간암의다양한병기분류법 : 현재사용중인병기분류를중심으로. Kim, Beom Kyung

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1 간암의다양한병기분류법 : 현재사용중인병기분류를중심으로 Kim, Beom Kyung

2 Importance of staging system 환자의예후예측 적절한치료방법적용 ( 수술, 방사선, 항암..) 의료진간의 tumor burden 에대한적절한의사소통 향후연구및 clinical trial 시연구집단의성격에대한객관적기준제시

3 Requisites for good staging system from the statistical aspects Homogeneity; small differences in survival among patients at the same stage within each system) Discriminatory ability; greater differences in survival among patients at different stages within each system Monotonicity of gradients; longer survival of patients at earlier stages than of patients at more advanced stages within the same system.

4 Requisites for good staging system from the statistical aspects

5 Tumor factor Common elements of staging systems of HCC Size, number, volume, vascular (portal) invasion, metastasis, tumor maker (AFP etc.) Underlying liver function Albumin, bilirubin, alkaline phosphatase, ascites, fibrosis, Child-Turcotte-Pugh class, MELD score General Status ECOG PS, Karnofsky PS scale

6 Diverse staging systems for HCC Okuda, CLIP, BCLC, CUPI, JIS, Tokyo, TIS, BALAD, HKLC, ITALICA TNM (modified UICC, AJCC, UNOS staging system)

7 Okuda system The first systematic staging system including both tumor factor and liver function. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Cancer 1985;56:

8 The Cancer of the Liver Italian Program (CLIP) score In one study, median survival was 36, 22, 9, 7, and 3 months for patients in CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. THE CANCER OF THE LIVER ITALIAN PROGRAM (CLIP)INVESTIGATORS. Hepatology Sep;28(3):751-5.

9 Chinese University Prognostic Index (CUPI) Leung et al. Cancer Mar 15;94(6):

10 Barcelona Clinic Liver Cancer (BCLC) stage BCLC staging system is used as treatment algorithm Llovet JM et al. J Natl Cancer Inst. 2008;100(10):

11 Derivatives from BCLC staging system 이식적응증확대 ( up-to-seven criteria ) Down-staging surgery 언급 Radio-embolization 언급 Early sorafenib use 언급 Bolondi et al. Semin Liver Dis Nov;32(4):

12 Derivatives from BCLC staging system (from Asan medical center) Ha et al. J Gastroenterol Hepatol Apr;29(4):787-93

13 Derivatives of BCLC staging system (from Korean HCC registry data) Lee et al. J Gastroenterol Hepatol Apr;31(4):842-7.

14 Japan Integrated Score (JIS) 우리나라에서적용되는 TNM staging (muicc) Kudo et al. J Gastroenterol 2003; 38:

15 Tokyo score Constructed and validated in patients who underwent local ablation therapy and hepatectomy Not for advanced HCC Tateishi et al. Gut Mar;54(3):

16 Taipei Integrated Scoring (TIS) system Hsu et al. J Hepatol Jul;53(1):

17 Bilirubin, Albumin, Lens culinaris agglutinin A reactive fraction of alfa-fetoprotein, Alfa-fetoprotein, and Desgamma-carboxy prothrombin (BALAD) score Stage can be evaluated with the use of only 1 serum sample. Toyoda et al. Clin Gastroenterol Hepatol Dec;4(12):

18 Recently developed staging system

19 Hong Kong Liver Cancer staging Intrahepatic VI: intrahepatic portal vein branch invasion, left or right portal vein invasion (Vp1~3), and main hepatic vein invasion Extrahepatic VI: main portal vein invasion (Vp4) and IVC invasion Yau et al. Gastroenterology Jun;146(7):

20 Hong Kong Liver Cancer staging Yau et al. Gastroenterology Jun;146(7):

21 Hong Kong Liver Cancer staging Yau et al. Gastroenterology Jun;146(7):

22 the American Joint Committee on Cancer (AJCC) 8 th edition Amin et al. CA Cancer J Clin 2017;67:93 99.

23 the American Joint Committee on Cancer (AJCC) 8 th edition Staging system based upon surgical specimens Concept of micro-vascular invasion Definition of major vascular invasion on imaging Vp 3, 4 Invasion of right, middle, or lef HV Invasion of right or left HA

24 the Italian Liver Cancer (ITA.LI.CA) staging and scoring system Borzio et al. Hepatology Nov 22. Farinati et al. PLoS Med Apr 26;13(4):e

25 BCLC guideline 을더이상추천하지않음. TNM staging 을언급하고있으나 AJCC, UICC 를특정하지는않음. UNOS TNM stage

26 Interpretation of staging system in real clinical practice

27 Understanding of differences in patients selection and intended use To evaluate the prognosis in untreated HCC; Okuda staging For HCC cases undergoing resection; AJCC TNM staging For HCC cases undergoing curative treatment Tokyo score, TIS score All HCC patients CLIP score, BCLC stage, JIS score,balad score To choose adequate treatment; BCLC, HKLC stage

28 Best staging system may vary according to patients background and treatment Patients background and prognosis are different among regions (countries). The suitable staging system may be different according to the treatment and its types. Many staging systems were proposed with good performances in published articles. However, there still is no consensus what is the best one.

29 Example of Same score, but different prognosis! Lin et al. Liver Int Jan;29(1):74-81.

30 Future perspectives To Include new prognostic factors in staging system New tumor maker New serum maker : VEGF Gene expression (micro-array)

31 Application of staging system Know the characteristics of each staging system. Select adequate staging system which meets your purpose. To choose treatment for your patients. To estimate prognosis after any treatment. To choose patients who meets a clinical trial.

32 Summary So far, many HCC staging systems has been proposed. There are some differences of ingredients and subjects in each staging system. Most HCC staging systems include tumor factors and liver function. Incorporation of detailed vascular invasion depth and biomarker become more important. So, recently developed staging system can provide more delicate prognostification.

33 Summary However, too complex system might be paradoxically impractical for clinicians, despite its better performance in statistical aspects. The features of each staging system should be understood and proper system should be used for adequate purpose and patients.

34 감사합니다.