Tumor-Type: Sarcoma and Thyroid Cancers

Transcript

• 00:00Great, so today I'm going to just talk
• 00:04about thyroid cancers and sarcomas,
• 00:06but as Melanie said, please just.
• 00:11Call out if you have any
• 00:13questions or put them in the chat.
• 00:16These are my financial displays
• 00:17which I know I have to let you know
• 00:20about in which those of you in
• 00:22regulatory hopefully know all about,
• 00:24because as part of the trials we do all
• 00:27have to fill out financial disclosure forms.
• 00:30So today I'm going to concentrate,
• 00:34hopefully on thyroid and sarcomas.
• 00:37If we get through all the slides,
• 00:39if we don't, I'll just do thyroid or
• 00:42however many slides we get through.
• 00:44So these.
• 00:45The top ten cancers that we see
• 00:49in the United States.
• 00:52This chart is put out by the
• 00:55American Cancer Society every year.
• 00:58And as you can see on the top,
• 01:00it's the number of new cases of
• 01:03cancer in men and in women and on
• 01:06the lower part of the slide are
• 01:08the number of deaths from cancer.
• 01:11At least the top ten cancer deaths
• 01:13in men and women.
• 01:15So you can see the two cancers that I'm.
• 01:18Can talk backstage thyroid
• 01:21hardly feature on this at all.
• 01:23So thyroid cancer is one of the.
• 01:27Most common cancers in women.
• 01:29It's #7 on this list,
• 01:32but because it has such a good prognosis,
• 01:36it doesn't appear on the top ten cancer
• 01:40deaths and sarcomas are quite rare.
• 01:44There's only less than 20,000 cases a
• 01:47year of all different types of sarcomas,
• 01:50and so they don't even appear
• 01:53on the number of new cases,
• 01:55leave alone on the number of.
• 01:57Test.
• 02:00So I'm going to talk through a couple
• 02:04of cases during this lecture today,
• 02:07and the first one is a 74 year old man
• 02:12who had differentiated thyroid cancer.
• 02:15So some of you in my.
• 02:17Team will recognize this patient as
• 02:20someone who's on one of our trials.
• 02:23So back in 2000 he was noted
• 02:25to have a high calcium.
• 02:28And a work up showed a
• 02:30papillary thyroid cancer.
• 02:31Now this is a little bit unusual.
• 02:33Most of the thyroid cancers that
• 02:35we see are found because someone
• 02:38feels a lump in their neck.
• 02:40But he came through a different route.
• 02:43He had a total thyroidectomy and
• 02:46then followed that with Radio ID.
• 02:49That almost 20 years later,
• 02:51he had progression of disease,
• 02:53so it just shows that many
• 02:55of these cancers will do very
• 02:57well for a long period of time.
• 02:59He started what is considered
• 03:00the standard treatment.
• 03:01That's length at the West Haven, VA.
• 03:06But then he progressed and we had
• 03:08a trial open a couple of years ago,
• 03:11which he was eligible for and he came
• 03:13over for that particular trial using
• 03:16a medication called regorafenib.
• 03:21So just a little bit of anatomy
• 03:23for you to take you back to.
• 03:26Biology at college or wherever
• 03:28you last saw this diagram.
• 03:30So the thyroid is sets.
• 03:33It's just below the larynx,
• 03:35the larynx, so you can feel the Adams
• 03:38apple as it's called in lay terms.
• 03:41So just below that is where the thyroid is.
• 03:44So if you have someone with a thyroid cancer,
• 03:46they'll often have a hard mass in
• 03:49that area or a new lump in that area.
• 03:52And here at the parathyroid glands.
• 03:54These are little glands that are.
• 03:57Involved in regulating calcium.
• 03:58And that's why our patient
• 04:01they looked for these plans,
• 04:03but they actually found something
• 04:05else when they were looking.
• 04:07So that this diagram is from the CDC,
• 04:10so it's beautifully illustrated.
• 04:11This one is something I made,
• 04:14so it looks like a 5 year old did it,
• 04:16but it's really just to show that the
• 04:19thyroid has different types of cells,
• 04:22so follicular cells normally
• 04:24make thyroid hormone,
• 04:26and they're the ones that give rise
• 04:28to two differentiated thyroid cancer.
• 04:30It's the most common thyroid
• 04:33cancer that we see.
• 04:3490% of all thyroid cancers.
• 04:37And 90% of those are
• 04:40papillary thyroid cancers.
• 04:41We also get some histological variants,
• 04:45and I've written some of these down here.
• 04:47Follicular hurthle cell
• 04:49poorly differentiated,
• 04:51but they're all considered
• 04:53part of this DTC subtype.
• 04:56Then we also get another type of cancer from
• 04:59these cells called anaplastic thyroid cancer.
• 05:02This is thankfully very,
• 05:04very rare.
• 05:04Only about 1% of all thyroid cancers
• 05:07because it's very aggressive.
• 05:10And the other 10% or so are
• 05:13Magill airy fairy cancers.
• 05:15They come from a different cell,
• 05:17so they make different tumor markers.
• 05:19So if you're involved
• 05:20in any of these studies,
• 05:22then some of the biochemical
• 05:26tests that we do,
• 05:27the data that you'll enter
• 05:28for medullary thyroid cancer,
• 05:30will be calcitonin and CEA.
• 05:33But for differentiated thyroid cancer,
• 05:35we wouldn't look for these,
• 05:37but we'd look for other things
• 05:39such as thyroid globulin.
• 05:42The staging of thyroid cancers
• 05:44has changed over the years,
• 05:46but it's it's very different from
• 05:48any other cancer that you'll
• 05:50see because it's based on age.
• 05:52So if someone is young by young,
• 05:55they mean less than 25.
• 05:57Then there's only two states at 55.
• 06:00Sorry, there's only two stages,
• 06:03stage one and stage two.
• 06:04This is because younger patients
• 06:07with differentiated thyroid cancer
• 06:09have such a great prognosis.
• 06:12So they don't have a stage three and four,
• 06:15but over the age of 55,
• 06:17reuse that staging system that
• 06:19many of you who have to enter
• 06:21data are very familiar with.
• 06:23It's called the TNM staging system,
• 06:26where T is the size of the cancer and
• 06:29is the number of nodes and M is has
• 06:32it spread or metastasized anywhere,
• 06:36and you put all those numbers in
• 06:38a special table which is unique
• 06:41to every single cancer.
• 06:42And you come out with a stage group,
• 06:44so stage 123 or 4.
• 06:49So most patients before they reach the
• 06:52CTO office for one of our clinical trials
• 06:56with differentiated thyroid cancer,
• 06:58will have had their thyroid removed,
• 07:00and they probably would have had radioiodine
• 07:03and 90% of patients are cured with this.
• 07:06So that's why we don't see a ton of thyroid
• 07:10cancer patients on our clinical trials.
• 07:13But we do see the ones who have
• 07:16radioiodine refractory disease,
• 07:17and that's about 10% or so mentioned.
• 07:20So the 10 year survival for someone
• 07:23with metastatic thyroid cancer is pretty
• 07:26good if they still take up radio ID.
• 07:29But it's only about 10% if
• 07:31there radio ID refractory,
• 07:33and for these patients their prognosis is
• 07:36much less than for the other three cancers
• 07:40with only a 2 1/2 to 3 1/2 year prognosis.
• 07:44So we definitely need new
• 07:46treatments for these.
• 07:46Patients.
• 07:48This is how we define radioiodine
• 07:51refractory disease.
• 07:52So even though they've had so much radio ID,
• 07:55they can't have anymore,
• 07:56or they have a lesion that grows
• 07:59either that takes that radio ID,
• 08:01but doesn't respond to treatment
• 08:03or that doesn't take up radio ID.
• 08:06Any of those three are considered
• 08:09radio ID refractory,
• 08:10so this is the standard treatments
• 08:12that we've had back in the 1970s.
• 08:16We only had chemotherapy and the
• 08:19survival on the studies that looked at
• 08:22chemotherapy was was about 8 months.
• 08:25Now.
• 08:26Many of those, I think,
• 08:28would have waited to treat patients until
• 08:31they really couldn't take anything anymore,
• 08:34surgery or anything else.
• 08:36Nowadays we put patients on
• 08:37trail a lot earlier,
• 08:39so some of these numbers may
• 08:40look a lot better,
• 08:41but they may not be as much of
• 08:44an improvement as you think.
• 08:46But nevertheless they are better,
• 08:48and these are all targeted therapies that
• 08:51are pills that we were involved with at Yale.
• 08:54So we were involved with the decision trial
• 08:57that looked at Seraphim versus placebo,
• 08:59and we were involved in one
• 09:01of the lend Bacnet trials.
• 09:03And,
• 09:04as you can see,
• 09:04the progression free survival is gradually
• 09:07gone up to almost a year in 2012,
• 09:11eighteen months in 2015 and
• 09:13the second line treatment that
• 09:15was just approved last year.
• 09:17The comment trial which we had open
• 09:19here the progression free survival,
• 09:21has not yet been reached in in the
• 09:25time when they published the data.
• 09:27So really good medicines coming out.
• 09:29But we do need even more,
• 09:32and one of the reasons is despite
• 09:35these medicines being active,
• 09:37they often have sides significant
• 09:39side effects.
• 09:40So those of you again who are
• 09:45or registered nurses involves.
• 09:47In trials will have to do these
• 09:51adverse event forms and fill in pretty
• 09:54much any adverse event can occur.
• 09:56But the most common being hypertension.
• 09:59Diarrhea, fatigue,
• 10:00weight loss, and proteinuria,
• 10:03so it's a difficult medicine for
• 10:06many of our patients to take.
• 10:08So these days,
• 10:10this is how I treat thyroid cancer.
• 10:12If they're doing very well in
• 10:15the disease isn't growing,
• 10:16then I won't do anything.
• 10:18I'll just follow them.
• 10:19I'll not give them any any treatment
• 10:21because I know they can often live for many,
• 10:24many years with just doing surveillance.
• 10:27But if they have progression of disease,
• 10:29then we do humor profiling that's.
• 10:32Sequencing of their tumor DNA
• 10:34to look for any changes if they
• 10:37don't have any or if they have
• 10:39what's known as a BRAF mutation,
• 10:41then I'll treat with Len Bat neighbor,
• 10:43one of the other tyrosine kinase inhibitors.
• 10:47But if they have a specific fusion
• 10:49that I know has a particular
• 10:52medication that's very active,
• 10:54then we would treat with one of
• 10:57those medications and you may find
• 10:59some of these names familiar.
• 11:01V and treatment trial.
• 11:03Which was the Star Trek 2 trial?
• 11:06What's great name for a study which
• 11:08we've been trying to closeout for
• 11:10about two years is we had open here
• 11:13at Yale and then Doctor Wilson in
• 11:16the Lung Group had the cell pick
• 11:19atnip Oarlocks 0292 trail open until.
• 11:24Recently
• 11:26so we've talked about DTC or
• 11:30differentiated thyroid cancer.
• 11:31This is another case this time.
• 11:33Medullary thyroid cancer patient who
• 11:36is 48 years old presented with a cough
• 11:40that his cat scan didn't show any lung
• 11:42mass that did show a thyroid mess
• 11:45and this turned out to be medullaris
• 11:48thyroid cancer with metastatic
• 11:50disease into multiple neck nodes.
• 11:54Imaginary thyroid cancer effects
• 11:56a different part of the thyroid,
• 11:59so not the follicular cells,
• 12:02but the parafollicular cells
• 12:04and these as I mentioned,
• 12:06make different proteins calcitonin
• 12:08and CEA and we can use these to
• 12:12monitor the patients disease.
• 12:14They're often associated with
• 12:17genetic and familial changes,
• 12:19and sometimes in some of the studies
• 12:22they'll require that we determine.
• 12:24Whether they are wrecked positive
• 12:26or RET negative as this might
• 12:30affect their prognosis.
• 12:32In our particular patient,
• 12:33he had a thyroidectomy but a few years
• 12:36later started to have a very large,
• 12:38very high calcitonin and CEA level.
• 12:42He also noticed a new lump in the
• 12:46right side of his neck and started
• 12:50a medication called Vendetta.
• 12:52So again, this is a case where.
• 12:56Up until recently,
• 12:58we only had one medication
• 13:01for this particular disease,
• 13:03which was vandetanib,
• 13:05but now we have cabozantinib,
• 13:08which is an alternative,
• 13:09and we know that if you have
• 13:12a specific reputation,
• 13:14you can use one of these medications
• 13:16that was on the other trial as well.
• 13:18So this is another slide as well.
• 13:20So this is how I approach a
• 13:23patient who's newly diagnosed
• 13:26with medullary thyroid cancer.
• 13:29Anaplastic thyroid cancer is a very
• 13:32rare and very aggressive disease.
• 13:35Less than 1000 cases a year,
• 13:37but almost everyone will die of the
• 13:40disease within about six months.
• 13:42It's probably the most aggressive
• 13:44cancer that we know in oncology today.
• 13:47There's no curative therapy,
• 13:49so we really need to find new treatments.
• 13:52That's where clinical trials come in.
• 13:56So one of the trails noticed that some
• 13:59of these patients had a mutation in breath,
• 14:02so we talk about the trials only taking
• 14:07patients with specific mutations.
• 14:10So in thyroid cancer,
• 14:11this pathway is very important and
• 14:14this is something that you'll see a
• 14:17lot in different kinds of cancers.
• 14:19This is a cancer cell.
• 14:20This is the nucleus at the the
• 14:24middle and this is the.
• 14:27This cell membrane with the site a
• 14:30person in between so many cancer cells.
• 14:33This particular one is the Melanoma
• 14:35will have a receptor on the surface.
• 14:39Which part of it is outside the
• 14:41salad so it can receive signals from
• 14:43outside the cell that activates an
• 14:45enzyme on the interior part of the
• 14:48receptor which then can activate
• 14:51different cells signaling pathways and
• 14:54these will tell the cancer cells to grow.
• 14:57To survive to spread,
• 14:59to invade other other things,
• 15:02and.
• 15:04Normally it's very very well regulated
• 15:07and you might say why would you
• 15:10want to have these cell signaling
• 15:13pathways in a normal cell anyway?
• 15:15And why, what's the point of them?
• 15:18Well,
• 15:18the point is normally when
• 15:21we're developing and growing,
• 15:22we want cells to grow.
• 15:24So you want your hand to grow from the
• 15:27size of their little infants hand up to.
• 15:30It's the size if your
• 15:31hand when you're an adult,
• 15:32but you then want it to stop,
• 15:34you don't want your hand to keep
• 15:36growing for the rest of your life,
• 15:38so there are stopping signals that
• 15:42will inhibit these pathways as well,
• 15:45so normally it's very very tightly regulated.
• 15:48The cells will grow to a certain point.
• 15:50They'll go to different parts of the body,
• 15:53but then they'll stop and
• 15:55stop growing in cancers.
• 15:56Some of these enzymes are always
• 15:59on the arm position.
• 16:00And they can't be turned off.
• 16:02So one of these is BRF
• 16:05which when it is mutated,
• 16:07can drive these cell signaling
• 16:10pathways forward.
• 16:11So over the years companies have
• 16:14found ways of inhibiting these
• 16:16enzymes and hopefully stopping
• 16:18these pathways from going forward.
• 16:21So this works pretty well with Melanoma.
• 16:24It doesn't work as well with
• 16:27many of our other cancers,
• 16:29but it was tested in patients
• 16:32with anaplastic thyroid cancer.
• 16:33By using inhibitors of this
• 16:36enzyme and this enzyme.
• 16:38And this is one of the trials results from.
• 16:43A few years ago,
• 16:45so all patients were treated
• 16:47with this combination.
• 16:49This line here the zero
• 16:51line means they're cancer,
• 16:52stayed the same size.
• 16:54Any bar above the line means it got bigger.
• 16:59And any bars below the line
• 17:01means the cancers got smaller,
• 17:03so you can see this is a disease
• 17:05where almost nothing had ever
• 17:07worked in the past and now you see
• 17:09almost every patient that cancers
• 17:11are getting a little bit smaller.
• 17:14Some of them may reach a partial response.
• 17:16That's what this line is here,
• 17:18and one patient had a complete
• 17:21response to treatment so.
• 17:24This is a clinical trial that
• 17:26really was very effective for
• 17:28this particular type of cancer.
• 17:31It's not a cure, unfortunately.
• 17:32Many of these patients did.
• 17:35After a few months start to progress again,
• 17:38but it was a huge step forward,
• 17:40so that's why we have to
• 17:42keep doing clinical trials,
• 17:44and these are some of the trials
• 17:46we've had at Yale for thyroid cancer.
• 17:48Many of them are closed,
• 17:49but we were one of the main sites
• 17:51for the decision trial that was.
• 17:54Using seraphinite about 10
• 17:56years ago and even longer,
• 17:58we were one of the first sites in
• 18:01the world to open the van debt nip
• 18:03trial for medullary thyroid cancer,
• 18:06and since then,
• 18:07we've had all of these studies.
• 18:09The most recent one is this
• 18:11study that we're doing with Dana
• 18:13Farber looking at regular F nib
• 18:15for medullary thyroid cancer in
• 18:17differentiated thyroid cancer.
• 18:19And I mentioned Doctor Wilson
• 18:21study looking at self be catnip.
• 18:24So any cancer that had a wrecked
• 18:27change in it.
• 18:28In our case it was medullaris and
• 18:31differentiated thyroid cancer.
• 18:34So once we get more trials open,
• 18:38I think we'll be able to get more
• 18:40patients with thyroid cancers seen here.
• 18:43But yeah,
• 18:44I don't think we have anything in the
• 18:47works for thyroid right now.
• 18:48The rest of my team might know I tend to.
• 18:52Forget what's on that list, but,
• 18:54but hopefully we'll be opening some soon.
• 19:00So.
• 19:05That was. Well, I wanted to say
• 19:07that thyroid I was going to spend
• 19:09the rest of the time on sarcomas.
• 19:12Anyone? See the chat so I can
• 19:17actually see. And if anyone's.
• 19:23Any? Comments in bet.
• 19:26Otherwise I'll keep going, so sarcomas.
• 19:31Or cancers of mezon kaimal tissue.
• 19:34So that's the bone connective,
• 19:36tissue, muscle, and adipose.
• 19:38There's over 50 different subtypes,
• 19:41and because it's so rare, there's less
• 19:44that is less than 1% of all cancers.
• 19:47It's often the most difficult
• 19:49cancer for many people to learn,
• 19:51because there's just so many different names,
• 19:54and we don't see very many of them.
• 19:58So here's a.
• 20:00A schematic of what?
• 20:03That means just to look at,
• 20:05so we see almost 2,000,000 cancers
• 20:08every year in this country.
• 20:11Most of them are what we call carcinomas,
• 20:13so that's things like lung cancer,
• 20:15breast cancer, prostate cancer,
• 20:17and thyroid cancer as well.
• 20:20We also see other cancers,
• 20:21as all of you are aware of.
• 20:23So leukemias and foamers melanomas
• 20:27neuroendocrine cancers, and here's
• 20:29sarcoma on the other end of the scale.
• 20:31So we still see 17,000.
• 20:34But when you compare 17,000 to 1.7 million,
• 20:39several orders of magnitude less,
• 20:42and so that's why many people
• 20:45either will never see a sarcoma or,
• 20:48or at least they won't.
• 20:50Get to know them as well as
• 20:52they do have their cancers.
• 20:53We split them broadly into 2 main types.
• 20:56There's soft tissue sarcoma and bone sarcoma,
• 21:00and as I've mentioned,
• 21:01there's many,
• 21:01many different types of soft tissue sarcoma.
• 21:06So here is some of the different
• 21:08types and these are all long names,
• 21:10so I'm not gonna read them all out.
• 21:12But we do have a trial that we're
• 21:16trying to open for leiomyosarcoma.
• 21:18We got the CDA sign so hopefully
• 21:22that will be on our list soon.
• 21:27We do partner with the pediatric group
• 21:30and they have or they often have trials
• 21:33for osteosarcomas and nearing sarcoma,
• 21:36and we have a trial for chondrosarcoma
• 21:39that we're opening or that we just
• 21:41opened and then we've had studies
• 21:44in other soft tissue tumors.
• 21:47These are not considered sarcomas,
• 21:49but intermediate grade tumors,
• 21:51which have the ability to return
• 21:54even after they've been respected.
• 21:56So these include desmoid
• 21:58tumors and giant cell tumors,
• 22:01which either we've had their own trials for.
• 22:05There was one through spring works
• 22:08that is still, it's close to a crawl,
• 22:11but we still have a patient on it.
• 22:16Usually sarcomas are what we call sporadic,
• 22:19so they they occur and we don't
• 22:22know why they affect one particular
• 22:25person rather than someone else,
• 22:29but occasionally we'll see other
• 22:31reasons why people get sarcomas,
• 22:34so some of them are more common in children,
• 22:36such as new wings and Raptor myosarcoma,
• 22:40some of them in younger adults,
• 22:42some of them can occur at any age,
• 22:44such as gastrointestinal stromal tumor.
• 22:47Which we also have a study for,
• 22:49and some of them mainly in the elderly.
• 22:53About 5% or associated
• 22:56with familial syndromes.
• 22:58And sometimes you can get exposures to
• 23:01certain things that can cause sarcomas.
• 23:04Radiation is the most important of that,
• 23:06and we're hoping to open a radiation
• 23:09induced sarcoma trial through
• 23:11swab that's still in a very,
• 23:13very early stage,
• 23:16and hopefully we'll go through
• 23:18their various committees,
• 23:19but probably won't be a year until
• 23:23we actually get the final protocol.
• 23:26Here's the staging of.
• 23:28Sarcoma this is actually the
• 23:30old stage in the 7th edition.
• 23:32It was a very simple staging system,
• 23:35but it included Gray.
• 23:36This is the one of the few cancers,
• 23:39if not the only cancer where
• 23:41the grade of the tumor is as
• 23:43important as the size or whether
• 23:45or not lymph nodes are involved.
• 23:47As you can see,
• 23:48if you've got a high grade tumor,
• 23:50even if it's very small,
• 23:52it can be the same stage stage
• 23:54three as a much smaller tumor that.
• 23:58Yes,
• 23:58then lymph native but also very important
• 24:01to work with the pathologists in sarcomas,
• 24:05but it under Esther or overestimated
• 24:08the prognosis for these patients
• 24:10in the old staging system.
• 24:13It was just divided whether patients
• 24:15were had tumors that were less than 5
• 24:18centimeters or greater than 5 centimeters,
• 24:21and we know that with sarcomas the
• 24:24disease free survival drop significantly
• 24:26as the size of the tumor gets bigger.
• 24:29So here we've got a tumor
• 24:32that's less than 5 centimeters,
• 24:3577% disease, free survival,
• 24:37and disease free survival
• 24:39drops according to the size,
• 24:41but these would all be
• 24:43considered the same stage.
• 24:44In the old staging system.
• 24:47So now in the new staging system,
• 24:49we have to look at the stage the
• 24:52the site where it is and also the
• 24:55the size of it in more detail.
• 24:58It's not perfect still,
• 25:00but it's a lot better than it was
• 25:03and the grade is very important
• 25:05that it's better to find these
• 25:07are the things that we have to
• 25:09notice on the pathology report.
• 25:11So if someone is on the sarcoma trail,
• 25:13the data will probably include
• 25:16all of this as well.
• 25:18So I said case is a man with
• 25:23gastrointestinal stromal tumor.
• 25:24He presented with dysphagia.
• 25:26That's trouble swallowing because
• 25:28of a big mass in his abdomen.
• 25:31He had progression of disease
• 25:33after it was removed and he got
• 25:35treated with standard treatment,
• 25:36which is imagining.
• 25:37But in 2020 had progression of his
• 25:40disease and was evaluated for our
• 25:45DCC 2618 study.
• 25:46So this is someone with a gist.
• 25:49You can see how big these tumors are.
• 25:51This is someone abdomen on a CAT scan.
• 25:54This is their leather with lots
• 25:56of spots where it's spread to and
• 25:58this is the original tumor here.
• 26:02This is someone who is treated
• 26:04with that medication in math,
• 26:05and if this was his disease before and
• 26:08you can see it's a very effective drug.
• 26:10A lot of the cancer in the liver
• 26:12has got much, much smaller that
• 26:14you can hardly see it anymore.
• 26:17And that's the standard treatment.
• 26:18Even now, for just at least
• 26:21in the first line setting,
• 26:23it's called a kit tyrosine kinase inhibitor,
• 26:27and almost everyone who gets this
• 26:30medication has a response to the disease.
• 26:32Either it slows it down,
• 26:34or it gets significantly smaller,
• 26:37and before Gleevec was the round,
• 26:40most people died within a year.
• 26:42If they had metastatic disease,
• 26:44but in the original trials.
• 26:47The one year survival meant that almost
• 26:50everyone who was treated survived a year,
• 26:53so this was a huge advance
• 26:56in the treatment of jest.
• 26:59Since then,
• 26:59we've had a few treatments approved.
• 27:02Signet Mabel Sutent was approved
• 27:04in the second line,
• 27:06regular F net, in the third line,
• 27:09and reprint Nip in the fourth line,
• 27:11and then we have another medication,
• 27:14Eva pregnant,
• 27:15which is very specific for just
• 27:17one particular type of jest.
• 27:19That's shown here.
• 27:21This medication here will print.
• 27:23NIB was the medication used in our study,
• 27:26the DCC 2618.
• 27:29It's been approved in the
• 27:31fourth line setting that.
• 27:32In the study they were looking to
• 27:34see whether it would be effective
• 27:36in the second line setting.
• 27:38Unfortunately, in that particular study,
• 27:40it was hopefully we'll
• 27:43get synthetic treatments.
• 27:45That's just one type of sarcoma,
• 27:47though for all the other soft tissue
• 27:50sarcoma is the best treatment is to
• 27:53remove the tumor and give radiation,
• 27:55at least if it's in the
• 27:59extremities of the body.
• 28:00We've sometimes give
• 28:02chemotherapy for local disease.
• 28:04But we know that it's not as
• 28:08effective as these two treatments,
• 28:11so most people get surgery and radiation.
• 28:17Sometimes we give radiation before
• 28:19sometimes we'll give it after.
• 28:21There are advantages of each,
• 28:24so if you give radiation before surgery,
• 28:27you get a smaller dose than
• 28:29field you give it afterwards.
• 28:31You have to give a larger field that
• 28:35might affect wound healing depending on.
• 28:40On the size and the amount of radiation,
• 28:43given that if you give
• 28:46radiation after surgery,
• 28:47then the patients get immediate
• 28:49surgery rather than having it
• 28:51delayed until the end of radiation.
• 28:57For chemotherapy we do give a
• 28:59lot of chemotherapy for specific
• 29:02types of sarcomas, and these are
• 29:05mainly the ones seen in children.
• 29:07This is a diagram of how we treat bones,
• 29:11soakings or osteosarcoma chemotherapy
• 29:14before and then surgery,
• 29:17and then more chemotherapy afterwards.
• 29:21Some trials have been done that have
• 29:25suggested medications are very useful,
• 29:28but then later on they've had to be
• 29:31rescinded and this was one of them.
• 29:33We actually had one of
• 29:35these trials open at Yale.
• 29:37This is the medication called avalara tumor.
• 29:40It's an antibody against PDVSA,
• 29:43one of those receptors that I
• 29:45mentioned earlier and the same
• 29:47receptor that another medication,
• 29:49which is also proof sarcoma.
• 29:52This afternoon it is active against.
• 29:55So here's that receptor here.
• 29:58Here's my pizap networks,
• 30:00and here's where Ularity map works,
• 30:03and there's a lot of excitement
• 30:05for this medication,
• 30:06because in the original trial it
• 30:08was looked at when it was compared
• 30:12when combined with doxorubicin,
• 30:14there was almost a year increase
• 30:16in survival for patients who
• 30:18got the combination,
• 30:20but this was a small phase two trail.
• 30:23The FDA approved the medication that said,
• 30:26you have to do a confirmatory
• 30:28phase three trial just to make sure
• 30:30these results were not a one off,
• 30:32and that it really is beneficial.
• 30:35And they also recommended to do a
• 30:38biomarker trial where you do biopsies
• 30:41before and after getting this medication.
• 30:44And this was the trial we had open at Yale.
• 30:48Unfortunately again,
• 30:48the phase three trial showed
• 30:51no advantage of adding these.
• 30:53Two medications together.
• 30:54In fact,
• 30:55it may have detrimental effects,
• 30:58so this medication went from being a
• 31:01savior of sarcoma to something that
• 31:04we're not allowed to use anymore
• 31:06because it's actually detrimental.
• 31:08So we do have to make sure we put
• 31:11all the data in properly and run the
• 31:14trials properly to make sure that we
• 31:17really know what these medications are doing.
• 31:21These are some of the trials
• 31:22we've had open at Yale.
• 31:24Here's that decipher a study
• 31:26that that patient went on.
• 31:29We've also had a medication that looks
• 31:33that were treated just liposarcomas
• 31:36selling X or and we have a couple
• 31:39of medications or trials that we're
• 31:42hoping to open or are currently open.
• 31:44Here's an alliance study for angiosarcoma,
• 31:48and we have an NCI trail for chondrocyte.
• 31:51Payments so again a very exciting time here.
• 31:56We also have studies using immunotherapy.
• 32:00It is if you who are not familiar
• 32:03with immunotherapy the way it's meant
• 32:05to work is you have a tumor cell
• 32:07that interacts with an immune cell.
• 32:10In this case AT cell, and by doing so,
• 32:14it tells the T cell.
• 32:16You've got to get activated and
• 32:18try and get rid of the tumor,
• 32:20but the tumor also has other proteins
• 32:23that turn off the activation of
• 32:25the T cell and stop it getting
• 32:28rid of the tumor cells.
• 32:30So what companies have done is try
• 32:32to stop this negative interaction
• 32:35with an antibody and anti PD one.
• 32:38In this case that will allow the the
• 32:41T cell to do what it was meant to
• 32:44do and try and cause tumor death.
• 32:49Many of you who have treated patients on
• 32:52immune checkpoint studies will know that
• 32:55there are many different adverse events.
• 32:58Here are some of the sites that can
• 33:00get inflamed and cause problems,
• 33:02and you can see that on average
• 33:06these occur within about 10
• 33:08weeks of starting the medication,
• 33:11but they can occur all the
• 33:13way out to over a year,
• 33:15so it's still important to ask questions.
• 33:18Of these patients, even if they've been
• 33:20on medications for a very long time.
• 33:24So I'm going to stop there.
• 33:29Just 'cause I wanted to keep
• 33:30this less than 40 minutes,
• 33:32but does anyone have any questions?
• 33:38I know we have some trails that
• 33:41again we're trying to open.
• 33:43And there's an angiosarcoma
• 33:45in a chondrosarcoma trail,
• 33:47and we don't have any thyroid
• 33:49ones that are accruing right now.
• 33:51But hopefully they will soon.