Hepatocellular Carcinoma | Colorectal Cancer
The most common types of liver cancer are the following:
Hepatocellular carcinoma (HCC). HCC makes up 72% of liver cancer cases.1 HCCs may be classified further based on the main molecular pathways and immune status of the tumor.2 Thus, HCCs can be categorized into the proliferation and nonproliferation classes or the immune-active, immune-exhausted, immune-intermediate, and immune-excluded classes.2
Intrahepatic bile duct cancer (cholangiocarcinoma). Intrahepatic bile duct cancer exhibits different clinical features from HCC and comprises 19% of liver cancer cases.1
Incidence in the United States
The incidence of liver cancer rates tripled over the past 4 decades and has 3 times higher incidence in men than in women.1 Based on cases reported from 2015 through 2019, the age-adjusted incidence rate of liver and intrahepatic bile duct cancers was 9.5 per 100,000 men and women per year.3 In 2023, it was estimated that 41,210 individuals would be diagnosed with liver cancer in the United States and that 29,380 individuals would die from the disease.1
Epidemiology in the United States
In 2023, liver cancer was estimated to be the fifth leading cause of cancer death among men and the seventh leading cause of cancer death among women in the United States.1 The stage of diagnosis influences survival rates, but fewer than half of patients with liver cancer are diagnosed at an early stage.3 In the United States, 5-year survival rates for patients diagnosed with localized, regional, and metastasized liver cancer are 36%, 13%, and 3%, respectively.3
Risk Factors
Cirrhosis is the greatest risk factor for HCC development and is present in 70% to 90% of those who have primary liver cancer.2,4,5 Common causes of cirrhosis include hepatitis B virus infection, hepatitis C virus infection, heavy alcohol consumption, non-alcoholic steatohepatitis (NASH), α1- antitrypsin deficiency, and hemochromatosis.1,2,5 In patients with chronic hepatitis C infection, antiviral therapies reduce—but do not eliminate—the risk of HCC.2 Other factors associated with increased risk of HCC include tobacco use, intake of aflatoxin b1 (fungal carcinogen present in food supplies), male sex, older age, persistent increase in alanine aminotransferase level, increased α-fetoprotein level, and progressive impairment of liver function.2,4
Unmet Need
Although survival rates have increased in recent years, liver cancer remains a highly lethal cancer, with a 5-year survival of only 21% (data from 2012-2018).3 To date, treatment options for patients with HCC are largely limited.6 Resection, transplantation, or ablative strategies are among the treatment options for certain patients with HCC.1,7 However, considering that only 44% are diagnosed at the early stage, treatment options are limited.3 Locoregional therapy such as ablation, arterially directed therapies, and external beam radiotherapy are also among the treatment options for certain patients.7
References: 1. American Cancer Society. Cancer Facts and Figures 2023. 2. Llovet et al. Nat Rev Dis Primers. 2021;7:6. 3. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. https://seer.cancer.gov/statfacts/html/livibd.html. Accessed September 1, 2022. 4. Bruix et al. Gastroenterology. 2016;150:835-853. 5. Herbst et al. Clin Liver Dis. 2013;1:180-182. 6. Rahib et al. Cancer Res. 2014;74:2913-2921. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed November 16, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.
Resources
Risk Factors for the Development of HCC
There are several factors that may increase a person’s chance of...
developing hepatocellular carcinoma (HCC). Here, Jun Gong, MD, and May Cho, MD, discuss risk factors commonly seen in people with liver cancer and how those risk factors can help in identifying treatment options.
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[Dr Cho]: The main risk factor for HCC is chronic liver disease, right? It may be either cirrhosis or just the chronic liver disease, and that includes multiple things: Alcohol, which is very common, especially in the US, viral hepatitis, metabolic syndrome, autoimmune disease, and some hereditary disease. So those are the risk factors that lead to the chronic inflammation in the liver and cirrhosis that [may] lead to the hepatocellular carcinoma.
[Dr Gong]: So the major risk factors for HCC, as Dr. Cho had clarified, always #1is cirrhosis, chronic liver disease, and then you have some causes, common causes of cirrhosis. In the eastern part of the world, that differs from the western part of the world, for example. Eastern part of the world, hepatitis B virus remains a major cause. Hepatitis C remains a major cause in the western part of the world. But then you have some rising causes of cirrhosis, such as nonalcoholic fatty liver disease and also alcoholic cirrhosis. You also have some rare hereditary cases. And I do agree that sometimes the etiology of the HCC can tailor your treatment for the HCC. It also dictates what kind of providers will also be involved in this care as well.
Etiology and Potential Development of HCC – How Do NAFLD and NASH Play a Role?
There are some important perspectives to share regarding the etiology and...
development of HCC. Here, Jun Gong, MD, and May Cho, MD, discuss the potential relationship between NAFLD/NASH and the development of hepatocellular carcinoma (HCC).
Click to expand transcript
[Dr. Gong]: So there have been some debates about if etiology can advance
HCC, the progression of its course. There’s been debate that perhaps hepatitis B
virus and related cirrhosis patients may have a chance for an earlier detection
because then they get detected and they get placed on screening, allowing for
earlier detection of hepatitis B and then prevention of cirrhosis and HCC in that
sequence as well. And so there has been some debate that this subgroup of HCC
patients may do a little bit better compared to some other causes of HCC.
[Dr. Cho]: One exception is that we often see people who have used actively
alcohol is the bilirubin may be high, and when they stop drinking the bilirubin
drastically goes down. Then the Child-Pugh score, you know, will improve. And so
their prognosis is a lot better than when they started out with. In terms of
etiology, this metabolic syndrome leading to the NAFLD and NASH has been
rising.
Navigating Etiology in Advanced HCC
Whether etiology can lend insight into hepatocellular carcinoma (HCC)...
causes or be used to alter the course of cancer is debatable. Here, Jun Gong, MD, and May Cho, MD, discuss their thoughts on the role etiology might play in advanced HCC.
Click to expand transcript
[Dr. Gong]: Now, in terms of how this affects prognostically sometimes you may need to
alter therapies based on comorbidities. But alternatively, there's been some literature
that's a little bit conflicted. There's been debate that perhaps hepatitis B virus and
related cirrhosis patients may have a chance for an earlier detection because then they
get detected and they get placed on screening, allowing for earlier detection of
hepatitis B and then prevention of cirrhosis and HCC in that sequence as well.
[Dr. Cho]: Right now, we don't have a very valid prognosis, or indications in terms of
when they developed the HCC. One exception is that we often see people who have
used active alcohol, their bilirubin may be high, and when they stop drinking, the
bilirubin drastically goes down. Then the Child-Pugh score will improve. And so their
prognosis is a lot better than when they started out with.
The Patient Journey in HCC
Hepatocellular carcinoma (HCC) can be a complex disease to manage. Here...
, Jun Gong, MD, discusses the typical journey for a patient with advanced HCC. He emphasizes the importance of educating patients and setting treatment goals with them.
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[Dr Gong]: The patient journey after — upon diagnosis of advanced HCC I think always begins with our initial meeting in our clinic, where the patient is meeting the provider, myself, my nursing team here. What we do is then we kind of lay out the next steps ahead, including what are the treatment options. Firstly, it’s also important to involve the family and caregivers that may be present at this visit as well, get an understanding of what their condition and what their diagnosis means, and then answer any questions. But most importantly, jump into what does it mean in terms of the context of treatment? We lay out the treatment options for them. We often discuss the potential side effects from treatment options. We also discuss goals: what are the goals of treatment for advanced HCC? Then also we talk about comprehensive care, which is involving nutritional aspects of management, symptom management. This often involves supportive care medicine as well. We also have a social worker that gets involved for social resources as well. I think this really sets them off on the first journey, first steps of their journey as we begin treatment for advanced HCC.
A Multidisciplinary Team Approach in Managing HCC
Hepatocellular carcinoma (HCC) presents a unique set of challenges...
during diagnosis and treatment that often requires a multidisciplinary team to ensure high-quality care and improve patient outcomes. Here, Jun Gong, MD, and May Cho, MD, share their approach to managing HCC.
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[Dr. Cho]: Hepatocellular carcinoma requires such a multidisciplinary team. So
hepatologists play such a role, transplant physician, surgical team, liver-directed
therapy play a role too, so interventional radiologists and medical oncologists all play
such a role in treating this disease and getting the best outcome.
[Dr Gong]: And, just to paint a scenario with these meetings, it's nice to have a
radiologist on board reviewing the images dynamically with all the providers and
healthcare staff members. Then you have the interventional radiologists weighing in on
the ability for local therapies, locoregional therapies. You often even have radiation
oncologists — that's a budding field of implementation on how they can manage local
disease. You always have the surgeons and the hepatologist as well, where they're
weighing in the options of transplantation in localized HCC patients. And of course,
medical oncologists there to weigh in for systemic options.
I think nurse navigators and other support care coordinators are very important. And
we find that navigating a complex discipline as well as condition can be daunting for
patients, whether it's making appointments, coordinating a lot of different
appointments to a lot of different providers, even arranging transportation. Having a
strong team, including a patient navigator, social work, case management, I think,
really adds an extra dimension to our care for this advanced disease.
The Staging of Disease in HCC
Staging of hepatocellular carcinoma (HCC) is important for both...
the prognostication and for deciding on the optimal treatment strategy. Here, Jun Gong, MD, and May Cho, MD, discuss staging in HCC and how it may guide their treatment paradigm.
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[Dr. Cho]: We use the Barcelona staging system in the hepatocellular carcinoma staging. You know, in other solid-tumor staging, we use TNM, and we never use TNM at all in HCC. Because, like I mentioned, this disease, we’re dealing with two diseases at the same time: 1) hepatocellular carcinoma,2) and cirrhosis by itself. How much of the liver function the patient has, you know, as a reserve? That plays such a big role. And then the third is patient functional status.
[Dr Gong]: I would like to echo Dr. Cho that the BCLC, or the Barcelona Clinic Liver Cancer score, is very important in how we manage our patients with HCC. If you had a BCLC score of zero[or A], this is usually a single tumor less than two to three centimeters in size. And here, you're really thinking about treatments such as surgery or ablation.
Then you move on to BCLC intermediate stage, where you may have multinodular disease; and here TACE has been nationally and internationally recognized as a treatment option. Then you move on to the more advanced stages, BCLC advanced 7stage here, where you have multinodular, metastatic M1, N1, or medical vascular invasion. And here is where medical oncologists are usually involved with systemic therapies. And then you have the most advanced stage, which is BCLC terminal stage, which is usually a poor performance that is ECOG of [>]2 and a Child-Pugh score of C.
Medical Education Gaps in HCC
Medical education is an area of unmet need within hepatocellular carcinoma...
(HCC). Here, Jun Gong, MD, and May Cho, MD, discuss the knowledge gaps commonly seen in liver cancer and how those gaps are impacting the clinical landscape and treatment decisions.
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[Dr. Cho]: I’m a big believer of prevention. Just like colonoscopy, we have a screening tool for hepatocellular carcinoma. I think that our primary care physicians, have to be aware of patients who have chronic liver disease and cirrhosis. And they have a guideline for every-6-month ultrasounds. The second one is education about these treatment options to multidisciplinary physicians. As we mentioned, this disease [often] has to be taken care by five or six different disciplinary. And there may be interventional radiology folks or surgeons that are not familiar with advancements in systemic therapy, they cannot incorporate in the armamentarium that we can use it for the patient. So I think the education about the overall treatment to this multidisciplinary physician, that's very important.
[Dr. Gong]: For educational gaps that can be studied and investigated upon to improve our management of advanced HCC, I think what's most important is that we also realize that there are very hard-working, busy community oncologists that may not be able to attend such conferences or, have the readily next available journal–publication of the New England Journal at their desk. So I think educational outreach is often very important and a very unmet need educational gap to address as well.
The Role of Biomarkers in HCC
The role of biomarkers in hepatocellular carcinoma (HCC) is poorly ...
understood, but recent advancements are investigating integration of biomarkers to inform the treatment of HCC. Here, Jun Gong, MD, and May Cho, MD, share their thoughts on the role of biomarkers in HCC.
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[Dr. Gong]: The role of the biomarker in management of HCC is poorly
understood. We were really limited in having alpha fetoprotein as our, really,
only biomarker we use. There’s only one agent that's approved for a
biomarker, AFP elevation level. In terms of do we routinely test for biomarkers?
I think that question could be expanded to doing profile, molecularly, of our
HCC tumor types. That is still an evolving field. I don’t think it's as mainstream
as some other tumor types that are more molecularly driven where you have to,
for the patient’s benefit, profile all tumors at diagnosis.
[Dr. Cho]: Yeah, so currently, in terms of biomarker [sic] in hepatocellular
carcinoma, we have, it’s AFP. We have one clinical trial that is defined by the
high level of AFP and then benefit to the anti-VEGFs. And but, you know, AFP,
just like all the, you know, biomarkers like CDA or CDA99, are not as sensitive
or as specific. So, we need to have more biomarker [sic] in this disease space.
[Dr. Gong]: I do think there are some trials that are seeking to integrate a
biomarker and advance our treatment, or systemic treatment of HCC. You have
some immunotherapy agents that now rely on a specific marker of-- to HCC to
help recruit T cells as a form of immunotherapy to deliver a new type of
systemic therapy. So I think this is one of the more exciting and eagerly looked upon types of agents and trial designs in advanced HCC integrating a
biomarker component of it.
The Link Between HCC Early Detection and Hepatitis B
There’s been debate that patients with hepatitis B virus and cirrhosis...
may have a chance for early detection of hepatocellular carcinoma (HCC). Here Jun Gong, MD, discusses the possible link between hepatitis and liver cancer.
Click to expand transcript
[Dr. Gong]: There’s been debate that perhaps hepatitis B virus and related cirrhosis patients may have a chance for an earlier detection, because then they get detected and they get placed on screening–allowing for earlier detection of hepatitis B and then prevention of cirrhosis and HCC in that sequence as well. And so there has been some debate that this subgroup of HCC patients may do a little bit better compared to some other causes of HCC.
Criteria for Transitioning From Locoregional Therapy to Systemic Therapy in Intermediate Stage HCC
When it comes to transitioning from locoregional therapy to systemic...
therapy in intermediate-stage hepatocellular carcinoma (HCC), there are varying philosophies. Here, Jun Gong, MD, and May Cho, MD, share their clinical perspectives.
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[Dr. Gong]: I believe actually in the BCLC-B or intermediate stage, this is where I think the multidisciplinary clinic is very important, because here you actually have a couple of options, not just systemic. Oftentimes with BCLC Stage C, it really comes tothe medical oncologist for systemic therapies and they’re no longer a candidate for surgery or locoregional therapies. And I think that's one broad stroke of how you can classify what separates the intermediate risk from the advanced stage, and when you decide when they need systemic therapy options. But in keeping with the intermediate stage, here, you know, international guidelines have historically recognized locoregional therapy, usually with TACE. TARE is another form that is growing in evidence.
[Dr. Cho]: Back in the day when we don't have a lot of systemic options, we were trying to TACE you know as many as we can, you know, to help the patients, right? So now, with these advancements of this systemic therapy, we are really defining the TACE refractoriness, you know? That's one.
[Dr. Cho]: For example, you know, after, two times of TACE and if this exists in the treated lesion doesn't have, you know, at least if they have 50% of the residual disease, that may be the time we need to transition to a systemic therapy. That's one of the ways we're trying to improve. 2) is, you know, even defining, you know, when we should be TACE-ing. So, you know, one of the criteria is up to seven criteria. So the maximum diameter of the lesion, plus how many—the number of the lesion, and, you know, what would be the best candidate for the TACE.
How Comorbidities in HCC May Impact Therapy
Hepatocellular carcinoma (HCC) may be complicated by the presence of...
comorbidities, which may affect liver function and limit treatment options. Here, Jun Gong, MD, and May Cho, MD, discuss comorbidities commonly observed among patients with HCC and how they may guide their treatment options.
Click to expand transcript
[Dr. Cho]: So when we decide for systemic therapy in terms of mechanism of
action, what you use for the patients, and like I said, it depends on how
much of a tumor burden the patient has, how much of liver function the
patient has. And the most important thing is the comorbidities the patients
has. If the patients have variceal bleeding, you know, often require
hospitalization and banding.
[Dr Gong]: So the major risk factors for HCC, as Dr. Cho had clarified,
always number one is cirrhosis, chronic liver disease, then you have some
common causes of cirrhosis. In the eastern part of the world that differs from
the western part of the world, for example. Eastern part of the world,
hepatitis B virus remains a major cause. Hepatitis C remains a major cause
in the western part of the world. But then you have some rising causes of
cirrhosis, such as nonalcoholic fatty liver disease and also alcoholic cirrhosis.
You also have some rare hereditary cases. And I do agree that sometimes
the etiology of the HCC can tailor your treatment for the HCC. It also
dictates what kind of providers will also be involved in this care as well. If
you have a hepatitis B patient, or C patient, you are, or need a new
treatment for antivirals for these disorders, a hepatologist will be involved.
With the nonalcoholic fatty liver disease, with the involvement of the
metabolic syndrome diabetes, obesity, insulin resistance, you’ll have a
multifaceted team of endocrinologists and primary care doctors involved in
having lifestyle modifications as well.
Unmet Needs in HCC
Despite substantial advances in the treatment of hepatocellular carcinoma...
(HCC), disparities persist among racial and ethnic minorities. Here, Jun Gong, MD, and May Cho, MD, discuss how limited biomarker data and continued racial inequalities contribute to unmet need in HCC.
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[Dr. Cho]: in terms of unmet needs in hepatocellular carcinoma is 1) we do not have any
biomarker to derive which sequence of the patient would be best suited for the patient.
So I think that, looking for biomarkers for these therapy selection will be important. 2)
is how to sequence all these armamentarium of the treatments. And 3), as we touch on
all of these systemic trials has been in Child-Pugh A and we have to move the needle
to the Child-Pugh B7 patients.
[Dr Gong]: I think some of the unmet needs that remain in HCC and also advanced HCC,
is that we also have some racial disparities that still exist in HCC, where although the
incidents for Hispanics are on the rise, you still have a lot of Black men and women with
HCC that often have the worst outcomes So actually, investigations into these
disparities and how to mitigate these disparities will remain a high unmet need in HCC.
And lastly, we've begun genomically profiling HCC, where we've been able to
understand that some of the more common molecular alterations include TERT, beta-1-
catenin, TP53, RB1 mutations in this advanced HCC and even all of HCC. But, as you
can tell, a lot of these targets are not druggable. So we know we have all this
knowledge, but we need to use it. And so I think this is another high unmet need to have
a more genomically-drlven therapy development in this population.
Hepatocellular Carcinoma | Colorectal Cancer
Colorectal cancer (CRC) was expected to be the third most common cancer diagnosis and third leading cause of cancer death in the United States in 2023.1 CRCs are classified into right- and left-sided on the basis of tumor origin. Right- vs left-sided tumors differ in histology, size, and genomic makeup, informing disease prognosis and response to treatment.2,3
Right-sided tumors originate from the ascending colon and proximal two-thirds of the transverse colon.2
Left-sided tumors originate from the descending and sigmoid colon, as well as the distal one-third of the transverse colon.2
Incidence in the United States
In the United States in 2023, CRC was estimated to represent ~8% of all new cancer cases,1 with an estimated 153,020 individuals expected to be diagnosed with CRC.1 CRC is more common in men, with an age-adjusted incidence rate of 43.4 per 100,000 men and 32.8 per 100,000 women (data from 2015-2019).4 An estimated 52,550 individuals were anticipated to die from CRC in 2023.1
Epidemiology in the United States
The median age at diagnosis is 66 years.4 Approximately 37% of patients have localized cancers, whereas the remaining patients present with regional (36%) or distant (22%) metastasis at diagnosis. The 5-year relative survival rate of patients with CRC is 65%; those with localized disease have a higher 5-year survival rate (91%) than do those with regional (73%) or distant (15%) metastasis (data from 2012-2018).4
Risk Factors
The greatest risk factor associated with CRC incidence is advanced age.5 Ninety percent of CRCs are diagnosed after age 50 years. Other potential risk factors include African American race, history of CRC in a first-degree relative (especially if before the age of 55 years), and inflammatory bowel disease.5
Unmet Need
The incidence of CRC is increasing in younger patients, but the disease is often not diagnosed until advanced stages.1 Because early-stage CRC does not typically cause symptoms, it is recommended that screening begin at age 45 years for patients at average risk of CRC.1
References: 1. American Cancer Society. Cancer Facts and Figures 2023. 2. Baran et al. Gastroenterology Res. 2018;11:264-273. 3. Mangone et al. BMC Public Health. 2021;21:906. 4. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Colorectal Cancer. https://seer.cancer.gov/statfacts/html/colorect.html. Accessed September 1, 2022. 5. National Cancer Institute. Colorectal Cancer Prevention (PDQ®)–Health Professional Version. https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq. Accessed September 1, 2022.
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