1. K Nouso, K Miyahara, D Uchida, K Kuwaki, N Izumi, M Omata, T Ichida, M Kudo, Y Ku, N Kokudo, M Sakamoto, O Nakashima, T Takayama, O Matsui, Y Matsuyama, K Yamamoto and the Liver Cancer Study Group of Japan British Journal of Cancer (2013), 1–4 소화기내과 R3 양 인 호 1

2. Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide Although screening patients with chronic liver disease, many HCCs are detected at an advanced stage 2

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4. Background Several other therapies have been evaluated - hepatic arterial infusion of 5-fluorouracil (5-FU) and cisplatin (HAIC) : most common regimen in Japan Purpose - large-scale retrospective study - determine the efficacy of arterial infusion therapy with 5-FU and cisplatin for advanced HCC 4

5. Materials and Methods Jan 2000 to Dec 2005 62315 pts with primary liver cancer newly registered by LCSGJ (-> biannually f/u) 5

6. 57445 HCC were registered 31743 HCC with complete data 10114 underwent surgical resection 9577 underwent local ablation therapies 9283 underwent TACE 1150 underwent chemotherapy 827 received other treatments such as radiation therapy 476 underwent continuous arterial infusion of 5-FU and CDDP* 674 underwent other chemotherapy 25702 were excluded due to insufficient data 1466 received no active therapy* Supplementary Figure 1. Flow of participants into the study. Survival of two groups with asterisk were co mpared. HCC, hepatocellular carcinoma; TACE, transcatheter arterial chemoembolization; 5-FU, 5-fluoro uracil; CDDP, cisplatin.

7. Materials and Methods Diagnosis of HCC - CT (1579, 81.3%), MR (257, 13.2%) US (1167, 60.1%), angiography (360, 18.5%), histology (87, 4.5%) Treatment effect 7

8. Statistical analysis Comparison of continuous variables : t-test Comparison of categorical variables : χ 2 test Estimation of surivival : Kaplan-Meier method -> comparison : log-rank test Univariate and multivariate analyses of primary cohort : Cox proportional hazard model Determination of the efficacy : propensity score matching analysis 8

9. RESULTS 9

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11. 1yr survival rate3 yr survival rate CR (n=19, 4.0%) 77.7%34.6% PR (n=129, 27.2%) SD (n=112, 23.6%)44.2%13.3% PD (n=41, 8.7%)23.7%10.3% 11 P<0.0001

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14. Survival Rate Months after diagnosis Patients at risk HAIC No therapy 18581 3918116 3 18538 171064 2 HAIC No therapy Supplemantary Figure 3. Survival of propensity score-matched patients with Child-Pugh A/B disease and more than three tumors. Patients who underwent hepatic arterial infusion of 5-fluorouracil and ci splatin (HAIC) or no active therapy (no therapy) were compared. Median survival times were 13.9 m onths (HAIC) and 3.7 months (no therapy) (P<.0001).

15. Months after diagnosis Survival Rate Patients at risk HAIC No therapy 18957 19841 18929 10743 3 HAIC No therapy - Supplementary Figure 4. Survival of propensity score-matched patients with Child-Pugh A/B diseas e and portal vein tumor thrombus. Patients who underwent hepatic arterial infusion of 5-fluorouracil and cisplatin (HAIC) or no active therapy (no therapy) were compared. Median survival times were 7.9 months (HAIC) and 3.1 months (no therapy) (P<.0001).

16. Conclusion Large scale retrospective study which demonstrated the effectiveness of HAIC Difficult to achieve long-term survival Result indicate that HAIC could be an alternative therapy for advanced HCC Further examination of the factors that can predict the therapeutic effect is important for achieving long survival in future 16