CLINICAL OUTCOME OF 251 PATIENTS WITH EXTRAHEPATIC METASTASIS AT INITIAL DIAGNOSIS OF HEPATOCELLULAR CARCINOMA: DOES TRANSARTERIAL CHEMOEMBOLIZATION IMPROVE SURVIVAL IN THESE PATIENTS? F1 KIM EUN YEONG Dong-Jun Yoo,* Kang Mo Kim,* Young-Joo Jin,* Ju Hyun Shim,* Gi-Young Ko,† Hyun-Ki Yoon,† Kyu-Bo Sung,† Jae-Lyun Lee,* Yoon-Koo Kang,* Young-Suk Lim,* Han Chu Lee,* Young-Hwa Chung,* Yung Sang Lee* and Dong Jin Suh* Departments of *Internal Medicine and †Radiology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea Journal of Gastroenterology and Hepatology 26 (2011) 145–154

Introduction  Most HCC are still diagnosed at advanced stages although the efforts for early detection  Very poor prognosis  Median survival time of metastatic HCC patients is less than 6 months.  In large scale RCT including s-chemo, TACE, immunotherapy, radioisotope therapy, molecular targeting agents   No significant survival benefit  Sorafenib; 3 months longer median survival benefit N Engl J Med 2008;359: The Lancet Oncology, Vol10 Is1, P25-34, January 2009  It is worth exploring other treatment modalities such as TACE

Introduction TACE; Survival benefits for intermediate HCC patients No data on the efficacy of TACE in metastatic HCC Cause of death of HCC patients with extrahepatic spread; intrahepatic HCC or hepatic failure, rather than extrahepatic metastasis  Local treatment modality, such as TACE, could offer some survival benefits Investigated the efficacy of TACE with/without systemi c chemotherapy (s-chemo) in metastatic HCC patients who had not been treated before diagnosis

Methods  Patients  January 2005 to December 2007  Total of 4674 patients newly diagnosed with HCC at Asan Medical center(Seoul, Korea)  Extrahepatic metastasis of these patients; 251(5.4%)  Treatment modalities  TACE (anticancer agent; 2 mg/kg cisplatin or 50 mg doxorubicin) for preserved liver function classified as Child–Pugh A–B  F/U using CT or MRI every 1~3 months  Additionally performed RT in gross PV invasion after one TACE/TACI session.  A few cycles of s-chemo, or sorafenib were combined with TACE/TACI sessions

Methods  Data collection  Survival analysis of all patients and subgroups, sorted according to liver function or tumor extent  Compared the survival rates of patients stratified by Child–Pugh liver function and intrahepatic HCC T stage according to the treatment modality  Multivariate analysis for potential prognostic factors  Statistical analysis  Main end-point; survival from the date of diagnosis  Survival curves were estimated according to the Kaplan–Meier method  Continuous variables using Student’s t-test  Categorical variables using x 2 -test or Fisher’s exact test.  Multivariate analysis using the Cox regression model

Results - Patient characteristics, Treatment modalities- 10: sorafenib 7: conventional chemo

Survival analysis according to Child–Pugh classification, AJCC/UICC T stage, and site of HCC metastasis 251 patients  240 died 18.7% 6.2%

Figure 2 Probability of survival of 251 metastatic hepatocellular carcinoma (HCC) patients according to Child–Pugh classification (a) Median survival 6.5 months 2.6 months 1.2 months

Median survival 8.5 months 3.9 months 4.9 months 1.9 months 27.2 months 12.2 months 3 months

Prior to evaluating the survival rates of 226 patients with Child-Pugh A-B liver function, according to treatment modality, we compared the baseline characteristics of each treatment group  Varied characteristics among different treatment groups

Efficacy of repeated TACE/TACI and chemotherapy in improving survival rates Median survival 27.2 months 12.5 months 3.9 months 6.9 months

Efficacy of repeated TACE/TACI and chemotherapy in improving survival rates Median survival 10 months 5 months 4.6 months 2.9 months

Efficacy of repeated TACE/TACI and chemotherapy in improving survival rates 7.1 months Median survival 2.6 months 2.8 months 1.6 months

Subgroup analysis of patients treated with both TACE/TACI and s-chemo 20.5 months 10 months Median survival

Causes of death

Factors affecting the survival of HCC patients with extrahepatic metastasis at the initial diagnosis of HCC

Conclusion  Repeated TACE could show significant survival benefits in metastatic HCC patients with conserved liver function and intrahepatic HCC T3 stage.  The survival data of our study could be used as a historical control for TACE monotherapy in future clinical trials evaluating combination treatments containing TACE in these patients.