Epidemiology & First option of treatment

1. Epidemiology & First option of treatment Do Young Kim Department of Internal Medicine, Yonsei University College of Medicine

2. Epidemiology

3. High HCC incidence in Eastern Asia Source: GLOBOCAN 2008

4. Top 10 Cancer incidence in Korea: 2012

5. HCC; incidence and prevalence Source: 2012 National Cancer Statistics(2014)

6. Trend of age-standardized incidence of HCC (1999-2012)

7. Trends of incidence and mortality in HCC (Age-standardized) Source: National Cancer Statistics(2013)

8. 5-year survival rates of major cancers in Korea Stomach Lung Colon Liver Thyroid Breast Ut.Cx Biliary Pancreas Prostate

9. Korean nationwide HCC registry data

10. Courtesy of Dr. Lim YS

11. Methods * Exclusions formiss-Dx, duplication, miss-data Courtesy of Dr. Lim YS

12. HCC characteristics - Age & Gender- P = 0.41 % 100 80 Female 60 Male 40 20 0 Random Voluntary Courtesy of Dr. Lim YS

13. Liver function & Tumor stage • TNM Stage (UICC v.6) • Child-Pugh Class P<0.001 P<0.001 100% 100% 80% 80% IV 60% 60% C III B II A I 40% 40% 20% 20% 0% 0% Random Voluntary Random Voluntary Courtesy of Dr. Lim YS

14. Cause & Treatment • First Treatment • Associated Disease P<0.001 P<0.001 100% 100% 80% 80% Systemic Tx EBRT Others 60% 60% Transarterial Tx Alcohol Local Ablation HCV 40% 40% LT HBV Resection 20% 20% 0% 0% Random Voluntary Random Voluntary Courtesy of Dr. Lim YS

15. Overall survival Voluntary Reporting (median surv. 29 mo.) % 100 Random Statutory (median surv. 17 mo.) 80 66.6% 53.6% 60 44.6% 54.9% Survival 38.6% 32.9% 40 42.5% 35.0% 31.1% 29.6% P<0.001 20 0 0 1 2 3 4 5 Years after Diagnosis Courtesy of Dr. Lim YS

16. First option of treatment

17. HCC Stage 0PST 0, Child–Pugh A Stage A–CPST0–2,Child–PughA–B Stage DPST > 2, Child–Pugh C Very early stage (0) 1 HCC < 2 cmCarcinoma in situ Early stage (A) 1 HCC or 3 nodules< 3 cm, PST 0 Intermediate stage (B) Multinodular,PST 0 Advanced stage (C) Portal invasion, N1, M1, PST 1–2 End stage (D) 1 HCC 3 nodules ≤ 3 cm Increased Associated diseases Normal No Yes Resection Liver transplantation RFA TACE Sorafenib Symptomatictreatment (20%) Survival < 3 months Curative treatments (30%) 5-year survival 40–70% Palliative treatments (50%) Median survival 11–20 months HCC staging: AASLD guidelines (updated 2010) Portal pressure/bilirubin Adapted from Bruix J, Sherman M. Hepatology. 2010.http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf. Llovet JM, et al. J Natl Cancer Inst. 2008;100:698–711. AASLD = American Association for the Study of Liver Diseases; PEI = percutaneous ethanol injection; PST = Performance Status test; RFA = radiofrequency ablation.

18. HCC Confined to the liver Main portal vein patent Extrahepatic metastasis Main portal vein tumor thrombus Resectable Child–Pugh A/B Child–Pugh C Yes No Solitary tumor ≤ 5 cm ≤ 3 tumors ≤ 3 cm No venous invasion Tumor > 5 cm > 3 tumors Invasion of hepatic/portal vein branches Resection/RFA (for < 3 cm HCC) Child–Pugh A Child–Pugh B Child–Pugh C Child–Pugh A/B Child–Pugh C Local ablation Transplantation TACE Supportive care APASL guidelines Sorafenib or systemic therapy trial APASL recommendations on HCC. Omata M, et al. Hepatol Int. 2010;4:439–74.

19. Japan Society of Hepatology:consensus-based treatment algorithm for HCC HCC Extrahepatic spread No Yes Child–Pugh A/B Child–Pugh B/C Liver function Child–Pugh C Child–Pugh A Vessel invasion No Yes No Yes Number 1–3 4 or more Single Within Milan criteria and age ≤ 65 Within Milan criteria and age ≤ 65 Exceeding Milan criteria or age > 65 Hypovascular early HCC Size ≤ 3 cm > 3 cm Intensive follow-up Ablation Resection Ablation Resection TACE (TACE + ablation) Sorafenib HAIC TACE Resection Transplantation (TACE/ablation for Child–Pugh C patients) Palliative care Sorafenib TACEHAIC (resection + ablation) Transplantation (TACE/ablation for Child–Pugh C patients) Treatment Sorafenib (TACE refractory) TAI = hepatic arterial infusion chemotherapy. Kudo M, et al. Dig Dis. 2011;29:339–364.

20. First-line treatment option in each mUICC stage

21. Single, less than 2cm HCC, Child-A, no or minimal portal hypertension (BCLC-0) Resection vs. RFA; many studies LT?

22. Single, more than 2cm HCC (BCLC-A) In case within Milan criteria

23. Multiple, less than 2cm HCC (BCLC-A or B) In case above Milan criteria

24. Single, less than 2cm HCC with vascular invasion (BCLC-C) According to Western guidelines Unusual presentation. Practically TACE preferred, Resection vs. TACE?

25. Multiple, more than 2cm HCC (BCLC-B or A) Mostly TACE, LT or RFA: limitedly applied

26. Hong Kong Liver Cancer (HKLC) classification Yau T, et al. Gastroenterology 2014

27. Single, more than 2cm HCC with vascular invasion (BCLC-C) Which modality is the best for this kind of HCC? No data

28. Multiple, less than 2cm HCC with vascular invasion (BCLC-C) Resection TACE may be preferred because of small tumor size

29. Advanced HCC without extrahepatic spread (BCLC-C) Only sorafenib has evidence.

30. Competitor (I)

31. Competitor (II)

32. Competitor (III) Gastroenterology 2010

33. HCC with extrahepatic spread (BCLC-C)

34. Conclusions • HCC incidence in Korea is slightly decreasing. • Still a major cancer related with significant mortality • Prognosis is being improved due to proper management • Selection of first treatment option does not always depend on evidence. • Guideline are just guidelines. • Heterogeneity of HCC presentation makes it difficult to keep algorithm for selecting treatment option.

35. Thank you for attention