Smilow Shares: Advances in Colorectal Cancer

March 19, 2021

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March 18, 2021

Presentations by: Drs. Pamela Kunz, Xavier Llor, Jeremey Kortmansky, Michael Cecchini and Vikram Reddy

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00:00On tonight to Smilow shares
00:03on colorectal cancer advances.
00:05This is timely because it's
00:07colorectal Cancer Awareness Month.
00:11So I have with a great lineup for tonight
00:14I will introduce myself 1st and Pamela
00:17Kunze and I'm an associate professor
00:19of medicine and medical oncology and
00:22I'm the director for the Center for
00:25Gastrointestinal Cancers at Yale.
00:26I'll be introducing and serving
00:28as a moderator for the Q&A,
00:30which is a reminder.
00:32Please send your questions through
00:33the chat throughout.
00:35The meeting will weaken interspersed
00:37some of the questions after speakers
00:40and we can also do it some at the end.
00:43I'd like to introduce shabbier you're
00:46he's a professor of medicine and
00:48gastro enterology he's the director of
00:50screening and Prevention program and the
00:53Co leader of the Colorectal Cancer program.
00:56He will be speaking tonight on
00:58colorectal cancer screening and
01:00prevention Doctor Vic Ready is an
01:02associate professor of surgery,
01:03specifically colorectal surgery and a Co
01:05leader of the Colorectal Cancer program.
01:08Hill speaking,
01:09speaking about surgical management.
01:11Doctor Jeremy Courtney on Ski is an
01:13associate professor of clinical medicine
01:16and medical oncology and the chief
01:18Network officer for Smilow Cancer Hospital.
01:21He'll be speaking about changing paradigms
01:23and rectal cancer and the emerging
01:26role of total neoadjuvant therapy.
01:28And last but not least,
01:30to doctor Michael Cicchini,
01:31assistant professor of medicine
01:33and medical Oncology and Co.
01:35Leader of the Colorectal Cancer program,
01:37and he'll be speaking about
01:40personalized treatments for patients.
01:41Living with metastatic colorectal cancer.
01:45So just to start us off,
01:47I'd like to provide some context.
01:49Colorectal cancer is the third
01:50leading cause of cancer in the United
01:53States for both men and women.
01:55This is the top 10 list.
01:58It's also the third leading cause of
02:00cancer death for both men and women,
02:03behind lung and prostate cancer for men
02:05and behind lung and breast cancer for women,
02:08the good news is there is a
02:10lot we can do about that,
02:12and the doctor you will be speaking about.
02:15This is a preventable disease in many cases,
02:17and we hope to teach you about that tonight.
02:20Colorectal cancer has been in
02:22the news quite a bit this year,
02:24certainly with and last year with the
02:26tragic death of Chadwick Boseman,
02:28who died of colorectal cancer to
02:31very young age.
02:32Also, because a new guideline,
02:34the United States Preventive Services
02:36Task Force is recommended that we
02:39start screening at an earlier age
02:40and this is still in draft form,
02:43but is very likely to be
02:45recommended informally approved.
02:46So just to give you a little bit
02:48of a teaser of some of the topics
02:52will will talk about tonight.
02:54So I will stop there and pass
02:57the baton to doctor your.
03:13And you're still unmute. There we go.
03:17Still haven't gotten used to
03:19zoom all the time anyways.
03:20Thank you very much.
03:22How is it is a pleasure to be here
03:25tonight to share these time with
03:27with our colleagues and all of you
03:30and trying to understand a little
03:32bit better about several aspects
03:34of colorectal cancer and so.
03:36Happy to hear I have.
03:38Know what I'm?
03:40Conflicts of interest to disclose and
03:43I always find that starting global
03:45kind of helps put things in perspective,
03:48and this is a world map of
03:51colorectal cancer incidence.
03:52That's that's from the
03:54World Health Organization,
03:55and it corresponds to the 2018.
03:58And basically this is the
04:00incidence of colorectal cancer
04:02and the darker it is the color,
04:04the higher the incidents it is.
04:07And as you can see,
04:09there's a huge, actually huge gay.
04:12Cap from there less than 6.2
04:14of the of the lower risk areas.
04:17Southeast Asia.
04:18For instance,
04:19some areas of South Sub saharian
04:21Africa to the match much higher
04:24level of more than 26.8 that we see.
04:26That's per 100,000 individuals
04:28of mostly coinciding with the
04:30more industrialized countries.
04:31So what we see really is that the
04:34richer in general the richer country gets,
04:37the more colorectal cancer we get.
04:40And that happens with other cancers too.
04:43But anyways,
04:43So what I'm trying to show is that
04:46this is something that can really
04:49be modified in changes quite a bit,
04:52and there's some data or some studies
04:54that show that individuals who
04:56move from low risk areas to higher
04:59risk areas by the next generation.
05:02That next generation was already
05:04having similar incidents as
05:05the locals lower heavy.
05:07So that really speaks a lot about so
05:10many factors that play a big role.
05:13Depending on where we live and.
05:16Probably what we eat in all these
05:18types of aspects and this is something
05:20that I'm gonna show right here.
05:22There are some factors that are clearly.
05:26We have a very clear Association in
05:28terms of either increasing the risk
05:30of colorectal cancer or actually
05:32preventing preventing wrist.
05:34This is expressed here as a relative risk,
05:37which would mean everything that's
05:39above one would be a higher risk
05:42than if we didn't have that factor,
05:44and so everything that is below
05:46one that would mean a preventively
05:48so meaning that that Association
05:51is is preventing,
05:52or that factor would prevent the
05:54development of colorectal cancer.
05:56In here we can see as as risk
05:59factors that increase risks.
06:02We have heavy alcohol consumption.
06:04Obesity consumption of red meat.
06:06We're talking about 100 grams a day.
06:09Processed meat also very important.
06:12Also smoking even former smokers do
06:14have do still have a an increased
06:17risk of colorectal cancer and
06:19about the preventive factors.
06:21Two of them seem to be quite clear right now.
06:25Physical activity,
06:26maintaining a good level of physical
06:29activity that decrease the risk
06:31again below one and at dairy product
06:34consumption that seems to have us.
06:36Also,
06:36at the cruise we so there are a lot
06:40of things that as you can see,
06:42we can do something about it
06:44and we can modify and that's
06:47modifying that can modify the risk.
06:50But we've also known for a long
06:52time that we see a lot of what's
06:54called familial clustering,
06:55so it's more likely that we have we have
06:58a family Member who's had colorectal
07:00cancer that we may have a colorectal cancer,
07:03and that's something that I'm showing here.
07:05Again, relative risk about
07:06one would be higher,
07:07just having one first degree relative
07:09pretty much like doubles our
07:11risk even a little bit more than.
07:13And if we didn't have any and
07:151st degree relatives,
07:16they usually are.
07:17We called first degree relatives
07:19or siblings that were.
07:20Parents and never had descendants are kids.
07:22Actually that's those are
07:24the first degree relatives.
07:26If we have one or more first degree
07:29relative and one of them at least
07:31one of them who developed that
07:33cancer at age younger than 50,
07:35they risk is even higher.
07:37Actually an having two or more
07:39first degree relatives,
07:40their risk is very high.
07:42One more second degree relatives
07:44and even one more first degree
07:47relatives with one advanced adenoma.
07:49Those polyps that we called
07:52premalignant that even that increases
07:54our risk of colorectal cancer.
07:56So really where we're getting into is
07:59that we have a set of factors that
08:02are playing a very important role
08:05and and really there the development
08:08of cancer is kind of like these.
08:11The result of the interaction of lifestyle,
08:14environmental factors,
08:15dietary factors.
08:16Engines in the majority of cases it
08:19is the environmental lifestyle factors
08:21that play a much more significant
08:23role an in a smaller percentage of
08:26cases but very significant percentage
08:28of cases where it really weighs
08:30heavily isn't genetic factors.
08:32But again,
08:33none of them really seem to work
08:36independently and we really have
08:38to keep any in mind that those
08:40are all important factors.
08:42Another important factor.
08:43I would like to mention is when
08:46we are talking about the genetics
08:49part of it is that if we take any
08:52individual who develops corrective
08:54cancer at each older than 50,
08:56it's gonna be between 5 and 10%
08:59that they're going to be justified
09:02by genetic factors.
09:03Some that are inherited from
09:05one generation to the next.
09:07But as we diagnose those cancers
09:09at a younger age,
09:11these percentage of the ones
09:13that really the genetic factors.
09:15Play a much bigger role that's go up to 20%,
09:19and if we take individuals who are
09:22diagnosed earlier than each 35,
09:23as we can see over 3035% of them
09:27will be due to genetic factors.
09:29So the younger our diagnosis is made,
09:32the much more likely it is that it was.
09:37The genic factors have a much bigger
09:40role in the development of this cancer,
09:43so that's something important to
09:45always keep in mind when we're seeing
09:48developing cancer at a young age.
09:51And that's the good news that
09:54I would like to give here.
09:56That really, this is the most exciting info.
10:00And I'm going to share tonight,
10:03which is these graph here?
10:05This is from 1930 until 2017.
10:08And now here what we have is rate,
10:12which is per 100,000 individuals
10:14and both for males and females
10:16we've seen since the mid 1980s.
10:19This very steady decline,
10:21very significant declining incidence of
10:23colorectal cancer and mortality, both.
10:25So that's been certainly a big success.
10:29Yeah, in terms of cancer, very,
10:32very encouraging trends here.
10:34And if we average it all out
10:37and between 2006 in 2015,
10:39the annual decrease in colorectal cancer
10:42incidence has been averaging about 3.7%.
10:45This is huge.
10:47This is very significant.
10:49That decrease that we've seen,
10:51and we've seen this decrease,
10:54particularly even among
10:55the older individuals.
10:56So really,
10:57a pretty formidable change in trend here,
11:00and we've seen that as we
11:03were seeing in this again,
11:05this is incidence since 2000.
11:08Going down at the same time as we've
11:11been seeing the use of screening tools,
11:14particularly here,
11:15we are showing colonoscopy use so really
11:18a good match between the increase
11:20use of screening tools and decrease
11:23in the incidence rate of colorectal cancer.
11:26Not everything is due to that.
11:28We know that because even we,
11:31when we started doing more
11:33systematic colon cancer screening,
11:35the trend for correcting cancer to go down.
11:38Had already been established,
11:40but certainly.
11:42Very likely this huge acceleration
11:45in the decrease of colorectal
11:47cancer incidence has had a lot
11:48to do with the generalization
11:50of colorectal cancer screening.
11:53So really,
11:54a success story of of public health.
11:58So,
11:58well,
11:59we've known for years that because
12:02of that decrease,
12:04because this clear Association
12:07with the increasing screening
12:09decrease in incidents that the US.
12:13The multi.
12:16USPSTF which is a group that
12:18basically what it does is it say
12:22independent group of researchers
12:24were what they do is they come up
12:28with using the current literature.
12:30They come up with recommendations
12:33when it comes to mostly screening
12:35and prevention initiatives and this
12:38is a very highly regarded group
12:41that documents had mentioned before
12:43that it was that really issues.
12:46Recommendations and and they
12:49are usually followed by mostly
12:51by our primary care community.
12:53So and in 2016 they they already
12:57had recommended screening for years.
12:59In 2016 they said well screening
13:02average risk, asymptomatic adults,
13:04people 50 to 75.
13:06It is of sustained substantial
13:09benefit that's been really proven,
13:11and there they really give this
13:15strong backing to that.
13:17The benefits of early detection and
13:20intervention for corrective cancer
13:22screening decline after age 75 and
13:24the decision to screen individuals
13:26from 70s and 85 starts really depends
13:29on the overall status of of every individual,
13:32because as we get older,
13:35if we have more other underlying conditions
13:38that can really be at all in our health,
13:41it may be it may not be as
13:44beneficial As for someone who still.
13:47In a pretty good health,
13:49even if they are at this range of age and
13:53after age 85. At, they really don't make
13:56a recommendation for screening because
13:58they think that the risks probably in
14:01most cases would outweigh the benefits,
14:03so that's where they were in 2016.
14:06And and for the for a number of years
14:10really screening starting at age 50 has
14:12been the norm and very well accepted
14:15public health measure that we know that
14:19saves lives and there are different
14:21ways of screening for colorectal cancer.
14:24The one most.
14:25Of eyes are more familiar
14:26with his colonoscopy,
14:28which is again taking using this
14:30flexible tube with the camera there
14:32that is introduced to the ****** and we
14:35look at the entire large bowel and it
14:38allows us also for removal of polyps
14:41which is really at the end of the day.
14:44What really saves lives are
14:46removing early lesions,
14:47so that's one of the tests
14:50that commonly is done,
14:51but there are other approaches that City
14:54colon ography for instance which is.
14:56As the name says,
14:58it's a form of CAT scan that's
15:01really developed specifically
15:02to look for colon lesions,
15:04and then there's two based tests
15:07that are basically looking at some
15:09of them looking at blood in so
15:12called blood in stool blood that
15:14we may not be able to see yet.
15:16Many tumors when they start being big enough,
15:19they start shedding some blood
15:21and we may not see it,
15:24but these tests to detect them.
15:26Another is actually detect blood
15:29and also some DNA alterations that
15:32come from the cells that could be
15:35being seated by the by the tumors.
15:37So in the recommendations I
15:40was mentioning before,
15:41there are the USPS TF did not
15:44make a strong case for any of them
15:47because the emphasis is really.
15:50They all work.
15:51The emphasis is the most important
15:54aspect is getting screening done.
15:56The technique is a little bit less important,
15:59much more important.
16:00Let's get Sprint for sure,
16:02so they separated between direct
16:04visualization test which is the colonoscopy.
16:06And if that's the case,
16:08is every 10 years sigmoidoscopies,
16:10which is the shorter version
16:12every five years?
16:13Or sigmoid osca P with with a
16:15cold blood test every year or
16:17city colonography every year,
16:19and then the stool based tests
16:21which are basically FFOBT?
16:23That's an old test that's pretty
16:25much no longer use, but then the.
16:28This fit test and this multi
16:30target DNA tests.
16:31That's called those are the
16:33ones that are recommended.
16:34And again,
16:35there's no emphasis and one of them
16:38is just to make sure that we we do it.
16:41Whatever works best for everyone.
16:43The not so good news is with Doctor
16:45comes just mentioned at the beginning.
16:47Also which is you know along with this
16:50very nice decrease in incidents on
16:52the of colorectal cancer among the young.
16:55Older than 50,
16:56we've seen this really steady rise.
16:58Uh of colorectal cancer among the
17:01younger ones in 20 to 49 that's
17:04been very steady and obviously
17:07a very worrisome trend to the
17:09point that if we look at
17:12the incidents of a 50 year old here
17:15in this graph here in the incidence
17:18of 45 year old basically it.
17:212015 the incidents of colorectal
17:24cancer for a 45 year old was
17:27exactly the same as the incidents.
17:30For a 50 year old in 1993,
17:33so for what we thought it
17:35was intolerable in 1993.
17:37It is right now.
17:38It's going down from 50 to 45.
17:41So really again, very worrisome
17:44trend and it's really a goddess.
17:47Uncertain an another important aspect
17:49we've known for a long time that
17:52African Americans do have higher
17:54incidence rates and they have been
17:56having also higher incidence among the
17:58younger individuals to Bud was, well,
18:01we've seen over the last few years.
18:03Is that actually the other groups,
18:06including non Hispanic whites,
18:07have seen that increase going
18:09up to the point that right now,
18:12basically among the young
18:13onset colorectal cancers among
18:15individuals who are younger than 50.
18:17The incident between African Americans
18:19and whites is pretty much the same,
18:22so the concern is for everyone seem so.
18:24the American Cancer Society a
18:26couple of years ago came up with
18:29these guidelines saying we need to
18:30move down to 8:45 for average risk
18:33individuals because of this translator,
18:35we're showing they they got some
18:37modeling done and they did.
18:39They figure out that this was a good
18:42public health recommendation to go
18:44down to 45 and his actor and showed.
18:47The USPSTF has.
18:48Review the recommendation to go
18:51down to 45 and from all we know.
18:54This is probably going to get
18:56approved pretty soon,
18:57and that's where we are going to
18:59get started screening for average
19:01risk individuals.
19:02So again,
19:03the message is the most important
19:05thing is get screen, no matter how,
19:07we just need to get screened
19:09and that's starting at 45.
19:11But obviously there's family history
19:13we need to talk about it earlier.
19:15We need to talk sooner than that,
19:17and that's kind of my message.
19:19Thank you very much.
19:24Thank you Doctor, you're so
19:26will I think what will do
19:28is move on to Doctor Reddy.
19:30Maybe we'll just kind of get
19:33through our presentations and I'll
19:35pass the virtual baton to you.
19:46So I'm back ready. I'm colorectal surgeon.
19:48Have been here at DL and I'm going to be
19:51talking about surgical management of colon
19:54and rectal cancers as I do a lot of these.
19:57Now when after Doctor Laura. You know,
20:01does a colonoscopy and finds a cancer.
20:03You know he sends the patients to us.
20:06And you know,
20:07usually when we look at colon cancer,
20:09colon cancer, and rectal cancer,
20:11we kind of approach them differently.
20:13So here's a picture of a colon.
20:15The appendix is somewhere
20:16right here in the corner.
20:17Here's the small intestine coming in.
20:19This is the first portion of the
20:21colon called the right colon,
20:23and then you come all the way down
20:25to the ****** which is down here.
20:27Normally we see this is the sort of the
20:30distribution of the cancers that we see,
20:32so 30% tend to be in the right colon,
20:3510% tend to be in this area
20:37called the transverse colon.
20:3815% tend to be in the left colon,
20:4125% in the sigmoid colon,
20:43and about 20% in the ******.
20:46Now when we see someone
20:47with colorectal cancer,
20:48we don't right away jump to surgery.
20:50We do some kind of initial work
20:53up before we go for surgery.
20:55And some of the first things that
20:57we do is that we get blood work.
21:00We get this cancer marker called
21:02a CEA to establish a baseline.
21:04And then we almost always get a CAT scan
21:07and the purpose of the CAT scan is to
21:09identify the staging of the patient.
21:11Now a lot of times patients
21:13ask me after a CAT scan,
21:15if if I can tell them if it's stage one,
21:182, three or four.
21:19The only thing we can tell on the
21:21CAT scan is stage four or not.
21:23Now how do we know it's stage four
21:25stage for basically means it's got
21:27to deliver or the long and in this
21:29picture I usually like to show my
21:31patients their CAT scans and in this
21:33picture you can see in the liver.
21:36There's a couple of lesions,
21:37so this is Stage 4, colon cancer,
21:39and usually if it's stage 4 colon cancer,
21:42they end up seeing someone like Doctor Kunz,
21:44director Courtney,
21:45Insecure Doctor Chaney for chemotherapy
21:47before we do any surgical resection.
21:49And sometimes you know you know you
21:51go in for before you go for surgery.
21:54We even have them go for another
21:56colonoscopy because let's say there
21:57was a cancer and we couldn't identify.
21:59Or you know when they did the colonoscopy
22:01they couldn't tell exactly where it was.
22:04Sometimes we have them go back in
22:06and put a little tattoo on that
22:08area so that we can identify it
22:11when we're doing surgery.
22:12Now whenever we go for surgery,
22:14you know people always ask me can you
22:16just take out a little piece of the colon
22:19and not take out like half the colon?
22:21Unfortunately,
22:22what determines whether we take
22:23out just a piece or a bigger piece
22:26is actually the blood supply of
22:27the colon. So, for example,
22:29if a colon cancer happens to be
22:31somewhere right in this area,
22:33we have to take out a bigger piece
22:35just so we can get all the lymph
22:37nodes get good margins in whatever
22:39remaining piece of colon is left,
22:41has good blood supply.
22:44So when we look at the
22:46management of this surgically,
22:47there's several different approaches.
22:48There's the traditional
22:49approach which is open surgery,
22:51which most patients end up with
22:53an operation and an incision
22:55which is about this big.
22:56All of these surgeries are equivalent,
22:58it's just that you know different
23:01surgeries you know you have
23:03bigger scars or lesser scars.
23:05You know,
23:06I tend to favor more of those
23:07lapre scopic surgery where
23:09you know we put little holes.
23:10We bump the belly full of air and
23:12then using these instruments,
23:14we go in and we do the surgery.
23:16In this case you can see this is
23:18the right colon and we're kind
23:20of dividing and taking the blood
23:22vessels in this area so that we
23:24can take out all the lymph nodes.
23:26And another option that we also give
23:28is this thing called robotic surgery
23:30and this is an example of a robot.
23:32It's one of the older robots
23:34and usually the way it works out
23:36is that you know the surgeon is
23:38sitting kind of in a corner.
23:40There's an assistant standing right
23:42by the bedside and the robot sits
23:44there and using these same little holes,
23:46it goes inside and we do the surgery.
23:50And when we do the surgery,
23:52it sort of looks like this
23:53and the inside of the belly.
23:55Here's here's the colon in the back.
23:57The blood vessels.
23:58The lymph nodes are usually in this area,
24:00and here are instruments working
24:02on all of these things.
24:04And usually the advantage of this
24:05minimally invasive surgery is that
24:07instead of having a big incision,
24:08you have a couple of small holes,
24:10and then an incision where
24:12usually the cancer is taken down.
24:14Now whenever we approach colon
24:16cancer surgery.
24:17The goals of the surgery is to
24:19thoroughly explore the belly to make
24:21sure there's no small nodules or
24:23anything that the CAT scan could not see.
24:26And then the primary goal is to
24:28respect the bowel segment which has the
24:30cancer in it and achieve negative margins.
24:32Meaning we take enough tissue on all
24:35sites that no cancer is left behind.
24:37At the same time,
24:38we take out a lot of lymph nodes
24:40which drained that piece of the
24:42bowel so that we can see if the
24:44cancer is scaped the colon and gone
24:46into the into the bloodstream or
24:48lymphatic system because the lymph
24:49nodes usually tend to catch them.
24:51Fortunately for us,
24:52when we take out all these lymph nodes,
24:54you know no part of the body swells
24:56up like they do in other parts and
24:59other cancers like breast cancer
25:01or cancers in the arm and leg. Um?
25:03So when we do right colon cancer surgery.
25:06So here you look at this is
25:08the cancer an even? If we?
25:09Even if the cancer is here,
25:11we can just take out this little piece.
25:13We end up taking out all of
25:14this even if the cancer is here,
25:16we end up taking out all of this.
25:18Believe it or not,
25:19it's as if the cancer is here.
25:21We actually to get a negative margin,
25:23we gotta take a little bit more.
25:26Similarly, for left cancer,
25:27if the cancer is here,
25:28we just take this piece out.
25:31Little bit lower if you notice,
25:33we take up almost always about a
25:34foot of colon and we also take out
25:37all the lymph nodes in this area.
25:39These are the blood vessels that
25:41supply we take out everything.
25:43Now for colon cancer.
25:45You know,
25:46after the surgery you're in the
25:48hospital for about three to four days.
25:49There are some restrictions on what
25:51you can eat for the first 2 weeks,
25:54but after that you can come sort
25:56of go back to normal activity
25:57and even after surgery you know
26:00depending on the lymph nodes.
26:01Depending on the pathology then you
26:03end up seeing the oncologist for
26:05chemotherapy and discussion of that.
26:06But you know,
26:07I won't go into the details
26:09of the chemotherapy,
26:10but usually even after surgery you end
26:12up getting blood work every three months.
26:15CAT scans every year unless you have
26:17some high risk features and usually
26:19we recommend a colonoscopy in a year.
26:21And based on what you find on
26:22that colonoscopy, you may get it.
26:24You know,
26:24every year or every two years or
26:27every three years or every five years.
26:29Now we talked about colon cancer,
26:31so let's talk about rectal cancer.
26:34You know,
26:35rectal cancer is something that I
26:37worked on a lot more for rectal cancer.
26:39Just like you know when a patient
26:41shows up with rectal cancer,
26:42we don't go right away for surgery.
26:44We actually get the CAT scan to make
26:46sure it hasn't spread anywhere else.
26:48If it hasn't spread anywhere else.
26:50We we, we still do the blood work,
26:52but in addition to the cats,
26:54can we get an MRI or ultrasound
26:56ultrasound used to be the older technique?
26:58We prefer the MRI because we
26:59can see much more features.
27:01For example in this patient.
27:03You can see this is the.
27:05This is the backbone.
27:07Here's the tailbone.
27:08And here's the ****** and the cancers here.
27:11So kind of close to the tailbone
27:13and this gives us pictures
27:14of here's the cancer again.
27:16You can see that it's not invading
27:18into the fact which is a good thing.
27:21Now we also use the MRI to identify
27:24any tumors to go into the fact,
27:26or any tumors that have gone into the
27:28left notes so that we can give them
27:31chemotherapy and radiation before we operate.
27:33Jeremy will be talking
27:35about total knee argument,
27:36chemotherapy and radiation,
27:37which is slightly different
27:38than what we used to do before.
27:40But it is a new technique and
27:43I'll let him talk about it.
27:45Now same thing. You know, one of the
27:48goals of surgery for rectal cancer.
27:50Again, we look all around.
27:51Make sure that we don't identify
27:54any natural somewhere else.
27:56You know, so that you know changes are
27:58management and the primary goal is to get
28:00rid of the cancer with negative margins.
28:03Yet all the love notes.
28:05But for rectal cancer,
28:06there are a few more important
28:08things that come into play one.
28:09Because it's lower down in the bottom,
28:12it's very hard.
28:13Sometimes in some patients to
28:14reattach their intestines.
28:15We do everything possible to reattach
28:18their intestines and avoid a bag.
28:20And if you take a part of the ******
28:22or most of the ****** I always explain
28:24to my patients that the ****** is
28:26sort of like the garbage can you know
28:28if you make it smaller you gotta go
28:30to the bathroom a lot more so you
28:32don't want to make it so small that
28:34you're going to bathroom 20 times.
28:36So we want to make sure that patients
28:38have acceptable functional results.
28:40Because you know,
28:41if you're going every hour,
28:42I think your life is limited.
28:45So for rectal cancer,
28:47the anatomy of the ****** is important
28:49because these are the muscles that
28:51control whether you poop or not and if
28:53the cancer is involving these muscles,
28:55it's actually better to take
28:57out the **** and give it back.
28:59Because if you do anything
29:01to damage these muscles.
29:03Then you're going to be incontinent.
29:05So for surgically you know,
29:07we start from the easiest
29:08to the most complicated,
29:10for the easiest ones.
29:11For these small lesions.
29:12So let's say there's a someone who's old
29:14who can tolerate a big operation award.
29:17The cancer is very small and
29:19very superficial.
29:20You know we go in through the ****
29:22and you know we we cut it out and then
29:24stitch it up so that the cancer is gone.
29:27Problem with this is that this has a
29:29higher chance of the cancer coming back,
29:30so we don't like to do it and someone
29:32who's healthy or someone who has
29:34got bad features in their cancer.
29:35We like to do these for polyps or some very.
29:40You know,
29:41very early cancers which have
29:43low potential for spreading.
29:45Now I'm same thing you know this
29:47the same tumor was higher up.
29:49If you notice this is very close
29:51to the bottom.
29:52If it's higher up we have these specialized
29:54equipment where we go in laparoscopically,
29:55Lee through the bottom through the **** go
29:58all the way up into the ****** and some.
30:00Even up to the colon,
30:02and we use these instruments and
30:04a camera with light shining down,
30:06and we're able to take these cancers again.
30:09These are not great for cancers
30:11that go anywhere deeper.
30:12These are mostly for cancers
30:14which are just on the surface.
30:17But our more traditional operation is,
30:19you know,
30:20in this case you can see this.
30:22Here's the cancer.
30:23It's in the upper portion of the ******.
30:25We take out the entire sigmoid colon
30:27and then we go a distance below the
30:30tumor and we take out all the lymph
30:32nodes in that area and the purpose
30:34of taking out the sigmoid colon is
30:36that we can take this healthy bowel.
30:38Higher rope and hook it into the ******
30:41so that you have full control in the old
30:43days before we knew things, you know.
30:46Whenever patients you know so.
30:47This is the ******. Here's the bottom.
30:49Let's say the cancer was here.
30:51What people used to do is just go
30:53right in the fat and left behind.
30:55Some of this fact.
30:56And when they did this,
30:58there was a higher chance of
30:59the cancer coming back.
31:01So. You know,
31:02for the past 3040 years,
31:04we've been doing this where we go
31:06and take out all this fat which
31:09contains all the love notes.
31:10Around the ****** in this area is
31:12called the measure ****** and we take
31:14it out so that we can minimize the
31:16chance of this cancer coming back.
31:18So let's say you know you never
31:20did chemotherapy radiation.
31:21Any of those even,
31:23even if you were recommended to do them.
31:25But if we just did this operation,
31:27that chance of the cancer coming
31:29back before if you did this port,
31:31if you sort of did this,
31:32the chance of it coming back was
31:34more than 20% just doing a proper
31:37operation dropped to less than 7%.
31:39So you know.
31:40So this is what we do nowadays,
31:42and this is called the total
31:45measure rectal excision.
31:46Again, this gives a picture,
31:47so if you notice,
31:48here's the tailbone we go almost
31:50on the tailbone to take out all
31:52this fat and all the lymph nodes.
31:54Take this out,
31:55take healthy tissue from higher up.
31:56Bring it down to the ****** and reattach it.
32:02This is more pictographic thing
32:03where you know when we're operating.
32:05This is what we see.
32:06We see the sacral bone.
32:07We see the coccyx we're digging things out.
32:10We have to preserve.
32:11You know the tubes called ureters,
32:13which are tubes that take *****
32:15from the kidney down to the bladder.
32:16We also tried to preserve these nerves.
32:18These nerves help with ****** function
32:20and you know we work hard to preserve
32:22these and if this was an open
32:24surgery would actually put a stapler,
32:26you know, cut it off here.
32:27You see the cancer.
32:28We cut it off so we get out of it
32:31and then we go through the bottom
32:33and come from the top and kind of re
32:36attached to intestines using the stapler.
32:38And a lot of them they see this
32:40in the pathology.
32:41They talk about Donuts and this
32:42is what the Donuts are.
32:43These are the little margins that
32:44we take out right at the area where
32:46we re attach to make sure there's no
32:48cancer and the margins are good and healthy.
32:52And sometimes you know for patients
32:54where they have no ****** left.
32:56We do this thing called the pouch so
32:58that there's some kind of a reservoir,
33:00because if you take a call
33:01and then hook it back to this,
33:03you're probably going to
33:04go about 10 times today.
33:06So what we do is we try to take
33:08make an artificial reservoir and
33:09attach it to the to the ******.
33:12And here's the sphincters.
33:13And if you notice we're trying to
33:15save as much of this thinker as
33:17possible so there's full control.
33:19Now for some patients where
33:20the muscle is involved,
33:21unfortunately there they don't.
33:23They're not candidate for
33:24this kind of operation,
33:25so for them we do a more radical
33:27operation where imagine this is the colon.
33:29The cancer is very low,
33:30we can't save it,
33:31we actually cut it off right here.
33:33Get rid of all of this,
33:35and then because we can't hook
33:37it down to the bottom,
33:38we bring it out to the skin as a bag back.
33:41Sort of looks like this when it's
33:43initially formed and because
33:44we're taking out the ****.
33:46You know,
33:46we actually cut it out and then stitch it up.
33:49So that you know there's no
33:51morinas left and we get rid of
33:53all the cancer tissue down there.
33:55And this is called an abdominal
33:57perineal resection.
33:57Usually after these operations
33:58you know most patients are in the
34:00hospital about three to four days,
34:02but sometimes you know when they get a bag,
34:04they stay in the hospital longer so
34:06that they get some training with the bag.
34:08There's definitely diet restrictions
34:09for about 2 weeks.
34:10Sometimes patients get a temporary
34:12back to allow this area to heal.
34:14And most of them are able to return
34:16to normal activity in about 6 weeks.
34:18We usually try to set you up with
34:20a nurse who can help you with the
34:23ostomy when you go home again.
34:24Just like for colon cancer,
34:26you know we do blood work every three months.
34:28CAT scans colonoscopy and in addition,
34:30because you may have a bag you
34:32know we also have, you know,
34:33have you see the ostomy nurse and
34:35teach you but bags and everything
34:37and this I'm not going to cover
34:39about **** cancer.
34:41So this is it for the column and
34:44rectal surgery for colorectal cancers.
34:46If you guys have any questions
34:48more than welcome.
34:52Thank you doctor Reddy.
34:54So we are. We're trying to tell
34:56a little bit of a story here,
34:59so we've learned some about diagnosis
35:01and screening and prevention.
35:02We then learned about surgery
35:04for colon and rectal cancer,
35:06and now a doctor court.
35:07Manske is going to build on a
35:09little bit of what we just learned
35:12from Doctor Reddy on how we start
35:14treating a localized rectal cancer.
35:17Thanks Jeremy.
35:32Alright, there we go.
35:34Alright thank you.
35:36So I will try to pick up a
35:39little bit after Anne and
35:42somewhat before Doctor Reddy.
35:45I apologize that I don't have
35:47as fancy pictures as he does.
35:55Jeremy, you somehow got muted again.
36:02Can you hear me?
36:03Yes, OK, I'll try not to.
36:06So the the important thing about
36:09treating rectal cancer is that it
36:13really requires multi modality
36:15care and what that means is that
36:18patients who have rectal cancer are
36:21treated by more than one physician.
36:24They need a medical oncologist,
36:27and surgeon, Anna gastroenterologist
36:29and radiation oncologist.
36:31Ann and all of us work closely together
36:34to really map out what is the best plan
36:38going forward and individual patients
36:40have individual needs based on their
36:43tumor location and the stage of their tumor.
36:47And so we we discussed these cases as a
36:52team to really come up with the best plan.
36:56As a background,
36:58and I'll I'm sorry if some
37:00of this is repetitive,
37:03but there are about 45,000 cases
37:06per year rectal cancer in the
37:09US and representing about 20 to
37:1130% of colorectal cases total.
37:14And patients can present when
37:17symptomatic with either rectal bleeding
37:19or changes in their bowel habits.
37:23And as Doctor Reddy mentioned,
37:25or typical staging,
37:26when somebody is first diagnosed
37:29includes a see T of the chest and
37:33abdomen to understand whether
37:35there is any spread of the tumor.
37:38Are rectal cancers are a little
37:40bit different than colon cancer
37:43in that the distribution of spread
37:45can be a little bit different,
37:48and so it really is important that we
37:52look at the whole body before we get started.
37:56The MRI of the pelvis gives us that
37:59information as well as very detailed
38:02staging information in terms of the
38:04depth of the tumor and whether there's
38:07any lymph nodes that are involved.
38:10And on occasion we we might need
38:13to do an endoscopic ultrasound or
38:15even a PET scan if we feel like
38:18there are lymph nodes,
38:20perhaps that we don't quite understand
38:22and want to learn more about.
38:27And we know that there are certain risk
38:30factors when we are treating rectal
38:33cancer that predicts patients who
38:36might have relapse of their disease,
38:39either locally or elsewhere in the body.
38:43And that includes T4 disease.
38:46And So what that means is cancers that
38:49have grown through the full thickness of
38:52the rectal wall and are involving nearby
38:55structures and sitting near the ****** is
39:00the the bones in the back and the bladder.
39:05The vaginal wall in females
39:08can be there as well,
39:10so all of those are considerations.
39:14Patients that have multiple
39:16lymph nodes that are involved.
39:19Patients that have that fatty tissue
39:22around the ****** involved and
39:24then when you look at the tumor,
39:27if there is vascular invasion as well,
39:30is also a potential risk factor.
39:35And so for. All patients surgery is the
39:40cornerstone of curative therapy that,
39:44without surgical resection,
39:46it is difficult to eradicate the disease.
39:52And we know that patients that
39:54have tumors that are the full
39:56thickness of the bowel wall or have
39:58lymph node positive disease, Sir.
40:00Surgery alone may not be may not be
40:04caritive that we may still need to do
40:06more to help get rid of the disease.
40:10An early on we would follow surgery
40:13with aggregate therapy in the form
40:15of either radiation or chemotherapy.
40:18But around 2004,
40:19an important study came from Germany with
40:23data that was duplicated in other sites.
40:27Showing that chemotherapy and radiation
40:30together prior to surgery was able to
40:33improve the outcome in many patients.
40:36And it did so.
40:38Because it could downstage
40:40the tumors made them smaller.
40:44Could increase.
40:47The likelihood that the sphincter
40:49is spared so that patients don't
40:52require a permanent ostomy like
40:54Doctor Reddy had described.
40:56And increase the pathologic complete
40:58response rate and what that means is
41:01that patients when their tumor is taken
41:03out and you look at it under the microscope,
41:06you don't see any cancer.
41:08You don't see any cancer in the bowel wall.
41:11You don't see any cancer in the lymph nodes.
41:15And that is an effect of the treatment
41:17because we had biopsies before we started
41:20that showed us that the cancer was there.
41:23The other thing that we learned
41:25from this is that giving the
41:27treatment prior to the surgery was
41:30better tolerated than trying to do
41:33a similar treatment afterwards.
41:34And so starting at about 2004,
41:37this became our standard approach.
41:41The pathologic complete response rate
41:44is important because it can improve
41:47how patients do and there have been a
41:51number of studies and I picked out these
41:54two which came out about a decade ago.
41:58That showed that the pathologic
42:01complete response rate with chemotherapy
42:03and radiation is somewhere between
42:0615 and 30% depending on the study.
42:10And that the patients that have a
42:14pathologic complete response rate do better.
42:17Long term, they have less incidence
42:20of disease recurrence.
42:22And we even see that there is sort
42:25of this continuum that the the
42:27better your responses.
42:29To the pre treatment,
42:31then the improved,
42:32then the better they relapse
42:34rate the incidence of distant
42:36metastasis and even local relapse.
42:39All of that improves with a better
42:41response to the pre operative therapy.
42:47For for many patients our paradigm
42:50Now then says after surgery
42:53will give you chemotherapy.
42:56And we know that for patients that
42:59have nodal involvement or patients
43:01that have tumors that involve the full
43:04thickness of their ****** chemotherapy
43:07does reduce their risks of recurrence.
43:10It's really actually more controversial
43:12in those patients that have tumors
43:14that are not the full thickness,
43:16even if that's the case because of
43:19the chemotherapy and radiation.
43:21And then the other challenge with
43:23chemotherapy is that it's hard
43:25to give it after somebody has
43:27already had a lot of therapy.
43:29It can be hard to give the the
43:32standard course because of.
43:33Of toxicity and delayed recovery
43:36from their prior treatments.
43:38Because blood counts are slower
43:40to recover and so only about 65
43:44to 70% of patients that we plan
43:47to give chemo agent chemotherapy
43:50to complete that treatment.
43:52Nonetheless,
43:53giving Chemoradiation prior to
43:56surgery and then agement chemotherapy
43:59afterwards is currently our standard.
44:03And So what has the question
44:06that has come up is,
44:08does reversing the order of our
44:10approach have an impact if we gave
44:14chemotherapy and chemo radiation?
44:16If you did all of that treatment
44:19prior to surgery, could we improve?
44:22How patients do an?
44:24There's a lot of potential
44:26advantages to doing that.
44:28One is that we could increase
44:30the number of patients that have
44:33a pathologic complete response.
44:35And we know that doing that
44:37can improve the outcome.
44:39We know that we can reduce
44:41the stage of the tumor,
44:43so even following that continuum,
44:45even if you can't make it go away completely,
44:48maybe you can make it less involved.
44:51It improves the potential to spare the
44:56sphincter and not have a permanent ostomy.
45:00And then a shorter time to stoma closure
45:03and this you know many patients,
45:05even if they're not destined
45:07to have a permanent ostomy.
45:09They sometimes have a temporary
45:11ostomy to allow their wounds to heal.
45:14And we tend not to let Doctor
45:16Reddy close that until after
45:19we're done with our chemotherapy.
45:21And so if we give our
45:24chemotherapy beforehand.
45:25It's a shorter period of time that
45:28someone would have that stuff by maybe
45:31only six weeks as opposed to five
45:34months with the chemotherapy beforehand.
45:37And giving the chemotherapy
45:38before is is a little bit easier.
45:42There's a higher completion rate.
45:44There's a lower toxicity.
45:46And so we can get through and take that
45:5165 to 70% and really get it closer to 92100%.
45:55Getting through their treatments.
45:58And then really turning turning
46:01things upside down,
46:02it opens up the potential for
46:06a non operative approach.
46:09And so a non operative approach
46:13or watchful waiting is an area
46:17that is still under under.
46:22Under development, I'll say that it
46:25requires a complete clinical response,
46:28so not a pathologic complete response,
46:31but now a clinical complete response
46:34which is determined through digital
46:37exams and OSCA P's and Mris.
46:40And it requires aggressive
46:44vigilant surveillance.
46:46With this screening,
46:47every three months in the first year,
46:49every four months in the second year,
46:52and then even out two years,
46:54three through 5.
46:58And there's been a fairly extensive
47:01international experience with this.
47:04The first papers actually were
47:07published back in in 2004.
47:11But really, the experience has
47:13grown over the past decade.
47:16And shows that in patients that have
47:18had a clinical complete response,
47:21the local regrowth rate.
47:23So the chances that the tumor
47:25will grow back in the ******.
47:28Is about 25% overall with 65% of those
47:32cases happening within a year of your
47:36treatments and 90% within two years.
47:41If the tumor were to return.
47:45Then those patients can go
47:48onto a surgery at that point.
47:52And So what that ultimately gives
47:55us is that about 80% of patients
47:58can have a surgery that preserves
48:01this sphincter so that they
48:04don't have a temporary ostomy.
48:06But even if we have to do a surgery,
48:10eventually we are able to control
48:13the risk of recurrence or the control
48:17that disease locally in about 90%.
48:20But we also know that about
48:2310 to 15% of patients do go on
48:26to develop metastatic disease.
48:28And what is interesting is that
48:30the majority of those patients
48:33who get metastatic disease.
48:35Also get recurrence locali.
48:40And so there are some limitations
48:43and this non operative approach is
48:45not really ready for prime time.
48:48I think that the concern is that when
48:51you look at the data that's available,
48:54the majority of the patients had a
48:57lower clinical stage to begin with.
49:00These were patients that had
49:02low nodal involvement, they had,
49:04they did not have full thickness tumors
49:07and so may already be speaking to a.
49:11A more favorable biology.
49:13Um, this approach definitely requires
49:16high vigilance in in follow up,
49:18and so you know it does have impact
49:21on patients who have difficulty
49:23getting their care on a regular basis.
49:27It has expense costs when you're getting
49:30all of these procedures and tests.
49:33And at the end of the day,
49:36our our gold standard is prospective
49:38data and there has yet to be a study that
49:42is comparing a non operative approach
49:44to an operative approach prospectively.
49:47And because we have.
49:49High concern of the risks
49:52of tumor reccuring locali.
49:55You know we haven't adopted this
49:58as an approach across.
50:00Off the board.
50:02Certainly there are patients where
50:04taking a non operative approach would
50:07be would be reasonable to consider.
50:10Based on the stage of their tumor,
50:12and again,
50:13that is the value of having multiple
50:15physicians contributing to the care
50:17to figure out the best thing to do.
50:22So just some future considerations in
50:25terms of management of multi modality,
50:28management of rectal cancer or
50:31questions like the optimal radiation
50:34or our standard approach is what we
50:37call long course with a combination
50:40of radiation over 5 weeks with
50:42five a few based chemotherapy.
50:45There is information or about short
50:48course meeting only 5 days of radiation,
50:51but at much higher doses than we
50:54might use on the longer course.
50:57And then some studies that are
50:59looking at not using radiation at all,
51:02and one example of that is
51:05the prospect trial.
51:06Which has completed enrolling patients
51:09and we're waiting for the data,
51:12but using the response to chemotherapy
51:16as a decision point of whether
51:20radiation is required or not.
51:23We're also still trying to figure out
51:26the optimal chemotherapy there is.
51:28Does giving all of that treatment
51:30upfront over treat patients who may
51:33not really need that chemotherapy?
51:35And in patients that do,
51:37what is the right chemotherapy?
51:38Should it be a standard approach like
51:405 if you and oxaliplatin shouldn't
51:42be a 3 drug approach for which there
51:45is some data as well and we don't
51:47really know the answers to that.
51:50And then also whether there is
51:52a role for biologic therapy or
51:54immunotherapy within this paradigm.
51:56And there are studies that are
51:59looking at that as well.
52:01What is GI002 which has looked
52:05at at both of those questions?
52:10And then also the optimal surgery,
52:12not just the concept of watchful waiting,
52:15but also the optimal interval between
52:17when you finish your treatment
52:19and finish your radiation and when
52:22you should go on to surgery or our
52:25senses that the longer we wait,
52:27perhaps the better the the response
52:29in the outcome might be.
52:31And so Doctor Reddy may say to
52:34you you finished your treatment.
52:36But I want to wait eight weeks
52:3910 weeks before I do my surgery.
52:42To make sure that we are experiencing
52:44the optimal benefit.
52:48So kind of putting this all together
52:50in terms of how we think about patients
52:53when they come to us with rectal cancer,
52:56the first step is our staging.
52:58And if it looks like it's a stage one cancer,
53:02we would recommend going right to surgery.
53:05And then seeing what happens afterwards
53:09and deciding whether patients need
53:13chemotherapy alone or whether they
53:16need chemotherapy and radiation.
53:19If patients have stage two or higher disease.
53:24Then we do consider a neoadjuvant
53:28approach giving chemotherapy followed
53:31by chemotherapy and radiation,
53:34and then surgery afterwards.
53:36And so this is really our.
53:40General paradigm that we are
53:42thinking about patients now,
53:44but there's clearly a lot of information
53:47that we're waiting to come through
53:49to really refine our approach.
53:55That's all I got, thank you.
53:58Thanks Doctor Krzeminski,
53:59that's great so we have
54:02one final presentation.
54:04And Jeremy, if you can stop
54:07share on your side, that's great.
54:09We are going to have a doctor
54:12Cicchini help finish things up
54:14here and talk some about treatment
54:17for metastatic colorectal cancer.
54:27At the stop shared a. Unmute, hold on.
54:33Alright. OK, thank you.
54:35Thank you for the opportunity.
54:37So I'm going to talk as doctors just
54:39mentioned about treatment for metastatic
54:41colorectal and how we personalize some
54:43of those treatments for patients living
54:46with metastatic colorectal cancer.
54:48These are my disclosures.
54:50So first I'll talk about the
54:52standard of care, cytotoxic chemo,
54:54the standard type of chemotherapy that
54:56we use to treat colorectal cancer.
54:58Then I'll talk about personalized
55:00medicine for colorectal cancer.
55:01Some of the targeted treatments,
55:03and I'll close pop talking
55:04about immunotherapy,
55:05which is of course a hot topic.
55:08So we talked a little bit about this,
55:12but if we think about a normal epithelium
55:16and normal lining of the colon,
55:18polyps develop small adenomas at
55:21the top of these polyps and they
55:24progress along become larger and
55:27potentially become invasive in.
55:30Become cancer at that point.
55:32I can potentially spread,
55:33but really there's two main
55:35pathways highlighted.
55:36These Red Arrows that cancer sort of
55:38kicks off for colorectal cancer either
55:40goes down this pathway that we call
55:42microsatellite instability or MSI,
55:45or it goes down this other pathway
55:47with specific genes mutated and
55:49will just say the APC pathway so
55:52it really starts in one of these
55:54two pathways and as as significant
55:56treatment ramifications later on for
55:58for what kind of systemic chemo or
56:01immunotherapy is we can give our patients?
56:04So it starts off along one of these
56:06pathways and then additional mutations
56:07come are required along the way,
56:09which I'll talk about in the coming slides.
56:12I'll highlight a couple K Rasen B rap.
56:18There's also a big difference
56:19between the left side of the colon
56:21and the right side of the colon
56:23that we've only relatively, well.
56:24We've known there's quite a quite a bit
56:26of a difference between the left and
56:28the right side of home for some time,
56:30but we've only realized it has
56:33significant treatment ramifications
56:34for maybe the last three to five years.
56:36We've known for some time that right
56:39side of right sided colon cancer
56:41tends to be more aggressive and it has
56:44certain and we've now realized that it
56:46has certain molecular differences of
56:48certain mutations that are different
56:50than the left side of the colon.
56:53Certain epigenetic changes which mean
56:55methylations or changes on top of DNA.
56:58Then there are differences like it's more
57:00common in women and there's different
57:02types of polyps in different types of tumors.
57:05When we look at them under the microscope,
57:07they behave differently.
57:08Why?
57:08Why would that be?
57:09It's all one colon.
57:11It actually went during development
57:12comes from 2/2 completely different
57:14types of embryological tissue,
57:15developmental tissue.
57:16The midgut is what we call the tissue
57:18that the left the right side of the
57:21column derives from in the hindgut
57:22for the left side of the colon,
57:24so that that explains the differences
57:26that we think rise to these
57:28different molecular features,
57:29meaning different DNA based features.
57:30It ultimately leads to different
57:32behaviors of the cancer.
57:36So what what do I think or or what?
57:39What do we think is medical oncologist
57:41are most important characteristics to
57:43know about patients colorectal cancer.
57:45So I encourage all my patients to
57:47know really, the at least these four
57:50things about their cancer because
57:52they are so significant in there.
57:54Really, some of the reasons about why we're
57:57delivering some of the treatments we are.
57:59So if if I were to in one
58:01or two sentence statement,
58:03communicate with one of my colleagues about.
58:06Why I'm treating a patient a certain way
58:08or the characteristics about their cancer,
58:10I would include these four aspects,
58:12and so again,
58:13I encourage patients to know these
58:14these these aspects about their cancers
58:16that so that they can understand why.
58:18Maybe we're not doing something,
58:20or maybe why we are doing a
58:22treatment for them.
58:22So the first is the
58:24microsatellite status at MSI.
58:25I talked about on the second or
58:27third slide and patients can be
58:28microsatellite stable or instability high.
58:30And it sounds like a bit of
58:32jargon and should certainly is.
58:34But most patients that we see
58:35will be microsatellites table.
58:37Meaning, immunotherapy may not be helpful,
58:39but for these for these patients,
58:40that might that are microsatellite
58:42instability.
58:42High immunotherapy is highly,
58:44highly, highly effective for them.
58:45So that's something even rare.
58:47You never want to miss in a patient,
58:50because very see significant implications.
58:51And then we look for mutations.
58:53Kay Rasen beer at mutations
58:55you're either mutated or not,
58:56and so these are DNA based
58:58changes just in the tumor.
59:00Though they are not inherited
59:02changes that people have.
59:03These are mutations that somebody's
59:05tumor acquires and it changes
59:07the behavior of the tumor.
59:08Change the treatments that we
59:09we use and I'll get to that in
59:11a slider to then as I mentioned,
59:13where the tumor started,
59:14is it on the left side of the colon
59:16or the right side of the colon?
59:17We used to just think that told us
59:19how the cancer was going to behave,
59:21but now we also realize it tells us
59:24what treatments may or not may not work.
59:26So what kind of chemo do we use?
59:29So Doctor Manske in his last
59:31presentation mentioned Folfox Folfiri.
59:33There's also treatment folfox theory,
59:35so we use three main drugs.
59:37Initially 5FU05 four years,
59:38so which some people might know.
59:41This is this infusion pump with oxaliplatin.
59:43Some people might know that is a drug
59:46that makes create sensitivity to cold.
59:48We user entity can a drug that can create
59:52diarrhea nickname is that run to the can.
59:57And we use these in different combinations
59:59and our goal is to get as much my.
01:00:01Out of these three drugs is possible.
01:00:03There are most effective
01:00:04drugs in this disease.
01:00:05Sometimes again will put all three
01:00:07together in a very young fit patient.
01:00:09Otherwise it will use them sequentially.
01:00:12You can imagine it's more toxic
01:00:14to do all three at the same time,
01:00:16but also potentially more
01:00:18efficacious in the right patients.
01:00:20We also add on drugs to these these
01:00:23chemotherapy backbones if you will.
01:00:25We call them Anna.
01:00:26We called them biologics,
01:00:28which are antibodies.
01:00:29So we have these chemo drugs that
01:00:31kill rapidly dividing cells that
01:00:33your folfox your full theory.
01:00:35They don't discriminate rapidly
01:00:37dividing cancer cell are
01:00:39rapidly dividing normal cell.
01:00:40That's why they're potentially
01:00:42associated with toxicities,
01:00:43but these antibodies are largely
01:00:45more targeted to whatever,
01:00:46whatever the antibodies programmed
01:00:48to bind to.
01:00:49And things that tell us what antibody to
01:00:52add on to the chemo K rasby reputations
01:00:54and what side the tumor started on.
01:00:56So that's so critical because
01:00:57I can't even tell somebody with
01:00:59their first treatment should truly
01:01:00be until I know if they have a
01:01:03reputation or be recommendation,
01:01:04or if it's a left or right
01:01:07sided colorectal cancer.
01:01:08So now I get into a few
01:01:10pathways in this part.
01:01:11Might be a little technical for a few slides,
01:01:13but so if we think of a cell,
01:01:15so this sets with this Gray is
01:01:17is the outer rim of a cell and
01:01:19we have a nucleus that brain of
01:01:21the cell is this integrate area.
01:01:23There's a lot of signaling that
01:01:24goes from the outside of the
01:01:26cell to the brain of the cell,
01:01:28and the end result of that signaling,
01:01:30largely in cancer,
01:01:30is to grow and divide,
01:01:32and that's why cancer grows in the 1st place,
01:01:34and so there's a lot of pathways there,
01:01:36like light switches that are just turned on,
01:01:38and so it's a big problem because that's
01:01:40why cancer just grows and grows and
01:01:42grows and it grows without ace optic signals.
01:01:45And this is a real critical pathway
01:01:48in cancer and colorectal cancer,
01:01:50and that there's a couple
01:01:52of these proteins here.
01:01:54Which are the machinery in the cell?
01:01:57DNA makes proteins ultimately,
01:01:59and proteins are made by
01:02:03transcription of DNA.
01:02:04And inhibiting these proteins can
01:02:06slow down the growth of the cancer.
01:02:08So if we so we look for Icarax mutation
01:02:111st and if we don't see it we can use
01:02:14drugs like cetuximab or panitumumab.
01:02:16These are antibodies we add on to
01:02:19chemotherapy and if we do see it,
01:02:21we add on better system at this
01:02:23side also plays a role in whether
01:02:25or not we truly add on September
01:02:27panitumumab right sided cancers
01:02:29we typically don't even if they
01:02:32don't have this mutation.
01:02:33So right away just this simple tests.
01:02:35Whether or not you have a
01:02:38recommendation tells us what we
01:02:39should be adding on to the chemotherapy.
01:02:42So these these drugs attachment
01:02:44panitumumab bind to the very
01:02:46start of this signaling pathway.
01:02:47So you can imagine if you're
01:02:50mutated down here below,
01:02:51where these drugs are binding the
01:02:53pathways already activated below hand.
01:02:55So that's why they don't work.
01:02:58What about lower down so B RAF?
01:03:00So beware is mutating about 10% of
01:03:02metastatic colorectal cancer and
01:03:04we've known for a long time that
01:03:06unfortunately it's associated with
01:03:07a more aggressive type of cancer.
01:03:09But now in the last couple of
01:03:11years we've also realized that
01:03:13we can actually stop the pathway
01:03:15at that level by using these new
01:03:17drugs and grafted into tux map.
01:03:19So using these two drugs in
01:03:21combination is highly effective
01:03:22for these be recommending cancers,
01:03:24apps again,
01:03:24absolutely critical to know that
01:03:26somebody has to be reputation
01:03:28otherwise you're not delivered.
01:03:29You're not going to be delivering
01:03:31them the proper therapy.
01:03:32What about K Ras mutations there?
01:03:34About 40 to 50% of colorectal
01:03:36cancer in their common.
01:03:38Unfortunately,
01:03:38we have not yet developed a drug
01:03:40that works to inhibit Kehres.
01:03:42Again, it tells me not to use that.
01:03:45Those medications I showed
01:03:46a couple slides ago,
01:03:47but we don't yet have it.
01:03:50A therapy that stops care as we
01:03:52do have a few drugs in the clinic
01:03:55that are being investigated
01:03:56to stop care as they seem to
01:03:58be very effective for a very,
01:04:00very rare subtype of care.
01:04:02Asking colorectal cancer that represents
01:04:03maybe 1% of colorectal cancer,
01:04:05but that's how this starts.
01:04:06We develop 11 inhibitor for a low
01:04:09percentage and then we develop
01:04:10another and another and then pretty
01:04:12soon we're covering the majority
01:04:14of these these patients lung
01:04:15cancer has been a great example
01:04:18of that over the last decade.
01:04:20And there are new or newer drugs
01:04:23coming every day in the clinic.
01:04:25So what about immune therapy?
01:04:27This is this is the.
01:04:30The most urgent need,
01:04:31I think,
01:04:32in colorectal cancer or most
01:04:34gastrointestinal cancers is
01:04:35making immunotherapy work for
01:04:37the majority of cancers.
01:04:38So what is immune therapy is
01:04:40therapy that takes the breaks off
01:04:43of the patients own immune system
01:04:45so that it will attack and kill.
01:04:47The cancer is incredibly complicated,
01:04:49but in over and over simplistic.
01:04:54Visual of it would be an immune
01:04:56cell which we call a T cell,
01:04:58in this case AT cell and the tumor cell
01:05:00and the tumor cell has this this marker
01:05:03called PDL one and it's almost like a
01:05:05hand that it sticks up when an immune
01:05:07cell gets close to it and tells it no.
01:05:10Thank you and it shuts
01:05:11down the white blood cell.
01:05:13So if we can put a drug in in the
01:05:16in the pocket of that receptor,
01:05:18anhand interaction and block the talk
01:05:20between the tumor cell and immune cell,
01:05:23at least block the negative, talk.
01:05:25The immune cells won't get shut
01:05:27down again next to the tumor cells.
01:05:29The problem is it doesn't work for
01:05:31the majority of colorectal cancer.
01:05:33It works for that very rare subtype
01:05:35that microsatellite instability,
01:05:36high colorectal cancer,
01:05:37so it's approved as initial therapy.
01:05:39But again, this only represents
01:05:41about 2 to 4% of patients.
01:05:43But for these two to 4%,
01:05:44patient is incredibly
01:05:46important to know this because.
01:05:47If we look at a curve of
01:05:49chemotherapy for this,
01:05:50this is again this rare subtype.
01:05:52Every patient here.
01:05:53But if we just take a look at this curve,
01:05:56and I realize most people are
01:05:57not very familiar with looking
01:05:59at these types of curves,
01:06:00but we pick a time here.
01:06:02This is 24 months,
01:06:03so two years.
01:06:05With pembrolizumab immune therapy
01:06:06in this case about only half of
01:06:08patients have had their cancer grow
01:06:10at all after two years of therapy,
01:06:12we compare that with chemo.
01:06:13About 20% have not had their cancer growth.
01:06:16That plane and roughly once you
01:06:18make it to the two year mark,
01:06:20it's rare that the cancer grows beyond that.
01:06:22So we're seeing these responses
01:06:24for these patients with this
01:06:25treatment is relatively non toxic.
01:06:27That just seemed to go on and on and on.
01:06:30Unfortunately it doesn't work for everybody,
01:06:32but for the patients it does work.
01:06:34Is some of the most.
01:06:36Dramatic responses that we'll
01:06:39see as oncologists.
01:06:42So in conclusion,
01:06:43the main the main treatments we use are
01:06:45these treatments called folfox and folfiri.
01:06:46It's certainly a bit of a world word salad.
01:06:49There we use a lot of abbreviations,
01:06:51which doesn't make things easy
01:06:52to keep straight in one's mind.
01:06:54All tumors should absolutely be set
01:06:56to be tested for these three things.
01:06:58In the fourth thing would be again,
01:07:00what side is the tumor come from,
01:07:02and so it is absolutely standard of care,
01:07:05and you should always ask your
01:07:06oncologist if it's not clear if any
01:07:08of these things have been looked for,
01:07:10it should.
01:07:11It should be looked for in every patient.
01:07:13The microsatellite status to test
01:07:15for immune therapy essentially in the
01:07:17K Ras status in the draft status,
01:07:19which also dictates initial chemotherapy.
01:07:20Frankly,
01:07:20and immunotherapy is standard of
01:07:22care for microsatellite instability.
01:07:23High colorectal cancer.
01:07:24We have numerous trials.
01:07:25I'm going to yell trying to make
01:07:27immunotherapy work for the other
01:07:2896% of patients.
01:07:29And sometimes we've had some
01:07:30successes and we're
01:07:31learning more and more every day. Thank you.
01:07:36Thank you Doctor Shakini so we have
01:07:39some time for from some questions so
01:07:42I will ask some both from the Q&A and
01:07:45I encourage our audience members to
01:07:48please continue submitting questions.
01:07:49We've been answering some of those as we go.
01:07:53I'll also start just by asking
01:07:55some questions, so I'm going to
01:07:58start with Doctor Your.
01:07:59You mentioned that we're starting
01:08:01to see or we've seen an increase.
01:08:04In colorectal cancer in young adults and
01:08:07in in our patients of the black community.
01:08:10And I'm wondering if you can speak
01:08:13to why you think we're seeing that.
01:08:19And you're on mute.
01:08:23So. The changes have are
01:08:26happening relatively fast,
01:08:28and when changes happen that fast,
01:08:30certainly it has to.
01:08:31It can have much to do with
01:08:34genetic changes which happened for
01:08:36which take a long time to happen.
01:08:39It has to be to have much more
01:08:42to do with environmental factors,
01:08:45nutritional factors, whatever.
01:08:46We do an an unfortunately
01:08:48environmental nutritional.
01:08:49All those things are a bunch of things
01:08:52that are like coming together in a person.
01:08:55It's very hard to.
01:08:57Separate out the effects and as
01:08:59as I should before some of them
01:09:02have been clearly associated,
01:09:04but I'm sure there are other things
01:09:07that were totally missing in terms of
01:09:10that the where the interesting thing
01:09:13is that we saw this increase in the
01:09:16African American Community 25 years ago,
01:09:18and that's why some societies have
01:09:20been recommending screening African
01:09:22Americans earlier starting at 45.
01:09:24And it's not until the last.
01:09:27Few years that the other
01:09:29communities are catching up.
01:09:31Unfortunately,
01:09:32catching up with the African Americans
01:09:34in terms of that increased risk,
01:09:37something that must have to do with again
01:09:40those environmental nutritional factors.
01:09:42Whatever we do, whatever we are exposed to,
01:09:46that's not sitting well with us, and it's
01:09:49equalizing us right now in a bad way.
01:09:53But we have not.
01:09:54I mean,
01:09:55besides the factors that we were sharing.
01:09:59With you, I think there's a lot of them.
01:10:01I've not explained because
01:10:02we put it all together.
01:10:03It still does not add up,
01:10:05so we're still missing someone we
01:10:07need to do more research for that.
01:10:10Great, thank you.
01:10:12Doctor Reddy I have a question for
01:10:14you so something that I know a lot of
01:10:17my patients ask and worry about is this.
01:10:20You know having a bag?
01:10:21Are they going to need to have a bag
01:10:24after a you know rectal cancer surgery?
01:10:27Can you speak to what that is
01:10:29like in terms of quality of life?
01:10:31How do you coach your patience
01:10:34through that so? For us,
01:10:36you know one of the best things
01:10:38that we have are the ostomy nurses
01:10:40and they give patients a preview of
01:10:42what life is to live with the bag.
01:10:44So there's two kinds of backs.
01:10:46There's a temporary bag,
01:10:48and there's a permanent bag.
01:10:49The permanent bag quality of life
01:10:51is good when we have looked at
01:10:54patients who have had permanent bags.
01:10:56There's only one negative thing
01:10:58that patients complain about,
01:10:59and it's usually males,
01:11:00and that's negative ****** body image.
01:11:02So when we looked at all patients
01:11:04five years down the road,
01:11:066 years down the road,
01:11:07that was the biggest complaint that we saw.
01:11:10The temporary bag is a little bit
01:11:12more of a problem because it's kind
01:11:14of watery diarrhea and a lot of times
01:11:17have to have to reassure patients.
01:11:19It's only for a temporary period of time.
01:11:21Just bear with it finished.
01:11:23The chemo will close it up.
01:11:26But it can still be, you know,
01:11:28emotionally distressing,
01:11:28because you know you get
01:11:29irritation around the skin.
01:11:30Now you're getting chemotherapy.
01:11:32The skin cells fall off a little bit easier.
01:11:34That bag doesn't stick,
01:11:35so there's lots of leaks.
01:11:37You know the ostomy
01:11:39program really helps them,
01:11:40their guides them through this and
01:11:42you know it is a hard time for them
01:11:45when they're going through this,
01:11:47and I think I think.
01:11:49You know when those patients
01:11:51complain about those bags?
01:11:52I think it is real and it is tough.
01:11:56Great thank you for
01:11:57answering the best thing
01:11:58that we used to have is.
01:11:59We used to actually have a
01:12:01program where we used to have
01:12:02them talk to other patients.
01:12:04To say that you know things do get better,
01:12:06I think now with HIPAA,
01:12:07and especially now with covid,
01:12:08I mean that's completely shut down.
01:12:12Yes, hopefully we'll get back to that so.
01:12:15So thank you Doctor Cartman see I
01:12:17want to ask you a question here.
01:12:19So, um, you talk you and Doctor Cicchini
01:12:22both talked about chemotherapy and
01:12:23you also talked some about radiation.
01:12:26Can you speak a little bit more about
01:12:28some of the side effects and you know,
01:12:31I think when we use the word
01:12:33chemotherapy you know it generates a
01:12:35lot of fear and I think that a lot of
01:12:38our treatments have gotten better.
01:12:41I think that's true.
01:12:43I think when we talk about chemotherapy
01:12:45and I at one of the main regiments
01:12:49that we use is this folfox regimen,
01:12:51at least in the neoadjuvant
01:12:54or agement setting.
01:12:56The generally it's well tolerated
01:12:58in that there can be some nausha.
01:13:01We do give medicines before treatment.
01:13:03We give medicines for
01:13:05patients to have at home,
01:13:07and if that doesn't work then we
01:13:10have other medicines that we can
01:13:13add to to the regimen to really
01:13:16try to get that under control.
01:13:18It can affect sense of taste.
01:13:21It can affect the blood counts.
01:13:25Can cause diarrhea?
01:13:26And and a lot of those side
01:13:29effects are temporary side effects
01:13:31that people have during during
01:13:34the course of their treatment.
01:13:36I think the the side effect that we
01:13:39worry about the most is really that
01:13:43oxaliplatin can cause neuropathy.
01:13:45It can cause nerve damage.
01:13:48That initially starts as just
01:13:50cold sensitivity.
01:13:50If you put your hands in the
01:13:53freezer or you drink something cold.
01:13:55It's going to be uncomfortable
01:13:57and that you know might last
01:13:59for a few days at the start,
01:14:01but by the end of your treatment may happen.
01:14:04You know, 1011 days into it.
01:14:07But it can also be cumulative,
01:14:10and it can last for a long time.
01:14:14After the treatment is done and
01:14:17So what I have found in terms
01:14:20of of a semi permanent.
01:14:22Toxicity of chemotherapy.
01:14:23It is that numbness and
01:14:25tingling to some degree.
01:14:29The nerves take along time to heal.
01:14:32They can take years to heal and some patients
01:14:36they have a little bit of discomfort.
01:14:39Afterwards, some patients they have more
01:14:41and we need to have them on medications
01:14:44to really help to get that under control.
01:14:47But you know, we really do give it a lot of
01:14:50attention and make adjustments in the dough.
01:14:52Sing, make adjustments in the duration
01:14:54and some of our research is also looking
01:14:57at whether we can cut back on the amount
01:15:00of oxaliplatin that people really need,
01:15:02because it is, you know,
01:15:04the most bothersome side effect.
01:15:08Great thank you and I think
01:15:10there have been some questions
01:15:12answered directly in the chat.
01:15:14I'm trying to incorporate some of
01:15:16those in the questions I'm going to
01:15:18ask Doctor Cicchini a question and
01:15:20something that's come up came up.
01:15:22I think during both your
01:15:24talk and doctor yours talk.
01:15:26Can you comment some on the differences
01:15:28we talk about sort of genetic testing.
01:15:30I think that can be a confusing topic
01:15:33in terms of are we testing the jeans
01:15:36that are passed from parent to child
01:15:38or retesting the tumor genes and?
01:15:40You just kind of define that
01:15:42a little bit for everybody.
01:15:45Certainly so as a as a medical oncologist
01:15:47and for the treatments that I talked about,
01:15:50I do a lot a of somatic testing.
01:15:53So what does that mean?
01:15:55That means I'm actually testing
01:15:56the tumor for mutations.
01:15:58I'm not testing the normal cells to see.
01:16:01Was there something that that I
01:16:02could have that somebody could have
01:16:04identified early on that would have
01:16:06predicted the development of cancer?
01:16:08That's what Doctor Lord's and I'm
01:16:11sure he'll comment after I do,
01:16:12but so we're sequencing the tumor and we're
01:16:15looking for those mutations that I mentioned.
01:16:18K rasby raff.
01:16:19We actually do much more than that.
01:16:22The ones that I mentioned
01:16:24are the bare minimum.
01:16:26I guess I would say,
01:16:28but at Yale and at other major centers
01:16:31will actually probably sequence around 160
01:16:33sometimes up to 400 other genes to see if
01:16:37we in the tumor itself only in the tumor,
01:16:40and see if we can identify
01:16:43a target for a drug.
01:16:45So we have drugs that sometimes
01:16:47target very obscur jeans.
01:16:49That we find in point 1% of colorectal
01:16:51cancer, 1% something very rare.
01:16:53That could be very meaningful
01:16:54for that 1% that has it.
01:16:56And you know,
01:16:57there's a lot of jeans and a lot
01:16:59of drugs being developed every day,
01:17:01so it all does add up,
01:17:03but the testing that we do
01:17:05standard of care on every patient
01:17:07is to is to test the tumor.
01:17:09Only.
01:17:09We sometimes do a brief comparison
01:17:11with the normal cells as part
01:17:13of our test here at Yale,
01:17:15but some patients may be familiar
01:17:17with their test being sent out
01:17:18to accompany by their doctors,
01:17:20such as foundation.
01:17:22Medicine Garden these are companies
01:17:24that that are that sequence
01:17:27tumors for oncologists.
01:17:29And those are just doing the tumor itself.
01:17:31We can even now sequence the blood
01:17:33and see if we can detect tiny amounts
01:17:35of cancer in the blood and look for
01:17:38mutations where we can sometimes
01:17:39identify some of those same mutations.
01:17:41As you can imagine,
01:17:42it's not quite as good as we when
01:17:44we do that because we're not going
01:17:46to the source and and really
01:17:48pinpointing everything,
01:17:49but it's it's pretty good in the
01:17:51technology is advancing quickly.
01:17:53I'll let Doctor Laura comment on the
01:17:55the germline sequencing that he does.
01:17:58Alright, we'll take on that so,
01:18:00so yeah, so we're more interested
01:18:02in that other Saturday.
01:18:03The side where we're looking at
01:18:05the jeans in the normal cells.
01:18:08Those are the ones that we inherit.
01:18:10One copy from Mom.
01:18:12One copy from that.
01:18:13And that's the one that most of
01:18:16the genetic diseases that get
01:18:17passed along where we detect them.
01:18:20And usually we do it with
01:18:22saliva tests or blood test.
01:18:24And that's how we can detect some of the
01:18:27underlying genetic disease that cost.
01:18:29Little cancer, for instance,
01:18:30machine drum or the public buses cases too.
01:18:34So those are the ones that
01:18:36when we have any suspicion that
01:18:39something may have been again.
01:18:42Have some genetic background
01:18:43in terms of developing cancer.
01:18:45That's what we were testing for.
01:18:49Great, thank you.
01:18:50I'm going to ask a question.
01:18:52It's just come up in the chat and
01:18:55I think Doctor Cicchini you maybe
01:18:57and typing an answer to this now,
01:19:00but it's a question on you know the
01:19:03duration of chemotherapy for stage
01:19:05four or metastatic colorectal cancer.
01:19:07And you know, is it given indefinitely
01:19:10are breaks part of the plan and
01:19:12maybe both Doctor Cicchini inductor
01:19:14court Manske can address that.
01:19:19Sure, yes. I was halfway through my response,
01:19:22but I'll just say that. So in general,
01:19:26we don't necessarily have a planned a
01:19:28plan from day one that we're taking a
01:19:30break at six months or one year when
01:19:32we're treating metastatic cancer.
01:19:34We're trying to control the disease.
01:19:35As long as we can, and we want to keep the
01:19:39pressure on the cancer as long as we can.
01:19:43So we don't have a plan that we're
01:19:45only doing so much, but this is.
01:19:47This is something we continually
01:19:48reassess every time we're seeing
01:19:50somebody is is a blood work OK?
01:19:52How do people feel is it?
01:19:53Is it the right time to do treatment?
01:19:55Do we need a break?
01:19:58And that's that's a case by case.
01:20:01Decission certainly between somebody's
01:20:02patients in their oncologists.
01:20:03I think other part of the question was
01:20:06how you know how long can the organs take?
01:20:09Indefinite chemotherapy and
01:20:10there's there's no.
01:20:11Again, it's very individualized,
01:20:13but certainly overtime.
01:20:14Certain toxicities build up and there are
01:20:16modifications that we make all along the way,
01:20:19and that's what that's what we're doing.
01:20:21Every time is medical oncologist were
01:20:23comparing blood work and symptoms
01:20:25and seen should the dose be this?
01:20:27Should we really be doing both drugs
01:20:30together this week or should we be
01:20:32lowering one of the doses or remove?
01:20:35Moving on into drugs after Manske management,
01:20:37drug oxide,
01:20:38platinum defects and nerves.
01:20:39Nobody ever gets that drug indefinitely.
01:20:41It causes neuropathy and everybody,
01:20:43and so usually around the 6th or the
01:20:458th dose were significantly reducing
01:20:46it or or eliminate it completely and
01:20:49switching to a maintenance type of
01:20:51chemotherapy that's preferred actually.
01:20:53Then,
01:20:53taking a break switching to maintenance,
01:20:55we actually know that's better
01:20:57than taking a break.
01:20:58Even if you were started when
01:21:01the cancer grows again.
01:21:03And we take a break and we lowered.
01:21:05The dose is down or an we switch to
01:21:08a maintenance of user that 5F you.
01:21:10Sometimes we use a pill form of it
01:21:12called Xeloda with Avastin together.
01:21:14And usually that's pretty tolerable.
01:21:16That's the goal of maintenance to
01:21:17keep the cancer and check you know,
01:21:19hit it hard initially with those
01:21:21multiple drugs,
01:21:22keep it in check with a lower dose
01:21:24maintenance for as long as we can,
01:21:26and then when necessary escalate again.
01:21:28But if patients cannot tolerate,
01:21:29tolerate that along the way.
01:21:31Absolutely breaks are incorporated,
01:21:32and there's certainly people that
01:21:34have a different.
01:21:34Biology,
01:21:35their cancer is not reading the
01:21:36textbooks and isn't it behaving as
01:21:38aggressively at certain at certain
01:21:39times when we might expect it to
01:21:41be in those patients certainly
01:21:42can get breaks and do really well
01:21:44with breaks of time,
01:21:45so it's very individualized.
01:21:49Great thank you Jeremy. Anything to add.
01:21:53Yeah I would just add a couple of points,
01:21:56I think also along the way,
01:21:58depending on the extent
01:22:00of somebody's disease,
01:22:01you know we make you know we get
01:22:03together as a group and we make a
01:22:06decision about whether there's an
01:22:08opportunity to treat individual
01:22:10sites of disease more aggressively
01:22:12with either surgery or radiation,
01:22:14which may then afford a break from treatment.
01:22:17And then even although at the beginning
01:22:20there are patients where it's clear.
01:22:23That their disease is growing very,
01:22:25very slowly,
01:22:26and if we know that our chemotherapy is
01:22:29not going to get rid of it completely,
01:22:32we could also take some time to
01:22:35figure out the right time to start
01:22:37the treatment and follow the disease
01:22:40closely with scans so that we don't
01:22:43introduce side effects too early while
01:22:45knowing that we're not going to impact
01:22:48the overall outcome of the disease.
01:22:53Great, thank you, so I'd
01:22:54like to kind of end on
01:22:56a positive note and I'm going to kind
01:22:59of push the same question to everybody.
01:23:02I'd like to know either what
01:23:05you're most hopeful for.
01:23:07Kind of advances what you're
01:23:08most excited about in the field,
01:23:10and I'm going to sorry Doctor Reddy.
01:23:13I'm going to pick on you first.
01:23:18You're on mute still.
01:23:22So for us you know the
01:23:24biggest thing is you know
01:23:26if we operate some way of doing it
01:23:28with the least impact on their life.
01:23:31I think we have made a lot of achievements
01:23:33by doing them laparoscopically, Lee.
01:23:35We have progressed so much and being able to
01:23:39reattach patients without a permanent bag.
01:23:43Even 10 years I've seen that evolve.
01:23:47And if we can somehow make
01:23:49it even slightly better.
01:23:51One crazy type that we have and
01:23:52we've always tried to work on is an
01:23:54artificial center so that even for
01:23:55patients where the muscle is involved,
01:23:57we can get out of the bag.
01:24:00Great, thank you. That's great doctor your.
01:24:06So I guess my my dream would be get
01:24:10getting all the oncologist out of business,
01:24:13not preventing patients
01:24:14from developing cancers,
01:24:16and that that we may dream.
01:24:18That's so I think that's so,
01:24:21as we've seen with colon cancer, there's a.
01:24:24There's a huge opportunity because
01:24:26we are able to see big differences,
01:24:29and therefore that means that there's
01:24:32a big chunk that is preventable
01:24:35from from different standpoints.
01:24:37One of them also including diagnosing
01:24:39earlier the genetic ones that
01:24:41even though they are a minority,
01:24:43they are a big part of what causes
01:24:46cancer and problems related to that,
01:24:48so that we may dream to really see
01:24:51how we can prevent it even more.
01:24:54And I'm very optimistic about that.
01:24:56There will be more probably blood
01:24:58based test that would allow us
01:25:01to do that in a much simpler way.
01:25:03Ann and again,
01:25:04hopefully not getting to the
01:25:06stages that we're talking about.
01:25:09Thank you Doctor Kurt manske.
01:25:13So I am so the the
01:25:17breakthrough of the year in.
01:25:20In our disease was all of the molecular
01:25:24developments in in GI cancers in general,
01:25:27so not just colorectal cancer,
01:25:29but across the board. Anne Anne.
01:25:34We already saw examples over that tonight,
01:25:37and I think that there is so much
01:25:40research that is going on really
01:25:43targeting these pathways and still
01:25:46investigating immunotherapy that
01:25:48I am optimistic of a future that
01:25:51doesn't include chemotherapy.
01:25:54Great doctor cicchini
01:25:57I'm pretty much echo with with
01:25:59Doctor Karman, Skeates said.
01:26:01I think the most exciting and
01:26:03hopefully the most promising approach
01:26:05for colorectal cancer is to make
01:26:08immunotherapy work for the 96% of
01:26:09patients that have microsatellite
01:26:11stable chlorophyll cancer metastatic,
01:26:12Microsoft and stable colorectal cancer.
01:26:16Numerous clinical trials investigating
01:26:18this this this paradigm through many
01:26:22different mechanisms and investigators
01:26:24all over the world working on this.
01:26:28So I think the future is bright. Great,
01:26:34well I I share in that optimism
01:26:36and I want to really thank.
01:26:39Our participants are both our panelists
01:26:41tonight, but also those of you in
01:26:43the audience who've been listing.
01:26:45And I think many of you have
01:26:48shared your personal stories,
01:26:49whether it's personally or
01:26:51with family and friends.
01:26:52We thank you for getting screened and getting
01:26:55colonoscopies and also really sharing that.
01:26:57I think that I'll maybe agree with
01:27:00Doctor your that I think that really,
01:27:02if we can prevent it.
01:27:05Um, you know,
01:27:06that's really a huge mission and I
01:27:08think one of the goals of colorectal
01:27:11Cancer Awareness Month is really
01:27:13spreading that message around screening.
01:27:15So please share that with
01:27:17your friends and family.
01:27:19Any screening is better than no screening,
01:27:22so thank you everyone for
01:27:24sharing your evening with us.
01:27:26We are very grateful and please,
01:27:28you know,
01:27:29come to our Cancer Center website and
01:27:32let us know if you have any needs.