Updates in Hepatocellular Carcinoma - Michigan Cancer · 2019. 11. 5. · Updates in Hepatocellular Carcinoma These slides are the property of the presenter. Do not duplicate without

Updates in Hepatocellular Carcinoma

These slides are the property of the presenter. Do not duplicate without permission.

The Global Impact of Liver Cancer

Akinyemiju T, et al. JAMA Oncol 2017.EASL CPG; J Hepatol 2018.


Incidence in the U.S.

White DL, et al. Gastro 2017.


Malignant Transformation

Normal liver

Liver cirrhosis

Hepatitis CHepatitis B

EthanolNASH

Epigenetic alterationsGenetic alterations

HCC[2]

Dysplastic nodules[1]

1. Tornillo L, et al. Lab Invest. 2002;82:547-553. 2. Verslype C, et al. AASLD 2007.


Incidence of HCC is rising

www.seer.cancer.gov


HCC Mortality from 1990-2015…

Fitzmaurice, et al. JAMA Oncol 2017.


High Mortality Rates in HCC

Khalaf N, et al. CGH 2016.

518 untreated patients: survival stratified by stage


HCC Risk Factors

El Serag HB. Gastro 2007, Bruix J. Hepatology 2010. Collier J. Hepatology 1998. Marrero JA. J Hepatol 2005.


Alcohol and HCC risk

Donato F, et al. Am J Epid 2002.


NAFLD and HCC risk

Kanwal F, et al. Gastro 2018.


HCC preventive interventions


Modifying HCC risk

Singal AG. Clin Gastro Hep 2010. Nishiguchi S. Lancet 1995. Valla DC. Hepatology 1999. Lok AS. Gastro 2011.


Impact of Universal Vaccination in Taiwan

Chang MH. NEJM 1997


Hep B viral load and HCC incidence

Chen CJ. JAMA 2006.

REVEAL Study (n=3,653)

10

6

4

2

0

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Cu

mu

lati

ve

inci

den

ce o

f H

CC

(% s

ub

ject

s)

12

8

Baseline HBV DNA level, copies/mL

≥106 (n=627)

105–<106 (n=349)

104–<105 (n=643)

300–<104 (n=1,161)

<300 (n=873)

Log rank test of trend

p<0.001

14.9%

12.2%

3.6%

1.4%1.3%

Year of follow-up


Antiviral Therapy in Hepatitis BP

ati

en

ts w

ith

dis

ease

pro

gre

ss

ion

(%

)

Time to disease progression (months)

“Proof of Principle”

LiawY-F et al. N Engl J Med. 2004;351:1521-1531.

Lamivudine (n=436)

Placebo (n=215)

P=0.001

21%

9%

25

20

15

10

5

0

30181260 36

n=198

n=173

n=417

n=385

n=43

n=122

24


HCV treatment reduces HCC risk

Kanwal, et al. Gastro 2017.

• SVR vs no SVR (0.90 vs 3.45 HCC/100 person-years; HR 0.28)• Cirrhosis + SVR vs. no Cirrhosis + SVR (1.82 vs 0.34/100 person-years; HR 4.73)


Surveillance for HCC

El-Serag HB. Gut 2011. Trevisani F. Am J Gastro 2002.


Surveillance improves early stage diagnosis

Singal, et al. PLoS Med 2014.


Surveillance for HCC Reduces MortalityA Randomized Controlled Trial

Zhang BH. J Cancer Res Clin Oncol 2004.

Time (Years)

Su

rviv

al P

rob

abili

ty (%

)

0 1 2 3 4 50

.8

.6

.2

.4

Screening

Control

HCC-related mortality reduced by 37%


Surveillance improves survival in cirrhosis

Singal, et al. PLoS Med 2014.



• Ultrasound every 6 months

• AFP with US increases sensitivity to 63.4% (clinical practice)

Bruix J, Sherman M. Hepatology 2010.Singal AG. AP&T 2009. Singal AG. Canc Epid Bio Prev 2012. Marrero JA. Gastro 2009.



Hepatology, 68(2), 2018


Surveillance rates for HCC

Singal AG. J Gen Int Med 2012.

Pooled meta-analysis: <20% surveillance rates for cirrhotic patients


PCP reported barriers to surveillance

Provider-reported Barriers Percent

Lack of knowledge about guidelines 68.2%

Competing interests in clinic 51.6%

Lack of time in clinic 41.5%

Difficulty recognizing at-risk patients 35.4%

Ultrasound capacity 23.0%

Doubt patients will complete 9.3%

Dalton-Fitzgerald, et al. CGH 2015.


Diagnosing HCC


• Vascular supply of HCC arises from the hepatic artery through neovascularization.

• Multi-phase imaging is key

• Radiological hallmark: arterial hypervascularity with washout in the venous/delayed phase

Yu JS. Am J Roentgenol 1999


Pre-contrast Arterial Phase Portal Venous/ Delayed

HCC Diagnosis


Arterial phase 2-min delayed

5-min delayedArterial phase

Washout in HCCWashout in HCC


Marrero, et al. Hepatology 2018.


30

HCC StagingPatient

TumorLiver

ECOG

PS

Child-

PughTNM

BCLC

• Staging is used for prognosis and to guide treatment

• Factors affecting staging systems

– Tumor stage

– Liver function

– Functional status

• Links stage with treatment options and prognosis

1. Llovet JM. Gastroenterol. 2005;40:225-235; 2. Marrero JA, et al. Clin Liver Dis. 2006;10:339-351; 3. Bruix J, et al. J Hepatol. 2001;35:421-430;

4. Llovet JM, et al. Semin Liver Dis. 1999;19:329-338; 5. Chevret S, et al. J Hepatol. 1999;31:133-141; 6. Schafer DF, et al. Lancet. 1999;353:1253-1257;

7. Leung T, et al. Cancer. 2002;94:1760-1769; 8. CLIP. Hepatology. 1998;28:751-755; 9. Makuuchi M, et al. World J Gastroenterol. 2006;12:828-829.


BCLC Staging System

Marrero JA. Hepatology 2005

100

Su

rviv

al P

rob

abili

ty 80

60

40

20

0

0 10 20 30 40 50 60 70

Log Rank PA vs. B P < .0001B vs. C P = .04C vs. D P = .01

A

B

CD

Time (Months)

BCLC Staging System

HCC Staging

• BCLC was best predictor of survival

• Homogeneity in survival across each stage

• Validated BCLC compared to other staging systems


Barcelona Staging

Marrero, et al. Hepatology 2018.


Bruix J, Sherman M. J Hepatol 2011.

HCC Staging & Prognosis


Treatment of Early Stage HCC

EASL CPG. J Hep 2018.


Outcome of Surgical Resection for HCC in Cirrhosis

Llovet JM. Hepatology 1999.

Patients with a single tumor <= 5 cm and Child A cirrhosis

Months

00

Pro

bab

ility

(%)

12 24 36 48

20

100

40

60

80

Log Rank 0.00001

60 72 84 96

Nl portal pressure, Bili <1

Portal pressure, Bili <1

Portal pressure, Bili 1

*Other surrogates for portal htn =

HVPG ≥ 10mmHg ; plt <100


Four -Year Survival

0

10

20

30

40

50

60

70

80

Unselected 1991 Milan Criteria Other Dx

40%

75% 76%

%

Surviving

Mazzafero V. NEJM 1996.

Liver Transplant for HCC


Intermediate HCC (Stage B)


Chemoembolization

Prolongs 2-yr survival: 63% vs. 27% for best supportive care (p<0.001)

Llovet JM. Lancet 2002.


Radioembolization with Yttrium (Y90) microspheres in HCC (TARE)

Kulik LM. Hepatology. 2008. Salem R. Gastro 2010. Hilgard P. Hepatology 2010. Sangro B. Dig Dis 2009.


TARE likely has a role for Intermediate Stage HCC

Salem et al. Gastro 2016.


Advanced HCC (Stage C)


SHARP: Overall Survival Sorafenib

Sorafenib median:46.3 weeks (10.7 months)(95% CI, 40.9-57.9)

Placebo median: 34.4 weeks (7.9 months) (95% CI, 29.4-39.4)

Llovet JM et al. NEJM 2008.


SHARP results

Llovet JM et al. NEJM 2008.


Subsequent negative HCC trials…


Lenvatinib is non-inferior to Sorafenib

Kudo et al. Lancet 2018.


Current treatment landscape…


Henry Ford HCC: Multidisciplinary Approach

Radiation

Oncology

Pathology

Oncology

Radiology

Hepatobiliary

Surgery

Hepatology


Conclusion – Key Learnings


Documents

Updates in Hepatocellular Carcinoma - Michigan Cancer · 2019. 11. 5. · Updates in Hepatocellular Carcinoma These slides are the property of the presenter. Do not duplicate without