of the
01:02:04beam and the shape of the beam,
01:02:06and ultimately that allows us to create
01:02:08what we call a dose distribution,
01:02:10which is seeing here where we are
01:02:12trying to conform the the higher
01:02:14dose region of the radiation to
01:02:16what we're trying to treat and then
01:02:18have it drop off away.
01:02:19So in this case on the right we're trying to.
01:02:23These images are done as if you're
01:02:24looking at someone from their
01:02:25feet towards their head,
01:02:26so this this kind of right side of the
01:02:28image is actually the left side of the body.
01:02:30And vice versa.
01:02:31So in this case we're really
01:02:32trying to avoid radiation dose,
01:02:34especially going to the right
01:02:36side of the brain.
01:02:38We go through an intensive process
01:02:40where we when we design the fields,
01:02:41we get this complicated graph called
01:02:44a dose volume histogram where every
01:02:46color here represents a different
01:02:48structure that we're trying to
01:02:50either treat or avoid,
01:02:51and so there's this iterative process
01:02:53with the physics crews saying OK,
01:02:54this plan was good or no.
01:02:56We need to.
01:02:56We need to shape the doses a little
01:02:58bit more to stay off the brain stem.
01:02:59We're off the copay or whatever it might be.
01:03:01So we're we look at these and
01:03:04and ultimately sign off on one
01:03:06that looks like the best balance.
01:03:08I'm moving to meningioma is an answer
01:03:10for real great statement from the the
01:03:13National Comprehensive Cancer Network
01:03:14saying just really hear treatment
01:03:16selection should be based on assessment
01:03:18of a variety of interrelated factors,
01:03:20including patient features,
01:03:21tumor features,
01:03:22potential for causing their logic,
01:03:24consequences of untreated presence
01:03:26and severity of symptoms and
01:03:28treatment related factors,
01:03:29and I'll skip the bond multidisciplinary
01:03:31input for treatment planning is recommended
01:03:33and this is where I feel so blessed to be.
01:03:35You know, part of this yellow
01:03:37network is really having these.
01:03:38Super skilled trusted colleagues where
01:03:40we have these weekly conferences and
01:03:43we can call each other anytime and get
01:03:45advice on a case or have someone seen
01:03:47and it's just really critical to have that.
01:03:51And it's nice to see it
01:03:53represented as as the you know,
01:03:55the goal according to national
01:03:57guidelines as well.
01:03:58So meningiomas again touched on
01:03:59a lot better detail and more
01:04:01thorough detail of Doctor Corbin,
01:04:02but just it's kind of a very quick overview.
01:04:06Again, sometimes we can do just observation.
01:04:08If these are small grade one tumors,
01:04:11but the game more advanced than
01:04:13we typically would do surgery.
01:04:15And if it's a grade one,
01:04:16it's usually just observation
01:04:17or sometimes radiation.
01:04:19If there is a further issue that we
01:04:21should be considering grade two, we,
01:04:23let's say most often do radiation,
01:04:25especially if there is a little
01:04:27tumor left behind and for grade
01:04:28through we definitely.
01:04:29Offer radiation radiation.
01:04:31This case is a little
01:04:33shorter than glioblastoma,
01:04:35it's it can be up to 30 treatments
01:04:37like wheel, bustamonte,
01:04:38sometimes a little less,
01:04:39but the dose per day is a little bit lower.
01:04:42And it's usually done as Monday
01:04:44to Friday course sometimes,
01:04:46especially if it's being done for a
01:04:49very small tumor and it's lower grade.
01:04:50We can do what's called
01:04:52stereotactic radiosurgery,
01:04:53where it's only one treatment
01:04:54or up to five treatments.
01:04:56But I'd say a lot of what we do is
01:04:58the is the multi treatment option
01:05:00and again I think that that just a
01:05:02short presentation case presentation
01:05:03is really helpful.
01:05:04So this was a patient who presented
01:05:07with Double Vision followed by
01:05:09a right I decreased vision and.
01:05:11You can see in the sand with the
01:05:13red arrow there's something that
01:05:15really doesn't belong there,
01:05:17and if you track if you look here,
01:05:18here's the eyeball and you see
01:05:19this darker Gray coming back.
01:05:21That's the optic nerve bringing
01:05:23the visual information coming back.
01:05:25So this tumor is really not only near
01:05:27some really important blood vessels,
01:05:29but is also near the Super important nerve.
01:05:32So what? What to do?
01:05:35Radiation alone is really not
01:05:37gonna be her best option.
01:05:39Uh,
01:05:40radiation is excellent.
01:05:41I'd say it's stopping millenniums
01:05:43from growing further and can
01:05:45make them slowly rest at least
01:05:47sometimes give enough time,
01:05:49but it's really not going
01:05:51to create a rapid shrinkage.
01:05:52It's not what we want someone's having
01:05:54these kind of symptoms like double vision,
01:05:55things we need. We need something.
01:05:59More quickly effective,
01:06:00and that's really comes down to surgery,
01:06:02so this late underwent a right sided
01:06:05craniotomy with Doctor Moliterno.
01:06:08And because of that location there next
01:06:10it was called the cavernous science or
01:06:12some of the special blood vessels are.
01:06:14It's really not possible to fully remove
01:06:16the tumor, but a lot of it was removed.
01:06:18It turned out to be a WHO grade one
01:06:20and she had a great great response.
01:06:23Revision came back to 2020 and had,
01:06:26I would say,
01:06:27a near resolution of the double vision.
01:06:29But ultimately fully resolved, so we
01:06:32got a postoperative MRI and as expected,
01:06:35there was a little bit of of residual,
01:06:37but much, much better as reflected
01:06:39by her symptoms as well.
01:06:40So you see the post op.
01:06:42Sorry pre op on the left
01:06:43and postop on the right.
01:06:45And of course we don't want this growing
01:06:48back and so we offered radiation.
01:06:50Similar idea in terms of the mask and so on.
01:06:52Using arcs again here working
01:06:54with the physics crew to design
01:06:57A set of radiation fields.
01:06:59If you look behind here,
01:07:00this is where the brain stem is,
01:07:02so we're trying to stay off
01:07:03that and off the eyeball,
01:07:04so we're able to create this really.
01:07:06As you say,
01:07:07conformal radiation technique and the
01:07:10combination of the surgery and then
01:07:13the radiation was able to rib really
01:07:16permanently control this tiller.
01:07:20Just a quick also shout out to to my
01:07:22colleagues and and doctor Bindra here
01:07:24just to just to further emphasize what
01:07:26Dr Milton and Doctor Corbin off said.
01:07:28You know,
01:07:29there's there's really great and and
01:07:31super detailed work that's going on with
01:07:33all these different mutations and you know,
01:07:35adults and the kids,
01:07:36and there's just a lot of work
01:07:38to be done and it's just really,
01:07:40really impressive.
01:07:40This is one one trial here,
01:07:43working on with the million gliomas and
01:07:46the Doctor Bindra had shared with me just.
01:07:49Look through and then another one
01:07:51looking at adolescence and young
01:07:53adults and other tricky glioma case
01:07:55where there's more work to be done and
01:07:58really great collaborations happening.
01:08:01Thank you very much.
01:08:02I'll be happy to answer any questions later.
01:08:07That was really an outstanding talk.
01:08:09Thank you Bruce,
01:08:11and there was already one question.
01:08:14If we want to take an hour later,
01:08:15but it was about how cyber
01:08:18knife radiation fits in,
01:08:19and I think that was with regards to glioma.
01:08:21So you can start thinking about that answer.
01:08:25You know well and then also what
01:08:27actually is the radiation as
01:08:29compared to an X ray or dental X-ray?
01:08:32So that's another radiation
01:08:34question coming your way.
01:08:36So we will conclude with Brian Jin
01:08:39who's the licensed social worker who
01:08:42leads our brain tumor support group.
01:08:44Along with our team Jillian Bongard,
01:08:48who's on as well and he's going to talk
01:08:51about probably even more important than
01:08:54surgery or radiation or chemotherapy.
01:08:57But how we can support our
01:08:59patients and their families?
01:09:02Hello hello everyone,
01:09:04thank you for that introduction.
01:09:06I have the privilege of facilitating
01:09:08the brain tumor support group with
01:09:10Jillian and they have taught me a
01:09:12lot and I think about them a lot
01:09:14as I'm doing this presentation,
01:09:15so I'll go ahead and bring up my funds.
01:09:31So I'm Brian Jean.
01:09:32I'm one of the clinical social
01:09:35workers at Smilow Trumbull.
01:09:37I work with primarily Dr and I
01:09:41have the privilege of facilitating
01:09:42the support group so my my role is
01:09:45primarily supporting patients and
01:09:47family both emotionally and also
01:09:49helping them navigate the system,
01:09:51find resources within the Community,
01:09:53and it looks different for everybody.
01:09:56So it really depends on what
01:09:59families and individuals bring
01:10:01to the table prior to diagnosis.
01:10:04Every family system is extremely complex.
01:10:07They bring different compositions.
01:10:09They have different rules,
01:10:10different stages of life,
01:10:12they have different.
01:10:13Previously existing diagnosis
01:10:15that might impact how they respond
01:10:18to maladaptive behaviors that
01:10:19help them cope at one point,
01:10:22but not that I don't know.
01:10:27Identify the work work and
01:10:30where we can have. So it's.
01:10:35The framework that helps me helps
01:10:38me navigate and support people,
01:10:41and also I'll go through some of
01:10:43the primary challenges that people
01:10:44experience with the brain tumor,
01:10:46and then I will go into ways
01:10:48that smilo and the community
01:10:50supports patients and families.
01:10:55So one of the frameworks I use to help me
01:10:57sort of identify and navigate and identify
01:11:00the work is by Doctor Wallin's family,
01:11:03system illness model and how it's useful.
01:11:06Is it? It really takes the
01:11:07whole family into account.
01:11:08It really spends time looking at the system
01:11:12and incorporating the medical team within it,
01:11:14looking at the various ways that
01:11:17families interact and support each other,
01:11:19what strengths they have,
01:11:21whether they bring culturally.
01:11:22It's a very broad and very fluid model.
01:11:25To use and then it breaks down the work,
01:11:28both the emotional aspects and dimensions.
01:11:31The concrete basic needs
01:11:33that need to be addressed.
01:11:34And also you know how these
01:11:39interplays work with each other,
01:11:41and then it takes it within
01:11:44each freight phase of time.
01:11:46What initially we experienced
01:11:48during that first diagnosis period,
01:11:50what it looks like when we become stable
01:11:52and we found a period of equilibrium.
01:11:55And then anytime we experience.
01:11:58I need to change.
01:11:59I need to adapt to a new
01:12:02struggle or limitation.
01:12:03So this is one of the ways it is
01:12:07extremely useful for supporting families.
01:12:10So the crisis phase.
01:12:12This is the most difficult time this
01:12:14is like being shot out of a cannon.
01:12:17Oftentimes I've sat and heard the
01:12:19stories of being diagnosed and being
01:12:21in the car and suddenly having a
01:12:23seizure and then waking up post
01:12:25surgery and how they adapt to that.
01:12:27How do they absorb that information
01:12:29that's coming at them?
01:12:30How their family is responding to suddenly?
01:12:32Maybe the primary bed breadwinner
01:12:34not being able to work.
01:12:36What do you do at that time?
01:12:37There's so many questions.
01:12:38There's so many unknowns.
01:12:40And fears that are arising at that time.
01:12:43One of the things that is a challenge
01:12:45is that they have to absorb this
01:12:47new information about the diagnosis
01:12:49that they would never assumed
01:12:51they would encounter.
01:12:52They have to understand medically,
01:12:54they have to understand how it's impacting
01:12:56their whole family system emotionally.
01:12:58They have to understand it in the
01:13:00short term and then the long term.
01:13:01What is my plan?
01:13:02What is what is my treatment
01:13:04options and that what is one of
01:13:06the things that helps people cope?
01:13:08Having a really grounded and supportive plan?
01:13:10Being connected to a medical providers
01:13:13that can guide them through so.
01:13:16These challenges as they arise,
01:13:20they take a lot out of the family,
01:13:22they they they they engender
01:13:24a lot of uncertainty,
01:13:26and one of the roles that I have
01:13:28to support people with and is
01:13:31identifying their strengths,
01:13:32identifying their sense of faith,
01:13:34what narratives they're using,
01:13:36their family resiliency,
01:13:37legacies that they have within themselves
01:13:40that have helped them through adversity.
01:13:43And we're looking for a stabilization.
01:13:44We're looking for a place for the difficult.
01:13:47Emotions a place for identifying
01:13:48what they feel at the moment,
01:13:51whether it be anxiety or feeling
01:13:53overwhelmed or shocked and then
01:13:55gradually lessening those giving
01:13:57those a chance to sort of dissolve
01:13:59and have their moment,
01:14:00but then move towards the positive side.
01:14:03And what is their course of action?
01:14:08One of the big emotional things that
01:14:10tends to come up that I see and oftentimes
01:14:13isn't always identified as grief.
01:14:15One a lot of times families are in the
01:14:17state of shock and they've lost something.
01:14:19They've even lost the ability to
01:14:21look at life as this is stable.
01:14:23This is known. This is safe.
01:14:25I've had a family member say I'm
01:14:26angry just looking at that family.
01:14:28Going to the diner because
01:14:30their life is so Monday.
01:14:31It's so normal and now we're suddenly
01:14:34thrown into a state of shock,
01:14:36and these are the really the
01:14:37challenges of the initial.
01:14:38Phase is recalibrated,
01:14:39finding order finding mastery,
01:14:42finding competency and trusting
01:14:43in their plan and collaborating
01:14:45with their medical providers.
01:14:49The next phase is.
01:14:50Titled the chronic phase and this is
01:14:53the the Phase I wish the support group
01:14:55could be here to to share because
01:14:58they're they're the they're the.
01:15:00They're the ones who should give the the
01:15:02master lesson and it's a difficult phase.
01:15:04It's it has its own unique challenges.
01:15:06One of the ones that universally
01:15:08here is living with uncertainty and
01:15:10any person who has had to go through
01:15:12a scan and wait for the results
01:15:14and knows what that feels like.
01:15:16It holds all the hopes.
01:15:18All the fears at the same time.
01:15:20And this is a really.
01:15:22Difficult thing to manage.
01:15:23It produces a lawn being anxiety,
01:15:25a lot of worry.
01:15:26I know a lot of questions
01:15:28that arise from that,
01:15:29and the tendency is to projectors the future,
01:15:32sometimes catastrophize and so
01:15:34it can be a very challenging.
01:15:38Emotional process to address,
01:15:39but it's something that's going to
01:15:41be universally have to be managed,
01:15:43and you know the support group is one
01:15:45of the the ways that we manage it.
01:15:47You get.
01:15:48Everybody coming together
01:15:49to share how they cope,
01:15:51everyone sharing the ways they managed it,
01:15:54and a lot of it is really for me.
01:15:56This is about being present,
01:15:58being present in the moment,
01:15:59connecting with what is good.
01:16:01Connecting with makes you you happy.
01:16:04You know that relationship
01:16:05with the providers you know,
01:16:07that's that's also there.
01:16:08You know sometimes you're going
01:16:10through all these treatments.
01:16:11And and I've had patients say I want to.
01:16:14I want a week off so I can go
01:16:16to a wedding or a graduation.
01:16:17And this is part of that.
01:16:19Responsibility and where the report comes,
01:16:23comes becomes so important and and and
01:16:26another part that my support group.
01:16:29Shared with me and is knowing your new
01:16:31limitations and how do you transcend them?
01:16:33What do you have to be sensitive to?
01:16:35What can you do?
01:16:36What can you have to modify and
01:16:38finding that New Balance in life?
01:16:40Which is is is a lot of work.
01:16:43And in the final phase is transitions anytime
01:16:46we have to find a new way of adapting.
01:16:48If we're meeting a new struggle,
01:16:50a new challenge,
01:16:51that's the stage of change,
01:16:54and that requires recalibration.
01:16:56Again, maybe not as shocking.
01:16:58Sometimes it is,
01:16:59but there's different work to be done.
01:17:02Sometimes this phase really hones in.
01:17:06What is our priorities?
01:17:07What is the most important
01:17:09thing for us to do?
01:17:10And it has its own special nuance.
01:17:14So from there,
01:17:16using this framework you know
01:17:18there's different things to address.
01:17:20Sometimes in that beginning it's a question
01:17:22of how do I meet the world doesn't stop,
01:17:25and unfortunately we have
01:17:26to pay bills we have to do,
01:17:29bring the kids to school.
01:17:30It depends on everybody's stage
01:17:31of life and where they are and
01:17:33who they're responsible for.
01:17:34And so one of the questions I
01:17:36often get is like how do I?
01:17:38How do I find the balance
01:17:39of making ends meet
01:17:41and prioritizing my health,
01:17:42which is now my job?
01:17:44Questions about disability,
01:17:45whether or not you have short
01:17:47or long term disability.
01:17:49Applying for Social Security disability,
01:17:51nobody gives us these this information
01:17:53out in school or college or anywhere,
01:17:56so these are one of the things you can access
01:17:57through your team through your social worker.
01:17:59You can ask your team if you
01:18:01need assistance and help.
01:18:02There are resources out in the community,
01:18:04including the Connecticut
01:18:06Bureau of Rehabilitation,
01:18:07which you know will help people reengage in
01:18:10a new profession or work with accommodations.
01:18:13Your team can also be a source of.
01:18:16Referrals to occupational health
01:18:19things that get you back on your feet.
01:18:22You're making you operate
01:18:24a little bit better.
01:18:25One of the big things for me is maintaining
01:18:28health insurance because anytime we
01:18:30have a shift from disability from employment,
01:18:32there's concerns about making
01:18:35maintaining health insurance.
01:18:37There are Cobra,
01:18:38there is Medicaid.
01:18:40There's the access health CT
01:18:42marketplace that's there.
01:18:44Sometimes people are
01:18:45transitioning to Medicare,
01:18:47and which you can reach the choices program.
01:18:49These are all very vital questions
01:18:51for a lot of people who are are are
01:18:53going through this process is how do
01:18:55I take care of my family and myself,
01:18:57both financially and health wise.
01:19:01Emotional challenges well for
01:19:03for brain tumors.
01:19:04It it's been impressed upon me.
01:19:08Just how much it is your identity.
01:19:11This is who you are.
01:19:11This is your signature.
01:19:12You may be losing.
01:19:14This might be your ability to drive,
01:19:16it might be tied to your passion and
01:19:18I think anytime I've worked with
01:19:20individuals who have had a brain tumor,
01:19:23there's been sometimes losses.
01:19:24And there's also been that work to connect
01:19:26to what it makes them feel good about life.
01:19:29What makes them feel passionate and resonate?
01:19:32And and this is something that our our
01:19:34support group talks about in terms of.
01:19:36How do you connect to gardening
01:19:38even if you have a little bit of
01:19:40limitations in terms of balance,
01:19:42you'll find a way and that work is is.
01:19:45Is there the two emotional
01:19:47processes that I typically see.
01:19:49I tend to focus on on very natural
01:19:53emotional processes that this can be
01:19:55a a traumatic event which triggers our
01:19:58fight or flight survival mechanism.
01:20:00A lot of times I see people in the crisis
01:20:02stage where they're I'm hypervigilant
01:20:04other than difficulty sleeping.
01:20:06I'm a little bit more irritable and
01:20:08I'm picking fights with my loved ones,
01:20:09which is home normal because the
01:20:11fact that you're in fight or flight,
01:20:13you're primed for it.
01:20:14Things are a little bit more difficult.
01:20:17The problem is when it becomes
01:20:18cyclical and it taps into anxiety
01:20:20and becomes a habitual process.
01:20:22Then we need to find a way to sort
01:20:24of address it and find ways to sort
01:20:25of pull you out of fight or flight.
01:20:27That could be meditation.
01:20:29It could be yoga and there'll be
01:20:31other resources I'll talk about at
01:20:32the end that you can connect to.
01:20:34The other part is the Greek process and.
01:20:36I always I'm a broken record with
01:20:39this one because anytime any person
01:20:41hits a limitation they suffer a brief
01:20:44process and so this is something we
01:20:46can't take a pill for. We can't avoid.
01:20:48It's really about feeling it and
01:20:50then doing good self care,
01:20:52not getting stuck in it.
01:20:53And so I really spent a lot of
01:20:55time with individuals.
01:20:58Talking about where is your safe
01:20:59place to feel these emotions?
01:21:00Who do you have to talk to about this?
01:21:02And a lot of times it's our
01:21:04spiritual practice because it sort
01:21:05of addresses it existentially.
01:21:09So this might seem strange.
01:21:11The Unsought yes of brain tumor.
01:21:15I I've been it's been remarkable how
01:21:17many people who have gone through
01:21:19such trials and hardships and loss.
01:21:22Say they wouldn't change a thing and and
01:21:24that's just an amazing thing to hear,
01:21:26because what they've gained
01:21:28from this experience,
01:21:28their gratitude, their appreciation,
01:21:30their recognition of what is most
01:21:32important in their life is irreplaceable.
01:21:35And it's not anything that can be replicated.
01:21:38And you know,
01:21:38that's it really taps into why we
01:21:41fight and what makes us happy.
01:21:42And it makes us more authentically ourselves.
01:21:45Some people have shared,
01:21:46like I wasn't happy before and
01:21:48now I'm spending my time baking
01:21:50bread and doing photography.
01:21:52And and this is one of the things
01:21:53that comes from this experience.
01:21:55It's like altering and part of the
01:21:57work that we do is making sure that
01:21:59people access what makes the map.
01:22:01What gives them purpose.
01:22:02And you know when we hit limitations,
01:22:04how do we transcend?
01:22:09But just a note for the caregivers,
01:22:11because there's a profound feeling
01:22:13of healthiness helplessness,
01:22:14being a caregiver,
01:22:15I like to tell them they're always doing.
01:22:17They're doing a great job.
01:22:18They're just being there.
01:22:19Being attentive, being attuned.
01:22:21It's it's. It's,
01:22:22they're doing enough and then self care,
01:22:25just in terms of putting 2 moral
01:22:28virtues together, you can never win,
01:22:30so it's really vital for both patient
01:22:33and family to spend time being soulful
01:22:36and taking care of themselves.
01:22:38So resources that we do have,
01:22:41we have the brain tumor support group.
01:22:43It's every third Monday,
01:22:44three to four by Zoom.
01:22:46You can reach out to me.
01:22:48I can add you to the the list service.
01:22:50We also have a caregiver support group
01:22:52that is the 1st and 3rd of every Thursday.
01:22:55It's in the evening to make it
01:22:56a little bit more accessible.
01:22:58Also by zoom, we have the meeting
01:23:01centered psychotherapy group,
01:23:02which is really,
01:23:03how do you tap into the
01:23:05meeting and through adversity?
01:23:07We also have a cognitive behavioral skills.
01:23:09Super Cancer Survivor is run
01:23:11by Doctor Kilkis.
01:23:12I put her email up there so if
01:23:13you'd like and you're interested,
01:23:15you can email her for the next session.
01:23:18Additional resources. We have nutrition.
01:23:20Any way to help you guys.
01:23:21Holistically take care of yourself.
01:23:23Support yourselves,
01:23:23stronger as much as you can.
01:23:26We have yoga guided imagery,
01:23:28meditation, a lot of this is by zoom.
01:23:30Unfortunately now we do have
01:23:32art therapy classes.
01:23:34We also have parenting at a challenging time.
01:23:36As specifically for parents
01:23:38with younger children.
01:23:39You want guidance and ask what to
01:23:42ask questions about communication,
01:23:44developmental stages,
01:23:45and how to share with their
01:23:47kids what they're going to.
01:23:48There's also palliative care,
01:23:50which is a very comprehensive
01:23:53team comprising psychiatry,
01:23:55psychology, chaplain, social worker,
01:23:58nurse, art therapy,
01:23:59the whole gamut and they can
01:24:01be very supportive and helpful.
01:24:05Community resources the
01:24:07Connecticut brain tumor alliance.
01:24:09They provide education and peer support.
01:24:11You can give them a call and you can
01:24:13just speak to somebody who truly
01:24:15understands what you're going through,
01:24:16and we'll help you through for cancer.
01:24:19There is ants place cancer care.
01:24:21It's kids, hugs for families with children.
01:24:25There's an American Cancer Society
01:24:27which has a lot of educational
01:24:29information and also some supports in
01:24:31terms of staying like if you needed
01:24:34to stay and receive radiation and.
01:24:36This isn't your local you could.
01:24:37You could access some of the
01:24:40resources there's family reach for a
01:24:42cancer patients which provides free
01:24:45financial planning within an advisor.
01:24:47There's the LIVESTRONG program,
01:24:49which is allows people to go to YMCA's
01:24:52for a tailored physical exercise
01:24:56routine to help strengthen their body.
01:24:59There's cancer in careers and triage cancers,
01:25:01which it really helps people navigate.
01:25:04Rejoining the workforce with their
01:25:06cancer diagnosis and it gives
01:25:08a lot of excellent resources.
01:25:09There's financial grants for cancer patients.
01:25:12There's cancer,
01:25:13Connecticut Cancer Foundation and the
01:25:15cancer cares for brain tumor specific.
01:25:18There's a lovemark foundation and also
01:25:20the Connecticut brain tumor alliance.
01:25:25And just a closing note on for me.
01:25:27You know. Occasionally people do require
01:25:30additional assistance, and for the
01:25:32younger patients I've been seeing,
01:25:34that's the personal care waiver program.
01:25:37The one thing that I've noticed is
01:25:38the wait list is four to five years,
01:25:40so if you ever have an opportunity
01:25:42to call your state representative,
01:25:44please do and say that's really unacceptable.
01:25:47For older individuals,
01:25:4865 years and older there is the Connecticut
01:25:51Home Care program and this is long term.
01:25:55There assistance at home
01:25:56which is sometimes needed,
01:25:58so these are these are the resources
01:26:00are available if you have any
01:26:02concerns reach out to your team.
01:26:03They will guide you to somebody that can
01:26:06help support you in any of these areas.
01:26:08I just want to thank everyone for the
01:26:11opportunity and just some references
01:26:12and I had known disclosures.
01:26:14Thank you guys.
01:26:18Thank you Brian. It's always such a
01:26:21beautiful talk and to hear you speak so
01:26:23passionately about it and thank you again
01:26:25to you and to Julian for the support
01:26:27Group One question are our support
01:26:29groups open to all patients or only
01:26:32those being treated at your institution?
01:26:34Absolutely open to all patients
01:26:36and so the more the better.
01:26:39And Brian, I don't know if you want
01:26:41to put your contact in the chat
01:26:43or do you want to put my contact
01:26:45in the chat or whichever but.
01:26:47Please reach out to us and and
01:26:50everybody is welcome to come to the
01:26:52support group and it's virtual,
01:26:54which makes it really easily accessible.
01:26:57All right, Bruce.
01:26:58Back to you for those two tough questions.
01:27:00So how does cyber knife radiation fit in
01:27:03and what actually is the radiation as
01:27:05compared to an X ray or dental X ray?
01:27:09Alright thanks yeah, great question.
01:27:10So cyber knife is really just the
01:27:13name like a brand name of one of the
01:27:16machines that does that stereotactic
01:27:19technique which is 1 to 5 treatments.
01:27:22There's quite a bit of
01:27:24advertising around that machine,
01:27:25especially in Connecticut.
01:27:28With something good,
01:27:29something I think a little misleading
01:27:31and and things are kind of implying,
01:27:33but it's a.
01:27:34It's a very nice machine and
01:27:36does a great job.
01:27:36There are other machines that are equally
01:27:39as good and are actually more flexible,
01:27:41so for example that stood protocol
01:27:42with six weeks of radiation that's
01:27:44not possible with the cyber knife
01:27:45that can only do the short treatment,
01:27:47so it's a great tool in certain
01:27:51programs and you know we used to
01:27:54have one in our system up in the.
01:27:58Through the same refills group that joined,
01:28:00but ultimately we decided that we
01:28:02like the the machines that are more
01:28:04flexible that can do the stereotactic
01:28:06and can do other treatments
01:28:07and focus more more on those.
01:28:09So a good machine, but with some limitations.
01:28:11I think
01:28:12I mean gamma radiosurgery
01:28:13essentially is is the same.
01:28:15It's just stereotactic radiosurgery.
01:28:17Maybe one thing if you could mention,
01:28:20I'm not sure if this is
01:28:21what the person was asking,
01:28:22but I think a good question that that
01:28:25I always get all the time is why.
01:28:28Why do you use?
01:28:29Why can't you use radio surgery for GBM?
01:28:31Whether it's cyber knife or gamma knife,
01:28:33why do you have to use? So
01:28:36yeah, that's a good question.
01:28:37So yeah, the gamma knife,
01:28:39which we do have it at Yale wonderful
01:28:42program with Doctor Veronica Chang
01:28:43Neurosurgery and then others helping
01:28:45out from radiation college and so on.
01:28:47But that machine uses radioactive
01:28:50cobalt sources to all focus in.
01:28:54It's really best at doing the
01:28:56single fraction treatments.
01:28:58The latest iteration can do
01:28:59two and three treatments,
01:29:00but it's probably it's best with
01:29:02the with the one treatment,
01:29:03and we especially use it
01:29:05for brain metastases.
01:29:06We have other machines like machine
01:29:08is showing the being of the talk.
01:29:09Those linear accelerators
01:29:10that can also do it but are.
01:29:11Let's say that's our number
01:29:13one machine for it.
01:29:14You know what's interesting about tumors
01:29:16is that radiation is is remarkably
01:29:18effective at a lot of different tumors,
01:29:21but it has its limitation.
01:29:23There's sometimes there's just not
01:29:24enough dose that we can get to,
01:29:25and sometimes we've we study what are called.
01:29:28Those escalation trials where we
01:29:29try to go higher and higher with
01:29:32this more sophisticated machinery.
01:29:34And sometimes you find that you know
01:29:35what it just doesn't work better.
01:29:37It there isn't as good as or no
01:29:39better than the lower treatment,
01:29:41or in fact it can be worse sometimes
01:29:43because we have more side effects
01:29:45and we're still not controlling
01:29:46the tumor any better.
01:29:48And so for glioblastoma in particular,
01:29:50I think in the earlier days of gaming and
01:29:52some of the machines people were saying,
01:29:55hey,
01:29:55this is a tumor that we're
01:29:56struggling with and we didn't
01:29:57know as much about some of these.
01:29:58MGMT and all these.
01:30:00These nifty things Doctor
01:30:01Chrome was pointing out,
01:30:03and so one thing would say hey,
01:30:05but let's do more radiation and
01:30:07I would say pretty uniformly.
01:30:10Those efforts and trials were failures.
01:30:12They just did not replace, didn't?
01:30:15They certainly didn't replace the surgery,
01:30:17can do, and even within radiation,
01:30:19they just really weren't adding lots.
01:30:22So at this point,
01:30:24you know we very selectively use
01:30:27radiosurgery techniques for people who had.
01:30:29Usually multiple recurrences where
01:30:31they are not a surgical candidate,
01:30:33and I think in that respect,
01:30:34and there's been a gap of time
01:30:36since the original radiation.
01:30:37It can be quite effective there,
01:30:39and we're studying it with in
01:30:41combination with certain other drugs,
01:30:43as if we can make it more effective,
01:30:45but but definitely not a substitute for
01:30:48for surgery when when at all possible.
01:30:52The other question,
01:30:53so most these machines that we're
01:30:56talking about whether cyber knife
01:30:58or you know a true beam or any of
01:31:01these ones are are using X rays.
01:31:03Really X rays,
01:31:04the gamma knife machine uses gamma rays
01:31:06as it's a radioactive pieces of cobalt,
01:31:09but most of them are these machines
01:31:10and so they really share a fundamental
01:31:13architecture with the same machine in
01:31:15your dentist office or a mammogram,
01:31:16or anything else.
01:31:18The difference is that those diagnostic
01:31:20X rays are in the kilovoltage.
01:31:23Range is the energy and when
01:31:24we treat with therapeutic
01:31:25relations, the mega voltage range.
01:31:28So it's 1000 times more energetic and
01:31:31really has some unique properties about
01:31:34how it can damage the tissues and which
01:31:38then sets up the type of shielding
01:31:39that's necessary and everything else.
01:31:41So they are X rays, they're just
01:31:43more powerful that we're using.
01:31:47Great thank you. There was one final
01:31:51question with regards to surgery.
01:31:53Somebody who's watching from Germany.
01:31:55So thanks for joining from Germany question
01:31:57do we have any thoughts on the autologous,
01:32:01all mental free flap technique from Doctor
01:32:04John Boockvar and has this been done at Yale?
01:32:07And so John is a a good friend of
01:32:10mine and I'm familiar with his trials.
01:32:12This one is is something just
01:32:15to to update others about.
01:32:17This is. Using a piece of
01:32:20laproscopically obtained omentum,
01:32:22which is highly vascularized with a pedicle,
01:32:26a vascular pedicle to it,
01:32:28and the idea there is to to bypass
01:32:30the blood brain barrier and he's had
01:32:32some other trials that had that same.
01:32:35From type of of thought behind them,
01:32:38bypassing the blood brain barrier
01:32:39to get more direct targeted
01:32:41therapy to the resection cavity.
01:32:43We personally don't have that trial here.
01:32:46We haven't tried that that trial here,
01:32:49but we'll certainly look to to John
01:32:51and his team to see how the the
01:32:54results are early on in that trial.
01:32:56I don't know if Zach you have
01:32:59any thoughts or comments.
01:33:01He does not.
01:33:02All right, well it is 807 and I think
01:33:05we are done with all of the questions.
01:33:08It's really been a pleasure having my
01:33:10friends and colleagues here tonight.
01:33:12So thank you again to Zach and
01:33:16Bruce and Brian.
01:33:17Really wonderful talks.
01:33:18Really a pleasure to work with all of you.
01:33:20Thank you for everything you do for our
01:33:22patience as part of the brain tumor center.
01:33:25Thank you for being here tonight and
01:33:27thank you to everyone for listening
01:33:29to us and please reach out anytime.
01:33:31Brian put his.
01:33:33Email in that chat for the support
01:33:35group and you can email me at
01:33:38anytime with anything, all right.
01:33:41So have a good night.
01:33:43Thank you so much goodnight,
01:33:45thank you.