"Management of Spinal Tumors" and "New Directions in Lung Stereotactic Body Radiotherapy"

December 08, 2021

Information

Yale Cancer Center Grand Rounds | December 7, 2021

Presentations by: Dr. Ehud Mendel and Dr. Henry S. Park

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00:00Thank you for coming.
00:02I'm happy introduce two speakers today.
00:04Our first speaker is Doctor Ehud Mendel.
00:08Who is executive Vice chair professor
00:10of neurosurgery here and director of
00:12the Spine and I called you program.
00:14He actually joined Yale recently in
00:16September of this year where he came
00:18from the Wechsler Wexner Medical Center,
00:20the Ohio State University,
00:22and the James Cancer Hospital.
00:25He received his medal called degree
00:27from Louisiana State University
00:28School of Medicine and further
00:29clinical training at the University
00:31of South Carolina and the University
00:32of Florida School of Medicine.
00:34And his team has pioneered new surgical
00:37techniques to reconstruct the spine
00:39following surgery to remove spinal tumors,
00:42including advancing minimally
00:44invasive neurological spinal surgery.
00:46So it's a great pleasure to welcome you to
00:48Yale and to your first grand rounds here.
00:51Thank you, but I appreciate the
00:53opportunity to give this talk and I
00:55want to thank all of you and Renee too,
00:58and make this arrangement for me.
01:00So I really wanted to.
01:04Talk about these Sid topic did it?
01:06I've been very passionate about over many
01:09years and that's the surgical management
01:12of patients with spine tumors. So.
01:15Uhm? Let's see how well this forward.
01:22Would you rather.
01:26Arrows.
01:30OK, so when we talk about
01:32patients with spine tumors,
01:33we're talking about two kinds of patients.
01:36Population patients with primary
01:39spine tumors means the tumor is
01:41growing directly from the bone
01:43itself within the spine itself.
01:45These are primary bone
01:47tumors coming from the spine.
01:49The most common type of tumors are patients
01:52who have ministered disease to the spine,
01:55and those are two very
01:56different patient population.
01:58The primary tumor growing from
01:59within the bone of the spine versus
02:02the metastatic spine tumors.
02:04The goal is different.
02:05The adjuvant therapy is different and
02:07the surgical options are very different.
02:09So the goal for primary tumors are really
02:12to try and cure the patient of the disease.
02:14The idea is to try and get
02:16this tumor out of there.
02:17It's the only side of disease,
02:19and the idea is to get a tumor out without
02:22interfering with the tumor capsule.
02:24So the idea is that if you take the
02:26tumor out in one piece without really
02:29breaking into the tumor itself,
02:31there is a potential of curing
02:33the patient of cancer.
02:34And sometimes, even if it's not feasible,
02:37the idea is to at least give him long term.
02:39Survival.
02:39When you're dealing with patients
02:41with menist attic disease,
02:42which is the most common issue,
02:45then you're really dealing more with
02:47palliation and quality of life.
02:49The Advent therapy is different
02:51for those two patient populations.
02:53Multiple agile in therapy,
02:55options for patient with metastatic disease.
02:58You can come in.
03:01And the primary ones, it's it's very limited.
03:04Surgical techniques are also very
03:05different to those two patient population,
03:08and I'm going to talk about both of them.
03:10I'm going to talk first about
03:12the metastatic spine tumors,
03:13because these are the most
03:15common patient population.
03:16So there is about 1.2 million new cancer
03:19cases per year in the United States.
03:21But more than half a million deaths per year.
03:25It's a major cause of death is
03:27complication due to metastatic disease,
03:29and if you look at this patient population,
03:32the skeletal system,
03:33the spine is the third most
03:36common site of disease after it
03:39spread to the lung and liver.
03:41And the spinal column is the most
03:44common sites of skeletal metastases.
03:46So third of this third patient population,
03:49the spine,
03:50is a is the most common place for
03:52it to end up with and as many as
03:5490% of cancer patients will have
03:56spinal metastases at autopsy.
03:58Studies and out of those 90%,
04:00ten to 30% of this patient cancer
04:03patient will suffer from symptoms.
04:06Symptomatic symptom,
04:07symptomatic spinal Mets,
04:08or whether they have severe pain or
04:11whether they're presenting with their.
04:13Significant or logical issues?
04:15The primary tumor,
04:17the other group that I've talked about
04:19a very different patient population.
04:20These are very unique tumors.
04:22They're growing typically from
04:23with the bone itself of the spine,
04:26and these are the osteoid osteomas,
04:28the osteoblastoma giant cell
04:30tumor aneurysm bounces, kodamas,
04:32chondrosarcoma,
04:32Ewing sarcomas,
04:33and medical ecology should deal with
04:37these type of patients are very
04:39familiar with this type of tumors.
04:41So when we think about surgeries
04:43on this patient population,
04:45we have to keep in mind whether this
04:47patient population that we're dealing with,
04:49especially the patient
04:51with metastatic disease.
04:52They are typically immuno compromised.
04:54They have decreased white blood cell count so
04:57they have higher risk of post op infection,
05:00high risk of bad infection.
05:01They have lack of fever response.
05:04They have lack of appeal cytosis.
05:06There are sometimes issues with these
05:08patients get cement injection into
05:09broken vertebraes those can get.
05:11Easily infected,
05:12which turns out to be a big problem.
05:15Their nutritional status is not that great.
05:18They lose a lot of weight there.
05:20They've increased catabolic state,
05:22decrease intake their serum of human is low,
05:24and so you have to think about
05:27preoperative nutritional support.
05:29They are typically on steroids to supplement
05:31some of the agents that they are on,
05:33which obviously leads to a multitude
05:36of side effects related to the
05:38steroids that are listed over
05:39here and for the sake of time.
05:40I'm not going to.
05:42And go over it.
05:43They are a lot of patients are
05:46coagulopathic with Trump cytopenia
05:48they may not be ambulatory,
05:50so they've increased for DVTS.
05:52So you have to think if you're
05:54doing surgeries on these patients
05:55or sometimes if you don't about DVD
05:58prophylaxis for these patients.
05:59And if you end up thinking about
06:01operating in these patients,
06:02some of these tumors are very vascular tumor,
06:05which means significant blood
06:06loss during the surgery itself.
06:09If you think about the primary bond tumor,
06:11you know the aneurysmal bone cyst,
06:13the giant cell tumor,
06:14the Himanshu Himanshu Paracetomol.
06:16These are known to be super vascular tumors,
06:18and as you get in there and
06:20start removing this tumor out,
06:21you encounter significant blood loss.
06:23In essence,
06:24any tumor that has the word him in
06:26it you have to worry about a very
06:28vascular tumor during surgery.
06:30And these are just the primary tumors.
06:32If you talk about the metastatic patients,
06:33the renal circle cinemas there,
06:35potassium, local cinema,
06:36the thyroid,
06:37the pheochromocytoma are also highly
06:39vascular tumors and you have to anticipate
06:42it as you're planning on getting these out.
06:46So in addition,
06:47and you thinking about all those
06:49issues on this patient population.
06:52Sometimes you have to think about
06:54wound closure and the reason is
06:56because sometimes the tumors is large,
06:58which leaves significant defects.
07:00Sometimes there is a risk of just
07:03the increase age they altered
07:05immune system capsia patients have
07:07been radiated on chemotherapy,
07:09so their wounds don't heal as well,
07:11and so they'll active won't
07:14breakdown or infection is higher.
07:16And so these are all the
07:19issues that gets into,
07:20you know,
07:21when do you need to start thinking
07:23about the wound issues when it
07:25comes to home closure and so plastic
07:27surgery becomes to be a very good
07:29friend of us when it comes to
07:31ability to close this wound and
07:33minimize the post op complication
07:35related to home closure.
07:37And this is just some of the
07:38issues we're dealing with.
07:38Here is a patient with sarcoma soft
07:41tissue tumor that invaded all the
07:43tissues of the spine so we can take this.
07:46Out, but clearly we need our plastic
07:48care colleagues to be able to
07:50deal with these types of tumors.
07:52And as we remove him out,
07:54it's not just about how to remove it,
07:56but planning on once the tumor is removed,
07:59how to be able to close it.
08:01So these are a lot of these cases tends
08:04to be multidisciplinary in nature.
08:06In the with the ability to remove
08:08the tumor and then the ability to
08:10do some sort of flap to be able
08:12to close these wounds.
08:14Sometimes you're dealing with
08:15a very large tumors.
08:16This is a large stake of
08:18Chordoma with big reconstruction.
08:20Again,
08:20gotta rely and plan on plastic
08:22closure to close these wounds,
08:25so I wanted to go over some cases
08:27just to kind of give you the.
08:28Run over the meal patient
08:31population that eyes,
08:32spine tumor person and deal with in
08:36a commonly and let's just take these
08:38cases and what's unique about the
08:40cases I'm going to show you is that
08:41they are all presenting the same,
08:43so these are patients are
08:45presenting with back pain.
08:46Here is a patient with multiple myeloma.
08:48Is 57 years old,
08:49has some pain in the back going to the
08:53legs already get maximum pain medications.
08:56Biopsy revealed multiple
08:58myeloma already underwent.
09:00Radiation stem stem cell transplantation
09:02still have progressive disease
09:04and is not logically intact,
09:06so this is very common in
09:07the multiple myeloma ward,
09:08where patients come in and they have
09:10back pain and you can see right here.
09:12Here's the MRI and you can see
09:14there's a fracture of the vertebrae
09:15in the lumbar spine here,
09:16so there's a broken vertebra
09:18related to the multiple myeloma,
09:20and so we get called and said,
09:22can you do something here?
09:23What can you do?
09:25You're the second case,
09:26presenting the same way, patient.
09:30It can't be back.
09:31Pain has metastatic renal cell
09:33carcinoma and you can see here
09:35the MRI kind of look the same.
09:37There is a metastatic lesion here.
09:38At L1 is a little bit of a fracture here.
09:41Maybe even new fracture at T 12 here,
09:44but the presentation is the same.
09:46The location of the tumor is
09:48in exactly the same place.
09:50The patient has no no logical deficit,
09:52just back pain.
09:53The only difference between
09:54those two cases is that the first
09:56case was multiple myeloma.
09:58The second case was a renal cell carcinoma.
10:00Are we going to treat it the same,
10:03or is the tumor biology
10:05dictate the treatment option?
10:07Here's a third case on a 52 year
10:10old again or logically intact.
10:12Just having back pain has a
10:14diagnosis of chondrosarcoma
10:16based on a CT guided biopsy,
10:18and you can see right here
10:20in other lumbar fracture.
10:21The first two cases were lumbar fracture.
10:23Multiple myeloma renal cell carcinoma.
10:25Here is a chondrosarcoma with a lumbar
10:28fracture right here at L4 representing
10:31exactly the same with back pain.
10:33So should we treat that tumor the same way?
10:36With reading the multiple myeloma adrenal.
10:38Tell casino.
10:39Here is a case 68 year old with thymic
10:42carcinoma coming in at the seed.
10:44Already radiation and you can
10:46see right here at T11 and T12.
10:48There's lesions right here at those
10:50two variables which may be a little
10:53bit of a fracture right here again.
10:54Tarako lumbar junction location is about
10:57the same, but the different type of cancer.
11:00So the question that we always asking
11:03ourselves all these cases require surgery,
11:06does their differences in the tumors or the
11:09tumor biology really makes a difference?
11:11And which approach should we take to
11:13treat and help these patient populations?
11:16And when it comes to my job as a surgeon
11:19dealing with these patients there,
11:20only these are the four options that I have.
11:23I can do what we call an intralesional
11:25resection where we enter the tumor
11:27with piece meal the tumor out.
11:29We take the tumor out in peace, mealing it.
11:32That's the intralesional component.
11:35We can do what we call an unblocker section,
11:37where in one piece we take the
11:40tumor out without.
11:40Interrupting the terminal capsule.
11:42We don't necessarily have to do surgery.
11:45We can do just chemotherapy,
11:47immunotherapy,
11:48conventional radiation,
11:49or stereotactic radiosurgery.
11:52Or sometimes we can just inject
11:54some end into the vertebrae just to
11:56restore some mechanical stability,
11:58which is minimally invasive.
11:59So I wanted to show you some specific
12:02cases because the four cases that I
12:04showed there are presented with the
12:07neurological non or logical deficit,
12:09which always increase the level of concern.
12:13But when they do have a neurological
12:15deficit and things becomes even
12:17more urgent as to what can be done,
12:19here is a 23 year old patient who comes
12:22in stood up complaining of some weakness.
12:25And when you look at the exam,
12:26the exam shows a little bit
12:28of weakness in her legs.
12:29Four out of five strength in
12:31both of her legs.
12:32And here is an MRI which showed 9 broken.
12:35There is severe tumor compressing
12:37the back of the spinal canal.
12:40Pressing this power code and
12:41unfortunately here she's in the emergency
12:43room and there is no diagnosis.
12:45We do not know what this looks like a tumor,
12:48but she presented the emergency room
12:50and this is what the MRI looks like
12:53and the question is what to do,
12:55and that's where we get called.
12:56Then.
12:57The unfortunate thing here is
12:58that unlike the first four cases
13:00where we knew the diagnosis,
13:01which can help us dictate what to do
13:04here we are faced with the situation.
13:05With a patient presenting with cord
13:08compression with mild weakness in the
13:11legs but no diagnosis and so here is
13:13some of the views you can see on the
13:16axial cut severe cord compression,
13:18the podis squashed.
13:19There's a lot of tumor around the
13:21vertebral body and but the patient is
13:24a very minimal weakness in her legs.
13:26And so these patients here is the CAT scan
13:29shows mild compression fracture at T9 and
13:32no surgical consultation was requested.
13:34And the question is should that each patient
13:36be taken emergently to the operating room?
13:39Because there is a little bit of
13:41weakness in the legs but no diagnosis.
13:44We don't know what it is or wait on
13:46the surgery trying to establish a
13:48diagnosis and based on the diagnosis
13:50make a decision of what to do.
13:53And so on. This case, the patient.
13:55Make that accommodation by the nose surgeon.
13:58On call was to take the patient to
14:00surgery and do a decompression.
14:01And so I Laminectomy was done and
14:04you can see right here.
14:05The back of the spine is removed.
14:07The canal has been opened up.
14:08You can see right here on
14:10the postoperative MRI.
14:11Did spinal cord looks a little bit better.
14:13There's nothing much compression there,
14:14but if you look at the axial cut
14:17the majority of the tumors left
14:18behind the entire vertebral bodies,
14:20encased in tumor and all of that was not.
14:25Touched by their purpose of the
14:27surgery was really to just take
14:28the portion within the canal that's
14:30pressing on the spinal cord.
14:32The postoperative specimen came
14:34back to be lymphoma.
14:37And so the question was,
14:38was that the right choice for the
14:41patient considering informer being
14:42a highly radiosensitive tumor,
14:44highly responding to adjuvant therapy
14:48and rarely actually needs any surgery,
14:51was there the right the right
14:53choice for the patient and part one
14:55of the downsides is not a patient
14:56needs to recover from the surgery.
14:58There's a fresh wound that will not
15:00tolerate with the Asian so quickly,
15:02so there's some downside for doing
15:04the surgery and now have to wait
15:07for the treatment.
15:08Now, let's say we take the same case,
15:09but instead of four out of five weakness,
15:11the patient only had two out
15:12of five weakness,
15:13and would that have made a difference when
15:16it comes to taking the patient to surgery?
15:19So how much of a weakness is acceptable,
15:22and how much of a weakness is not acceptable?
15:24That becomes a very difficult
15:26question to decide whether to take
15:28to the patient's surgery or not.
15:30It is another patient with a 51 year
15:32old 51 year old who comes in with
15:35weakness and some incontinence,
15:37and you can see there is a tumor.
15:38In the sacrum there's a lot of
15:40tumor in the canal pressing on the
15:43spinal canal explained incontinence,
15:45and some of the weakness and you
15:47can see another MRI here shows
15:49the finding of a broken sacrum.
15:52Some tumor in the canal and
15:54the patient under men.
15:55Emergent surgical intervention
15:56with the Laminectomy and fixation,
15:59but unfortunately this turns out to be a
16:01primary bound tumor with a counter sarcoma,
16:03and when they found out it
16:05was a conscious or
16:05comma, the patient underwent
16:07stereotactic radiosurgery.
16:09Unfortunately, this is one of those
16:11tumors were the recommendation is
16:12to try and do an unblocker section.
16:14Once you enter this tumor and you
16:16take it in piece meal version,
16:19then there is 100% chance of recurrence.
16:21So really the only chance of the queue
16:23for this patient would have been during
16:25the first surgery with attempt to remove
16:27it in one piece without entering it,
16:29unfortunately here.
16:29The patient may have done
16:31well with the decompression,
16:34but the tumor have entered and death
16:36leads to spillage in the surrounding,
16:38which ultimately leads,
16:39will lead 100% to recurrence.
16:41And sure enough,
16:42this patient came back three years
16:44later and presented with this little
16:46bump in the back they thought was maybe
16:48one of the screws are getting loose.
16:50But when you look at the MRI you see
16:52that the entire tumor is now recurring,
16:54and in fact that bump is actually a
16:57metastatic disease underneath the skin,
17:00which was expected considering
17:01that the surgery.
17:02It was done with unfortunately intralesional
17:04instead of an unblocker section in.
17:06Not only dead.
17:07Now the rise is broken and then ended up
17:10taking this back patient back to surgery.
17:12We remove the lesion itself
17:14in an unblock fashion,
17:16but it really makes no difference
17:17now since the tumor has spread,
17:19and here is a specimen revising the
17:22cancer here and the plastic surgeons
17:23came by and did a flap to close this one.
17:26So the take home message meant
17:28message in all these is that
17:30this could be a miss management.
17:32In a way of trying to think through
17:34the process of what to do here
17:36and it could be related to bad
17:38timing operations or sometimes
17:40operation with no diagnosis where
17:41you don't really know what to do,
17:43and so I'm just.
17:44I call it a triple W phenomena to be
17:46aware of the triple W of the wrong
17:48operation on the wrong patient,
17:50sometimes by the wrong surgeon,
17:52or emphasizing neurological issues
17:54versus uncle logical issues.
17:56So when you're dealing with that this
17:58type of tumors and I'm going to go out
18:00fast just for the sake of time I mentioned.
18:02Some of these issues here when it
18:04comes to the goal and a lot of these
18:06things has to be done with making
18:08the right diagnosis and now what
18:10it is that you're dealing with.
18:12Biopsy is extremely critical
18:13as much as possible.
18:15Anytime you have a chance,
18:17you have an option of doing a biopsy.
18:19Make sure that you do the biopsy up front.
18:21It is a patient that they supposedly
18:23thought that it has a contractor comma
18:26or a chordoma will schedule the surgery.
18:28A biopsy was done and it turned out
18:30that this was in a pending Mama,
18:32which was a completely.
18:34Different tumor require completely
18:35different surgery,
18:36so biopsies are very critical.
18:38Make sure on this particular case
18:41is that you avoid a transol or a
18:45trans rectal biopsies because.
18:47If the idea is to take the
18:49entire piece of tumor out,
18:51the track itself can lead to contamination,
18:54and so we typically mark where the
18:56track of the biopsy is being done,
18:59and then we'll remove the entire
19:00specimen with the track itself to
19:02make sure that the whole specimen
19:04is being removed in one piece,
19:06and you can see right here some of
19:08the cases where the place where the
19:10skin was violated with that biopsy is
19:12being removed with the specimen itself,
19:15which means that the biopsy needs
19:16to be very close to the midline.
19:18Stay away from these type of issues
19:21where the biopsy is done very far way
19:23out to the side where we are unable to
19:25remove the track itself with the specimen.
19:28The biopsy needs to be very
19:29close to the midline.
19:30Uhm, I mentioned some of these intra
19:33lesional options unblock options.
19:35These are really the surgical
19:36options that we have.
19:37The Intralesional the
19:38mentions of peace meals.
19:40Here's a patient with two level
19:42metastatic disease at T3 and T4.
19:45We as surgeons need to be comfortable
19:47with being able to approach
19:48the spine from any direction.
19:50Possible weather through the front
19:52to the side through the back.
19:54It is a case where the spinal
19:55cord is being suspended.
19:56The nerve roots has been ligated
19:58and you can see that gives us access
20:00to the interior of the tables.
20:02Find through the vertebres we can.
20:04They then put the screws in our
20:06place and then we can actually
20:08remove the vertebral bodies through
20:10the back and then get underneath
20:12this power cord and sneakers a cage
20:14to replace the broken vertebras.
20:17And that's what it looks like
20:18after the surgery.
20:19The unblocker sections where we
20:21going in around the tumors are much
20:23more complicated is it is what
20:25we actually want to achieve with
20:27the entire segment of the spine
20:28is being removed in one piece
20:30without interrupting it and that.
20:32Takes a lot of planning when it
20:34comes to work to make the cuts,
20:35ultimately to be able to remove
20:37the specimen in one piece and you
20:39can see in this picture again,
20:41the tumor has not been violated
20:43on a primary bone tumor and you
20:45can see right here are the entire
20:46segment of the vertebrae.
20:48Is able to be removed from around
20:50the spinal cord without interruption.
20:52Radiation obviously is a huge
20:53component to what we do.
20:55There is a conventional option just
20:57so the Asian there is a surgery
21:00followed by radiation and then
21:01here it's Milo.
21:02And in major cancer hospital we have
21:05the option of spinal radiosurgery.
21:08We've written about there's a lot of
21:10cases out there about radiotherapy
21:11and radiation treatment option for
21:14patients with metastatic disease,
21:16and what are the indications for this thing.
21:18Recently we just published our series
21:20when I was at the James Cancer Hospital,
21:23but postoperative stereotactic body
21:25radiotherapy for spa metastasis
21:27and predictor of local control,
21:29and it's an amazing tool.
21:32To supplement our.
21:35You know our intervention and maintaining
21:38control of these these tumors,
21:41so you know the data is very promising.
21:43This is some of the cases you can see.
21:45These are cases that don't need surgery.
21:47Single met.
21:48Here is a tumor with a recurrence
21:50around vertebral artery,
21:52and so really this is a totally
21:55non invasive alternative adjuvant
21:56treatment there to surgery.
21:58Cement injections allow you mentioned
22:00this patient know that this is
22:02a very good tool for patients
22:04with mild fractures who needs to
22:06continue going with treatment who
22:08cannot go through major surgeries.
22:10So either you do it you plasty
22:12is or you can do a kyphoplasty
22:14is where we put a ballooning.
22:16You can inflate the balloon,
22:18correct some of the deformity
22:20removed the balloon and then
22:22inject cement into the bone.
22:24There's lots of papers that they
22:26would have been looked at the
22:28show that these treatments of
22:30cement injections are an amazing,
22:32not just diagnostic,
22:33but also therapeutic indications
22:35for patients with spine tumors.
22:38Sometimes we can't do it.
22:39You know if there's a lot of fracture,
22:41bad, fractional sometimes.
22:42That bone is already in the canal.
22:44The idea is to make sure that
22:46cement doesn't leak into the
22:48canal and press the spinal cord,
22:50then lead to us nor logical issues.
22:52Or sometimes you can see
22:53right here with the tumor.
22:54It's through the back of the bone
22:55and write it right through it.
22:57So there are some contraindications
22:59of when not to do it.
23:00This is what we don't want to
23:02see happen with cement leak
23:04into the spinal canal or right
23:06here where you can see a lot of
23:08cement was injected and cement.
23:09Its kind of overlying the
23:11entire pickle sake sometimes.
23:13You see cement in other places,
23:14even in the brain you can see
23:16particle of cements going to.
23:18Here is a case where you don't
23:20want to see again with cement was
23:21injected in the a lot of the cement
23:24leak into the canal leading to a
23:26patient presenting right after the
23:28surgery with neurological deficit.
23:29So you gotta watch for those things.
23:31Here is a patient who have a lesion
23:34in the odontoid and we used to treat
23:37this with significant reconstruction
23:39of the cervical spine to help with
23:42mechanical mechanical neck pain.
23:43But now,
23:44if you really push the limits,
23:45cement is a huge tool and on this
23:47case is now we're getting to the point
23:50where we don't need to do big surgeries.
23:52We can actually go through the back
23:54of the mouth and injects cement
23:56directly into the odontoid and
23:58you can see what it looks like,
24:00what it looks like after the
24:02surgery and we actually published
24:04this technique where we can use
24:07the stereotactic CT guided images
24:09and fluoroscopy,
24:10unable to go through the back of
24:12the mouth without EMT colleagues
24:13and able to inject the cement.
24:15Right into the broken vertebrae.
24:16Instead of putting the patient
24:17through some sort of an
24:19exhibit cervical fixation,
24:20so some of those country
24:22indication we can refute them,
24:23and we actually publish
24:24our series at MD Anderson.
24:26When it comes to when to do
24:28it and when not to do it,
24:29and a conclusion was that relative
24:32contraindications can be relaxed
24:33for patient without other options
24:36with no clinically significant
24:38increase in complications.
24:39So I want to, for the sake of time,
24:42just go quickly through my last slide.
24:45Here, you know the key if
24:47you want to take one.
24:48Slide audible this is that this is
24:50when we're thinking about Sergio.
24:52We're thinking doing surgery for
24:54patient when we think that we
24:55can make a difference that we
24:57can after the prognosis we think
24:58about doing surgery when there is
25:00significant spinal instability.
25:02The spine is so broken that the the
25:04patient unable to get out of bed
25:06with thinking to do surgery when
25:09there isn't nor logical deficits and
25:11painted by itself even without deficits,
25:13is also an indication for surgery.
25:16And so. Spine instability.
25:18Clearly,
25:19if you look at these MRI you
25:20can see that the fan is broken.
25:22This is something we can fix with
25:24surgery and there are now a scale
25:26that helps us that we have developed
25:28to define what is finding stability
25:30in patients with metastatic disease.
25:32And I'm not going to take you through it,
25:34but it's a very nice since code
25:36that you can Add all these numbers
25:38and if you Add all these numbers
25:40when it comes to location pain that
25:42abolition it is is there alignment
25:44or know how much of their bodies
25:46involved you can Add all of these?
25:48Points and that will lead to deciding
25:50whether the patient is stable and unstable,
25:53which may help deciding whether
25:55to do surgery or not.
25:56Nor logical deficit is clearly
25:58something that we get called on and
26:01then we have to make a decision as to
26:04whether to go on with surgery or not.
26:06And as I mentioned,
26:07just pain sometimes also helps
26:09us help with surgery,
26:11especially when we deal with the
26:13mechanical type NC traumatology
26:15which indicate a fracture.
26:17When you thinking about surgery,
26:18just always make sure that it's
26:21physically technically feasible
26:22to do adequate approach.
26:24Good strategy, satisfaction,
26:25reconstruction, and that ultimately
26:27it's going to give it doable.
26:29Patient benefits,
26:30because ultimately these are
26:32this can end up to be, you know,
26:35very very large lesion for these patients,
26:39so I just want to get to the last
26:41part and that is the primary tumors.
26:44These are not metastatic disease,
26:46these are the most challenging cases.
26:49Some of them can be treated
26:50with adjuvant therapy,
26:51but most the converse of trauma
26:53in the chordoma cannot,
26:55and some of them can response
26:57to preoperative chemotherapy.
26:58But most don't.
26:59They good example,
27:01for example,
27:01is denosumab,
27:02which helps very much in patient
27:04with giant cell tumor.
27:05We used to think that all
27:07this patient needs surgery,
27:08but you can see they
27:09present with big holes in
27:10the vertebrae. But on denosumab,
27:12here is a patient with an L3 fracture.
27:14You can see on the CAT scan.
27:16There is no L3,
27:17it's completely eaten away by the.
27:19Tumor and you can see the PET scan over here.
27:22Here is the CT reconstruction
27:24of this L3 lesion.
27:26Very large region,
27:27but you can see that with the NASA
27:29map you know the voter becomes very
27:32calcified and strong to the point that
27:34there may not be a role for surgery
27:36anymore for this patient population.
27:38Here is a pharmacist again, the odontoid.
27:40The C2 vertebra is completely eaten away.
27:43There's almost nothing
27:44left of the C2 vertebrae.
27:45All we did here is we stabilize is fine.
27:48We did not take the tumor out.
27:50You can see right here.
27:51There's posterior stabilization and
27:53within couple of months the entire
27:56bond filled in here and there is
27:58normal hall that was there before,
28:01so there is definitely a clear
28:03role for Asian therapy.
28:05Now why these unblock resections?
28:07Because that's really the only way
28:09to give a chance for these patients.
28:12And here is a patient with a
28:14Seiko tumor that we can go in.
28:15We can like get a tickle
28:17sakkinen and unblock fashion.
28:18You can see the margins or
28:20clean all the way around it.
28:21And we know from all the data that's
28:24out there that unblock resection can be
28:26can lead to Q of this patient period.
28:29The patient with sarcoma in the meter at 6
28:32pine we don't want to enter this terminal.
28:34We want to be able to remove
28:35this tumor out in one piece.
28:37Will plan where we going to make
28:39our accounts to deliver this
28:40vertebra from around the spinal
28:42cord and ultimately able to remove.
28:44The entire vertebrae in one piece
28:47without entering it and able to then
28:50reconstruct it and and and give the
28:52patient a chance for Q of patient.
28:54The sacral tumors are the
28:56biggest ones to deal with,
28:58and are the most complicated one.
29:00There are lots of methodologies,
29:02and I'm sharing some slides here
29:04about how we approach these tumors.
29:05There are lots of techniques that
29:07I'm not going to get into this.
29:09Most surgery oriented talk
29:12about how to be able to remove.
29:14A lot of these sacral tumor and
29:17ultimately able to achieve an
29:18unblocker section on these tumors.
29:20Some of these techniques we have
29:23described here is some big example of
29:25the counter sarcoma that's going up
29:27to the lumbar spine up to the pelvis.
29:29List is obviously combined with
29:32multidisciplinary approach,
29:33or an unblocker section was
29:35performed with orthopedics and
29:36urology and plastic surgery,
29:38and this tumor was removed
29:40with vascularized bone graft.
29:41We published this technical
29:43aspect of using a talaga.
29:45Bone graft.
29:46And dental reconstruction obviously
29:49was significant issue about how to
29:52reconstruct these tumors when it comes
29:55to be able to do this type of surgery.
29:58This is these are very highly
30:00very is a big time surgeries.
30:03This is one of the stories
30:04that we've done that
30:05ended up being the front cover
30:07of the general node surgery.
30:08These are highly complex type
30:10surgeries when it comes to do and
30:12you can see interactive pictures of
30:14the vascular grafts that has been.
30:16Use on this particular patients,
30:19and these patients ultimately
30:21fuses very well.
30:22This is the post operative picture
30:23of the patient a year later,
30:25so there are some fair frontiers
30:27that have been looked at when it
30:30comes to getting engineering involved
30:32with personalized model 3D printers.
30:35Try to predict which voters
30:36are going to break.
30:37We're looking at animal models in
30:40unblock tissue characterization.
30:42We aiming toward personalized.
30:44Surgeries and its patients take the
30:47patients CAT scan the patient MRI,
30:50creating these 3D reconstruction
30:52models for these patients,
30:54creating those models,
30:55and then ultimately figuring out
30:57this is some of the 3D models
30:59that we have done on the lady
31:01with breast cancer and figuring
31:02out what type of surgeries with
31:05benefits these patients at the most.
31:07And then you can see some of the
31:09implants some of the 3D implants
31:11vertebres that can be patient
31:13specific for the patient you can see.
31:16Half his sacrum patient specific
31:19for these particular patients,
31:21we're looking at different
31:23modeling to reconstruct the spine.
31:25Again,
31:26these are all specifically
31:27for the patients itself,
31:29so it's just some of the slides
31:33that we are doing right now.
31:35So in conclusion,
31:36the management is challenging,
31:37it can restore and protect
31:39neurological function.
31:40It can improve pain,
31:42it can impact the quality
31:43of the patients life.
31:44Understanding the biology of these
31:46tumors is critical in defining
31:48the goal of treatment in a given
31:50patient and determining the most
31:52appropriate therapeutic options.
31:53Surgeons dealing with this neoplasm
31:55really should be familiar with.
31:56All surgical approaches as well as
31:59complex anterior posterior construction
32:01techniques in order to provide
32:03optimal care for these patients.
32:05So overall I want to end up as saying it,
32:08try it. Don't try to be good.
32:10Uhm, thank you.
32:12OK,
32:13thank you very much for a really fascinating
32:15talk and let it challenging field.
32:17Unfortunately, since we're running late,
32:19we won't have time for questions.
32:20I know there are some,
32:21so please direct your questions
32:23directly to Doctor Mandel,
32:25but we do have a second speaker today.
32:27Thank you very much.
32:28Thank you so our second speaker
32:30today is Henry Park and you
32:31can maybe get your slides up.
32:33Henry is an assistant professor
32:35of therapeutic radiology here and
32:37chief of Rip Thoracic radiotherapy.
32:40He received his undergraduate
32:41and medical degrees from Yale
32:42and completed internal medicine.
32:44Training of the Harvard system then
32:47returned to Yale for radiation oncology.
32:49He specializes in radiation therapy for
32:51lung cancer and had neck cancer and
32:54brain tumors and is also quite active
32:56in comparative effectiveness in health
32:58services research as well as Serbian.
33:00As our program Director,
33:02residency director in in
33:04therapeutic radiology.
33:06So Henry on the floor is yours.
33:08OK, thank you very much for
33:11the very kind introduction.
33:12So today I'll be speaking about
33:13the new directions in Lung SBRT.
33:18So here my disclosures.
33:21So that my my my goals today to
33:24discuss updated evidence on the
33:25role of SBRT in early stage.
33:27Non small cell lung cancer as well
33:29as long although ministered disease
33:30will also be reviewing our lung cancer
33:32clinical trials that involve longest
33:34period T that we've had open here at Yale.
33:38So first we'll start with early stage,
33:39non small cell,
33:41medically inoperable patients.
33:42So if here we have an elderly patient
33:45with lung nodule that's deemed
33:47medically inoperable to because
33:49of the patients pulmonary status,
33:51how do we treat so really?
33:53It's all about the real estate mantra.
33:55It's about location, location,
33:57location.
33:58How we end up treating this so SPFT
34:01those fractionation just to kind of
34:02walk you through a few terms here
34:04when we talk about conventionally
34:06factoring fractionated radiation,
34:08we talk about low dose per fraction,
34:09about two grade per day over many fractions,
34:12usually about 30 to 35 fractions
34:14over six to seven weeks.
34:16Hypofractionated radiation is
34:17a moderate dose per fraction,
34:19about three to seven grade per day
34:21over a fewer number of fractions,
34:23about 8 to 20 on SBRT would be
34:25a high dose per fraction,
34:27so usually tend to 18,
34:28but really up to even 34 grave over
34:30a very few number of fractions,
34:32which is defined in the US as
34:34one to five fractions.
34:36I'll also talk about this concept,
34:37called biologically effective dose orbed.
34:40This speed increases with higher dose
34:43per fraction and actually increases.
34:46With a lower number of fractions,
34:48so 54 Gray and three fractions
34:50is actually higher in bedded,
34:52in 60 Gray and five fractions,
34:54and that is higher than 60
34:56grade 15 fractions,
34:57which is there which is afterwards are
34:59higher than 60 Gray in in 30 fractions.
35:03So in an effort for us for tumors that
35:06are outside was called No fly zone,
35:08we call this the the fly zone,
35:10which is within two centimeters of
35:12proximal tracheal bronchial tree.
35:14Anything that's peripheral to that are
35:16outside of it can be treated in in,
35:18in in the user with a high
35:20dose 3 fraction regimen,
35:22so we know from the chisel trial the best
35:24party is is superior to conventionally
35:26fractionated radiation for stage one
35:28non small cell lung cancers like this.
35:30But we know that if you're treating
35:33within the central region of this.
35:35This area, then the plastic can be too high,
35:38whereas the opening treat outside of it.
35:41The outcomes of an excellent 98% control at
35:43three years and 90% control in five years.
35:48Uh so so we did some work here as well
35:50as some other places where we looked
35:52at for central tumors. How do we?
35:54How do we proceed with SBRT here?
35:56So this is a program that was started
35:58by Roy Decker several years ago
36:00and really to decrease the dose,
36:02but also standard fractionation
36:03to five sessions.
36:05So using looking at your retrospective data,
36:08we found that overall survival local
36:10control and toxicity were similar
36:12between central and peripheral tumors
36:14that have been followed up with an
36:16RPG 0813 trial phase one two study.
36:19How that that was using those escalation
36:21with five fractions to see that
36:23there really it it really all there,
36:25the doses that they were using.
36:27This is safe and effective.
36:29For central tumors.
36:31So we have a trial here that I've
36:33been working with Doctor Peters
36:34for the last several years.
36:35This is a dose deescalated
36:363 fraction measurement.
36:37We need to call it dream.
36:39This is for central but not
36:41Ultra central lung tumors.
36:42So either primary non small cell
36:44lung cancers or metastases that
36:46uses a similar BB to current five
36:48fraction regiments but lower than
36:50current three fraction regiments
36:51to be more convenient for patients.
36:54Given that we're not necessarily
36:55sure that those D escalation as
36:58well as extending fractionation
36:59is really essential in this case.
37:01So we're looking at a lower dose 3
37:04fraction instead for the central tumors,
37:06we define this as being within 2 centimeters,
37:08but not a budding the the the Safa,
37:11guess hard or or the tricky monkey tree.
37:14So as a phase one two study,
37:16we're targeting 60 patients in total
37:17over the course of five years.
37:19We had this open for the past year
37:21and have a clear about 13 patients.
37:22So we were pretty much on target here.
37:24Our primary endpoints are grade three
37:26plus toxicity as well as local control.
37:30Also, for Ultra Central tumors,
37:32were there either a budding or within a
37:34centimeter or critical central structures.
37:37Do we avoid SBRT altogether and then
37:38use a more fractionated Benjamin?
37:41It's the highest trial here,
37:42just published this year that looked
37:44at high dose 8 fraction regiments
37:45with a similar be the to the current
37:48five fraction regiment and found
37:49actually the closer you get to the
37:52mainstem bronchi or the trachea,
37:54the higher likelihood of fatal toxicities.
37:56So it's a very serious.
37:59This news in general,
38:00but but actually even having
38:02grade 5 toxicity was up to the
38:04even the 30 to 40% of Maine.
38:05When you get that close to the
38:08mainstem bronchi or trachea.
38:09A much lower risk if you're on
38:11your low bar bronchus instead.
38:13So these are things that are very
38:15concerning to us with using these very
38:17high doses and ultra central tumors.
38:19So what do we do instead when
38:20they're not candidates for SBRT
38:22based on either tumor size or based
38:24on location like we talked about?
38:25You know we've been doing some work
38:28with with this medical students here.
38:31Nadia Saeed and all sassy and using the
38:34National Cancer database of you know,
38:36with retrospective studies showing that
38:37there was higher survival among stage one.
38:39Non small cell lung cancer patients
38:41who are receiving hyperfractionated
38:43radiation compared to conventionally
38:44fractionated radiation,
38:45especially when using a higher higher BD.
38:48So we also look I'm looking
38:51at a yield databases as well.
38:53Comparing a lower dose 15 fraction
38:55regiment to a higher dose eating
38:57fraction regimen to those who are not
38:59candidates for SBRT and we hope that.
39:01One day I will be.
39:02We can maybe compare this winter
39:04to do an SPRT veg.
39:05And for those who are,
39:06you know,
39:07maybe a lower dose SP regimen to see what
39:10works best for these ultra central teams.
39:13On a different topic here
39:16for multiple targets,
39:17if we have multiple nodes,
39:18muscle lung cancers,
39:19which we sometimes do encounter,
39:21can they be treated simultaneously with SPRT?
39:24This is work that we just published
39:26this past week that looking at
39:27and we look at our own data here
39:29among 60 patients treated over the
39:31last 12 years to 126 lesions and
39:34found 87% local control and 70%
39:36overall survival at the two year
39:39mark with acceptable toxicity.
39:41.3% Grade 2 toxicity and only 3% grade.
39:43Three plus toxicity in both of those cases
39:46we would have used a different regimen.
39:47These days those were both treated.
39:51A long time ago.
39:54So now moving on to SBRT plus
39:56systemic therapy so you know,
39:58we know from the surgical that is shared.
39:59Putting some some words,
40:01you know those done done here from Dan
40:03Buffa and his group that that patients
40:05may who undergo surgery may benefit
40:08from chemotherapy and even more recent
40:10trials showing that immunotherapy may
40:12help in selected patients as well.
40:15So can SBRT patients also benefit
40:17from systemic therapy as well?
40:19We looked at our data here that showed
40:21that patients who were perceived.
40:24Mantis stomach therapy,
40:25you know did have a lower risk
40:29of regional distant failure,
40:31so but we do also do know that
40:33chemotherapy is is challenging in
40:35this offering fail SPT population,
40:37which has garnered a lot of interest
40:39in using immunotherapy instead,
40:41so can be immune checkpoint inhibitors.
40:43One study we have two studies open here
40:45at Yale that are looking at this question.
40:47One is the keynote 867 trial,
40:49which is a phase three study
40:51targeting 500 patients.
40:52This would look at SBRT plus.
40:54Concurrent in admin panel is a man versus.
40:58For stage one and two non small
41:00cell lung cancer this is open.
41:01It's been opened at the in New Haven
41:03and North Haven only at this point,
41:04but this would be a cute free week infusion.
41:08Either way,
41:09whether you get the immunotherapy or placebo.
41:12But the endpoints being event free
41:14survival and overall survival,
41:15we also are about ready to activate
41:17this new study.
41:18SWOG S 1914,
41:19which has been activated nationally but ready
41:22to open here and all of our care centers.
41:24So it's a phase three that's
41:27targeting 480 patients.
41:28Similar question,
41:29but the slightly different SBRT plus minus
41:31MU Advent concurrent attachment therapy,
41:34which will be in this case
41:36different mean therapy would be.
41:39No friend only for six months instead of 12.
41:41A big difference is that.
41:46Truly just got the SBRT and then
41:49there's only including high risk
41:51factors which are size greater than
41:54two centimeters SUV Max of 6.2 or a
41:56grade of two to three on lapsing.
41:59And again this will be open at all care
42:02centers that have yellow radiation.
42:04So moving out the early station
42:06as muscle lung cancer.
42:07Medically operable patients,
42:08so can ask European alternative to
42:11surgery for medically operable patients.
42:13First was work from there,
42:14from James you and Kerry Gross.
42:16Looking at CR Medicare,
42:18looking at a retrospective study here
42:20that founded overall survival was
42:22improved for patients who received
42:24surgery versus those who received SPRT.
42:27The short term plasticity did
42:28seem to favor SPRT,
42:30but then even out by by about
42:32two years out in in the.
42:34National Cancer Database from Denver
42:35Office Group found that overall
42:37survival was higher among those who
42:38got surgery than those who got SPRT
42:40even after adjusting for known confounders,
42:43including selecting for only
42:45patients who had refused.
42:47He had refused surgery,
42:49but we're recommending surgery
42:51for those who had no committees
42:54or Hello Committee score.
42:56However,
42:56we know that selection and indication
42:58bias is a concern when comparing
43:00surgery and SBRT retrospectively
43:01there have been there's work out of
43:03here as well as other places showing
43:05that patients who are considered
43:07operable who do receive SPRT do
43:09have higher overall survival and
43:11progression free survival compared
43:12to those who are inoperable,
43:14so it's difficult to compare these patients.
43:18Contracted an apples to apples
43:19comparison even though they do have
43:22similar local control and regional
43:24distant failure as well among operable
43:28versus inoperable SBRT patients.
43:30So I think that because like this,
43:33this this,
43:33this four part reviews here that
43:35I've drawn a few figures from.
43:37You know one thing you should
43:39use was showing here is that
43:41randomized phase three trials of
43:43surgery versus SBRT are ongoing,
43:44but have been historically difficult
43:46to recruit in these four here have
43:49accrued a total of 2.9% of the targets,
43:51so really they all had the
43:53clothes being very underpowered.
43:56There's a Fowler study at the VA that is
43:58probably the most promising ongoing trial.
44:00So far as accrued more than I think more
44:02than all these have combined so far,
44:04yet this is targeting 670 patients and is
44:07not due to read out for at least five years.
44:10So in the meantime,
44:12what do we do?
44:13What do we do?
44:14We know that the stars and roselle
44:16trials have been actually merged
44:18together and pooled analysis
44:20that again both underpowered and
44:21closed early due to poor accrual.
44:23They did find it.
44:25In this case.
44:26A surprising result that SBRT
44:27patients actually had higher overall
44:29survival and in this population.
44:30Which was a very small population again,
44:33but it was similar in recurrence Crucible.
44:36A larger study was done more
44:37recently a nonrandomized study,
44:39so single ARM SBRT trial that that had
44:42better accrual but from Indy Anderson
44:44that looked at that actually had a
44:46protocol specified comparison to
44:48an institutional surgical cohort and
44:50found that certain outcomes in this
44:52population was similar to surgery
44:54and overall survival progression.
44:55Free survival and other outcomes
44:57and and again surprising results
44:59that 87% overall survival.
45:00At five years for SBRT so hard to know
45:03how to extrapolate some of the older
45:05studies that included patients who were
45:08not great surgical candidates in terms,
45:10especially in terms of overall survival.
45:12So at the end you know with
45:14the fact that it beckoned,
45:15and several Members who are here
45:17right now is at the love you
45:20know from different disciplines.
45:22We all got together and and it's been
45:24working on this four part yield guideline.
45:26That's a collaboration
45:27that that transformative,
45:29practical framework for weighing short term
45:31versus long term benefits and downsides.
45:33So this is one of many figures in this
45:35paper that are are looking at, you know how?
45:37How can we go through all the
45:39data that's out there right now,
45:40as imperfect as it is, and?
45:42Trying to figure out which patients
45:44you may benefit from SPRT, lobectomy,
45:47sublumbar resection, or ablation,
45:49and as you can see in this figure,
45:50there's nuances with and patient selection
45:54that's really critical and and and,
45:56and that was very proud of
45:57how well our team has worked,
45:59as in in in a tumor board,
46:01as well as just on the phone.
46:02Otherwise working through these.
46:05Working through the decisions about
46:08how to handle each individual patient.
46:11So I'm moving on to long arguments
46:13that disease,
46:14uhm,
46:14I so here we pick up all the mess
46:17that disease as a intermediate state
46:19between local and systemic disease
46:22where the the kind of original
46:24helmet and excellent definition was
46:26that there may be a small subset
46:28for whom radical local treatment of
46:30primary cancer and almost at legions
46:33might have a curative potential,
46:34often defined as 123 or one to five patients.
46:37So we know the surgery or radiation may
46:39have a larger role in localized disease.
46:42With an stomach there be having
46:43a much smaller role in Wylie,
46:44metastatic disease is really the opposite,
46:46where it's stomach therapy is a primary
46:49role over surgery and radiation.
46:51But alchemist axes disease,
46:52there may be a role for both.
46:54So here this is some going for
46:57the papers here that some trials
46:59that are phase two looking at
47:02local consolidative therapy.
47:04In this case the Gomez studied in the
47:07Anderson showed that either surgery
47:08or SBRT for stage four non small
47:10cell lung cancer patients with one to
47:12three metastases and no progression
47:14after three plus months of chemo,
47:16actually had increased progression,
47:18free survival and overall survival.
47:20Median of 41 versus 17 months
47:23compared to to not.
47:24Using a local resolves OK and then use it
47:28stomach therapy alone after this point.
47:31This was also shown you know this
47:33this study just the best PRT but
47:35similar population stage four non
47:37small cell lung cancer from the
47:39southwestern after three plus
47:40months of chemotherapy this had
47:42to be stopped early because of
47:44the very clear progression free
47:46survival improvement this was.
47:47This was shut down by the IRB
47:49because it's not about to be
47:51ethical to continue this study.
47:52Uh, and then come see if a comment
47:55looked at at all domestic cases of
47:57any primary and found the five year
47:59overall survival of 42% versus 18%.
48:02So actually quite similar to the
48:04Golden study showed that really,
48:06that's where 4.5% in this case.
48:08So they they did have three
48:09that's in this population,
48:10but there was no quality of life
48:12difference among among the best.
48:13So you know, there's always caution.
48:15Of course it needs to be taken
48:16when you when you do this,
48:18all those were the chemotherapy alone era.
48:20Now we're in the immunotherapy area as well.
48:22So energy LU002 is the current
48:25ongoing phase three study that's
48:27looking at a similar population,
48:29but now allowing for immunotherapy in
48:31there in the most recent amendment.
48:33So I think we still quite relevant
48:36question to ask at this point.
48:38They do require that you use
48:39SBRT for at least one lesion,
48:41but can use surgery for other
48:44regions as well.
48:45So now for long, oligo progressive disease.
48:48This is a somewhat different concept
48:50in that there you may not necessarily
48:53have just a few minutes up front.
48:55You may have several types of disease and
48:56have good control with stomach therapy,
48:58but when you stay on this systemic
49:00therapy or when you're off of it,
49:02if one or a few areas grow,
49:05then you're faced with choices.
49:07Do you switch therapy to continue therapy,
49:10or do you add therapy and so
49:12so so so this is some workouts
49:14from from staff get injured.
49:16I'm looking at the SBRT for oligo,
49:18progressive mounts, muscle lung cancer.
49:20After immunotherapy,
49:21a small study of 26 patients
49:24who had acquired resistance to
49:26immune checkpoint inhibitors,
49:2715 of them had local therapy without
49:29immediate salvage systemic therapy,
49:31so they either were treatment holiday
49:33systemically or just remain on
49:35their on their same amino therapy.
49:37It's a somewhat busy the figure here,
49:39but the in essence the green
49:41is where they were able to.
49:42The circles are where you got local therapy.
49:44The green is when they were able to stay on.
49:47Immunotherapy and then Gray is when
49:48they had to switch to something
49:50else to your overall survival was
49:5292% and quite a few patients were
49:54able to maintain mean checkpoint
49:55inhibitors for years.
49:57In some cases after local therapy.
50:01So this is a state from
50:02Redecan Allison Campbell,
50:03an investigator initiated trials here that
50:06looked at SBRT for all the progressive,
50:08non small cells lung cancer.
50:09After immunotherapy as well,
50:11this is a 21 patients faced
50:13one and two study where he gave
50:15Pembroke until progression,
50:16then SBRT and then then
50:18restarted Kimbrough again.
50:19Right afterwards the endpoint was
50:21overall response rate and non irradiated
50:23legions to really to investigate.
50:25Can you reinvigorate this
50:26immune response and maybe even
50:28get enough scope of response
50:29to sites that were not treated?
50:31Disease Control overall was 57%,
50:34but interestingly there were two patients.
50:3710% of the group that had a partial
50:39response for more than a year and and,
50:41and there's lots of ongoing studies now
50:44investigating more about about who this
50:46you know the the the factors that may
50:48have led to that for those patients.
50:50So just Astro the last month was presented
50:55this curb study out of MSK that looked
50:58at a similar population of knots,
50:59muscle lung cancer patients,
51:01or breast cancer patients,
51:02and interestingly,
51:03found a large PFS benefit for SBRT for
51:06non small cell lung cancer patients,
51:08but not for breast cancer patients.
51:10You can see in lung 44 nine weeks
51:13whereas breast was 18 versus 19.
51:15No difference there.
51:16Paper still yet to come out,
51:18so I think there's still a lot
51:19of questions here, but this is.
51:20Intriguing data that maybe this is not this.
51:23Maybe Histology independent in
51:25terms of the the the role of SBRT
51:28in this context stuff Joe Hung is
51:30about to activate this study as
51:32well for renal cell carcinoma.
51:34This is a phase two study where
51:35we're looking at ICI until
51:37disease progression and then SPRT.
51:39And then I see I again at the end
51:40point being progression free survival.
51:42So there's there's a lot going
51:44on in this arena.
51:45Just again for the CD three study.
51:47We do include all capacities,
51:49all progressive disease as well.
51:51This teams that are central,
51:53so we've had this review here that we were
51:55last here on local updated therapies.
51:57If you want more details,
51:58feel free to refer to this
52:00on other studies that have
52:01come out as well.
52:03So in summary, we come we for
52:06early season of muscle lung cancer.
52:09You know our future directions here are that
52:11we're really looking to optimize patient
52:14selection and SBRT dose fractionation
52:16for peripheral tumors for central tumors,
52:18or we have this D3 trial like I mentioned,
52:20as well as Ultra central tumors,
52:22which we're currently investigating
52:23retrospectively and hopefully
52:24leading to a prospective study.
52:25At some point we're looking to add
52:28immunotherapy to SPRT and seeing to
52:30investigate whether that is helpful or not,
52:32in which populations may be useful.
52:34Two ongoing trials open it, yell as well.
52:37The keynote and the swab
52:38studies Olga Ministik.
52:40Another progressive disease,
52:41optimizing patient selection,
52:42and those fractionation as
52:44well as sequencing,
52:45combining SPRT without CI.
52:47So we
52:49make sure that the prospective
52:53studies. If you're if credit,
52:55that's his name going forward.
52:58So outside the scope today we
52:59have a lot of exciting, ongoing,
53:01pending trials at and pending
53:03trials at the yield a lung dart,
53:05as well as the T Red Dart.
53:06I'm not going to get into this today,
53:07but locally advanced non small cell
53:09lung cancer limited stage and extensive
53:11stage small cell lung cancers.
53:12There's a lot going on,
53:14so we're excited to be working on that.
53:17And finally, like to acknowledge our
53:19yield domestic radiotherapy program,
53:21the members of our team have been phenomenal.
53:23We've been working weekly
53:24and chart rounds ever since.
53:25I had the honor of taking this over
53:27this program in 2019 from Roy Decker,
53:29who's been just amazing mentor of
53:31mine and we really started the SPRT
53:33program here at Yale several years ago,
53:35and among our six sides,
53:37we go over all of radiation plans
53:39having to do with lung cancer every
53:42week to be sure we're improving
53:44communication and quality assurance
53:45and standardizing practice and then
53:48sharing and sharing information.
53:49So I I just I'm very blessed to
53:52work with this wonderful team.
53:54Thank you all very much for your time today.
53:58Thank you Henry.
53:59It's very impressive results.
54:00Some of the trials you showed
54:03us are there questions.
54:04I see someone has a hand up,
54:06but I can't see who that is.
54:09Or the questions in the chat.
54:23No questions.
54:26So so Henry in your time here,
54:29what do you think has been the
54:30biggest step advance? In radiotherapy
54:34specifically, I think our ability
54:38to really use the imaging that
54:40we have of and and and be able to
54:44target even more precisely overtime,
54:46and I think you know we're excited
54:47to have a new reflection machine.
54:49You know that's coming in soon to be able
54:52to target all of them attached season Algo.
54:53Progressive disease.
54:54I think that's really the future
54:56here in terms of, you know,
54:58using local therapy to supplement the
55:01excellent events that we've made in systemic.
55:03Therapy.
55:03There's been so impressive and
55:05and especially in lung cancer,
55:07where we see just, you know,
55:09so much better survival than
55:10we've ever seen before.
55:11Vestige for patients you know and
55:13combine this with with you know
55:16with with targeted agents and
55:18immunotherapy and chemotherapy to
55:19really extend survival and and,
55:21you know, are we going to seek?
55:23You know we're seeing more
55:24patients at that 10 year Mark?
55:25Now you know even more who are still
55:27disease free, so you know, it's it's.
55:29It's very exciting time that you know,
55:31as a technology improves in our.
55:33Ability to select patients
55:35properly for this improves.
55:36We're hoping to really see
55:39more patients benefit from,
55:40you know,
55:41from from using SBRT
55:42in this setting. Perfect
55:44we have doctor D. Do you have a question?
55:50I see a hand. Uhm, maybe not.
55:54OK, well thank both speakers again.
55:56It was a terrific series and I
55:57learned a lot and I hope the
55:58audience did. Also thank you.
56:01Thank you.