HCC: Is it an oncological disease? - No

Transcription

1 June 13-15, 2013 Berlin, Germany Prof. Oren Shibolet Head of the Liver Unit, Department of Gastroenterology Tel-Aviv Sourasky Medical Center and Tel-Aviv University HCC: Is it an oncological disease? - No Disclosure of Potential Conflict of Interest: Nothing to Disclose

2 HCC: is it an oncological disease? Oren Shibolet, M.D Liver Unit, Tel-Aviv Sourasky Medical Center 2

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4 HCC Lecture layout Introduction (2 minutes) HCC epidemiology (3 minutes) surveillance & prevention (3 minutes) Treatment (5 minutes) HCC is a liver disease (1 minute) Integrated approach (1 minute)

5 Pictures from my last debate

6 Oncology Oncology (from the Ancient Greek onkos (ὄγκος), meaning bulk, mass, or tumor, and the suffix -logy (-λογία), meaning "study of") is a branch of medicine that deals with cancer. 6

7 Oncology Oncology is concerned with: The diagnosis of any cancer in a person Administration of any therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) Follow-up of all cancer patients 7

8 Who do you think should treat hepatic cancer 8

9 Simple facts (1) Out of the first 100 pubmed articles on HCC, 83 were authored by hepatlologists, surgeons gastroenterologists & radiologists Only 17 were by onclogists

10 Simple facts(2) I asked 40 internal medicine, surgeons & family doctors if they had a cirrhotic patient with a liver mass who would they refer him to? Only 2 would refer him to an oncologist!!!

11 The BCLC staging system 11

12 Hepatocellular Carcinoma-facts (1) 700,000 cases/yr worldwide 6 th among cancers worldwide Leading cause of cancer-death Asia & Middle East 85% of HCC cases occur in Eastern and South-east Asia and Sub Saharan Africa Leading cause of death in cirrhotic patients

13 El-Serag H et al, Gastroenterology 2007 Mortality rates from HCC

14 Hepatocellular Carcinoma-facts (2) Most patients with HCC in have liver cirrhosis Hepatitis B virus is the most frequent underlying cause world wide In the US, HCV-related HCC is the most prevalent (50-70% of cases) Other risk factors include alcohol use, NAFLD, inherited liver disease, hemochromatosis 14

15 Aging HCV population and the risk of HCC Davis GL, Gastroenterology

16 Incidence of cirrhosis is increasing El-Serag HB, Gastroenterology

17 Where do HCC patients come from? Surveillance or Sporadic 17

18 Surveillance guidelines EASL-EORTC AASLD Llovet JM et al 2011 Bruix & Sherman 2010

19 Randomized controlled trial of screening for hepatocellular carcinoma 18,816 people, aged years with HBV or CLD. Randomly allocated to screening (9,373) or control (9,443). Screening group had AFP & US every 6 months. The primary outcome measure was HCC mortality. Zhang BH J Cancer Res Clin Oncol 2004

20 Effect of CLD treatment on HCC prevalence 20

21 Effect of SVR on HCC development Morgan TR et al, Hepatology 2011 Ogawa H et al, J Hep 2012

22 Effect of HBV vaccination on annual incidence of HCC in Alaska McMahon BJ et al, Hepatology 2011

23 Primary Prevention of HCC Vaccinate to HBV! Treat HCV with effective treatment Suppress HBV Abstain from alcohol Phlebotomize if pt has iron overload Weight loss

24 HCC treatment 24

25 The BCLC staging system 25

26 Level of Evidence 26

27 Liver Transplantation 27

28 HCC Transplantation outcome in the early 1990s Schwartz M. Gastroenterolgy 2004

29 Overall Survival (%) Overall Survival (%) Liver Transplantation for Small HCC: Milan Criteria Criteria Met Criteria Not Met Months After Transplantation Patients at Risk Criteria Met Criteria Not Met Months After Transplantation 24 8 P=0.01 by the Log-Rank Test 21 6 Patients at Risk Mazzafero, et al, NEJM 1996

30 Liver Transplantation for HCC Milan Criteria 1 lesion 5 cm 2 to 3, none > 3 cm + Absence of Macrovascular Invasion Absence of Extrahepatic Spread Mazzaferro et al, NEJM 1996

31 Liver Transplantation for HCC: Outcomes Applying Milan Criteria Authors N Selection Criteria Recurrence 5-yr Survival Mazzaferro (1996) 48 Single <5 cm 3 nodules <3 cm 8% 74% Bismuth (1999) 45 Single <3 cm 3 nodules <3 cm 11% 74% Llovet (1999) 79 Single <5 cm 4% 75% Jonas (2001) 120 Single <5 cm 3 nodules <3 cm 16% 71% Schwartz M. Gastroenterology. 2004;127(5 suppl 1):S268-S276.

32 Local Ablation Therapy 32

33 Trans-Arterial Chemoembolization TACE 33

34 Treatment of HCC: Chemoembolization Normal liver gets 75% of blood supply from portal vein and 25% of blood supply from hepatic artery Tumor Catheter placement for chemoembolization Tumor receives most of its blood supply from the hepatic artery Injection into the hepatic artery spares most of the normal liver Liver Portal vein Hepatic artery Embolization of the hepatic artery induces ischemic necrosis of tumor

35 TACE for HCC Meta-analysis of Six RCT (2-year survival) Llovet JM and Bruix J. Hepatology

36 Radiofrequency Ablation-RFA 36

37 Ablation of HCC Percutaneous ethanol injection (PEI) Cryotherapy Radiofrequency ablation (RFA)

38 RFA vs Percutaneous Ethanol Injection for HCC: a Meta-analysis Mortality rates Germani G et al J Hepatol 2010;52:

39 Systemic therapy 39

40 Survival probability SHARP: Median Overall Survival Sorafenib (n=299) Median: 10.7 mo Placebo (n=303) Median: 7.9 mo HR 0.69 (95% CI: ) P< Time from randomization (months) Llovet JM, et al. N Engl J Med. 2008;359(4):

41 Survival probability Asia-Pacific Study: Overall Survival Sorafenib Median: 6.5 mo (95% CI: ) Placebo Median: 4.2 mo (95% CI: ) HR (S/P): % CI: P= Months Patients at Risk Sorafenib Placebo Cheng A, et al. J Clin Oncol. 2008;26. Abstract Updated from oral presentation at ASCO; Chicago, IL; June 2008.

42 New Therapies Under Investigation Local Therapy Radiation Therapy 90 Yttrium microspheres (Therasphere/SIRsphere) Stereotactic RadioSurgery (Cyberknife) Doxorubicin Eluting Beads (DC Bead) Photoactive chemicals (Litx) * Sorafenib approved November 2007 Chemotherapy Sorafenib* (Nexavar) Erlotinib (Tarceva) Sirolimus (Rapamune) Capecitabine (Xeloda) Floxuridine (FUDR) Bevacizumab (Avastin) Sargramostim (Leukine) Oxaliplatin (Eloxatin) Imatinib (Gleevac)

43 What are the complications? Hepatic de-compensation!!! 43

44 Who would you want to treat those

45 Multi-disciplinary Management of HCC Guy J CGH

46 Staff Hepatocellular cancer center Dedicated MDs: Hepatologists Invasive Radiologists Oncologists Diagnostic Radiologists Hepato-Biliary& transplant surgeon Dedicated Skilled staff: Nurses Center coordinator Secretary Hepatocellular cancer center shared Facilities Shared MDs: Internists Pathologists (other specialists as needed-cardiologists, surgeons, dermatologists) Shared skilled staff: Social workers Nutritionists Shared Dedicated out Patient Unit Invasive radiology -Inpatient Wards Pathology Lab Internal Medicine Ambulatory Chemo Surgery &radiation Oncology

47 Summary HCC is managed most of the time by hepatologists/gastroenterologists The best approach is a MDT headed by a hepatologist As treatment advances different disciplines may become more involved.

48 Thank You For Your Attention 48