STOP Hepatocellular Carcinoma

Transcription

1 STOP Hepatocellular Carcinoma Laura Tenner MD MPH, Amit G. Singal MD MS, Mamta Jain MD, Barbara Turner MD, Barbara Riske MS ReACH Center and Dept of Medicine UT Health San Antonio Dept of Medicine UT Southwestern Medical Center Dallas

2 Overview Hepatocellular Carcinoma (HCC) epidemiology Focus on Texas Risk factors for developing HCC Focus on HCV Value of screening and prevention Treatment options Focus on opportunities if early stage

3 Epidemiology of HCC

4 HCC Worldwide Sixth most prevalent cancer; 2nd leading cause of cancer-related deaths; mortality rate close to incidence rate

5 Liver Cancer and HCC in U.S. Estimated new cases and deaths from liver and intrahepatic bile duct cancer nationally New cases: 35,660 Deaths: 24,550 HCC is the most common type of primary liver cancer American Cancer Society: Cancer Facts and Figures Atlanta, Ga: American Cancer Society, 2015.Available online Exit Disclaimer. Last accessed July 1, 2015.

6 Incident of HCC in the US,

7 U.S. (SEER) Incidence of Liver and Bile Duct Cancer

8 U.S. Incidence Rates by Age

9 U.S. Incidence Rates by Sex

10 U.S. Death from Liver/Bile Duct Cancer

11 U.S. Incidence and Deaths for HCC/Bile Duct Cancer

12 5 Year Survival Liver/Bile Duct Cancer

13 U.S. Survival by Stage of Disease

14 Liver Cancer Fastest Growing Cancer-related Death Rate in the US Trends in US Cancer Mortality Rates All Other Cancers (Average) Corpus & Uterus, NOS Testis Lung & Bronchus (Female) Esophagus Thyroid Liver Annual Percent Change ( )* National Cancer Institute Website. Available at:

15 National Trends Overall cancer death rates decreased during by: o An average of 1.8 percent per year for men. o An average of 1.4 percent per year for women. o Liver and Bile duct cancer death rates increased in both men and women

16 HCC in Texas

17 Mortality from Liver Cancer in US 2014 Mokdad AH, Dwyer-Lindgren L, Fitzmaurice C, et al. Trends and Patterns of Disparities in Cancer Mortality Among US Counties, JAMA. 2017;317(4): doi: /jama

18 Texas HCC Incidence Doubled in the Past 15 Years

19 HCC in Texas Texas HCC mean incidence 9.3/100,000 persons: 2 nd highest in U.S. National mean incidence is 7.9/100,000 2,000 new cases in Texas this year Incidence in Dallas county is 11.7/100,000 Incidence in South Texas as high as 19.1/100,000

20 Risk Factors for HCC

21 Risk Factors for HCC Cirrhosis from any etiology Viral hepatitis (Hepatitis B and/or C) Nonalcoholic fatty liver disease (Obesity and Diabetes) Heavy alcohol use Hereditary hemochromatosis Environmental toxins Aflatoxin, contaminated drinking water, betel nut chewing

22 Trends in HCC Etiology ~50% increase in HCV-related HCC between Others: 21% Others: 38% Others: 46% HBV: 4% NAFLD: 11% HBV:10% NAFLD:7% HBV: 4% Alcohol alone: 25% Alcohol alone: 19% Alcohol and HCV: 17% Alcohol alone: 45% Alcohol and HCV: 7% HCV alone: 18% HCV alone: 28% Yang JD, et al. Mayo Clin Proc. 2012;87:9-16.

23 El-Serag HB, Rudolph KL Gastroenterology 2007: 132:

24 HCC Risk Factors Prevalence in general population Risk estimate of HCC Current prevalence in HCC cases Population attributable fraction HBV 0.5-1% % 5-10% HCV 1-2% % 20-25% Alcoholic liver disease Metabolic syndrome 10-15% % 20-30% 30-40% % 30-40% El-Serag HB, Rudolph KL Gastroenterology 2007: 132:

25 HCV infection and HCC

26 HCV 4x as prevalent as HIV and HBV in U.S. Total No. Infected (millions) Million 21% unaware of infection HIV Undiagnosed Diagnosed ~800,000 to 1.4 Million 65% unaware of infection HBV 3 to 5 Million up to 75% unaware of Infection HCV Chak E, et al. Liver Int. 2011;31(8):

27 Time from HCV infection until serious complications

28 Chronic HCV in Texas In 2000, nearly 400,000 Texans (1.79%) were estimated to be chronically HCV-infected There is a 17 fold higher risk of developing HCC in HCV-infected individuals Yalamanchili K. Proc (Bayl Univ Med Cent) Jan; 18(1): 3 6.

29 US Preventive Services Task Force (USPSTF) Guidelines One time screening of all baby boomers (born 1945 through 1965) for HCV infection (USPSTF Rating: Class I, Level B) Reflects evidence that newer highly effective anti-hcv drugs can cure HCV infection and, in many cases, prevent serious complications of disease Photo source: Centers for Disease Control and Prevention

30 Reflects high incidence in past 2 of 3 Americans infected with HCV from x higher prevalence than other birth cohorts (3.4 vs. 0.5%) 81% of HCV infected adults and 73% of HCV mortality Smith et al MMWR 2012; 61(RR04): 1-18 Rein et al Ann Int. Med 2012; 156(4):

31 Other Risk Factors for HCC

32 Diabetes and HCC: Meta-analysis Chen J et al Eur J Cancer Prev Mar;24(2):89-99.

33 Obesity (BMI >35) Increases Risk of Death from Liver Cancer (Men in a Prospective U.S. Cohort) Calle EE et al. N Engl J Med, 2003;348:

34 Obesity-related non-alcoholic liver disease and HCV The combination of NAFLD and HCV worsens fibrosis progression and increases risk of developing HCC even further

35 Obesity Prevalence 2014 High obesity prevalence in Texas and other southern states likely increases risk of HCC even further /data/prevalencemaps.html

36 Alcohol and HCC NIH-American Association of Retired Persons Diet and Health Study (N=494,743) Persson EC et al. Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev. 2013;22(3):

37 HCC Prognosis and Treatment

38 Why Is HCC So Deadly? Cirrhosis is often not diagnosed Rarely produces symptoms until advanced stage Most are diagnosed late often multifocal invades blood vessels spreads lymphatically and hematogenously Stage Prevalence 5 yr Survival Localized 42% 30.5% Regional 28% 10.7% Distant 18% 3.1%

39 Treatment for HCC Can Be Effective if Early Stage AASLD Guidelines Bruix et al. Hepatology 2011

40 Treatment for HCC Can Be Effective if Early Stage AASLD Guidelines Bruix et al. Hepatology 2011

41 Sorafenib: Overall Survivability Sorafenib median overall survival of 6.5 months compared with 4.2 months in the placebo arm HR 0.68, p=0.014 Cheng, Ann-Lii, et al. "Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, doubleblind, placebo-controlled trial." The lancet oncology 10.1 (2009):

42 Sorafenib: Symptom Free Progression There was no meaningful significant difference for Time To Symptom Progression (TTSP) Sorafenib 3.5 mo Placebo 3.4 mo Cheng, Ann-Lii, et al. "Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, doubleblind, placebo-controlled trial." The lancet oncology 10.1 (2009):

43 New Treatments for HCC Immunotherapy: Checkmate % Response Rate 4.3mo Median duration of Stable disease No Overall Survival data Regorafenib: Resource 10.6mo versus 7.8mo (HR 0.63) Bruix et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389(10064): p Jan 2017

44 HCC Screening

45 Guidelines 2010 American Association for the Study of Liver Diseases (AASLD) guideline Liver ultrasound every 6 months

46 Patients for Whom Surveillance Is Recommended Cirrhosis from any etiology (represents > 80% of HCC patients in the US) Hepatitis C Alcohol-related cirrhosis Non-alcoholic steatohepatitis Hepatitis B Other causes: Hemochromatosis, primary biliary cirrhosis, alpha-1 antitrypsin, etc Bruix J, et al. Hepatology 2010 Simonetti RS, et al. Dig Dis Sci. 1991

47 HCC Surveillance Associated with Improved Survival in Patients with Cirrhosis 2010 American Association for the Study of Liver Diseases (AASLD) guideline = liver ultrasound every 6 months Author Lead Time Survival Rates Significance El-Serag days Median survival 298 vs. 130 days OR 0.81 (95%CI ) Tong days 3-year survival 62.5% vs. 36.6% p=0.007 Wong days 2-year survival 49.4% vs. 28.6% p=0.035 Tanaka days Median survival 6.3 vs. 5.3 years p=0.016 Trevisani days Median survival 30 vs. 20 months p<0.001 Singal et al PLOS Medicine 2014

48 Impact of Screening on Stage of HCC at Time of Diagnosis

49 Impact of Screening on Survival

50 Low Surveillance Rates for HCC Singal AG et al. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med Jul;27(7):861-7

51 HCC Prevention

52 Ways to Reduce Risk for HCC Advise Patients to: What do we do about HCV? Avoid alcohol or drink in moderation Get immunized for Hepatitis B virus Weight loss and exercise We now have a CURE! Sofosbuvir/Simeprevir Sofosbuvir/Ledipasvir Paritaprevir/r, Ombitasvir, Dasabuvir

53 Reducing HCV burden remains the highest yield target to reduce HCC incidence in TX.

54 Curing HCV Reduces the Risk of HCC Non-SVR Non-SVR SVR SVR For patients with cirrhosis, continue screening even after cured Ashahina et al., Hepatology 2010

55 Guidelines: High Risk Groups to Screen for HCV Unexplained chronic liver disease or high ALT Injection-drug use (even once) or intranasal drug abuse Ever in jail Long-term hemodialysis (ever) Transfusions or organ transplants: before July 1992 or clotting factor given before 1987, HCV+ transfusion Tattoo in an unregulated setting Children born to HCV-infected women Healthcare/public safety workers exposed to HCV+ blood HIV infection Born in a high risk country

56 Baby Boomers (Born ) Account for 76.5% of HCV in the US 1 Estimated Prevalence by Age Group 2 Number with chronic HCV (millions) < s 1930s 1940s 1950s 1960s 1970s 1980s Birth Year Group An estimated 35% of undiagnosed baby boomers with HCV currently have advanced fibrosis (F3-F4; bridging fibrosis to cirrhosis) 3 CDC. MMWR. 2012;61:1-32; Adapted from Pyenson B, et al. Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer Epidemic of Liver Disease. New York, NY: Milliman, Inc; May 18,

57 Risk-Based Screening is NOT Enough

58 USPSTF and CDC New Recommendation In addition to screening individuals with high risk behavior for HCV, a one time HCV screening is recommended for all persons born between 1945 and 1965 (baby boomers).

59 Fighting HCC in Texas!

60 Liver cancer: fastest growing death rate of cancers in U.S. Texas has the 2 nd highest prevalence of HCC Texas has high prevalence of risk factors for HCC including HCV, infection, and obesity New USPTSF and CDC guidelines recommend universal screening of baby boomers born for HCV Early detection and treatment of HCV can decrease the incidence of cirrhosis and HCC

61 Acknowledgements TexasHepCA

62 Thank you for your attention!