Smilow Shares: Colorectal Cancer - What You Need to Know and What's New

Name: Smilow Shares: Colorectal Cancer - What You Need to Know and What's New
Uploaded: 2026-03-27T14:20:17.6533333Z
Duration: 1 h 3 min 31 s
Description: March 26, 2026 Hosted by: Dr. Michael Cecchini Presenters: Kimberly Johung, MD, PhD and Anne Mongiu, MD, PhD

March 27, 2026

March 26, 2026

Hosted by: Dr. Michael Cecchini
Presenters: Kimberly Johung, MD, PhD and Anne Mongiu, MD, PhD

About the speakers

Kimberly L. Johung, MD, PhD
Associate Professor of Therapeutic Radiology; Vice Chair for Education, Therapeutic Radiology; Director of Residency Training Program, Therapeutic Radiology; Chief, Gastrointestinal Radiotherapy Program, Therapeutic Radiology; Chief, VA Radiotherapy Program, Therapeutic Radiology
Michael Cecchini, MD
Associate Professor of Medicine (Medical Oncology); Co-Director, Colorectal Program in the Center for Gastrointestinal Cancers; Phase 1 Investigator, Yale Cancer Center; Director, GI Clinical Research Team Yale Center for GI Cancers
Anne Mongiu, MD, PhD, FACS, FASCRS
Assistant Professor of Surgery (Colon and Rectal); Co-Chair, Lower GI Tumor Board; Co-Director of the CRC Program, Surgery

Information

ID: 14010
To Cite: DCA Citation Guide

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00:04Hello, and thank you for
00:06joining us for the for
00:08the smile shares for colorectal
00:10cancer in twenty twenty six.
00:12This is colorectal cancer awareness
00:14month, and here at the
00:15Yale Smilow Cancer Hospital and
00:17the Yale Center for GI
00:18Cancers,
00:19we're gonna have a presentation,
00:21for
00:22GI medical oncology,
00:24surgical
00:25colorectal surgery,
00:26radiation oncology, and how we
00:28comprehensively
00:29care for patients with colorectal
00:31cancer.
00:32I'll start by,
00:34introducing each speaker,
00:37in each presentation,
00:38moderating
00:40a q and a session.
00:41So, again, my name is
00:42Michael Cecchini. I'm one of
00:43the GI medical oncologists and
00:45codirector of the colorectal cancer
00:46program and director of GI
00:47clinical research.
00:49I'd like to introduce my
00:50colleague, doctor Kim Joheng, one
00:52of the radiation oncologists. I'll
00:54let you introduce yourself.
00:57Thanks, Michael.
00:59Kim Joheng.
01:00I treat mostly GI cancers
01:02with radiation,
01:04and we'll be talking a
01:04little bit more about that,
01:06after Michael's talk.
01:09Doctor Anne Monju from Colorectal
01:11Surgery, who's also one of
01:12the codirectors of the colorectal
01:14cancer program.
01:16Hi. Anne Monju. I'm a
01:17colorectal surgeon here at Yale,
01:19and, my part of the
01:20team is to help with
01:21surgery to remove the cancer
01:23when the time is right.
01:26And so just some housekeeping,
01:28ish,
01:29topics. If you can put
01:31your questions in into the
01:32chat through the q and
01:33a, I will then repeat
01:35your questions,
01:36to the appropriate speaker.
01:38And I will be,
01:40starting off today talking about
01:42some of the medical oncology,
01:44aspects of colorectal cancer surgery.
01:46So I am going to
01:47share my screen here.
01:55Excellent.
01:56So,
01:58I've been going to talk
01:59about
02:00medical oncology management and personalized
02:02treatments for colorectal cancer,
02:04and here are my disclosures.
02:08I'm gonna talk a bit
02:08about staging, and then I'm
02:10gonna talk about how as
02:11medical oncologists,
02:13we think about some of
02:14the personalized treatments and chemotherapies,
02:16targeted therapies, systemic therapies, and
02:17even immunotherapies we use for
02:19these diseases.
02:21So how do we stage
02:23colorectal cancer?
02:25It's often made the diagnosis
02:27is often made, by colonoscopy,
02:30and then we have, the
02:32question of whether or not
02:33this is localized disease or
02:34metastatic disease.
02:35This will the this workup
02:37will often include some blood
02:38tests at first to assess
02:40some very
02:42straightforward
02:43measurements, such as liver function
02:45tests, blood counts like hemoglobin,
02:47white blood cell count, and
02:49as as well as a
02:50CEA, which is a blood
02:51marker that kind of gives
02:52us an indication
02:54of the presence,
02:56and and of colorectal cancer
02:58and sometimes whether or not
02:59that colorectal cancer is is
03:00worsening or or improving to
03:02our therapies.
03:04We also use a test,
03:05a sophisticated test at times
03:07called circulating tumor DNA. We
03:09typically use this test after
03:11surgery to to help determine
03:13whether or not there's any
03:14residual cancer left behind.
03:16There are many this is
03:17a very, detailed test,
03:19and is a lecture,
03:21to itself. But it's essentially
03:23a test that we can
03:24do after a surgery
03:25where we kind of find
03:26if there's any,
03:28evidence of DNA fragments of
03:30residual cancer floating around in
03:31the bloodstream. And we can
03:32tell that those DNA fragments,
03:35apart from normal DNA in
03:36our blood.
03:38And if they're present, it
03:39really suggests that there is
03:40residual cancer.
03:42And then also, we will
03:43always do a CT scan
03:45to to identify whether or
03:46not there's any spread
03:48of a cancer,
03:49micrometastases,
03:51or small areas of metastases.
03:53We're looking for any evidence
03:55the cancer may have spread
03:56to the liver,
03:58the abdominal cavity, or the
04:00lungs would be the three
04:01most common,
04:02sites.
04:05So we are also sometimes
04:07doing surgery even when this
04:08cancer has spread. And so
04:10we call it we call,
04:12limited spread of the disease
04:14oligometastatic
04:15disease,
04:16typically meaning it's gone to
04:17one organ, sometimes even multiple
04:19sites in in the organ.
04:21The definition for this is
04:23varied,
04:24depending on, depending on what,
04:26what guideline you follow. But
04:28the the the overall term
04:30oligometastatic
04:31disease means limited metastatic disease.
04:33So despite the cancer having
04:35spread, it hasn't spread,
04:37as,
04:38as much as,
04:41other
04:42other other instances. And and
04:43usually with oligometastatic disease, our
04:45goal is to address the
04:47disease with more than just
04:48surgery. So if we think
04:49about a colon tumor, the
04:50most con colorectal
04:52tumor, the most common site
04:53that that may spread to
04:55would be the liver. And
04:56once it's spread to the
04:57liver or the lung or
04:58the abdominal cavity,
05:00by definition, it is stage
05:01four disease. It is it
05:02is broken out of the
05:04colon and the lymph nodes
05:05in that area and and
05:06spread to other organs.
05:09Whereas a cancer that's that's
05:11only spread to a lymph
05:12node but not distantly would
05:13be a stage three disease,
05:14and cancers that have more
05:16minorly invaded into the wall
05:17of the colon but not
05:18spread to any lymph nodes
05:19or distantly
05:20would be a stage two
05:22disease, and and minimal
05:23invasion into the colon wall
05:25might be a stage one
05:25tumor.
05:27And so one of the
05:28first questions we have, as
05:30a group in our multidisciplinary
05:32tumor boards when we see
05:34somebody diagnosed with ole comatostatic
05:36diseases, does this patient still
05:37have a pathway to cure?
05:39And we work together
05:40to usually use some combination
05:42of chemotherapy,
05:43radiation,
05:44and surgery to maybe,
05:47completely remove and eliminate all
05:49the cancer. And, here's an
05:50example.
05:51So this is a CAT
05:52scan. And in this CAT
05:54scan,
05:55we're looking up from this
05:56patient's feet. So,
05:58if we if, if that's
06:00the case, this would be
06:00the right side of the
06:01patient,
06:02with my cursor. So left
06:04side of the screen, right
06:04side of the patient. Left,
06:07the the this would be
06:09the left side of the
06:10patient. This is the back.
06:11So you can see the
06:12spinal bone, one of these
06:13vertebral bones right there, and
06:15the chest,
06:16at the top of the
06:17screen. And this patient's laying
06:19on their back. We're looking
06:20up up from their feet,
06:22and they're sliced like a
06:23loaf of bread, and this
06:24is one of those slices.
06:25So this big gray area
06:27would be the liver, and
06:28in it is a a
06:29tumor there that you can
06:30see that I'm, running the
06:32cursor around right there. So
06:34this is an isolated,
06:36isolated frame of the CAT
06:37scan, but this was an
06:38isolated,
06:39disease,
06:41that was
06:42able to be removed by
06:44surgery.
06:45On the other hand, here's
06:46another example. Same orientation,
06:48right side,
06:49left side,
06:51chest, back. But we can
06:52see here this this patient's
06:53liver, unfortunately, has numerous cancers,
06:56and it's not so much
06:57a oligometastatic
06:58disease that we,
06:59are optimistic upfront that we
07:01can get that patient,
07:02get all that,
07:04all all those tumors removed.
07:05But perhaps with the combination
07:07of chemotherapy
07:08and potentially other treatments, we
07:09can shrink down those tumors
07:10enough to change the the
07:12scenario there and get that
07:13patient to surgery.
07:16One of the other things
07:17that we we know and
07:19and try and subtype the
07:20cancer a bit differently is
07:22that there's a difference between
07:23tumors that arise on the
07:24left side of the colon,
07:26which is, again, your right,
07:29or the right side of
07:30the colon, which would be
07:30your left because this is
07:32a a diagram of looking
07:33straight at somebody's colon. So
07:34this would be the start
07:36of the colon,
07:37as stool moves, follows this
07:39path and ultimately ends up
07:40in the rectum and then
07:41is x-rayed through the anus.
07:43So we've, we've,
07:45identified as a field that
07:47when we find a tumor
07:48in the right side of
07:49the colon
07:50and versus the left side
07:51of the colon and we
07:52sequence that that cancer to
07:54find out what mutations are
07:55present in the cancer or
07:57look at different methylation profiles,
07:58which are other DNA changes
08:00in the tumor,
08:01we find that they're very
08:02different cancers. And the reason
08:04is,
08:05they the the tissue that
08:07the, the normal colon
08:11comes from different embryological origin
08:13cells as our bodies are
08:14forming. And this leads to
08:16just different behaviors of, of
08:18these normal cells that can
08:19ultimately
08:20develop into cancer. And this
08:22helps me as a medical
08:23oncologist
08:24realize that,
08:25there are different treatments to
08:27use,
08:28or certain tests to do
08:30to identify
08:31the nuances,
08:32that may be present for
08:33the to to establish the
08:34differences of those tumors. There
08:36is also some differences in
08:38how these cancers may even
08:39spread. So we find that
08:41these cancers on the right
08:42side tend to more be
08:43more likely to have a
08:44BRAF mutation, which is a
08:45targetable mutation,
08:46to be more likely to
08:47be MSI high, which means
08:49immunotherapy may be indicated,
08:51when the when the cancer
08:53has spread.
08:55And whereas the cancers on
08:56the left side are less
08:56likely to have those mutations,
08:58and we can use other
08:59targeted therapies for those tumors
09:00such as panatumumab, of course,
09:02it talks about.
09:04So from a biological perspective,
09:07we think of,
09:08colon cancer as arising
09:10through a process called the,
09:12adenoma to carcinoma sequence,
09:15where we we start with
09:17a normal,
09:18a normal intestinal, what we
09:20call epithelium,
09:21normal intestinal lining. And what
09:23can happen over time is
09:25polyps form through the disruption
09:27of this normal lining, a
09:28normal epithelium.
09:29And so then you get
09:30a small polyp and then
09:32a large polyp. And along
09:33those way along the way,
09:35these cells can start to
09:36have some abnormalities
09:37and accumulate
09:39mutations,
09:40which lead these tumor cells
09:41to become dysregulated,
09:43invasive,
09:44and and ultimately,
09:46if they're invasive, become cancerous
09:48cells. And that's that's essentially
09:50how this whole process, proceeds
09:52in in most tumors are
09:53formed.
09:55And that the, the the
09:56typical time frame this takes
09:58is on the order of
09:59years, which is why we
10:00do colonoscopies,
10:02in,
10:03every ten years for patients
10:04that are are standard risk.
10:07Now for medical oncologists, we
10:09do,
10:10we do quite extensive tumor
10:12profiling to determine what are
10:14the best therapies we should
10:15be offering our patients. So
10:17we do some testing, which
10:18is called immunohistochemistry,
10:20which means we stain the
10:21tumor tissue.
10:23I should say, we order
10:24this testing. Our our our
10:25pathologists do this.
10:27But we order immunohistochemistry
10:29testing,
10:30which means the tissue is
10:31stained and it's looked at
10:32under a microscope by the
10:33pathologist to see the presence
10:34or absence
10:35of of certain proteins. And
10:37some examples would be looking
10:38for mismatch repair proteins. That's
10:40trying to identify whether or
10:41not a tumor is MSI
10:42high and therefore sensitive to
10:44immunotherapy.
10:45Or maybe looking at HER2,
10:46which is a different protein,
10:48and there are targeted therapies
10:49for that. And and we
10:50then we also sequence the
10:52DNA of of virtually all
10:53tumors now,
10:54and try and identify whether
10:56mutations in KRAS, BRAF,
10:59or or other,
11:00alterations are present because we
11:01have targeted therapies for these
11:03these these scenarios.
11:06And so a biopsy may
11:07be used again,
11:08from a a lung biopsy
11:10if this cancer is spread
11:11to the lung and then
11:13stained for some of these
11:14immunohistochemistry
11:15tests. We can even do
11:16liquid biopsies now. So we
11:18don't even need to always
11:19biopsy the tumor and sequence
11:20the tumor. Sometimes we can
11:21just get those little DNA
11:23fragments from the blood and
11:24sequence those and be confident
11:26that there's a KRAS mutation
11:27or the or a KRAS
11:28mutation is absent. So it's
11:30absolutely standard of care,
11:32everywhere and certainly at Yale.
11:33We'd be doing all of
11:35the testing that's here on
11:36this page, testing the DNA,
11:37testing the tissue to personalize
11:39the treatment and make sure
11:40we're offering our patients the
11:41most effective therapy.
11:43So these are the the
11:44tests that I advocate that,
11:47that, all of my patients
11:49should know the results from,
11:51to make sure that they're
11:52getting,
11:54the most effective,
11:55therapies. And and we need
11:57every last detail here to
11:58be confident that we're actually
11:59giving the right drug to
12:00the right patient at the
12:01right time. So we need
12:02to know the microsatellite
12:03state
12:04status. And for patients that
12:07are
12:08metastatic when the tumors
12:11metastasized,
12:12most of those tumors are
12:13going to be met microsatellite
12:14stable. So ninety six percent
12:16of the time, we find
12:17that tumors are microsatellite stable,
12:19which means at present, there's
12:20not a large role for
12:21immunotherapy.
12:23But for these,
12:24two to four percent of
12:25patients that are diagnosed with
12:26microsatellite instability high tumors or
12:28MSI high tumors, immunotherapy
12:31is is,
12:34the main treatment we're using
12:35for these patients, and it's
12:36highly effective. So this is
12:38a can't miss kind of
12:39marker that we need to
12:40test all of our patients
12:41for. And then we also
12:43now need to know about
12:43KRAS mutations.
12:45Is it present or is
12:46it not? What is the
12:47KRAS mutation? If it's present,
12:49we may have drugs that
12:50target that KRAS mutation. If
12:51it's absent, that gives me
12:52insights
12:54about using specific therapies.
12:56And then the BRAF v
12:57six hundred e mutation, which
12:58historically has been a very
12:59aggressive mutation, but we have
13:02targeted therapies for this in
13:03there. It's important they're instituted
13:05early, and we we know
13:06that there's great data that
13:08backs that up,
13:09as well as HER2 status
13:10that gives us,
13:13insights about using HER2 targeted
13:15therapies. And lastly, again, the
13:17sightedness. I need all five
13:19of these,
13:21these details for every patient
13:22I see, every new patient
13:24I see, every established patient
13:25I see, and make sure
13:26they're getting the right treatment,
13:28the right drug for the
13:28right patient at the right
13:29time. So I encourage my
13:31patients to be empowered that
13:33that this is this is
13:34information,
13:35that they they should be
13:36requesting if if it's not
13:38done for some reason.
13:40So we initially, we're typically
13:41using chemotherapy, FOLFOX,
13:44FOLFIRI, FOLFOXURI
13:45sometimes. These are chemotherapies.
13:47They're not targeted. We use
13:48five fluorouracil,
13:49which is a a drug
13:51we deliver through a five
13:52of fusion
13:53pump over forty six hours.
13:54We use oxaliplatin
13:56given along with that,
13:58and or or folfury,
14:01five of fluoroeracil with our
14:02Inatecan.
14:04These are the initial chemotherapies
14:05we'll start with for most
14:06patients.
14:07We'll often add on a
14:08drug on top of them,
14:10called either bevacizumab
14:11or panetumab and cetuximab. And
14:13these and and which what
14:15what we add in the
14:16red here depends on
14:18what mutations are present.
14:20And, also, again, we'll add
14:21on, a BRAF inhibitor if
14:23a BRAF b six hundred
14:24e mutation is present. Again,
14:26why we need to know
14:27all these little details is
14:28because we personalize each treatment
14:31to each patient to make
14:32sure we're being as effective
14:33as
14:34possible,
14:35towards the patient. And so
14:37I'm gonna just show a
14:38couple slides about how these
14:40drugs work, how targeted drugs
14:41work. So if we think
14:43about a cancers,
14:44cancer cell, this would be,
14:46the membrane or the outside
14:48of a cancer cell, and
14:49and below here would be,
14:50like, the inside, and the
14:51nucleus would be, like, the
14:52brain of the cancer cell.
14:54Cancer cells, unfortunately,
14:56often have a lot of
14:57active signaling, and that stimulates
14:59growth. So whereas the all
15:01these arrows is just kind
15:02of a, like a light
15:03switch on or a waterfall
15:04on into the brain of
15:05the cell telling it to
15:06grow. And when we can
15:07shut that process down, we
15:09can, kill cancer cells. We
15:11can certainly slow growth quite
15:12effectively. And
15:14the idea is to target
15:15the cancer cells that have
15:16this all activated and spare
15:18the normal cells, whereas chemotherapy
15:20is more poison oriented and
15:22and is not so focused
15:23on,
15:24specific pathways. So we know
15:26when when a KRAS mutation
15:28is present, if we can,
15:30if we can,
15:32target it, we can shut
15:33down this pathway. And we
15:35know that when there's no
15:36KRAS mutation present, we can
15:38we can,
15:39target these receptors with eGFR
15:41inhibitors,
15:42lcetuximab
15:43or pantetumumab,
15:45and,
15:47and that that adds to,
15:48how well patients do, how
15:50often the cancer shrinks down,
15:51how long patients,
15:52they're disease controlled. Whereas if
15:54there's,
15:56a mutation present at KRAS
15:57BRAF, we know that targeting
15:59these receptors up here,
16:01are less is less impactful
16:02when we use a drug
16:03like bevacizumab,
16:04which is why I need
16:05to know, again, whether or
16:06not a KRAS mutation or
16:08a BRAF mutation is present
16:09right away.
16:11Now we have
16:13we have drugs that inhibit
16:15specific KRAS mutations. So if
16:16you have a KRAS g
16:17twelve c, there's FDA approved
16:19drugs,
16:20that,
16:22that,
16:24that target that. If there's
16:25a KRAS g twelve d
16:27mutation, there's numerous clinical trials
16:28looking at g twelve b
16:30and so on. So these
16:31are targetable mutations with approved
16:32drugs and many clinical trials
16:34that may be relevant for
16:35to know this information.
16:37Whereas, if there's a BRAF
16:38mutation present, we have,
16:41a BRAF inhibitor called encorafenib
16:43and cetuximab. So we wanna
16:44shut the we wanna shut
16:46that growth pattern down right
16:47at its source, right at
16:48the BRAF mutation. And we
16:49know you the the recent
16:50approval of these drugs within
16:52the the last year literally
16:53doubled the survival
16:55for for for, patients with
16:57BRAF mutations.
17:00There's similar targeted treatments if
17:02there's abnormalities in HER2 on
17:04the cell surface, something called
17:05tucatinibetrizumab.
17:07Again, why we need to
17:08know the details of personalizing
17:10these treatments as well as
17:11in HER2 for HER2 positive
17:13colorectal cancer.
17:14And and then
17:16to conclude talking about some
17:18of these more targeted based
17:19treatments is immunotherapy.
17:21So for that two to
17:22four percent of patients that
17:23have metastatic
17:25disease but have MSI high
17:27tumors, we know that,
17:28they're highly sensitive
17:30to immunotherapy because the tumors
17:32have many mutations.
17:34And therefore,
17:35the immune system, given enough
17:37push by our immune therapies,
17:39has an easier time
17:41recognizing the cancer as foreign
17:43and,
17:45and,
17:47can eliminate it. So
17:49this is,
17:50this is some results on
17:52the left here from our
17:53initial
17:54trial with immunotherapy comparing it
17:56to chemo chemotherapy
17:57for these patients
17:58with MSI high colorectal cancer.
18:00And we saw that, again,
18:02on
18:03as time progressed,
18:04more patients on pembrolizumab,
18:06an anti PD one inhibitor
18:08in immunotherapy,
18:09had not had their cancer
18:11grow and and and were
18:13alive compared to those that
18:14got chemotherapy. The majority of
18:16those patients at some point,
18:17for example, here at two
18:18years, had had their had
18:19their cancer progressing and and
18:21grow. Whereas on on pembrolizumab,
18:24roughly half of those patients
18:26were still stable.
18:27Now with,
18:29two immune drugs, we're we're
18:31seeing at the two year
18:32mark here,
18:34that,
18:35roughly at two years,
18:37seventy ish percent of patients
18:39have not had their cancer
18:40progressed. So we are, literally
18:42probably curing,
18:45more than half of the
18:46patients by giving them
18:48ipi and nivo, ipilimumab and
18:50nivolumab with MSI hypoalleric cancer.
18:53A rare subtype, but this
18:54is something we can't miss
18:55because the results can be
18:56so impact.
18:57So in conclusion, we need
18:59multidisciplinary
19:00care for all patients to
19:01determine the optimal care plan
19:02whether or not we can
19:03do surgery.
19:04We still use our traditional
19:06chemotherapies for the majority of
19:08patients, but all tumors need
19:10testing for microsatellite
19:11status, ARAF status, BRAF status,
19:13HER2 status, as well as
19:15sidedness,
19:16to make sure we're giving
19:17the optimal results. And I
19:18think patients should be empowered
19:20to, to to know the
19:21status piece.
19:22And, immunotherapy
19:23is is, you know, making
19:25some,
19:27big impacts for patients with
19:28MSI high disease.
19:30So I'll stop there,
19:32and,
19:34if there are questions,
19:36I will,
19:38answer them throughout the,
19:40the presentations, but I'm gonna
19:42pivot now to doctor Jo
19:43Hong to discuss radiation oncology.
19:53We're muted. Sorry. I'm here
19:55now. Thanks, doctor Cicchini.
19:57So I'm gonna be talking
19:59about this is a very
20:00similar title to doctor Cicchini's
20:01title, A Personalized Approach to
20:03Radiation Therapy,
20:05for Rectal Cancer.
20:07So as shown here, there's
20:08three main modalities for treatment
20:10of rectal cancer,
20:12represented today actually on our
20:13webinar. So this is what
20:14doctor Cicchini does. He delivers
20:16the systemic therapies, either chemotherapy,
20:19or some of the targeted
20:20agents or immunotherapy that you
20:21heard about.
20:23This is doctor Maggio's area
20:24of expertise removing your actual
20:26tumor. So she's the hero
20:28there.
20:28And this is what I
20:29do, radiation therapy, which is
20:31a little more foreign to
20:32people. So I thought I
20:33would start talking first a
20:35little bit about the radiation
20:36care path. How does radiation
20:38work?
20:39And then we'll talk about
20:40two different ways we can
20:41deliver radiation,
20:43when you might be able
20:43to avoid radiation,
20:45specific scenarios for that,
20:48certain scenarios where you might
20:49have an excellent response to
20:51the chemo and the radiation,
20:52and you might not need
20:53the surgery.
20:55And then I'll touch upon
20:56what doctor Chiquini was mentioning
20:58was the oligometastatic
20:59state or when your cancer
21:01really has spread but only
21:02to limited sites and where
21:04radiation might come into play
21:06in that scenario.
21:08So a little bit of
21:08a,
21:10short radio biology lecture, which
21:12is basically how does radiation
21:13work to kill cancer cells.
21:15So radiation therapy really is
21:17relying on the use of
21:18ionizing radiation
21:20directed at cancer cells. It's
21:22delivered by these big machines
21:23called LINACS,
21:25really directing radiation with high
21:27precision,
21:28at your tumor.
21:29And what the radiation is
21:31doing is causing damage in
21:33the DNA of your cancer
21:34cells. I like to think
21:35of these as kinda like
21:36the building blocks of your
21:37cancer cells. And so if
21:38we use radiation to damage
21:40the DNA when the cells
21:41try to divide and multiply,
21:44they realize they're damaged and
21:45they die off instead. But
21:46we think of this as
21:47a local therapy because I'm
21:48really targeting the tumors,
21:50that I can see on
21:51your on your scans, whether
21:53it's CAT scan or MRI.
21:55This is an example of
21:56the treatment delivery machine and
21:58the treatment delivery room.
22:00So the radiation is coming
22:01from the head of the
22:02Linac here. We have panels
22:04on either side that are
22:05really imaging panels that help
22:07make sure that your body
22:08is in, the exact right
22:10position for treatment. So we
22:11can either do CAT scans,
22:13or X-ray imaging really to
22:15make sure that you you
22:16are accurately positioned for treatment
22:18on a day to day
22:19basis.
22:21And in order to spare
22:22the healthy tissue,
22:24the radiation is actually delivered
22:26from all angles. So this
22:27machine will spin around you.
22:29And so if beams are
22:30coming from different angles,
22:32it's really the intersection point
22:34that gets the full dose
22:35of radiation, and the tissues
22:37that the beams are passing
22:38through will get a much
22:40lower dose of radiation.
22:42And we use this this
22:43is kind of what it
22:44looks like if you were
22:45to look up in the
22:46head of the machine. So
22:47there's these tungsten leaves. They
22:49look really big in this
22:50picture, but they're actually just
22:51a couple of millimeters thick.
22:53And what they do is
22:54they're gonna be moving around
22:56during treatment with the shape
22:58of that field,
23:00matching kind of the shape
23:01of your tumor target from
23:02that angle. What they also
23:04do is they will move
23:05in and out of the
23:06field during treatment, and that
23:08can,
23:09modulate the intensity of the
23:11radiation beam.
23:12And that allows us to
23:14deposit this dose of radiation
23:16in your body that fits
23:17kind of a three-dimensional
23:18shape that matches the three-dimensional
23:21shape of your tumor. So
23:22these are just a little
23:23bit of the technical aspects
23:24of how we are able
23:25to safely deliver tumor,
23:27radiation to your tumor and
23:29avoid,
23:30radiation dose elsewhere in the
23:32tissues.
23:33A little bit about what
23:35it involves to get a
23:36course of radiation completed. So,
23:38obviously, there's a consultation process
23:40where we meet you and
23:41talk to you about the
23:42indications for radiation and what
23:43you can expect.
23:45And then we have all
23:45these weird terms, and so
23:47I go through them if
23:47you were to embark on
23:48a course of radiation,
23:50we start with what we
23:51call is is a simulation,
23:52and I would think of
23:53that as a planning process.
23:54So we're gonna get your
23:55body in position
23:57for treatment, and then we
23:58need to scan your,
24:00tumor region
24:01in that position so that
24:03we can see where the
24:04tumor targets lie when your
24:05body's in position for radiation.
24:07Most often, we place rectal
24:08cancer patients,
24:10prone, so on your belly,
24:12for treatment. And what this
24:13does is that it allows,
24:15the healthy bowel to kind
24:17of fall forward and away,
24:19from the treatment area so
24:20we deliver less radiation to
24:22the healthy bowel. I like
24:23to think of this as
24:24a nice massage table,
24:26pillow where you have the
24:27hole for your face here
24:28and you're comfortably positioned.
24:31After the CT scan process,
24:33we work with,
24:35physicists who are called dosimetrists.
24:36What they're doing is they're
24:38helping us, you know, angle
24:40the beams and devise a
24:41computer pace,
24:42based plan to deliver radiation
24:44that sort of really tightly
24:46fits the tumor targets. There's
24:48kind of a physics QA
24:49process, and then you embark
24:50on treatment,
24:52which tends to be daily
24:53treatments, and we'll talk about
24:54the reason for that shortly.
24:56This is just an example
24:57of what treatment planning looks
24:59like. So we've identified on
25:01a slice of a scan
25:02kind of the nodal lymph
25:04node regions that are at
25:05risk, and this is what
25:06a plan would look like
25:07showing the distribution of the
25:09radiation dose to those lymph
25:10node regions,
25:11but kind of carving the
25:12dose away from what I'm
25:14showing up here with the
25:15cursor is healthy bowel in
25:17the middle of those lymph
25:18node regions.
25:20I mentioned that radiation is
25:22typically delivered on a daily
25:23basis, Monday through Fridays.
25:25The reason for breaking the
25:27radiation dose into these,
25:29daily smaller doses,
25:31is that cancer cells have
25:33a decreased ability to repair,
25:36the damage, to their DNA
25:38from radiation, whereas healthy tissues
25:40are more able to repair,
25:42the damage from the radiation.
25:43So we break out the
25:44dose into little doses. The
25:46healthy tissues are repairing, whereas
25:48the cancer cells are less
25:49likely to repair.
25:50And then that's how we
25:51get cancer kill over time
25:53without wreaking too much havoc
25:54on the healthy tissues.
25:56So when would radiation be
25:58part of your treatment plan
25:59for rectal cancer treatment? So,
26:01doctor Cicchini mentioned a little
26:03bit about the staging of
26:04rectal cancer. And, like all
26:06things for cancer treatment, the,
26:08determination of when to employ
26:10radiation depends on the stage
26:12of your tumor.
26:13Part of that is how
26:14deep the tumor extends into
26:15the wall of the rectum.
26:17So we usually get involved
26:18for the deeper tumors, the
26:20t three category or the
26:21t four category,
26:23and then whether or not
26:24your tumor has spread to
26:25nearby lymph nodes,
26:27and we are typically involved
26:28if there's evidence,
26:30of cancer involving the lymph
26:32nodes,
26:33around the rectal area.
26:36This is just
26:38a a couple of graphs
26:39to show you, what is
26:41the benefit of using radiation
26:42for rectal cancer. So an
26:44example from kind of two
26:45classic trials showing you that
26:47when we add radiation to
26:49surgery, the benefit is what
26:51we call local control or
26:53preventing the cancer from being
26:54able to grow back. So
26:55the cancers are gonna recur
26:57locally in the pelvis,
26:59more often if you, have
27:01surgery alone. But when you
27:03add in radiation, we can
27:04reduce that likelihood of recurrence.
27:07And this is just showing
27:08you that if you apply
27:09the radiation
27:10before or after surgery,
27:12it's actually more effective
27:14before surgery. And in part,
27:15some of that is that
27:16we have a target that
27:17we can clearly see, and
27:18we're not kind of treating
27:19the space where the tumor
27:21used to be.
27:22In those two trials that
27:24I mentioned in the previous
27:25slide, the radiation was delivered
27:27in very different ways.
27:28So the first trial was
27:30delivering radiation in these five
27:32larger treatments
27:33without chemotherapy.
27:35And the second version was
27:36delivering radiation in daily doses,
27:39Mondays through Fridays over the
27:40course of five and a
27:41half weeks.
27:42And that's given with a
27:44light dose of chemotherapy that
27:45kinda synergizes with the radiation.
27:49So these are two, you
27:50know, quite distinct ways of
27:52giving radiation. So how do
27:53we choose between one or
27:54the other?
27:55I'll start by saying that,
27:57in the US, the long
27:59course of radiation over five
28:01and a half weeks is
28:02more commonly used just by
28:03practice patterns.
28:05The shorter course of radiation
28:06is more commonly used in
28:07Europe.
28:08But if we look at
28:09data comparing the two approaches,
28:12so the different colors,
28:13on these graphs are just
28:15patients who either receive the
28:16short course of radiation or
28:18the longer course and what
28:19is their,
28:20overall survival after cancer treatment.
28:23The bottom line is that
28:25in general,
28:26survival and rates of local
28:28recurrence are the same if
28:29you deliver radiation in these
28:30two ways. So as a
28:32patient, I would say, well,
28:33I want the faster way,
28:34and I don't want a
28:34chemo pill. So why don't
28:35we just do the five
28:36treatments and and be done
28:37with it? So we get
28:39a little more nuanced with
28:40it. One of the analyses
28:42shows that if you have
28:43a cancer that is lower
28:44down in the rectum, so
28:46quite close to the anus
28:47and, you know, a benchmark
28:49that over a threshold we
28:50use is about five centimeters
28:51from the anus,
28:53in that particular population of
28:54patients. And maybe doctor Manjo
28:56can touch upon this. Oftentimes,
28:58the surgery can be more
28:59complex. And so in that
29:01situation,
29:02you know, shrinking the tumor,
29:04if you will, with radiation
29:05first,
29:06can can lead to,
29:08more successful surgery and less
29:10likelihood that there's residual tumor
29:12that may grow back after
29:13surgery. So I think that
29:14would be one of the
29:15instances for sure where we're
29:17considering,
29:18a longer course of radiation
29:19rather than the short course.
29:21And then this is a
29:22really complicated slide just to
29:23show you, that in a
29:25trial that, the difference between
29:27the two treatment,
29:29pathways,
29:30one of the differences was
29:31that some of the patients
29:32had the short course radiation
29:33and some had the long
29:34course radiation.
29:35This trial was also looking
29:37at other things, like having
29:38chemo before surgery versus chemo
29:40after surgery.
29:42We now use the chemo
29:44before surgery in most cases
29:45because of some studies showing,
29:47you know, survival benefits to
29:48that. But what I want
29:50to point out from this
29:51trial is that if it
29:52is a way to compare
29:53the shorter course and the
29:54longer course.
29:56And this particular trial involved
29:58patients with really much more
29:59advanced tumors,
30:01meaning the t fours deeper
30:02in the rectum,
30:03those with n two disease,
30:05so a lot more lymph
30:06node involvement, and then these
30:07other more technical kind of
30:09risk factors that we look
30:10at as a team.
30:12And in these kind of
30:13higher risk patients,
30:15when we compare the two
30:16arms, the patients that received
30:18the shorter course radiation
30:20actually had a higher risk
30:22of local recurrence in the
30:23pelvis at about ten percent,
30:26versus more like, you know,
30:27six percent with the longer
30:28course.
30:29So, again, I think if
30:30you have a more advanced
30:31tumor, we certainly want to
30:33be proceeding
30:34with the longer course of
30:35radiation,
30:38for for this reason,
30:39and this trial supporting that.
30:41So just kind of a
30:42summary of that is that,
30:44we definitely prefer the longer
30:46course radiation for tumors that
30:47are low close to the
30:49anus,
30:50for tumors with these higher
30:51risk factors like the t
30:53four tumors or a lot
30:54of lymph node involve involvement.
30:57Another scenario would be if
30:58we wanna really maximize local
31:00control because we're thinking about
31:01maybe trying to avoid surgery,
31:03and I'll talk about that
31:04in the next few slides.
31:05But that the short course,
31:07we can consider for patients
31:08who have,
31:09less advanced tumors that are
31:11not getting close to kind
31:12of the edge of where
31:13doctor Maggio would be cutting
31:15for surgery,
31:16and tumors that are not
31:18really low in the rectum.
31:19And so we use this
31:20for select patients, but I
31:22think really default more to
31:23the longer course radiation with
31:25the chemo pill.
31:26How else can we individualize
31:28treatment, and the use of
31:30radiation? So we know that
31:31rectal surgery obviously is gonna
31:33affect your bowel function,
31:35and also that the combination
31:37of radiation and rectal surgery
31:38can also affect your bowels,
31:40also your bladder, also sexual
31:41function.
31:42So are there instances where
31:44we can avoid some of
31:45these treatments and try to
31:46reduce toxicity but not,
31:49you know, have a negative
31:50impact on cancer outcomes.
31:52So I'll talk first about
31:54organ preservation,
31:55which is what the term
31:57we use for,
31:59trying to maybe,
32:00defer surgery,
32:02unless needed.
32:04So this is an example.
32:05We have studies that showed
32:07us that in patients who
32:08have,
32:09a complete response, so you
32:10can achieve a complete response
32:12to chemotherapy
32:14followed by that long course
32:15of radiation that I that
32:17I described,
32:18complete response to the best
32:19of our abilities to detect
32:21that. So based on MRI,
32:23based on a good rectal
32:24exam, based on a scope
32:26going up and looking inside
32:27the rectum.
32:28And so if we take
32:30those patients who had a
32:31complete response
32:32and,
32:34watch them closely,
32:35what are the outcomes,
32:37in deferring surgery?
32:39This particular study was actually
32:41asking that question by just
32:42looking at two different sequences
32:45of therapy. So we have
32:46patients with stage two or
32:47three rectal cancer.
32:48Either they had their radiation
32:50first, and then they went
32:51to see doctor Cicchini and
32:52had their four months of
32:53chemo, or they started with
32:55doctor Cicchini and then came
32:56to me.
32:57For this stage of patients,
32:59and they were probably highly
33:00selected as all patients are
33:01on a clinical trial,
33:03if you looked at them
33:04about eight to twelve weeks
33:06after their therapy,
33:07in both of those approaches,
33:09about three quarters of them
33:11had a complete response so
33:12they could be offered,
33:14what we call active surveillance.
33:16So what is this active
33:17surveillance? So,
33:18it's a lot of poking
33:19and prodding,
33:20rectal exam and a scope
33:22every four months for the
33:23first two years and then
33:24every six months,
33:26MRI at least twice a
33:27year for two years and
33:28then annually.
33:30What we found was that,
33:32or what this study found
33:33was that in about half
33:34of the patients,
33:36it turned out that their
33:37tumor didn't recur, that complete
33:39response was sustained,
33:41and they did not need
33:42to have a surgery. And
33:43then if you look at
33:44how they did and their
33:45survival overall compared to what
33:47we call historical controls or
33:49just what we know can
33:50be expected of patients who
33:52received kind of the whole
33:53standard treatment paradigm,
33:55the survival seemed comparable.
33:58And so, you know, from
34:00these kinds of studies,
34:01what we learned is that
34:02we have to be very
34:03selective.
34:05This requires certain stage of
34:07tumor where we expect a
34:08complete response.
34:09If we do see that
34:10complete response,
34:12in a patient who is
34:13willing to be really actively
34:15followed closely,
34:17thinking about deferring surgery is
34:20an option,
34:21that we would make as
34:22a multidisciplinary
34:24team,
34:25and really can be applied
34:26in select cases, but with
34:28obvious benefits.
34:30Then I'm gonna talk a
34:32little bit about what about,
34:33options where you could,
34:35maybe not need to use
34:37radiation.
34:38And so this comes into
34:40play for patients that are
34:41kinda just meeting the criteria
34:43where you would consider radiation.
34:45So maybe you have some
34:46lymph nodes but not that
34:47many, or maybe there's depth
34:49that takes you to the
34:50t three stage but not
34:51the t four stage.
34:54So,
34:55in this study, they were
34:56letting those patients have the
34:57standard radiation going on to
34:59surgery and then chemo afterwards,
35:01or saying, okay. If we
35:02give them the chemo first
35:04and they look like they're
35:05responding, at least a response
35:07of twenty percent by MRI,
35:09What happens if we just
35:10don't radiate them, go straight
35:11to surgery?
35:12And in the patients where
35:14they didn't seem to respond
35:15to chemo, we'll give them
35:16the standard radiation. And it
35:18turns out most patients, majority,
35:20really, like ninety percent of
35:21patients were responding and had
35:24their radiation emitted,
35:26and a smaller fraction needed
35:27to have the radiation.
35:29So really, this is saying,
35:30can we use chemo first,
35:33and then selectively use
35:36radiation only for that small
35:37fraction that aren't responding to
35:39chemo? How does that affect
35:40the overall outcome?
35:42And the bottom line is
35:43there was no difference in
35:44local control of the tumor,
35:46survival disease free or overall
35:49survival.
35:49Again, a really select group
35:51of patients, so this is
35:52not for all comers with
35:53locally advanced rectal cancer.
35:55These are for the lower
35:56risk category where your tumors
35:58up higher,
35:59maybe a t two or
36:01a t three with limited
36:02or no lymph node involvement.
36:05Absolutely. If we're not gonna
36:06use pelvic radiation, you're gonna
36:08need doctor Mangio to remove
36:09the tumor with surgery.
36:11So just another,
36:13scenario where we can kind
36:14of tweak the, standard treatment
36:16course,
36:17for specific criteria,
36:19of your particular tumor presentation.
36:23And then, obviously, there are
36:25some benefits to not having
36:26radiation as part of your
36:27treatment course, and I think
36:29I'll focus on the long
36:30term benefits, which are really
36:32that,
36:33a year after surgery, if
36:34you looked at these patients
36:35who did not need radiation,
36:37they had lower rates of
36:38fatigue and neuropathy,
36:40but really better sexual function
36:42and also something that is
36:43important, especially with younger population
36:45of patients,
36:46being diagnosed with rectal cancer,
36:49better preservation of fertility
36:51and ovarian function. So one
36:53thing that can happen with
36:54pelvic radiation involving the ovaries
36:56is that we can induce
36:58early menopause in those patients
36:59that are premenopausal.
37:00So some advantages for sure
37:02for being able to avoid
37:03pelvic radiation when feasible.
37:06And then lastly, I wanna
37:07talk about how we can
37:08be helpful in the scenario
37:10of oligometastatic
37:11disease.
37:12So this is what doctor
37:14Cicchini described as rectal cancer
37:16or colorectal cancer, really,
37:19that has metastasized but in
37:20a limited fashion.
37:22So we have learned that
37:24metastasis
37:24to,
37:25up to five sites really
37:27behaves differently and can be
37:28treated more aggressively
37:30than rectal colorectal cancer that
37:31has spread more diffusely within
37:33the body.
37:35Oftentimes, we remove those limited
37:36sites of metastatic disease with
37:38surgery.
37:39But when surgery is not
37:40feasible,
37:41we can use radiation, and
37:43the type of radiation is
37:44slightly different. It's something we
37:46call stereotactic,
37:48body radiation or stereotactic
37:50ablative radiation. I always say
37:51to my patients, we're just
37:52trying to sound cool with
37:53all these fancy names.
37:56Some people even shorten the
37:57stereotactic ablative to saber.
37:59What this means is we're
38:00giving a high dose that
38:01we can get away with
38:02because the tumor is small,
38:04and we're rapidly dropping that
38:06dose off right with a
38:07right outside of your tumor
38:09and taking in advantage of
38:11technological,
38:13advances such that we can
38:14account for how your tumor
38:16is moving. We can precisely
38:18localize your tumor for treatment
38:20with imaging during treatment,
38:22to make sure that we
38:23can safely deposit a really
38:25high dose of radiation to
38:26these small tumors that can
38:28have kind of a definitive
38:29ablative effect on the tumor.
38:32This is one study and
38:33an example of how that's
38:35beneficial.
38:36So this is looking at
38:37patients with kind of mixed
38:38tumor types.
38:39Colorectal was one of them
38:41in that oligometastatic
38:43state with up to five
38:44metastases.
38:45And the study asked, well,
38:47if we just give them
38:47their standard of care chemotherapy
38:50or we add in SBRT
38:51to all of the limited
38:53metastatic sites, is there a
38:55benefit?
38:56And the bottom line is
38:57the addition of SBRT to
38:59the limited oligometastatic
39:00sites actually improved progression free
39:03survival,
39:04and overall survival.
39:06So
39:07I think, the stereotactic radiation
39:09as well as the surgical
39:10approach and other local therapies
39:12are,
39:13increasingly being employed in patients
39:15who have limited,
39:17sites of metastatic disease.
39:19And I'll end just with
39:20saying that we do have
39:21a new program here at
39:22Smilow Cancer Hospital, which is
39:24one way of treating oligometastatic
39:26disease.
39:27So this is new technology
39:29called the reflection,
39:30which is a pet directed
39:32radiation therapy machine.
39:34And it can be advantageous
39:35in certain cases,
39:37particularly
39:38if you have disease that's
39:39in the lung.
39:41And so I'll explain why
39:42that is. So a lung
39:43tumor is gonna move as
39:44you breathe.
39:45And for typical stereotactic
39:47radiation,
39:48we see your tumor.
39:49We watch a video. We
39:51can get a video CAT
39:52scan that shows us how
39:53your tumor moves as you
39:55breathe, and then we expand
39:57the treatment volume to encompass
39:59kind of the path your
40:00tumor takes as you breathe.
40:02With the pet directed therapy,
40:04the treatment machine, you receive,
40:07an injection of the pet
40:08tracer before treatment,
40:10and the treatment machine can
40:12detect the pet tracer from
40:13your tumor. So actually the
40:15radiation field will move with
40:17your tumor as your tumor
40:19moves during treatment. So rather
40:20than expanding the radiation field
40:22and treating a bigger area
40:24to encompass kinda where the
40:25tumor moves as you breathe,
40:27we're kinda moving the radiation
40:28field with your tumor as
40:30it moves with the benefit
40:31being that we don't have
40:32to expand and kind of
40:34radiate all this healthy tissue
40:35around.
40:37So like all things, right,
40:38there's specific criteria that your
40:40tumor would need to meet
40:41in order to be eligible
40:43for this type of treatment,
40:44but I think really an
40:45exciting innovation that we have
40:47here at Smilow as one
40:48modality
40:49to try to aggressively treat,
40:51oligometastatic
40:52disease.
40:54So I'm gonna end there.
40:56Little summary,
40:57just we know pelvic radiation,
41:00plays a key role in
41:01curative therapy for locally advanced
41:03rectal cancer, but we can
41:04tweak the radiation
41:05based on your tumor characteristics
41:07and what your goals of
41:08care are. We, in general,
41:10prefer the long course daily
41:12radiation for five weeks, especially
41:14for the high risk tumors
41:15that are lower down or
41:16have deeper involvement of the
41:17rectum or lymph node involvement,
41:20or if you're thinking about
41:21preserving the rectum and not
41:23needing surgery.
41:24Organ preservation with this active
41:26surveillance of MRI and scope
41:28can be considered in very
41:29select cases
41:31if you do achieve a
41:32complete response to chemo and
41:33radiation.
41:35We can think about omitting
41:36radiation for certain favorable risk,
41:39rectal cancer patients that don't
41:41have a lot of involvement
41:42of lymph nodes or not
41:43as deep in the rectum.
41:44And finally, we can think
41:45about the stereotactic radiation as
41:47well as surgery and other
41:48local therapies
41:49if you have, limited metastatic
41:51disease.
41:52Hopefully, I didn't take up
41:53too much time. I'm gonna
41:54pass the baton to doctor
41:55Mangio.
41:57Thank you, doctor Johan. Just
41:58to,
42:00ask one question about radiation
42:01is can you expand a
42:02little bit on the side
42:03effects of radiation?
42:05So side effects when we're
42:06treating the pelvis really are
42:07related to the organs that
42:08are in the pelvis. And
42:10so what we're talking about
42:11is bowel,
42:12and bladder primarily. So,
42:14when you're in the midst
42:15of a course of radiation,
42:17you can experience looser stools,
42:18frequent stools, diarrhea as a
42:20result of radiation.
42:22That can be typically,
42:24controlled with Imodium or other
42:26anti diarrheal medications.
42:28You can experience frequency of
42:30urination from inflammation to the
42:32bladder or maybe a little
42:33bit of slight burning with
42:34urination,
42:35a little bit like a
42:36mild urinary tract infection.
42:38Most patients tell me that's
42:39annoying, but it's tolerable.
42:41There's a lot of talk
42:42about skin reaction with radiation.
42:44If we're treating a higher
42:45rectal tumor that's really, you
42:47know, kind of within the
42:48pelvis, the dose to the
42:49skin should be minimal. There
42:50may be a little bit
42:51of a redness of the
42:52skin, but it should be,
42:54something that is, you know,
42:55not barely
42:56noticeable.
42:57We really worry more about,
42:59skin reaction when we're dealing
43:00with those really low tumors
43:02that are coming to the
43:02anus.
43:03There, we're driving the dose
43:05of radiation right to the
43:06perianal skin, and that's where
43:08redness and skin breakdown there,
43:10particularly when you're having diarrhea,
43:12can be a little bit
43:12more challenging to manage,
43:14but temporary and typically heals
43:17within two to three weeks
43:18after treatment.
43:19Long term side effects, I
43:20touched upon the, you know,
43:22for an a younger woman,
43:23early menopause,
43:25fertility issues. There can be
43:27low risk of more severe
43:29kind of bowel side effects
43:31from inflammation and scar tissue
43:32that can develop, so, like,
43:34obstruction of bowel and things
43:35things like that. But, thankfully,
43:37those risks are much lower,
43:39and things that we don't
43:40expect to see.
43:43Yeah. There's another question about
43:44radiation to the lung, but
43:45you answered it during during
43:47your discussion there. And I'll
43:48just answer the one question
43:49about KRAS g twelve d.
43:50Yes. Yale has a number
43:51of clinical trials focused on
43:54tumors with KRAS g twelve
43:55d, including a trial for
43:56patients that have, are receiving
43:58their initial treatment for metastatic
44:00colorectal cancer as well as
44:01a number of trials patients
44:03that have received prior chemotherapies.
44:04And now I'd like to
44:05introduce doctor Anne Manju from
44:07colorectal surgery.
44:09Hi. Thanks, everyone. Let me
44:11share my screen.
44:18Alright.
44:21So I'm gonna talk about
44:22a little bit of the
44:23plumbing work, and so that's
44:24surgical therapy for colon and
44:26rectal cancers.
44:29So where do I fit
44:30in? And we kind of
44:31heard everything. Someone you get
44:32a bit taken out, you
44:33get a biopsy, so you
44:35name it. You stage it
44:36with all the imaging, and
44:37then we treat it. And
44:39finally, you come,
44:40for rectal cancer, you'll often
44:42come to me at the
44:43end. For colon cancer, you
44:45may come to me at
44:46the beginning depending on
44:48what the stage of your
44:49cancer is.
44:51So sort of brings us
44:52to what's a colectomy?
44:54So a colectomy is our
44:56surgical term for removing a
44:58part of the colon.
45:00And so when we think
45:01about the colon, I just
45:03like to break it down
45:04into sort of five parts.
45:05So it looks backwards here.
45:07The r and the l
45:08are for right and left
45:08because this is how we
45:09are always thinking about things
45:11looking at imaging studies. So
45:13the colon starts here on
45:14the right side. This is
45:15the right colon. It goes
45:16across the middle. That's the
45:18transverse colon. It comes down
45:20left side. We call that
45:21the left colon or the
45:22descending colon. It makes this
45:24little s shaped swoop here.
45:26This is the sigmoid colon.
45:28And finally, down here, you've
45:29got the last part which
45:30is the rectum. And we'll
45:31we'll talk a little bit
45:32more about the rectum a
45:33little bit later.
45:35So when we talk about
45:36removing the colon when you've
45:38got cancer, well, wherever your
45:40cancer is, we're gonna remove
45:42that part of the colon.
45:43So if it's in the
45:44right colon, we're gonna remove
45:45the right colon and we
45:47do it not only just
45:48taking the wall of the
45:49colon itself, but then we're
45:51gonna take the blood
45:55vessels supply that area.
45:57And we want to get
45:58everything that is feeding that
46:00area because we know that
46:01around all those blood vessels
46:03are your lymph nodes. And
46:04the lymph nodes are sort
46:06of the first sign of
46:07escape. So if you've come
46:09to see me and you
46:10have an early colon cancer
46:12and they've done your CT
46:14scan of your chest and
46:15your belly and your pelvis,
46:17and they didn't see any
46:18spread anywhere else, the lungs
46:20and the liver and all
46:20the other solid organs are
46:22clear, we're gonna go to
46:23the operating room. But what
46:24we're gonna want to know
46:26and what doctor Ciacchini is
46:27gonna want to know after
46:28surgery is, well, were any
46:30of the lymph nodes positive?
46:31So when we go and
46:32take each of these major
46:34blood vessels, so for the
46:35right colon, we're gonna take
46:36this part of the artery
46:38right here, and we're gonna
46:39take in any of the
46:40blood supply that feeds this
46:41whole area. And we wanna
46:42get good healthy tissue
46:44around wherever your tumor is.
46:46If your tumor is here,
46:46we may take a small
46:47part of the small intestine
46:49and and the colon, but
46:50we don't wanna see it
46:51when we're taking it out
46:52because we want the tumor
46:54to be safely on the
46:55inside with good clean margins
46:56on either side. We wanna
46:58take the blood vessel nice
46:59and low or nice and
47:01high, basically very close to
47:03this big guy in the
47:03back and that's your aorta.
47:05And with it, we're gonna
47:06take all of the fat
47:08that's surrounding all those blood
47:09vessels in that whole part
47:10of the colon. And when
47:12we do that, we get
47:13all the lymph nodes that
47:15are hiding in there. That
47:16goes to the pathologist who
47:17then actually pick them out
47:19one by one, look at
47:21each and every one, look
47:22to see if there's cancer
47:24in those lymph nodes, and
47:25then put together a final
47:26report that comes about seven
47:28to ten days after surgery.
47:31Okay. There are lots of
47:33types of colectomies
47:34you can do. And when
47:35we're talking about cancer, we
47:37tailor it to the blood
47:38supply
47:39that serves each
47:41part of the colon. So
47:42I put little asterisks here
47:44to give you an idea.
47:45These are all different places
47:47that you could have a
47:48tumor in your colon,
47:50and we would look at
47:51the appropriate blood supply and
47:53then take that part of
47:54the colon always trying to
47:56center it. Now there's a
47:57couple down here where you
47:58see we're taking out a
47:59lot of the colon, and
48:00these are some special circumstances.
48:02Patients who may have something
48:04like inflammatory bowel disease, such
48:06as ulcerative colitis or Crohn's
48:07disease, who may not only
48:09have had this disease for
48:10a long standing period, but
48:11now they have prevented with
48:12a with a cancer. And
48:13in those special circumstances,
48:15we we often will have
48:16to remove most of the
48:17colon at that time because
48:18the risk to remaining colon
48:20is quite high.
48:23Okay. So this now is
48:25sort of to come back
48:26to what doctor Joheng was
48:27talking about,
48:29rectal cancer is sort of
48:31we think about it a
48:32little bit differently than colon
48:33cancer. So when you have
48:34a colon cancer, I'll just
48:36go back here for a
48:36moment, and let's call colon
48:38cancer anything that is sort
48:41of
48:42above this area, anything that's
48:44really above
48:45this line right here,
48:47that's gonna be a colon
48:48cancer. When we drop into
48:50the last fifteen
48:52centimeters
48:53of the of the large
48:54bowel, that's the rectum. And
48:56the rectum lives about two
48:58thirds of the way underneath
49:00this sort of line here,
49:01which is called the peritoneal
49:02reflection, which separates it from
49:04the main part of the
49:05abdominal cavity.
49:06The top part of it
49:07right here, the top one
49:09third is in the regular
49:10part of the abdominal cavity
49:11with the rest of the
49:12colon.
49:13And depending on the stage,
49:15sometimes we will treat this
49:16upper rectal cancer as a
49:18colon cancer and operate it
49:20on it right away.
49:21But when it is below
49:23this line, so that's a
49:24cancer that would be up
49:25here.
49:26But once we're talking about
49:27a rectal cancer that's below
49:29here, that's when you would
49:30see both doctor Cicchini
49:32and doctor Johan
49:34well before May to get
49:36a full amount of treatment
49:37beforehand like they talked about
49:38with the total neoadjuvant therapy.
49:41And then we would come
49:42in afterwards and take out
49:43these tumors.
49:45And so
49:46important parts to note here,
49:48and this is something that
49:48we think about and go
49:50with what I'm gonna talk
49:51about next. But at the
49:52very bottom
49:53of the rectum, we have
49:54what's called the anal canal,
49:56and we have these two
49:57really important muscles here. And
49:59these are called your anal
50:00sphincter muscles or your anal
50:02sphincter complex. There's an inner
50:03muscle
50:04and an outer muscle. And
50:06we need those to to
50:08maintain continence or to hold
50:09poop on the inside when
50:10we don't want to come
50:11out. So as we get
50:13lower and lower,
50:15we have to think increasingly
50:17about, well, where is this
50:19tumor
50:20in relationship
50:21to these
50:22muscles? And are we able
50:24to get a clean or
50:26negative margin
50:27beneath this tumor?
50:29And so as we get
50:30down to right about the
50:32top of the muscles, that's
50:33about as far as we
50:34can go with surgery and
50:35we'll talk a little bit
50:36more about the types of
50:37surgery in a second.
50:39But once we get down
50:41here where you have a
50:42tumor that's,
50:43adenocarcinoma,
50:44which is a typical type
50:45of colon or rectal cancer,
50:47not a skin cancer that's
50:48crawled from the outside in.
50:50Once we get down here,
50:51this usually means that we're
50:53unable to save the anus,
50:55this bottom part, and the
50:57sphincters down there because in
50:58order to get rid of
50:59the cancer completely, we'll have
51:00to take that out.
51:02And so that brings me
51:03back to the question I
51:04get very often when I
51:06sit down with someone. Well,
51:08what is a stoma or
51:09an ostomy or a bag
51:11or a colostomy bag, and
51:13am I going to need
51:14one?
51:15And so
51:16ostomy or stoma comes from
51:18the Greek and Latin words
51:19for mouth, and they've actually
51:20been around for a very
51:21long time.
51:23And it's where we pull
51:25a small amount of the
51:27colon or the small bowel
51:29through the skin,
51:31fold it over like a
51:32turtleneck, sew it to the
51:33skin, and the stool no
51:34longer comes out your bottom,
51:36but it comes out through
51:38this opening and it empties
51:39into a little bag
51:41that collects the stool.
51:43So not everyone
51:44is going to need an
51:46ostomy bag. In fact, that's
51:48really permanent ostomy bags are
51:50something that we are really
51:52well able to avoid in
51:54what we do today.
51:57Going back here,
51:58looking at this lowest
52:00level of tumor, the kind
52:02of tumor that's growing within
52:03the anal canal that gets
52:04its upfront treatment
52:06with its total neoadjuvant
52:08therapy,
52:09If it responds completely like
52:11doctor Joheng was talking about
52:12and there's no tumor remaining
52:14and you're up for a
52:15lot of prodding and poking,
52:17we can often do what's
52:18called watch and wait, and
52:19you get to avoid me.
52:21And we watch it very
52:22closely in the clinic over
52:23time to make sure that
52:25it doesn't grow back, but
52:26that does allow some people
52:28to to preserve their sphincters
52:30when otherwise they would not
52:31be able to.
52:33You know, forward.
52:36Alright.
52:36Then there's this idea of
52:38temporary versus permanent stoma bag.
52:41So a lot of times,
52:43especially in cases of rectal
52:44cancer where you have received
52:46upfront treatment, and even though
52:48the tumor isn't so low
52:49that we can't get it
52:50out, we can still save
52:51the sphincter muscles
52:53because that tissue
52:54is
52:56a little bit, we'll say,
52:57jeopardized by the fact that
52:58it's had the radiation, the
53:00chemotherapy. It makes its healing
53:01potential in the moment
53:04a little bit lower. And
53:05what we know is when
53:06you're trying to bring two
53:07ends of the colon together
53:09after you've taken out the
53:10segment
53:11containing the tumor, it's very
53:13important that it heals absolutely
53:14perfectly so you don't get
53:16what's called a leak.
53:17We know that when you've
53:18been radiated,
53:20that oftentimes that risk of
53:21leakage
53:22goes up substantially. And so
53:24for many patients who have
53:25rectal cancer who get full
53:27treatment beforehand, we make what's
53:28called a temporary stoma. And
53:30temporary in our world is
53:32four to six weeks. We
53:33do a little leak test
53:34at the six week mark,
53:36and then we close the
53:37stoma right after that. And
53:39so really at this point
53:40in time, there are very
53:41few patients that we have,
53:44that require
53:45a permanent stoma. It's really
53:46those with a tumor that
53:47doesn't respond to treatment
53:49that's very low down and
53:51and well within the anal
53:52canal involving the anal sphincters.
53:56Alright. So how do we
53:57do colon surgery today?
54:00This is the photo that
54:01hung on the wall where
54:02I trained in Boston, and
54:04this is a a picture
54:05of the the first surgery
54:06that was ever done under
54:08anesthesia. And this was at,
54:10the math general.
54:11So people really literally sat
54:13around in the stadiums and
54:14and watched, and it was
54:15done open, and they didn't
54:17have scrubs.
54:18We continue to do open
54:20surgery for a really long
54:21time.
54:22But by the time we
54:23got to the nineteen eighties,
54:25laparoscopic
54:26surgery had really come into
54:29being.
54:30As you can see, you
54:31had sort of an old
54:32screen and people holding these
54:34long skinny instruments on sticks
54:36with a camera and tiny
54:37instruments,
54:38and this is called laparoscopic
54:39surgery.
54:41We still do a lot
54:42of laparoscopic
54:43surgery today.
54:44It usually involves at least
54:46two people because you you
54:48need an extra pair of
54:49hands because we currently
54:50only have two hands. And,
54:52someone's got a hold of
54:53a camera, and you need
54:54at least two working hands
54:56to do an operation to
54:57take out a part of
54:57the colon.
55:00More recently
55:01and stuff that you may
55:02have heard of or seen
55:03on TV, but within the
55:04last twenty years, we've gone
55:06on to robotic surgery.
55:09This is a picture of
55:10the intuitive DaVinci robotic system,
55:13and that's what we use
55:14at Yale. In fact, actually,
55:16this is the last version
55:17of it, and we have
55:19actually upgraded our entire system
55:20to the d b five
55:22intuitive system, which is the
55:23newest robot that's on the
55:24market.
55:26And so
55:27I would say we have
55:28probably one of the largest
55:30robotic programs
55:31in the northeast just by
55:33the sheer
55:35number of robots that we
55:36have here at Yale. And
55:38robotic surgery is kind of
55:39fun. It's also really interesting.
55:42So what you're looking at
55:44in this picture is the
55:45patient would be here laying
55:47on the table, and this
55:48is the intuitive surgical robot.
55:50It has four arms that
55:52can be controlled by one
55:54person. So you have a
55:55camera,
55:56which is right here, and
55:57you get three operating arms.
55:59There's always someone at the
56:01bedside because you have to
56:02exchange the instruments manually, and
56:04it uses the exact same
56:06kind of ports that you
56:07use when you're doing laparoscopic
56:09surgery.
56:10But instead, they have a
56:11little adapter on them that
56:12clips into the robotic arms.
56:15The instruments themselves from a
56:16distance appear very similar. We
56:18have scissors. We have graspers.
56:21We have really nice cameras.
56:23But what's really great about
56:25the robotic instruments is that
56:27they're what we call wristed.
56:29So a typical laparoscopic
56:31scissors, like a scissors, like
56:32you cut with, is straight.
56:33It it it can cut
56:34in one plane. It's on
56:36a stick so you can
56:36move it up and down,
56:37up and down, and that's
56:39how you can cut or
56:40divide the tissue that you
56:41need to divide to take
56:42out a part of the
56:42colon.
56:43When it comes to robotic
56:44surgery,
56:45it has an actual wrist
56:47and it has more degrees
56:48of freedom or more ability
56:49to rotate on an axis
56:51than the human wrist does.
56:53And all of the instruments,
56:55that the robot uses are
56:57the same way. And the
56:58camera is actually not a
56:59single camera. It's two
57:01high resolution cameras within one
57:03camera body, which means when
57:05you're looking through the console,
57:06which is about five feet
57:07away from the patient, you
57:09actually are in a three
57:10d viewer headset. So everything
57:12that you see
57:14is in three dimensions, and
57:15the magnification
57:17is much higher than it
57:18would be. And there's no
57:19glare coming off of a
57:20flat screen like you would
57:21in laparoscopy, but you're actually
57:23seeing
57:24in three dimensions.
57:26Another area when it comes
57:27to colon surgery that's of
57:29particular interest is the fact
57:30that the robot also has
57:31a near infrared light source
57:33or laser built into it,
57:35and that can excite certain
57:37injectable chemicals to allow us
57:39to see where there is
57:40blood supply.
57:42Like we talked about in
57:43the very beginning,
57:44the blood supply to each
57:45part of the colon determines
57:47where we're gonna take it
57:48out and how we decide
57:49how much of the colon
57:50around the tumor we're gonna
57:51take out. In this case,
57:53when we get ready to
57:54divide the tumor and we
57:56want the tumor to be
57:57in the area of the
57:58colon that's coming out, and
57:59we've taken away the blood
58:01supply there, but we wanna
58:02make sure that new connection
58:03that we make is gonna
58:04be healthy enough so that
58:05when we bring the ends
58:06together, they heal.
58:08We'll inject this green this
58:09this liquid. It's called endocyanine
58:11green,
58:12and we inject it in.
58:13It actually lights up all
58:14the blood vessels. So you
58:15can see this area here
58:16is really bright green, and
58:18that corresponds to the same
58:19part of the colon right
58:20here.
58:21It tells us it's got
58:22great perfusion. But the part
58:24where the tumor is, this
58:25is the back end of
58:26of the upper part of
58:27the tattoo here on this
58:28side. It all looks the
58:29same. It all looks pink.
58:30But when we look here,
58:31you see it's not very
58:32green, and that tells us
58:33that this area doesn't have
58:34good blood supply. So we
58:36know when we're gonna cut
58:37the tumor out, we're gonna
58:38cut right here into the
58:39healthy green area, and that's
58:40the area that has a
58:41good blood supply that we're
58:42gonna use to make that
58:44connection.
58:44So that's another benefit.
58:46This is just a little
58:47bit about what does the
58:48data actually show for robotic
58:50surgery compared to more old
58:52fashioned surgery, which is open
58:54surgery.
58:55A lot shorter hospital stays
58:57return to normal activity and
58:59wound complication rates. It has
59:01been pitted
59:02together, especially in colon and
59:04rectal surgery in particular,
59:06head to head with laparoscopic
59:08surgery along a number of
59:10different clinical trials. And robotic
59:12surgery has been equally efficacious
59:14with the same cancer outcomes,
59:16but other quality of life
59:17outcomes such as sexual function
59:19are actually better in robotic
59:21surgery.
59:22And that's thought to be
59:24due to the extreme stability
59:25and precision of the viewing
59:27platform with the three d
59:28viewing, which allows us to
59:29spare a lot of the
59:30nerves, which sometimes you just
59:32can't see with laparoscopic
59:33surgery.
59:35Alright. So that's a little
59:36bit about the nuts and
59:38bolts. And without cutting too
59:40much into what Mike talked
59:41about, I just want to
59:42mention one thing that's near
59:43and dear to my heart
59:44with just a couple slides
59:45as we wrap up. What's
59:47new?
59:48I I don't think you
59:49can avoid the news.
59:51Shame with the passing of,
59:52mister Vanderbeek, but
59:55colon cancer is rising in
59:56young people. It's now the
59:58number one cancer killer among
60:00adults under fifty.
01:00:01It's increased twofold in adults
01:00:03under fifty since the nineteen
01:00:05nineties.
01:00:06And now one in five
01:00:07new colon cancers will be
01:00:08under the age of fifty
01:00:10five. And oftentimes, we're seeing
01:00:12young people
01:00:12present with really advanced stage
01:00:14disease, and this is because
01:00:16we're even we've went from
01:00:17a screening age of fifty,
01:00:18and in twenty twenty one,
01:00:19we rolled it back to
01:00:20forty five.
01:00:22But even still, we're catching
01:00:23people younger than that because
01:00:24we're not screening people in
01:00:25their thirties.
01:00:28I get asked this a
01:00:29lot in my clinic and
01:00:31why are more young people
01:00:32getting colon cancer. And the
01:00:34real honest answer is we
01:00:35don't have a very good
01:00:36answer to that question.
01:00:38There are a lot of
01:00:39factors that are probably involved
01:00:41in this. That includes the
01:00:42diet and your food environment.
01:00:44We know that there's a
01:00:45rising rate of obesity, type
01:00:47two diabetes, and metabolic syndrome,
01:00:49and we know that there's
01:00:50actually very good data that
01:00:52sugary beverage consumption between the
01:00:54ages of thirteen and eighteen
01:00:55and obesity in that age
01:00:56range
01:00:57predicts later obesity driven cancers
01:01:00of which colon cancer is
01:01:01one of them. We know
01:01:02that our food environment changes
01:01:05the natural healthy bacteria that
01:01:06live in our gut,
01:01:08and we know that changes
01:01:09in those bacteria can lead
01:01:10to more inflammatory states, which
01:01:12can promote carcinogenesis.
01:01:14And again, we talked about
01:01:15genetics as well earlier.
01:01:17I wanted to talk about
01:01:18one last area that's sort
01:01:20of new to what we're
01:01:20doing at Yale and something
01:01:22that is part of our
01:01:23loving your guts and food
01:01:24is medicine campaign, which is
01:01:27understanding how your ZIP code
01:01:29affects your cancer risk, how
01:01:30food environment is involved
01:01:33in in carcinogenesis.
01:01:34And one of the things
01:01:35that we know is there
01:01:36areas that don't have good
01:01:37food supply, whether it's access
01:01:39to healthy food or being
01:01:40surrounded by a preponderance of
01:01:42unhealthy food, which is what
01:01:44a food swamp is.
01:01:45And we know that this
01:01:47can have an impact on
01:01:49can early onset colorectal cancer
01:01:51and its outcomes.
01:01:53We have been doing a
01:01:54lot of research on this
01:01:55by mapping out everything in
01:01:56the entire state of Connecticut.
01:01:58And what we have found
01:01:59in our original Yale data
01:02:01where we mapped everyone at
01:02:02Yale was that certainly we
01:02:03saw worse cancer outcomes in
01:02:05our early onset cancer patients
01:02:07who lived in unhealthier food
01:02:09environments.
01:02:09And more recently, as we
01:02:11expanded this to go to
01:02:12the entire state of Connecticut,
01:02:14with the with the assistance
01:02:15of the Connecticut tumor registry,
01:02:17What we're seeing in the
01:02:18state of Connecticut is actually
01:02:19a significant survival difference in
01:02:21in our youngest patients with
01:02:23cancer who live in unhealthy
01:02:24food environments.
01:02:26And so I say this
01:02:27as we keep talking about
01:02:28finding healthy foods to eat,
01:02:30but this is something that
01:02:31we really there are a
01:02:31lot of modifiable risk factors
01:02:33that people can
01:02:34can look forward to. And
01:02:36as part of our Yale
01:02:37teaching kitchen, we've been trying
01:02:38to work on having
01:02:39healthy eating
01:02:41teaching kitchen video webinars that
01:02:43can talk about how you
01:02:44can cook healthy high fiber
01:02:45meals for good colon health
01:02:47for under four to five
01:02:49dollars per serving. And so
01:02:50this is something that we've
01:02:51been really working on, over
01:02:53the last year and a
01:02:54half.
01:02:55I wanna say thank you
01:02:56to everyone for coming tonight.
01:02:57I'll stop my share, and
01:02:58I'm happy to take any
01:02:59questions.
01:03:03Thank you, doctor Manju.
01:03:05I think we're we're at
01:03:07time,
01:03:08and the questions have been
01:03:10answered in the chat as
01:03:11they came available.
01:03:13So thank you all for
01:03:14your attention this evening. As
01:03:17as noted previously and in
01:03:19the chat, this will be
01:03:20posted online,
01:03:21and a link will be
01:03:22sent out to anybody that
01:03:23registered for the event.
01:03:25Thank you again, and thank
01:03:27you to my my co
01:03:28panelists here. Have a great
01:03:29night.