Liver Cancer Awareness

September 14, 2020

Information

September 13, 2020

Yale Cancer Center

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00:00Support for Yale Cancer Answers
00:02comes from AstraZeneca dedicated
00:05to providing innovative treatment
00:08options for people living with
00:12cancer. Learn more at astrazeneca-us.com.
00:14Welcome to Yale Cancer Answers
00:16with your host
00:17Doctor Anees Chagpar.
00:19Yale Cancer Answers features the
00:21latest information on cancer care by
00:23welcoming oncologists and specialists
00:25who are on the forefront of the
00:27battle to fight cancer. This week
00:29it's a conversation about liver
00:31cancer with Doctor Stacy Stein.
00:33Doctor Stein is an associate professor
00:35of internal medicine in medical oncology
00:37at the Yale School of Medicine,
00:39where doctor Chagpar is a
00:41professor of surgical oncology.
00:44So Stacy, we don't know
00:46a whole lot about liver cancers.
00:48We certainly talk a lot about
00:50breast cancer and colon cancers,
00:52but tell us a little bit more about
00:54how we think about liver cancers.
00:57Yeah,
00:58you're right.
00:59I don't think it gets the same
01:01attention as some other cancers
01:03in the public.
01:05But I think it's a really important
01:07cancer to talk about because it's
01:10actually one of the few cancers that is
01:13still on the rise in our country.
01:15Some people might be familiar
01:18with some of the traditional causes of
01:21cirrhosis which causes liver cancer.
01:24Worldwide this is a very
01:26prevalent cancer,
01:29especially because of hepatitis B
01:31and mother's passing it on to their
01:34babies. In the United States,
01:37we see more people that have
01:40developed cirrhosis from hepatitis
01:42C or alcohol use, but
01:44another cause is actually on the
01:46rise in the United States that
01:49we don't talk about a lot and that
01:53is something called NASH Cirrhosis,
01:55which is related to the obesity epidemic,
01:58and we're seeing that more commonly now and
02:02I think it's something important
02:05that people are more aware of and primary
02:08care physicians are more aware of,
02:11to screen their patients.
02:13How exactly do they do that
02:16and is that the same concept of
02:19fatty liver that we sometimes hear about?
02:22And is there screening for it? And
02:25if so, what is that?
02:26Often you know
02:29who is at risk
02:30for those kind of factors,
02:32so it's people that are
02:34older that may have obesity,
02:35high blood pressure,
02:36diabetes, right?
02:37So a lot of these common diagnosis
02:39that travel together and then you
02:41know it's also not uncommon for
02:42people with all these diagnosis
02:44to be on several medications,
02:46and then they may have
02:48blood work where their liver enzymes
02:50are a little bit out of range,
02:52but I think it usually gets
02:53ascribed to maybe a side effect of
02:56one of the medications that they
02:57were on instead of thinking about
02:59underlying liver disease and so
03:02it's important when we see
03:04elevations in liver enzymes to
03:07be thinking that this might be
03:09a primary liver issue.
03:13Interesting, and
03:15because we've talked on this show so
03:17much and on others about how there really
03:21is this obesity epidemic and
03:24over 40% some people even say over 50% of
03:28our population are overweight or obese,
03:31how often should you be getting
03:34those liver enzymes checked?
03:36And if they are abnormal,
03:38what should ensue?
03:40Yeah, that's a good question,
03:42so I think the screening needs to be updated.
03:45You know most of the screening
03:48and efforts in the
03:50hepatology guidelines really focus around,
03:51which is still very important,
03:54screening people for hepatitis B
03:55and hepatitis C because we have
03:58treatment now for hepatitis C.
03:59We have treatment
04:01for not curatives, but we have
04:03suppressive treatment for hepatitis B.
04:07And the question is then who should we be
04:10screening for this NASH Cirrhosis?
04:12You know the guidelines are not
04:14completely set the same way as
04:16they are for these other causes,
04:18but I think certainly when you
04:21see someone that's having elevated liver
04:23enzymes or potentially decreased platelets,
04:25that could be a sign.
04:27And portal hypertension,
04:29or people have had imaging for
04:31other reasons and you find changes
04:33that are consistent with cirrhosis.
04:35I think it's important to really go
04:38down the path of fully working that up.
04:42But I don't think the guidelines
04:44are really clear yet of how we
04:47screen for NASH Cirrhosis.
04:48But I think it's going to
04:50be important to
04:53give better direction to
04:54people in primary care about that.
04:58You mentioned that there's good screening
05:00for hepatitis B and C, and
05:03certainly we have vaccines for both of those,
05:05but let's talk a little bit about how we
05:08screen for those HEPAs as well.
05:11I mean, should that be something that
05:14is routine at your doctors office.
05:16How frequently should that happen?
05:18Or is that something that you only
05:21really screen for if you're at
05:24risk of getting those hepatitides
05:26and what are those risk
05:28factors?
05:30In the United States, all babies are
05:33given a series of hepatitis B vaccines,
05:36so it's really more of an issue of screening
05:39people that were not born in this country,
05:42especially Asian populations
05:44where the numbers are the highest.
05:46For hepatitis C, it's recommended
05:49that especially everyone from the baby
05:52boomer generation is screened at least once,
05:55and then certainly you know if there's
05:58any concern for a more acute liver
06:01process, that could be repeated.
06:03There are initiatives
06:05through primary care,
06:07and especially through the VA system.
06:09Unfortunately,
06:10there's a large burden of hepatitis
06:13C to really make sure that everyone
06:16is screened at least once,
06:19because we do have treatment now,
06:22which is important to know
06:25and make sure that's started in
06:27a timely fashion.
06:31And screening is a routine blood test,
06:37so if you haven't had a blood test
06:40and are in that baby Boomer generation,
06:43or you have been born in another country,
06:46it's a good idea
06:48to at least get checked and
06:51see if you have one of these two
06:54hepatitides which may put you at
06:57risk of developing liver cancer.
06:59So let's talk a little bit about
07:01that next step when you
07:04were talking about how if your
07:06liver enzymes are elevated that
07:08should really spur people on to
07:11thinking about liver cancer as a
07:14potential cause for that, so
07:16aside from an abnormal blood test of
07:19your liver enzymes being elevated,
07:21are there other symptoms that people
07:23should be looking for in terms
07:25of liver cancer or can it be
07:28completely asymptomatic?
07:30That's a good question.
07:32So what's so interesting about liver cancer
07:35is that it's so tied to Cirrhosis
07:37and underlying liver disease,
07:39and so those two things obviously
07:41are separate but also very related.
07:44So you know the symptoms of the cancer
07:46may not be traditional symptoms.
07:49People think about,
07:50we don't have a lot of nerve endings
07:53inside the liver.
07:55So often people don't feel a difference
07:57necessarily the way someone might feel
08:00a mass somewhere else in their body.
08:02And unless there's really tumor
08:05pressing on the capsule of the liver
08:07where there are a lot of nerve endings,
08:10they probably won't feel any different.
08:13So a lot of the screening really winds
08:15up being identifying the people at
08:18risk of for Cirrhosis and identifying
08:20cirrhosis and then looking at that
08:22group and screening them with
08:24imaging for liver cancer.
08:26Because we know that the cure rate and
08:29the success at treatment is better
08:33the earlier we can find it.
08:36So for patients that present with
08:38a single liver lesion and they
08:40have good liver function,
08:42they could be candidates for surgery
08:44where the tumor is able to be removed.
08:47For some patients who have still
08:50pretty limited disease and they
08:52may also have some cirrhosis,
08:54or declining liver function,
08:57and there's a lot of rules surrounding this,
08:59but they could potentially be
09:01candidates for liver transplant and that
09:03could also be a curative option,
09:05but if the cancer is found later,
09:07then we don't have those kind of options
09:10and we have to then think about
09:12other treatments.
09:14So it's important to find it
09:17at an early stage as with so many cancers.
09:21Tell us a little bit about the
09:23imaging that needs to happen.
09:26You may be feeling completely asymptomatic.
09:28You hear this on the radio and you
09:31decide to go and see your doctor
09:34because maybe you are overweight.
09:36Or maybe you have
09:39a history of alcohol in the past and
09:42and are worried about cirrhosis or maybe
09:46you've been screened for
09:48hepatitis B or C and your doctor
09:51does that screening test and says,
09:53your liver function
09:56studies are a little bit abnormal.
10:00So imaging is the next thing that you should
10:02expect in order to try to find a liver
10:05cancer early, right?
10:06So there's a few ways to image the liver,
10:09so sometimes for screening they
10:11start with just an ultrasound,
10:13which is pretty easy to get, noninvasive.
10:15There's a probe that is
10:16put over the abdomen and is kind of pushed down,
10:19and then there's
10:21images that show up,
10:22and they could often find changes
10:24of Cirrhosis and possible tumor.
10:26And when we're really
10:28concerned that there is cancer,
10:29and we best want to characterize it,
10:32the best imaging, what's considered
10:35the gold standard is really an MRI
10:37for patients that are not able to
10:40get an MRI for one reason or another,
10:43we're able to do a CAT scan with
10:45something called triphasic imaging,
10:47where we're able to get a very
10:49good look at the liver also so
10:52most patients once there's
10:54any real concern,
10:57they usually getting an MRI,
10:59and if not
11:00a CAT scan and so
11:02what's the next step?
11:04A biopsy now?
11:06That's an excellent question.
11:09You know, for every cancer,
11:11I think most patients would identify a
11:14biopsy as being the next step, right?
11:17So if we have imaging that's concerning,
11:20typically as oncologists,
11:22we always order a biopsy for cancers and
11:25that really gives us the definitive answer.
11:28Interestingly in the history of liver
11:31cancer imaging has been so good at
11:33looking at specific characteristics
11:36of the cancer that traditionally you
11:39have not needed a biopsy to identify
11:42each HCC or hepatocellular carcinoma,
11:45and we've been challenging that
11:48a little bit more recently because
11:51there's a lot of caveats
11:55where you could have mixed tumors
11:58of bile duct cancers with HCC.
12:02Or you know, as tumor profiling
12:05is becoming more commonly used,
12:08we really like to have tissue biopsy
12:11so that we could do these molecular tests,
12:15and so it has become more common to
12:18have a biopsy before we start treatment.
12:21But I would say historically a
12:24lot of patients wind up getting treated
12:27for liver cancer in the absence of a biopsy,
12:31which is definitely
12:34unusual as compared to other cancers.
12:37And I guess the other thing that is unique
12:40about the liver or somewhat unique is
12:43that it's a good place for cancers that
12:46start in other places to go not just as
12:50a place for cancers to arise.
12:53How can you tell the difference between
12:56a primary liver
12:59cancer that starts and grows in
13:01the liver, often in a cirrhotic liver,
13:04versus a cancer that started somewhere else,
13:06say in the colon or somewhere else and
13:09goes to the liver.
13:11And so that's always the first question.
13:14When you see a mass in the liver,
13:16did it start there or did it spread
13:19there from somewhere else so the
13:21imaging does help with that.
13:24If you do what's called this triphasic
13:26imaging, when the
13:28contrast is injected into someone,
13:29they look at certain phases.
13:31So that the liver has two blood supplies,
13:34there's a
13:34blood supply from arteries and
13:36from veins so the liver is unique in
13:38that way and there's kind of a
13:41characteristic appearance that
13:43is different between metastases
13:45and liver cancer.
13:46But that being said,
13:48sometimes the imaging is not as clear and
13:51you don't feel confident
13:54and that's really where a biopsy is
13:58helpful.
13:59And so once you get that biopsy,
14:02you can figure out is this primary cancer.
14:05Is this a secondary cancer?
14:08And hopefully get a little bit
14:10more in terms of clues that
14:12can help you to treat it.
14:14Absolutely
14:16and also what's interesting
14:18is that liver cancer can
14:20occur as a single tumor,
14:24which is what happens in most cancers, right?
14:27Most cancers start out as a
14:29single tumor and then can spread.
14:31With liver cancer
14:33sometimes it's what's
14:34called Multi focal disease,
14:35meaning that it's not really one
14:37area that spread to other areas.
14:40But that because of the cirrhosis
14:42you could think of the whole liver as
14:45being at risk for developing tumor,
14:47and so sometimes there's actually
14:49more than one area at the same
14:51time that has developed a tumor.
14:53Well, we're
14:54going to dig into all kinds of aspects
14:57in terms of the qualities of tumors
14:59in the liver and how we go about
15:02treating them right after we take a
15:04short break for a medical minute.
15:06Please stay tuned to learn more
15:08about liver cancer with my guest
15:11Doctor Stacey Stein.
15:12Support for Yale Cancer Answers
15:15comes from AstraZeneca, providing
15:18important treatment options for
15:20various types and stages of cancer.
15:23More information at astrazeneca-us.com.
15:27This is a medical minute
15:28about head and neck cancers,
15:30although the percentage of oral
15:32and head and neck cancer patients
15:35in the United States is only about
15:375% of all diagnosed cancers,
15:39there are challenging side effects
15:41associated with these types of
15:43cancer and their treatment.
15:44Clinical trials are currently
15:46underway to test innovative new
15:48treatments for head and neck cancers,
15:50and in many cases less radical
15:52surgeries are able to preserve nerves,
15:54arteries and muscles in the neck,
15:56enabling patients to move, speak,
15:58breathe, and eat normally after surgery.
16:01More information is available
16:03at yalecancercenter.org.
16:04You're listening to Connecticut public radio.
16:09Welcome back to Yale Cancer Answers.
16:11This is doctor Anees Chagpar
16:13and I'm joined tonight by
16:15my guest doctor Stacy Stein.
16:17We're talking about GI cancers
16:19in particular liver cancer,
16:21and right before the break we talked
16:23a little bit about all of the risk
16:26factors that can really put you at risk
16:29of developing primary liver cancer,
16:31which can be an isolated event,
16:34or it could be multi focal. So Stacy,
16:37when we talk about liver cancers,
16:40how often are these
16:42found as a single spot in the liver
16:44versus more extensive disease?
16:46That's a
16:47good question, so I think it
16:49really depends on which
16:51group of people you're looking at.
16:54For patients who have known that
16:55they have underlying risk factors
16:57and they've been getting screens,
16:59they are much more likely to
17:01be found with early disease.
17:03But I would say, unfortunately, I see patients all the time who
17:07present with much more advanced disease.
17:10Because you they either
17:12were not being followed by anyone,
17:15or they didn't realize that they
17:17had cirrhosis and so they could
17:20present with disease
17:22that's already
17:24not eligible for surgery or transplant.
17:26The disease may have metastasized already,
17:29and so we certainly see
17:32people that have either presented with
17:35disease very late or after treatment.
17:38For early disease, the disease has
17:41progressed and
17:42as we talked about before the break,
17:45I mean certainly it's always better
17:47if you can find cancer early
17:49when it's most treatable and when
17:52either surgery or local
17:54therapies are an option to get
17:57rid of the primary cancer.
18:00But when that cancer is locally
18:02advanced or even metastatic when
18:05it spread and those local therapies
18:08are no longer an option,
18:10we still have options to treat
18:13these patients.
18:14And that's really the area
18:16that I've been most focused in.
18:18I'm very lucky at Yale
18:21to have a fantastic multidisciplinary
18:22liver team and I just want
18:26to mention we actually meet weekly.
18:28We have our own separate conference
18:30just for liver cancer and there's
18:33such a great group of people.
18:35We work with the surgeons, the
18:37transplant surgeons, the hepatologist,
18:39the Interventional radiologist.
18:44There's Oncologists.
18:45We really have a great group that
18:49focuses on all aspects of treatment.
18:52My focus as an oncologist
18:55is really more in patients
18:58who are not candidates
19:00for these curative intent
19:03treatments like transplant or surgery.
19:07For patients with local disease where
19:09the disease is still confined to the
19:12liver and there's not more than a few
19:15separate tumors that Interventional
19:16radiologists have really played a
19:19large role in treating those patients,
19:21and they treat with a wide variety
19:24of modalities where they could apply
19:26some chemotherapy or heat or cold,
19:29or they do ablation techniques,
19:31and then at some point either
19:34because someone is developing more tumors or
19:37if there's any metastatic disease,
19:39meaning tumor has left the liver,
19:41then we really focus on what
19:43we call systemic therapies.
19:45So either the treatment is a
19:47pill form or intravenous form,
19:48but then the drugs are
19:50absorbed in the body and go everywhere,
19:53and I have to say over the time that
19:57I've been at Yale, in the last 10 years,
20:00we have made tremendous strides
20:02in the last few years and having
20:05more treatment options that are
20:08more effective for liver cancer,
20:10so that's been really exciting.
20:13So tell us more about those developments.
20:16I mean for many people the concept
20:18of chemotherapy is really scary,
20:20but you mentioned that some
20:22of these therapies that you
20:24give actually can be oral.
20:27The first drug that actually showed a benefit
20:30in helping people live longer with liver
20:33cancer is a drug called sorafenib
20:35and that's actually a pill form of treatment.
20:38It's not really traditional chemotherapy,
20:40we call them
20:42tyrosine kinase inhibitors.
20:44So it's more targeted therapy.
20:46While sorafenib had some benefit,
20:48we all recognize that it wasn't enough.
20:51And then if patients didn't
20:53really tolerate it,
20:54than their cancer started to grow again.
20:57You know there were many years
20:59where we really didn't have
21:01other good treatment options.
21:02And then in the last few years there's
21:05been a lot of success in both finding
21:08more of these tyrosine kinase inhibitors
21:10that are more effective potentially.
21:17and then the other area that's been
21:19really exciting has been the use
21:22of immune therapy in liver cancer,
21:24so I want
21:25to dig into both of those kind
21:28of arms of the equation first.
21:30You know when we talk about
21:34tyrosine kinase inhibitors
21:35sometimes that's very similar to
21:37what we talk about in breast cancer.
21:40For example, many of our
21:43listeners may know about HER2
21:45and the fact that we can have
21:48a targeted agent against HER2
21:51that can be very effective.
21:53So with these tyrosine kinase
21:55inhibitors in liver cancer,
21:57are there particular receptors
21:59that you're going after?
22:00So are there markers that you can
22:03look at a cancer and say, ah, ha,
22:06Mrs Jones
22:08has this particular receptor and
22:10I have a drug that can target.
22:12Yeah, that's a really
22:14good question and there's a
22:16few things that you asked
22:18that I want to address and one is
22:21do we have a biomarker?
22:22Which really means is there some way
22:25from the patient that I'm treating
22:27either from their blood work or something
22:29from there from their biopsy that I
22:31could identify that would predict
22:35whether they would respond
22:36to treatment or not,
22:38and unfortunately the answer is we really
22:40don't have a biomarker for liver cancer
22:43the way that we could test
22:45HER2 expression in breast cancer,
22:48or other cancers and say this
22:49drug is more likely to work.
22:51We do follow something
22:54called the AFP.
22:55The Alpha fetal protein and
22:56in about 80% of liver cancers
22:58that protein is made and so the
23:01value of it and it going up or down
23:04gives you a sense of response,
23:06but it doesn't actually predict what drug
23:09he would respond to if there is a
23:11real need for finding a biomarker
23:13that would predict response to any
23:16particular drug, but the truth is,
23:18we don't have one,
23:19and so we really are giving these
23:22drugs without really knowing who it is
23:25that is going to respond or not,
23:27and we're trying
23:29sequences of drugs.
23:31I wish we did have a biomarker.
23:34There's a lot of interest in
23:37developing one when you ask what
23:39target are we hitting with
23:42this tyrosine kinase approach,
23:43the truth is these are what we
23:46call dirty tyrosine kinases,
23:48meaning they don't target just one protein,
23:50so one of the proteins they target
23:53is something called veg F.
23:54The vascular endothelial growth
23:56factor which is involved in blood
23:58vessel formation for the tumors.
24:00We do know that that's an
24:02important target for liver cancer,
24:04but it's not the only one that's
24:06targeted by these drugs,
24:08so there's there's other pathways
24:10that are being targeted and they
24:12probably have some role in the
24:14benefit of these drugs too.
24:16And you know, there's still
24:18a lot more to really understand
24:21about how these drugs work in this
24:23cancer.
24:25It would be nicer if you could
24:28biopsy a tumor and say,
24:30this tumor has a very high veg F
24:32level and you have a specific drug
24:35that would target that and Voila,
24:37the cancer magically disappears,
24:39but I guess we're a bit far off from that.
24:43And what's interesting too is
24:45that in immune therapy
24:47there's been so many recent
24:48studies looking at the role
24:50of different immune therapy,
24:52drugs, and liver cancer,
24:53and even then for a lot of
24:56cancers you could check something
24:58called the PDL one expression,
24:59and by looking at the number
25:01of immune cells infiltrating,
25:03in the tumor on the biopsy,
25:07you could have some kind of
25:09sense of prediction of how likely it is
25:13someone would respond to immunotherapy,
25:15but even that for liver cancer
25:18has been very unreliable.
25:19The expression of that protein
25:21does not predict who will respond
25:23to immunotherapy either.
25:25Interesting that really is
25:27unique, I think
25:30for liver cancer, because I know in
25:33other cancers we actually do look at
25:36that and say, if we see
25:40PD L1 expression then we know that
25:43immunotherapy is going to be more effective.
25:45So how do you decide who
25:47to give immunotherapy to?
25:49And who to treat with a TKI or a chemotherapy?
25:53Yeah, that's
25:54a great question, and
25:56until very recently the
25:57treatment has been a TKI
25:59first and then immune therapy,
26:01but I want to tell you about one of the
26:04newest combinations that's been looked at,
26:07which is a combination of an immune
26:09therapy drug called atezolizumab.
26:11So that's what we call a PDL1
26:14antibody and it targets the immune system
26:16and then it was given in combination
26:19with bevacizumab which is an antibody
26:21against veg F which I had just
26:24mentioned before and that combination
26:25and we had participated
26:28at Yale in the phase one study
26:30looking at this and I will tell you that out
26:34of the patients that I had on that study,
26:37I actually have two patients who had a
26:40complete response to treatment which was
26:42amazing to me,
26:44and they're both still doing very well with
26:47no disease that could be seen on their MRIs
26:50which is something that I had
26:52never had happen before,
26:53so that was really exciting and the
26:56phase one study was positive and based
26:58on those results there was a large
27:01phase three study so they
27:04compared this combination back to sorafenib,
27:06which had been often given,
27:09as a first treatment and
27:11they showed that there was
27:13a benefit of giving this combination
27:15immunotherapy and so that just got approved
27:18by the FDA a couple of months ago.
27:21And for patients who are good candidates
27:23for that which some people may not be a
27:27good candidate for getting that treatment,
27:29either because of the immune therapy
27:31part or thebevacizumab part,
27:34that's become the new standard of
27:36care to give this combination.
27:38We see higher response rates.
27:40We see patients have longer responses
27:43to treatment.
27:45We don't have a biomarker to predict who is
27:48going to do the best with that combination,
27:51but this is really
27:52a big change in our practice,
27:56just in the last few months to think
27:58about giving this type of combination
28:00to patients before starting with
28:02the tyrosine kinase inhibitor.
28:04So you know,
28:05we think carefully about each patient,
28:08and certainly there's other
28:10immune therapy drugs to give and there
28:12still are tyrosine kinase inhibitors to give,
28:16but the discussion now about how to
28:19sequence these treatments has become
28:23much more relevant.
28:25There's other
28:27studies looking at combination
28:29therapies that the full data
28:31has not been presented yet.
28:32It hasn't been published yet,
28:34but there's other studies that are
28:36showing more positive data than just
28:39giving a tyrosine kinase inhibitor by itself,
28:42and so it's just been really exciting.
28:44Doctor
28:45Stacy Stein is an associate professor
28:47of internal medicine in medical oncology
28:50at the Yale School of Medicine.
28:53If you have questions,
28:54the address is canceranswers@yale.edu
28:56and past editions of the program
28:58are available in audio and written
29:00form at Yalecancercenter.org.
29:01We hope you'll join us next week to
29:04learn more about the fight against
29:07cancer here on Connecticut public radio.