Treatment of Colorectal Cancer

Transcript

00:00 --> 00:02Support for Yale Cancer Answers
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00:13 --> 00:15Welcome to Yale Cancer Answers with
00:15 --> 00:18your host doctor Anees Chagpar.
00:18 --> 00:20Yale Cancer Answers features the
00:20 --> 00:22latest information on cancer care by
00:22 --> 00:23welcoming oncologists and specialists
00:23 --> 00:26who are on the forefront of the
00:26 --> 00:28battle to fight cancer. This week,
00:28 --> 00:30it's a conversation about colorectal
00:30 --> 00:32cancer with Doctor Michael Cecchini.
00:32 --> 00:34Doctor Cecchini is an assistant
00:34 --> 00:35professor of medicine and medical
00:36 --> 00:37oncology at the Yale School of
00:37 --> 00:40Medicine where Doctor Chagpar is
00:40 --> 00:41a professor of surgical oncology.
00:43 --> 00:45So Mike, maybe we can start
00:45 --> 00:47off by you telling us a little
00:47 --> 00:49bit about colorectal cancer.
00:49 --> 00:51A little bit about the epidemiology.
00:51 --> 00:54Who gets it? How common is it?
00:54 --> 00:55How lethal is it?
00:55 --> 00:57And then we'll get into some
00:58 --> 01:00of the more recent updates with
01:00 --> 01:02regards to screening of colorectal cancer.
01:02 --> 01:05I am a gastrointestinal
01:05 --> 01:07medical oncologist, and I see a variety
01:07 --> 01:10of GI cancers, colorectal cancers and it is where
01:10 --> 01:13I focus the majority of my research.
01:15 --> 01:17It's quite common.
01:17 --> 01:19There are about 150,000 cases diagnosed
01:19 --> 01:21annually in the United States and
01:21 --> 01:23more than 50,000 annual deaths.
01:24 --> 01:28And I do think it needs to be stated
01:28 --> 01:30that there is also a rise in incidence
01:30 --> 01:33in adults less than age of 50.
01:33 --> 01:35Although it is like many cancers,
01:35 --> 01:37predominantly a cancer of older
01:37 --> 01:39individuals, for some unclear reason,
01:39 --> 01:41the incidence is actually rising
01:41 --> 01:43in adults less than age of 50,
01:44 --> 01:47while it is going down overall,
01:47 --> 01:50due to effective screening by
01:50 --> 01:53colonoscopy for adults over the
01:53 --> 01:57age of 50.
02:03 --> 02:05Patients with a personal history or
02:05 --> 02:08family history of colorectal cancer are at
02:08 --> 02:11increased risk for developing the disease.
02:11 --> 02:13Personal history for large polyps etc.,
02:13 --> 02:15certain polyps with certain characteristics
02:15 --> 02:18increase the risk for colorectal cancer,
02:18 --> 02:20but it is mostly sporadic,
02:20 --> 02:21not familial.
02:21 --> 02:23There are conditions like
02:23 --> 02:24inflammatory bowel disease,
02:24 --> 02:27prior radiation and then in rare
02:27 --> 02:29circumstances inherited syndromes such as
02:29 --> 02:31Lynch syndrome and something called FAP.
02:31 --> 02:33Familial adenomatous polyposis syndrome.
02:34 --> 02:35And other polyp syndromes.
02:35 --> 02:37So when thinking about
02:37 --> 02:39the fact that the majority
02:39 --> 02:41of these are sporadic,
02:41 --> 02:44are there any risk factors
02:44 --> 02:47that people who don't have a family
02:47 --> 02:49history should really be cognizant of?
02:49 --> 02:51So I'm thinking here about
02:51 --> 02:53things like you know,
02:53 --> 02:56people often ask about smoking or alcohol,
02:56 --> 02:59or smoked meats or other
02:59 --> 03:02things that might increase their risk.
03:02 --> 03:02So there
03:02 --> 03:04isn't this clear association
03:04 --> 03:05with some carcinogen,
03:05 --> 03:07some cancer predisposing factor,
03:07 --> 03:11like there is with lung cancer and smoking,
03:11 --> 03:12for example.
03:12 --> 03:16I'd say that the data is a bit mixed on
03:16 --> 03:19how important certain risk factors are.
03:19 --> 03:21Certainly things like obesity,
03:21 --> 03:23diabetes and red or processed meats
03:23 --> 03:25increase risk and
03:25 --> 03:28they may affect the rate to some degree,
03:28 --> 03:31but the data again isn't
03:31 --> 03:32always consistent.
03:32 --> 03:34The smoked meats issue is
03:34 --> 03:37more thought to be related to
03:37 --> 03:39gastric cancer or certainly seems
03:39 --> 03:41to play a bit more of a role.
03:41 --> 03:43Race also plays a role.
03:43 --> 03:45African Americans have the highest
03:45 --> 03:46colorectal cancer rates in the
03:46 --> 03:48United States and mortality
03:48 --> 03:49is also higher compared to
03:49 --> 03:50other ethnic groups.
03:50 --> 03:53So do we know why we see some
03:53 --> 03:55of these epidemiologic trends?
03:55 --> 03:57Why is it that more African
03:57 --> 03:58Americans get colorectal cancer?
03:58 --> 04:01Why is it that we're now seeing
04:01 --> 04:03more colorectal cancer occurring in
04:03 --> 04:05adults younger than the age of 50?
04:05 --> 04:06What are the factors in
04:06 --> 04:07these particular populations
04:07 --> 04:08that's increasing their risk?
04:08 --> 04:09The short
04:09 --> 04:11answer would be we don't know,
04:11 --> 04:13and where there's a tremendous
04:13 --> 04:15effort in trying to understand some of
04:15 --> 04:18the risk factor and some of
04:18 --> 04:20the reasons for the increased risk in
04:20 --> 04:23the groups that you just articulated.
04:23 --> 04:25Interesting and to get back
04:25 --> 04:27to the younger age group.
04:27 --> 04:29It's not just that the incidence
04:29 --> 04:31has been static in that group,
04:31 --> 04:33it's increasing and so we do
04:33 --> 04:35think that it has some lifestyle factors,
04:35 --> 04:36perhaps diet is a factor that is
04:36 --> 04:38playing a role here,
04:38 --> 04:39but we really don't know,
04:39 --> 04:41and there's a tremendous area of
04:43 --> 04:45research to try and understand why these incidences
04:45 --> 04:47are increasing in the young adults.
04:47 --> 04:48But we don't know.
04:49 --> 04:52And so as we see more incidence
04:52 --> 04:55in younger people, one of the
04:55 --> 04:58questions that might come up is,
04:58 --> 04:59you know historically,
04:59 --> 05:01and I know that the screening guidelines
05:01 --> 05:03have recently changed to include
05:03 --> 05:06younger people in terms of routine
05:06 --> 05:08screening for asymptomatic people.
05:08 --> 05:10But when we think about the fact that
05:10 --> 05:13over the last several several years,
05:13 --> 05:15we're starting to see more
05:15 --> 05:17colon cancer in younger people,
05:17 --> 05:20how is it that they present because
05:20 --> 05:23they wouldn't have presented on a
05:23 --> 05:24routine asymptomatic colonoscopy,
05:24 --> 05:26presumably because historically the
05:26 --> 05:28guidelines had recommended starting
05:28 --> 05:30colorectal screening at the age of 50.
05:30 --> 05:34So how are we picking up these cancers in
05:34 --> 05:35younger people?
05:35 --> 05:37Unfortunately, it's the last thing
05:37 --> 05:39on many caregivers minds,
05:39 --> 05:41medical professionals minds that
05:41 --> 05:44somebody symptoms would be related to
05:44 --> 05:47colon cancer if they are a younger adult.
05:47 --> 05:49But the majority of patients, about
05:49 --> 05:523/4 of patients ,will have some
05:52 --> 05:54nonspecific change in their bowel habits.
05:57 --> 05:59Half will have bleeding.
05:59 --> 06:01There's a palpable rectal mass
06:01 --> 06:02in about 1/4 of patients,
06:02 --> 06:05and iron deficency, or anemia isn't actually
06:05 --> 06:07a sensitive as you might think.
06:07 --> 06:10It's fewer than 20% of patients,
06:10 --> 06:11especially young adults that
06:11 --> 06:14would present with iron deficiency anemia.
06:14 --> 06:15So unfortunately,
06:15 --> 06:17I have numerous patients in my
06:17 --> 06:19practice that had some lower GI
06:19 --> 06:21bleeding that was attributed to
06:21 --> 06:23hemorrhoids and incidence wise.
06:28 --> 06:29Individuals should also
06:29 --> 06:30listen to their bodies,
06:30 --> 06:32and if something's not right,
06:32 --> 06:34change in bowel habits,
06:34 --> 06:34bleeding,
06:34 --> 06:35they should take
06:35 --> 06:36those very seriously,
06:36 --> 06:37even if they're younger.
06:37 --> 06:39Is it the case that,
06:39 --> 06:41as we've seen this increasing
06:41 --> 06:42incidence in younger people because
06:42 --> 06:44they are presenting with symptoms?
06:44 --> 06:46Presumably because screening was
06:46 --> 06:47not recommended for
06:47 --> 06:49people who were younger than age 50?
06:49 --> 06:51Is it the case that these
06:51 --> 06:53younger people that we were
06:53 --> 06:54seeing colorectal cancers in
06:54 --> 06:56were actually presenting
06:56 --> 06:57with a higher stage,
06:57 --> 06:59and what implications does
06:59 --> 07:01that have for prognosis?
07:01 --> 07:04Yeah, that's completely correct.
07:04 --> 07:06Unfortunately, when you have a disease
07:06 --> 07:08that is presenting because symptoms
07:08 --> 07:11develop instead of asymptomatic screening,
07:11 --> 07:13generally this stage is higher,
07:13 --> 07:15so these younger adults generally
07:15 --> 07:17are diagnosed at a more advanced
07:17 --> 07:19stage and sometimes have even
07:19 --> 07:21more aggressive biology overall.
07:21 --> 07:25So again, the stage is going to be higher.
07:25 --> 07:27The younger adult population tends
07:27 --> 07:29to do better than the older adult
07:29 --> 07:32population for when you're matching them
07:32 --> 07:35by stage, because they can probably
07:35 --> 07:37withstand treatment better but they
07:37 --> 07:40are diagnosed at a more advanced stage
07:40 --> 07:43then the patients that are
07:43 --> 07:45diagnosed by asymptomatic screening and
07:45 --> 07:48so now the American Cancer Society has
07:48 --> 07:51come out and said that they recommend
07:51 --> 07:54starting screening at the age of 45.
07:54 --> 07:57Can you tell us more about
07:57 --> 07:58their recommendations?
07:59 --> 08:00Absolutely.
08:00 --> 08:03The American College of Gastroenterology
08:03 --> 08:05initially recommended
08:05 --> 08:07dropping the screening age to
08:07 --> 08:0945 for adults at average risk,
08:09 --> 08:12but the most widely followed
08:12 --> 08:14guidelines are actually the US
08:14 --> 08:16preventative Task Force guidelines,
08:16 --> 08:18which the majority of primary
08:18 --> 08:19care physicians follow,
08:19 --> 08:22and they did change their
08:22 --> 08:25recommendation about a year or two ago
08:25 --> 08:28to propose a Grade B recommendation
08:28 --> 08:30for adults over the age of 45.
08:30 --> 08:33But they still kept the greater
08:33 --> 08:36recommendation for adults over the age of 50.
08:36 --> 08:37But just yesterday this was
08:37 --> 08:39updated and now for all adults,
08:39 --> 08:41they've listed a strong recommendation
08:41 --> 08:43for adults over the age of 45,
08:43 --> 08:45so I think now going forward that's really
08:45 --> 08:48going to be the age we start screening
08:48 --> 08:50almost all asymptomatic adults.
08:56 --> 08:58Colonoscopy is a very powerful screening procedure,
08:58 --> 09:00not only because they can diagnose
09:00 --> 09:02a cancer that's there and then we
09:02 --> 09:04can deal with surgery
09:04 --> 09:06or chemo as necessary,
09:06 --> 09:08but they also remove
09:08 --> 09:09premalignant conditions.
09:09 --> 09:11So they are helping prevent
09:11 --> 09:13the development of colorectal
09:13 --> 09:14cancer even down the road.
09:15 --> 09:17And there are
09:17 --> 09:19so many screening tests now
09:19 --> 09:21are recommended or that at
09:21 --> 09:23least individuals could consider.
09:23 --> 09:25So colonoscopy is often thought
09:25 --> 09:27of as the gold standard,
09:27 --> 09:29but some of these other tests
09:29 --> 09:31seem to be really quite easy.
09:31 --> 09:33Tell us a little bit about the
09:33 --> 09:35different tests and the advantages
09:35 --> 09:37and disadvantages of each.
09:37 --> 09:39What do you recommend for patients
09:39 --> 09:42who come to you and say,
09:42 --> 09:44I heard about the updated guidelines,
09:44 --> 09:47I'm now 45. What test should I have?
09:48 --> 09:50I can comment a little bit there.
09:50 --> 09:52It's not exactly my area.
09:52 --> 09:52Unfortunately,
09:52 --> 09:54the majority of patients I see have
09:54 --> 09:56already been diagnosed with cancer,
09:56 --> 09:57but absolutely colonoscopy is
09:57 --> 09:58still the gold standard,
09:58 --> 10:00so that would be my kind of
10:00 --> 10:02blanket recommendation. For those
10:02 --> 10:04that aren't ready to do that,
10:04 --> 10:06but are interested in doing some screening,
10:08 --> 10:10there are test for fecal occult blood,
10:10 --> 10:12so for small amounts of undetectable
10:12 --> 10:14blood and
10:14 --> 10:16that's an imperfect way to
10:16 --> 10:18assess whether or not there's a
10:18 --> 10:20cancerous or precancerous condition.
10:20 --> 10:21Again, the colonoscopy offers the
10:21 --> 10:23power to remove precancerous lesions,
10:23 --> 10:25which probably are not doing
10:25 --> 10:27much at that point in time,
10:27 --> 10:29but maybe missed by a test
10:29 --> 10:31we're trying to detect small
10:31 --> 10:33amounts of blood in the stool.
10:33 --> 10:35There are also tests that actually try
10:35 --> 10:38to detect DNA in in the stool, and
10:38 --> 10:41that may be a more sensitive way,
10:41 --> 10:43but also we're not removing anything
10:43 --> 10:45premalignant with that we have
10:45 --> 10:47yet to develop a blood based test
10:47 --> 10:49that's diagnosing cancer before
10:49 --> 10:52it develops, or at an early stage.
10:52 --> 10:54So there are companies that
10:54 --> 10:55are working on that,
10:55 --> 10:57but we have a ways to go,
10:57 --> 11:00but most of these patients are seen
11:00 --> 11:03by my colleagues in Gastroenterology
11:03 --> 11:05for their screening discussions and
11:07 --> 11:10they are able to give some more eloquent answers
11:10 --> 11:10on that
11:11 --> 11:12than I am.
11:12 --> 11:15Mike, the other question, and this might
11:15 --> 11:17be a tough question as well,
11:17 --> 11:20is why the magic number of 45?
11:20 --> 11:22I mean, if we're seeing patients with
11:22 --> 11:25younger colon cancers, why is it 45?
11:25 --> 11:28Why not 40 or 42 or 38?
11:28 --> 11:30How do people come up with
11:30 --> 11:33these numbers as to at what age
11:33 --> 11:34people should start screening?
11:35 --> 11:37That's a great question and
11:37 --> 11:38somebody asked the same question just last night.
11:45 --> 11:47And I feel
11:47 --> 11:48that same sentiment as well.
11:50 --> 11:53I think that this is a first step and we
11:53 --> 11:56may be recommending 40 in a few years,
11:56 --> 11:58but we'll have to see how the data and
11:58 --> 12:00the number needed to treat the
12:00 --> 12:02number of colonoscopies done to really
12:02 --> 12:04prevent one colorectal cancer holds up
12:04 --> 12:07over time at these younger age groups.
12:07 --> 12:08There's also
12:08 --> 12:10as you know,
12:10 --> 12:12I think different opinions on
12:12 --> 12:15the age of of mammography as well.
12:15 --> 12:16But again,
12:16 --> 12:19getting back to the time it takes
12:19 --> 12:22for colorectal cancer to develop in
12:22 --> 12:26general somewhere on the order of a decade,
12:26 --> 12:28I think by lowering the age to 40
12:28 --> 12:30we're really capturing that group.
12:30 --> 12:32If we were to lower the age of 40
12:32 --> 12:34we're really capturing that group
12:34 --> 12:36in the 45 to 50 range versus right
12:36 --> 12:39now with this age of 45.
12:39 --> 12:41Or probably
12:41 --> 12:42we're helping prevent higher
12:42 --> 12:44incidence in that 50 to 45 range.
12:44 --> 12:46But as we started out the discussion
12:46 --> 12:49really less than 50 is still seeing
12:49 --> 12:51an increased incidence of colon cancer.
12:51 --> 12:53So I think this is a moving target and
12:53 --> 12:56we will benefit over time
12:56 --> 12:58lowering the age,
12:58 --> 12:59and I certainly, unfortunately,
12:59 --> 13:02see patients in my practice below the
13:02 --> 13:04age of 40 and 30 sometimes.
13:05 --> 13:07Certainly it's going to be a
13:07 --> 13:09moving target that we will follow,
13:09 --> 13:12but for right now we're going to take
13:12 --> 13:15a short break for a medical minute.
13:15 --> 13:17Please stay tuned to learn
13:17 --> 13:19more about the treatment of
13:19 --> 13:21colorectal cancer with my guest doctor
13:21 --> 13:23Michael Cecchini.
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14:10 --> 14:15You're listening to Connecticut public radio.
14:15 --> 14:15Welcome
14:15 --> 14:17back to Yale Cancer Answers.
14:17 --> 14:19This is doctor Anees Chagpar
14:19 --> 14:22and I'm joined tonight by my
14:22 --> 14:24guest doctor Michael Cecchini.
14:24 --> 14:26We're talking about the treatment
14:26 --> 14:28of colorectal cancer and Mike right
14:28 --> 14:30before the break we were talking about
14:30 --> 14:32the new updated screening guidelines,
14:32 --> 14:34which now are recommending
14:34 --> 14:35screening for colorectal cancer
14:35 --> 14:38going back to the age of 45.
14:38 --> 14:40One last question with regards
14:40 --> 14:42to screening, before the break,
14:42 --> 14:44you had mentioned that there
14:44 --> 14:45are certain racial groups,
14:45 --> 14:48for example, African Americans
14:48 --> 14:52that tend to be diagnosed at a higher frequency,
14:52 --> 14:54tend to have a worse prognosis
14:54 --> 14:56than their Caucasian counterparts.
14:56 --> 14:58So are the screening guidelines any
14:58 --> 15:00different for African Americans
15:00 --> 15:01versus Caucasian
15:01 --> 15:03patients?
15:03 --> 15:04There are slightly different recommendations
15:12 --> 15:14Just as of yesterday the
15:14 --> 15:16US preventive taskforce has
15:16 --> 15:18changed it 45 and above for all
15:18 --> 15:20adults and so I think there
15:20 --> 15:22were some high risk groups
15:22 --> 15:23including African Americans that were
15:23 --> 15:24recommended 45 and above previously.
15:24 --> 15:27But now it's just everybody 45.
15:27 --> 15:29One wonders whether they will,
15:29 --> 15:32as we were talking about before the
15:32 --> 15:35break and edging even earlier,
15:35 --> 15:37whether they would make that now
15:37 --> 15:40a new age for higher risk groups.
15:40 --> 15:43But I want to switch gears now and
15:43 --> 15:45talk a little bit about what happens
15:45 --> 15:48to patients after they have been
15:48 --> 15:50diagnosed with colorectal cancer.
15:50 --> 15:52So somebody goes and they get
15:52 --> 15:54their colonoscopy and you know,
15:54 --> 15:56we talked about colonoscopy being a
15:56 --> 15:58great modality that can actually
15:58 --> 16:01find premalignant lesions and remove them.
16:01 --> 16:03But let's suppose on colonoscopy
16:03 --> 16:05a patient is found to actually
16:05 --> 16:07have an invasive cancer.
16:07 --> 16:09Tell us a little bit more about
16:09 --> 16:11how the treatment really works
16:11 --> 16:14in terms of managing patients
16:14 --> 16:16with colorectal cancer.
16:16 --> 16:18Absolutely so it's a very
16:18 --> 16:19multidisciplinary effort,
16:19 --> 16:20meaning there's numerous care
16:20 --> 16:22providers that are involved in
16:22 --> 16:24navigating somebody through a
16:24 --> 16:26diagnosis of colorectal cancer.
16:26 --> 16:28There's myself as a medical oncologist,
16:28 --> 16:30there are our surgical colleagues.
16:30 --> 16:33There's our pathologists, radiologists,
16:33 --> 16:35our radiation oncologists.
16:35 --> 16:36Our nutritionists, social workers,
16:36 --> 16:38everybody really involved here,
16:38 --> 16:40so the first step to really
16:40 --> 16:42know how we're going to treat
16:42 --> 16:43somebody's cancer is the stage.
16:43 --> 16:45So that's not unique to colorectal
16:45 --> 16:47cancer, it is very common in cancer.
16:47 --> 16:50The stage will help dictate
16:50 --> 16:53what the care is going to be.
16:53 --> 16:56Stage 1,2,3 and four is how we stage
16:56 --> 16:58the cancer and I could probably spend
16:58 --> 17:00hours talking about all of this.
17:00 --> 17:03But stage one is basically a small
17:03 --> 17:04cancer that's barely invaded
17:04 --> 17:06into the wall of the colon.
17:06 --> 17:09If we think of the colon as a tube,
17:09 --> 17:10it's barely in.
17:10 --> 17:12It starts on the inner part of that tube.
17:12 --> 17:14It's barely invaded through the wall,
17:16 --> 17:19and a tumor like that is just excised by surgery.
17:19 --> 17:21They may never even see me as a
17:21 --> 17:22medical oncologist because surgery
17:22 --> 17:25is curative in the majority of cases.
17:25 --> 17:27A stage two cancer has gone a
17:27 --> 17:29little bit further into that wall,
17:29 --> 17:30but hasn't spread to any lymph nodes.
17:30 --> 17:32Those patients will see a medical
17:32 --> 17:34oncologist and it
17:34 --> 17:36will be discussed whether or not
17:36 --> 17:38they get chemotherapy after surgery to
17:38 --> 17:40increase their cure rate and eradicate small
17:40 --> 17:42amounts of possible residual disease
17:42 --> 17:44based on risk factors.
17:44 --> 17:45Stage three cancer means it's gone
17:45 --> 17:47to the lymph nodes,
17:47 --> 17:49so it's behaving a bit
17:49 --> 17:51more aggressively so a patient
17:51 --> 17:53with an invasive mass, a colonoscopy is done.
17:53 --> 17:54A surgery is done,
17:54 --> 17:56lymph nodes are removed at
17:56 --> 17:57the time of surgery
17:57 --> 17:59in addition to the tumor if
17:59 --> 18:01there's cancer in the lymph nodes.
18:01 --> 18:03So if it's a stage three cancer,
18:03 --> 18:05all of those patients are going
18:05 --> 18:07to see a medical oncologist.
18:07 --> 18:08And almost universally,
18:08 --> 18:10as long as they're healthy afterwards,
18:10 --> 18:12will get chemotherapy to hopefully increase
18:12 --> 18:15their care.
18:15 --> 18:16Like with many other cancers,
18:16 --> 18:18stage 4 means it's spread more distantly,
18:18 --> 18:20so cancer that started in the colon
18:20 --> 18:22spread to the liver, the lung,
18:22 --> 18:24the lining of the abdomen,
18:24 --> 18:25which we call the peritoneum,
18:25 --> 18:28would make a cancer stage four.
18:28 --> 18:30One of those spots would make
18:30 --> 18:31a cancer stage four,
18:31 --> 18:34and there still may be a role for surgery.
18:36 --> 18:38But chemotherapy is generally.
18:38 --> 18:39Generally, where we will start,
18:39 --> 18:42we think of it as a systemic disease
18:42 --> 18:43throughout the body,
18:43 --> 18:45and chemotherapy works throughout the body.
18:45 --> 18:47When it's working in those stage
18:47 --> 18:49four cancers, though, there's
18:49 --> 18:52a lot that we need to know to
18:52 --> 18:54personalize the therapy for the cancers.
18:54 --> 18:56We do a lot of tests in the lab
18:56 --> 18:58and to characterize the cancer,
18:58 --> 19:00is it mismatch, repair, deficient or not?
19:00 --> 19:02Are there mutations in genes
19:02 --> 19:04called RAFS or not?
19:04 --> 19:07And they tell us how we tweak the chemo,
19:07 --> 19:09or maybe even offer immunotherapy
19:09 --> 19:11to the patients, and then again,
19:11 --> 19:13we will sometimes consider surgery to
19:13 --> 19:16remove distant metastases in select cases,
19:16 --> 19:18and that's why it's so important
19:18 --> 19:20to have a multi disciplinary team.
19:20 --> 19:23So a true team involved in
19:23 --> 19:25the care of these patients,
19:25 --> 19:28even with stage four disease and all
19:28 --> 19:30of these cases are reviewed at our
19:30 --> 19:33tumor board with that whole team,
19:33 --> 19:36I articulate how best
19:36 --> 19:38to approach somebody's care in
19:38 --> 19:40terms of these molecular genetics.
19:40 --> 19:42The RAF mutations,
19:42 --> 19:43the mismatch repair
19:43 --> 19:45mutations you mentioned those in terms
19:45 --> 19:47of tweaking chemotherapy for stage four,
19:47 --> 19:50are those also used in
19:50 --> 19:51kind of tailoring therapy
19:51 --> 19:54for people with earlier stage disease?
19:54 --> 19:56If I could only know a couple
19:56 --> 19:58things about the molecular
19:58 --> 20:00characteristics of somebody's tumor,
20:00 --> 20:02it would be the mismatch repair status,
20:02 --> 20:05which is also sometimes called the
20:05 --> 20:06microsatellite status or their
20:07 --> 20:09RAF status.
20:09 --> 20:10So in localized disease,
20:10 --> 20:13the mismatch repair status is very important.
20:13 --> 20:16The RAF and the RAF status
20:16 --> 20:17is not so important,
20:17 --> 20:20so we often only send the latter
20:20 --> 20:21component for metastatic disease.
20:21 --> 20:24But for localized cancer mismatch repair,
20:24 --> 20:25deficient, or microsatellite instability
20:25 --> 20:27high cancers generally have
20:27 --> 20:29a more favorable prognosis,
20:29 --> 20:31and sometimes we will take that
20:31 --> 20:33information and say you don't even
20:33 --> 20:34need chemotherapy after surgery
20:34 --> 20:37because of this
20:37 --> 20:39finding of mismatch repair deficiency
20:39 --> 20:40or microsatellite instability
20:40 --> 20:43and it's less likely to come back
20:43 --> 20:46and therefore you don't need chemotherapy.
20:46 --> 20:48There's a lot of other factors
20:48 --> 20:49that come into play there,
20:49 --> 20:51so I don't want to say that all mismatch
20:51 --> 20:53repair division microsatellite instability
20:53 --> 20:54high tumors don't need
20:54 --> 20:55chemotherapy after surgery,
20:55 --> 20:57but it's generally thought to
20:57 --> 20:58be a good prognosis.
20:58 --> 21:00And we know from metastatic disease,
21:00 --> 21:01those tumors are much more
21:01 --> 21:02sensitive to immunotherapy.
21:02 --> 21:04Some of the most sensitive cancers
21:04 --> 21:06that there are in fact to immunotherapy,
21:06 --> 21:08and it's being investigated whether
21:08 --> 21:10or not immunotherapy is going to
21:10 --> 21:11increase cure rates in that population.
21:11 --> 21:13And we have some of those
21:13 --> 21:14clinical trials going on.
21:15 --> 21:17That brings me to the next question,
21:17 --> 21:19which is about clinical trials.
21:19 --> 21:21Colorectal cancer has been around
21:21 --> 21:24for a long time and is one of
21:24 --> 21:26the leading cancers
21:26 --> 21:28affecting both men and women,
21:28 --> 21:30and so presumably there are some
21:30 --> 21:33pretty standard regimens in terms of
21:33 --> 21:35chemotherapy that we offer these patients.
21:35 --> 21:37So tell us a little bit about when
21:37 --> 21:40you offer people a standard regimen,
21:40 --> 21:42and when you offer them a
21:42 --> 21:44clinical trial?
21:44 --> 21:47Clinical trials play a tremendous role in the management
21:47 --> 21:50of a disease like colorectal cancer.
21:50 --> 21:52And are really how we move the field
21:52 --> 21:55forward and we've doubled and tripled the
21:55 --> 21:57survival rate especially for metastatic
21:57 --> 21:59disease over the last few decades.
21:59 --> 22:01And that's because clinical trials
22:01 --> 22:03brought new agents and drugs and
22:03 --> 22:06treatment approaches into the fold and the
22:06 --> 22:08treatments we have for metastatic disease,
22:08 --> 22:10we use some of them again
22:10 --> 22:11after surgery we use drugs, and
22:11 --> 22:14we like our acronyms or abbreviations so we
22:14 --> 22:18we have a regimen we call folfox which is 5FU,
22:18 --> 22:19and oxaliplatin and a
22:19 --> 22:20vitamin called leucovorin.
22:20 --> 22:23It's really two chemo drugs together and we have
22:23 --> 22:25another chemo regimen called FOLFIRI.
22:27 --> 22:30so again two chemo drugs together just a
22:30 --> 22:32second one instead of the oxaliplatin,
22:32 --> 22:35and that's really the backbone of our care,
22:35 --> 22:38and we can usually control a metastatic
22:38 --> 22:40colorectal cancer patient for years
22:40 --> 22:41with those two regimens together,
22:42 --> 22:44but at some point we run out of
22:44 --> 22:46mileage with those agents,
22:46 --> 22:46resistance develops,
22:46 --> 22:48tolerability becomes an issue,
22:48 --> 22:50something that necessitates us
22:50 --> 22:51moving on from those regimens.
22:51 --> 22:53And we really don't have great
22:53 --> 22:55agents after that,
22:55 --> 22:57so I'm often thinking about clinical trials,
22:57 --> 22:59novel clinical trials after those
22:59 --> 23:00regimens have stopped working,
23:00 --> 23:03but I am often thinking about clinical
23:03 --> 23:05trials even initially where those
23:07 --> 23:09agents will be added on,
23:09 --> 23:10or different treatment approaches
23:10 --> 23:13will be added onto those chemo drugs,
23:13 --> 23:15so they are good chemo backbones.
23:15 --> 23:17We can do better and we are
23:17 --> 23:18investigating numerous ways,
23:18 --> 23:20adding an immunotherapy, new targeted drugs,
23:20 --> 23:22new chemo drugs to those regimens.
23:22 --> 23:24But we're also investigating
23:24 --> 23:26completely new regimens in the
23:26 --> 23:283rd and the 4th line setting.
23:28 --> 23:30There are third and fourth line
23:30 --> 23:31drugs available for patients
23:31 --> 23:33with colorectal cancer,
23:33 --> 23:35and there's a drug called task 102.
23:38 --> 23:40But the effect of those is marginal
23:40 --> 23:42compared to those
23:42 --> 23:44other therapies that I mentioned.
23:44 --> 23:46It sounds like clinical
23:46 --> 23:49trials have two kind of roles.
23:49 --> 23:51One is after our standard tried and
23:51 --> 23:53true regiment have failed and
23:53 --> 23:55And we're looking for the best thing that might
23:57 --> 24:00help and move us further afield.
24:00 --> 24:02And the other is in investigating novel
24:02 --> 24:04therapies and straight out of the box.
24:04 --> 24:05Is that right?
24:05 --> 24:06Yeah, that's
24:06 --> 24:06definitely right.
24:08 --> 24:10These treatments like folfox and folfiri
24:10 --> 24:12have doubled and tripled the survival rate.
24:12 --> 24:14But we can still do better than that.
24:14 --> 24:16But they are the standard of care,
24:16 --> 24:18and since they are so effective,
24:18 --> 24:20we add on to those and we should add
24:20 --> 24:23on to those so that patients get the
24:23 --> 24:25best treatment available to them.
24:25 --> 24:26When we've moved on to our
24:26 --> 24:28third and our first fourth line,
24:28 --> 24:30treatments is task one or two
24:32 --> 24:33and start chemo pills.
24:33 --> 24:35There is not a great alternative.
24:35 --> 24:37They are not tolerated super
24:37 --> 24:39well and their time
24:39 --> 24:41with Disease Control is not
24:41 --> 24:43not as good as we would like,
24:43 --> 24:45so that is a time that we try a
24:45 --> 24:48more novel approach generally.
24:49 --> 24:52So tell us a little bit more about
24:52 --> 24:54your research and some of the
24:54 --> 24:56things that you're particularly
24:56 --> 24:59excited about in this field.
24:59 --> 25:01I guess maybe I'll start by
25:01 --> 25:04talking about some of the things
25:04 --> 25:06I'm excited about more broadly,
25:06 --> 25:09and one area that I think has garnered a lot
25:09 --> 25:12of attention lately for colorectal cancer
25:12 --> 25:15is something called circulating tumor DNA,
25:15 --> 25:17where we can detect minimal
25:17 --> 25:19amounts of circulating tumor DNA
25:19 --> 25:22in the bloodstream after a surgery.
25:22 --> 25:26So, for example, patients with stage two
25:26 --> 25:29colorectal cancer that happens to have
25:29 --> 25:31a blood test done that
25:31 --> 25:33circulating tumor DNA is detected.
25:33 --> 25:37Now we know that that patient is probably
25:37 --> 25:41going to relapse if we don't do anything
25:41 --> 25:41besides observation,
25:41 --> 25:44so we can use a tool like that
25:44 --> 25:45to decide who's high risk,
25:45 --> 25:47who's low risk and that gives
25:47 --> 25:48us opportunities to intensify
25:48 --> 25:49and deintensify treatment.
25:49 --> 25:51So trying to increase cure rates
25:51 --> 25:53for those that are high risk but
25:53 --> 25:54also knowing when somebody is
25:54 --> 25:56going to do well and maybe avoid
25:56 --> 25:58circumstances of over treatment.
25:58 --> 26:00So that's something as a field
26:00 --> 26:01I think we're learning
26:01 --> 26:03how to use these tests.
26:03 --> 26:05We know they correlate really well with
26:05 --> 26:07whether or not the cancer is going to come
26:07 --> 26:09back when you're only doing observation,
26:09 --> 26:11but we don't know how well it
26:11 --> 26:13predicts for benefit from chemo
26:13 --> 26:16and most our studies are ongoing.
26:16 --> 26:18We have some of those studies
26:18 --> 26:20ongoing here at Yale.
26:20 --> 26:22I also have
26:22 --> 26:24a busy clinical practice and
26:24 --> 26:26research program studying more novel
26:26 --> 26:28therapies in colorectal cancer.
26:28 --> 26:30So we have different types of
26:30 --> 26:33trials we develop here at Yale.
26:33 --> 26:35We have trials where we call them
26:35 --> 26:38industry sponsored trials where we
26:38 --> 26:40have worked with a company who's
26:40 --> 26:43developed a drug and opened their
26:43 --> 26:45trial that they came up with
26:46 --> 26:49maybe with some input than us from us,
26:49 --> 26:53but we've had a little bit less
26:53 --> 26:56involvement, perhaps in a trial like that,
26:56 --> 26:57and designing the trial,
26:57 --> 27:00and in analyzing the data so those
27:00 --> 27:01are industry sponsored
27:01 --> 27:03trials that we have here.
27:03 --> 27:06But we also have a robust program of
27:06 --> 27:08investigator initiated trials here,
27:08 --> 27:10and I have a couple open and one
27:10 --> 27:12specifically in that third line,
27:12 --> 27:14colorectal cancer Group, for example.
27:14 --> 27:17This is a trial where we've come
27:17 --> 27:18up with the idea,
27:18 --> 27:21and maybe we've written a grant or
27:21 --> 27:24we've partnered with a drug company to
27:24 --> 27:27tell them in a way that we think that
27:27 --> 27:30we could look at a new subtype of cancer,
27:30 --> 27:33or a new way to look at
27:33 --> 27:36their drug to leverage that and
27:36 --> 27:38for patients with that disease,
27:38 --> 27:40so I have an investigator initiated trial
27:40 --> 27:42for colorectal cancer that is received
27:42 --> 27:44two different types of chemotherapy,
27:44 --> 27:46where we look for a marker called MGMT.
27:46 --> 27:48So we basically meet a patient,
27:49 --> 27:51if they are potential candidate we will
27:51 --> 27:53test their tumor for this marker,
27:53 --> 27:56and if they have this marker
27:56 --> 27:58which ends up being about 40% of
27:58 --> 28:00patients if they have this marker,
28:00 --> 28:02we will then offer them enrollment
28:02 --> 28:03in a clinical trial.
28:07 --> 28:10So we basically identify this subgroup
28:10 --> 28:12of colorectal cancer and then we had this
28:12 --> 28:14trial that we came up with here at Yale.
28:14 --> 28:16And we're also studying the
28:16 --> 28:18outcome of patients with this to make
28:18 --> 28:20sure that we're actually helping people,
28:20 --> 28:22but also studying the science to develop
28:22 --> 28:24the next generation of trials which,
28:24 --> 28:27in my opinion will be leveraging the immune
28:27 --> 28:29system to make it work for the majority
28:29 --> 28:31of patients with colorectal cancer
28:31 --> 28:33as my colleagues in lung cancer and Melanoma
28:33 --> 28:36have been doing for the last decade.
28:36 --> 28:38Doctor Michael Cecchini is an assistant
28:38 --> 28:40professor of medicine and medical
28:40 --> 28:43oncology at the Yale School of Medicine.
28:43 --> 28:44If you have questions,
28:44 --> 28:46the address is canceranswers@yale.edu
28:46 --> 28:48and past editions of the program
28:48 --> 28:50are available in audio and written
28:50 --> 28:51form at yalecancercenter.org.
28:51 --> 28:54We hope you'll join us next week to
28:54 --> 28:57learn more about the fight against
28:57 --> 29:00cancer here on Connecticut Public Radio.

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June 13, 2021

Yale Cancer Center

visit: http://www.yalecancercenter.org

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