ࡱ > t v m n o p q r s R 2| bjbjOO A -a -a
+ 8 I L ) % % % % C' * L =, $ r $ , C' C' , , % % H ]F ]F ]F , > % % aw \
]F , ]F ]F 7\ 3_ % ]G #> ] Mw 0 ] ^ Ό A J Ό 4 3_ 3_ N Ό h , , ]F , , , , , _C , , , , , , , Ό , , , , , , , , , / : Name of journal: World Journal of Gastroenterology
ESPS Manuscript NO: 4773
Columns: ORIGINAL ARTICLE
Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma
Kim HC et al. Transarterial chemoembolization in early-stage HCC
Heung Cheol Kim, Ki Tae Suk, Dong Joon Kim, Jae Hoon Yoon, Yeon Soo Kim, Gwang Ho Baik, Jin Bong Kim, Chang Hoon Kim, Hotaik Sung, Jong Young Choi, Kwang Hyub Han, Seung Ha Park
Heung Cheol Kim, Department of Radiology, Hallym University College of Medicine, Chuncheon 200-704, South Korea
Ki Tae Suk, Dong Joon Kim, Jae Hoon Yoon, Yeon Soo Kim, Gwang Ho Baik, Jin Bong Kim, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 200-704, South Korea
Chang Hoon Kim, College of Medicine, Upstate Medical University, State University of New York, Syracuse, NY 13210, United States
Hotaik Sung, Department of Biology, Stanford University, Stanford, CA, 94305, United States
Jong Young Choi, Department of Internal Medicine, Catholic University College of Medicine, Seoul 137-701, South Korea
Kwang Hyub Han, Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul 542-804, South Korea
Seung Ha Park, Department of Internal Medicine, Inje University College of Medicine, Busan, 614-735, South Korea
Supported by A Grant from the Korea Healthcare Technology R and D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020); by The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2010-0021482)
Author contributions: Kim HC and Suk KT designed the study and wrote the manuscript; Kim HC and Suk KT contributed equally to this work; Kim DJ designed and performed the study and edited the manuscript; Choi JY and Han KH provided vital reagents and analytical tools, were involved in editing the manuscript, and provided financial support for this work; Yoon JH, Kim YS, Baik GH, and Kim JB coordinated and collected all of the human data; Kim CH, Sung H, and Park SH were involved in editing the manuscript.
Correspondence to: Dong Joon Kim, MD, PhD, Department of Internal Medicine, Hallym University College of Medicine, Anyang-si, Chuncheon 200-704, South Korea. skt@yonsei.ac.kr
Telephone: +82-33-2405647 Fax: +82-33-2418064
Received: July 22, 2013 Revised: October 17, 2013
Accepted: October 19, 2013
Published online:
Abstract
AIM: To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 and A hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).
METHODS: Between January 2001 and September 2011, 129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled. Patient characteristics, routine CT and TACE findings, survival time and 1-, 5-, and 10-year survival rates, risk factors for mortality, and survival rates according to the number of risk factors were assessed.
RESULTS: The mean size of HCC tumors was 2.4 1.1 cm, and the mean number of TACE procedures performed was 2.5 2.1. The mean overall survival time and 1-, 5-, and 10-year survival rates were 80.6 4.9 mo and 91%, 63%, and 49%, respectively. In the Cox regression analysis, a Child-Pugh score > 5 (P = 0.005, OR = 3.86), presence of arterio-venous shunt (P = 0.032, OR = 4.41), amount of lipiodol used (> 7 mL; P = 0.013, OR = 3.51), and female gender (P = 0.008, OR = 3.47) were risk factors for mortality. The 1-, 5-, and 10-year survival rates according to the number of risk factors present were 96%, 87%, and 87% (no risk factors), 89%, 65%, and 35% (1 risk factor), 96%, 48%, and unavailable (2 risk factors), and 63%, 17%, and 0% (3 risk factors), respectively (P < 0.001).
CONCLUSION: TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC. The Child-Pugh score, arterio-venous shunt, amount of lipiodol used, and gender were related to mortality after TACE.
2013 Baishideng. All rights reserved.
Key words: Carcinoma; Hepatocellular; Chemoembolization; Therapeutic; Survival; Stage; Efficacy
Core tip: In this study, transarterial chemoembolization (TACE) was associated with a relatively good survival rate in patients with stage 0 and stage A Barcelona Clinic Liver Cancer (BCLC). The Child-Pugh score, presence of arterio-venous shunt, amount of lipiodol used during TACE, and female gender were correlated with mortality in patients with BCLC stage 0 and stage A hepatocellular carcinoma who underwent TACE. Patients with more than 2 risk factors should be treated by other curative-intent treatments after the first TACE.
Kim HC, Suk KT, Kim DJ, Yoon JH, Kim YS, Baik GH, Kim JB, Kim CH, Sung H, Choi JY, Han KH, Park SH. Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma.
Available from: URL:
DOI:
INTRODUCTION
Hepatocellular carcinoma (HCC) is a major health problem and is the sixth most common neoplasm in the world ADDIN EN.CITE Parkin200511117Parkin, D. M.Bray, F.Ferlay, J.Pisani, P.Unit of Descriptive Epidemiology, International Agency for Research on Cancer, Lyon, France.Global cancer statistics, 2002CA Cancer J ClinCA: a cancer journal for cliniciansCA Cancer J ClinCA: a cancer journal for cliniciansCA Cancer J ClinCA: a cancer journal for clinicians74-1085522005/03/12AdolescentAdultAgedChildChild, PreschoolEpidemiologic StudiesFemaleGeographyHumansIncidenceInfantInfant, NewbornInternational CooperationMaleMiddle AgedNeoplasms/*epidemiology/*mortalityPrevalenceRisk Factors*World Health2005Mar-Apr0007-9235 (Print)
0007-9235 (Linking)15761078http://www.ncbi.nlm.nih.gov/pubmed/15761078eng[HYPERLINK \l "_ENREF_1" \o "Parkin, 2005 #1"1]. The incidence of HCC is increasing in Europe and the United States, and it is currently the leading cause of death among cirrhotic patients ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_2" \o "Sangiovanni, 2006 #2"2-4]. Eighty percent of patients with HCC have cirrhosis. The annual incidence of HCC in patients with cirrhosis is 3%-5% ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_2" \o "Sangiovanni, 2006 #2"2]. Hepatitis B virus infection is the main risk factor in Asia and Africa ADDIN EN.CITE Jin201155517Jin, S. Y.Choi, I. H.Department of Pathology, Soon Chun Hyang University Seoul Hospital, Soon Chun Hyang University College of Medicine, Seoul, Korea. jin0924@schmc.ac.kr.Early hepatocellular carcinomaKorean J HepatolThe Korean journal of hepatologyKorean J HepatolThe Korean journal of hepatologyKorean J HepatolThe Korean journal of hepatology238-411732011/11/222011Sep2093-8047 (Electronic)
1738-222X (Linking)22102393http://www.ncbi.nlm.nih.gov/pubmed/2210239310.3350/kjhep.2011.17.3.238eng[HYPERLINK \l "_ENREF_5" \o "Jin, 2011 #5"5]. In Western countries, hepatitis C virus infection is the main risk factor ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_6" \o "Lee, 2010 #6"6, HYPERLINK \l "_ENREF_7" \o "Altekruse, 2009 #7"7]. The rising incidence of HCC has sparked widespread interest in research regarding the clinical management of HCC.
The Barcelona Clinic Liver Cancer (BCLC) staging system was constructed based on the results obtained in several randomized controlled and cohort studies ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_8" \o "Llovet, 2005 #8"8-10]. The BCLC staging system has been validated by several groups in Europe and the United States ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_11" \o "Cillo, 2004 #11"11-13], and the treatment of HCC has dramatically changed in the last few years ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_14" \o "Reig, 2010 #14"14]. Patients with BCLC stage 0 and stage A HCC are candidates for curative therapies such as resection, transplantation, or radiofrequency ablation. The survival rate of patients with BCLC stage 0 and stage A HCC approaches 50-70% at 5 years after curative therapy ADDIN EN.CITE Llovet200315151517Llovet, J. M.Burroughs, A.Bruix, J.Barcelona-Clinic Liver Cancer Group, Liver Unit, Digestive Disease Institute, IDIBAPS, Hospital Cli;nic i Provincial, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.Hepatocellular carcinomaLancetLancetLancetLancetLancetLancet1907-1736293992003/12/12*Carcinoma, Hepatocellular/diagnosis/mortality/surgeryEmbolization, TherapeuticHumans*Liver Neoplasms/diagnosis/mortality/surgeryLiver TransplantationPrognosisSurvival Rate2003Dec 61474-547X (Electronic)
0140-6736 (Linking)14667750Research Support, Non-U.S. Gov't
Reviewhttp://www.ncbi.nlm.nih.gov/pubmed/1466775010.1016/S0140-6736(03)14964-1eng[HYPERLINK \l "_ENREF_15" \o "Llovet, 2003 #15"15]. Five-year recurrence rates vary according to the therapeutic modality ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_16" \o "Livraghi, 2008 #16"16-18].
Transarterial chemoembolization (TACE) is the only intervention recommended by current HCC treatment guidelines for intermediate-stage patients ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_19" \o "Llovet, 2003 #19"19]. In general, TACE has not been recommended as a first-line therapy for patients with BCLC stage 0 and stage A HCC, based on the results of a single retrospective study ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_20" \o "Arii, 2000 #20"20]. However, this study reported the results of TAE, not TACE, and little evidence comparing TACE with other curative therapies in patients with early stage HCC is available ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_21" \o "Hsu, 2011 #21"21, HYPERLINK \l "_ENREF_22" \o "Bargellini, 2011 #22" 22]. Thus, considerable controversy still remains regarding appropriate patient selection for TACE. In this 10-year retrospective study, we evaluated the clinical characteristics of patients with BCLC stage 0 and stage A HCC after TACE.
MATERIALS AND METHODS
Between January 2001 and September 2011, a total of 129 patients with BCLC stage 0 (n = 40) and stage A HCC (n = 89) who underwent TACE were retrospectively enrolled (Figure 1). All of these patients were either unable to or refused to undergo resection, transplantation, or ablative therapy. Contraindications for these modalities included an unacceptably high risk of surgery, unacceptably high risk of ablation due to the location of mass (close to the gallbladder, liver hilum, liver capsule, diaphragm, or pericardium), financial constraints, or patient refusal. Thirty-three patients who were treated with surgery after TACE were excluded. Patient characteristics, routine pre- and post-treatment CT findings, TACE findings, and 1, 5, and 10-year survival rates were reviewed and assessed. The study protocol conformed to the ethical guidelines established by the 1975 Declaration of Helsinki and received a priori approval by the participating hospitals institutional review boards for human research.
Baseline evaluations were conducted including family and alcohol history, X-ray, electrocardiography, electrolyte panels, liver function tests, and viral markers. The diagnosis of HCC was established by - f e t o p r o t e i n ( A F P ) > 2 0 0 n g / m L , l i v e r b i o p s y , a n d i m a g i n g t e s t s , w h i c h i n c l u d e d M R I o r c o n t r a s t - e n h a n c e d C T s c a n n i n g i n t h e a r t e r i a l a n d p o r t a l v e n o u s p h a s e s . R e v i e w s o f C T a n d T A C E i m a g i n g w e r e p e r f o r m e d b y a s i n g l e r a d i o l o g i s t ( H . C . K . ) w h o h a d o v e r 1 5 y ears of experience with the TACE procedure. The clinical characteristics and medical reports were reviewed by 1 hepatologist (K.T.S.). The diagnosis of liver cirrhosis was established by liver biopsy and/or imaging tests such as ultrasound and/or contrast-enhanced CT in conjunction with laboratory data and by observing clinical complications of cirrhosis (presence of ascites, hepatic encephalopathy, and esophageal varices). Kaplan-Meier survival analysis and Cox regression analysis were used to investigate risk factors for mortality. Survival rates, as classified by the number of risk factors, were also evaluated and compared.
TACE procedure
All patients gave informed consent prior to the procedure. All TACE procedures were performed using the Seldinger technique by a board-certified attending interventional radiologist who specialized in interventional oncology (H.C.K.), ADDIN EN.CITE Higgs200523232317Higgs, Z. C.Macafee, D. A.Braithwaite, B. D.Maxwell-Armstrong, C. A.Division of Gastrointestinal Surgery, Queen's Medical Centre, Nottingham NG7 2UH, UK.The Seldinger technique: 50 years onLancetLancetLancetLancetLancetLancet1407-936694942005/10/18AdultCatheter Ablation/instrumentation/methodsCatheterization/*history/instrumentation/methodsEponymsFemaleHistory, 20th CenturyHumansSwedenVaricose Veins/therapy2005Oct 15-211474-547X (Electronic)
0140-6736 (Linking)16226619Biography
Case Reports
Historical Articlehttp://www.ncbi.nlm.nih.gov/pubmed/1622661910.1016/S0140-6736(05)66878-Xeng[HYPERLINK \l "_ENREF_23" \o "Higgs, 2005 #23"23]. After arterial access was obtained via the common femoral artery, a 5-French catheter (RH, ANA MD Company, Seoul, Korea) was introduced, and diagnostic angiography was performed of the celiac axis and superior mesenteric artery to assess arterial anatomy and to confirm patency of the portal vein. After the tumor feeder vessel was identified, a 2.9-French microcatheter (ASAHI Stride Microcatheter, Vascular Perspectives Ltd, Manchester, United Kingdom) was coaxially inserted through a 5French catheter and advanced into the hepatic artery supplying the targeted tumor. Depending on the size, location, and blood supply, the tip of the catheter was advanced into the hepatic artery and the feeding branch.
After appropriate catheter placement, a chemotherapeutic emulsion of 2-10 mL of iodized oil (Lipiodol Ultra-Fluide, Andre Guerbet Laboratories, Anlney-Sous-Bois, France) and 10-50 mg of doxorubicin (Adriamycin, Ildong pharmaceutical CO. LTD, Seoul, Korea) was injected. The doxorubicin-iodized oil emulsion was prepared by dissolving doxorubicin into a solution of nonionic water-soluble contrast medium and saline solution and mixed with lipiodol by shaking manually approximately 10 times. The dose of anticancer agent used for the TACE procedure was determined by the radiologist based on the size, number, and blood supply of the target tumors. The maximum dose of doxorubicin for a single TACE session was 50 mg. The injection was performed under fluoroscopy. If the slowing of antegrade blood flow was achieved, the chemotherapeutic infusion was discontinued, and subsequent embolization was performed using a gelatin sponge (Cutanplast, Mascia-Brunelli, Spa, Italy). In patients with decompensated liver function (classified as patients with Child-Pugh class C disease), if a large amount of extratumoral liver tissue was at risk for infarction due to reflux of emboli or segmental TACE, gelatin sponge embolization was not performed. TACE was terminated when the hepatic vein was visualized, the tumor vessels were completely filled with drug, and the tumor blush disappeared on subsequent angiographic imaging.
After the initial TACE treatment, patients underwent CT scans at 1, 3, and 6 mo after the procedure to evaluate the status of their tumors. In the case of an incomplete TACE, as evidenced by tumor recurrence or progression, a second TACE was performed after the follow-up CT scan.
Response after TACE
Imaging response was classified according to the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and the Modified RECIST (mRECIST) criteria ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_24" \o "Llovet, 2008 #24"24, HYPERLINK \l "_ENREF_25" \o "Forner, 2009 #25"25].HYPERLINK \l "_ENREF_17" \o "Forner, 2009 #50" According to RECIST, a complete response (CR) is defined as the disappearance of all target lesions. A partial response (PR) is defined as a 30% minimum decrease in the sum of the longest diameter of the target lesions, taking as reference the baseline sum of the longest diameter. Progressive disease (PD) is designated as a 20% minimum increase in the sum of the longest diameter of the target lesions, taking as reference either the smallest sum of the longest diameter recorded since the start of treatment or the appearance of one or more new lesions. Stable disease (SD) is indicated by insufficient tumor shrinkage to qualify for PR. According to the EASL guidelines, CR is defined as the absence of enhancing tumor areas, reflecting complete tissue necrosis. PR is defined as a > 50% decrease in the enhancing areas, reflecting partial tissue necrosis. PD is defined as a > 25% increase in the size of a single, measurable lesion or the appearance of new lesions, and SD is defined as a tumor response between PR and PD. The response categories, according to the criteria of mRECIST, are as follows: CR is defined as a disappearance of any intra-tumoral arterial enhancement in all target lesions; PR is defined as at least a 30% decrease in the sum of the diameters of viable target lesions; SD is defined as any cases that do not qualify for either CR or PD; and PD is defined as an increase of at least 20% in the sum of the diameters of viable target lesions.
Time to recurrence was defined as time from treatment to recurrence. Time to progression was defined as the time between treatment and radiological progression. The definitions of recurrence and progression were based on the mRECIST amendments. Patients alive and free of recurrence or progression at the end of follow-up were censored. Progression-free survival time was defined as the time between treatment and either radiological progression or death ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_24" \o "Llovet, 2008 #24"24].
Statistical analysis
Quantitative data were expressed as the mean SD, unless otherwise stated. Numerical differences between the groups classified by categorical variables were assessed using the Pearson chi-square test. To evaluate differences between the continuous variables among the groups, the independent t-test was used. Survival was expressed as the mean (standard error). Mean survival times were obtained using the Kaplan-Meier method and the log-rank test. Cox regression analysis was used to investigate independent predictors of mortality. Age, gender, and other plausible risk factors from the results of the univariate analysis (P < 0.500) were used in the Cox regression analysis. For the Cox regression analysis of lipiodol and doxorubicin, an area under the receiver operating characteristic (AUROC) was used to select the appropriate amount (lipiodol 7cc and doxorubicin 27cc). Subsequently, the Enter method was used to determine the Odds ratio (OR) and the risk factors for the Cox regression analysis. Risk factors are presented in terms of the OR and 95%CI. The times to recurrence and progression, recurrence-free survival, and progression-free survival were estimated using the KaplanMeier method. Data were analyzed using statistical software (SPSS, version 13.0, SPSS Inc., Chicago, IL, United States). A P value < 0.050 was considered significant for all tests.
RESULTS
Patient characteristics
A total of 129 patients were enrolled in this study (40 with BCLC stage 0 and 89 with BCLC stage A). The mean size of the HCC tumors was 2.4 1.1 cm, and the mean number of TACE procedures performed was 2.5 2.1. There were no significant differences among the continuous variables between the BCLC stage 0 and BCLC stage A groups (P > 0.050), with the exception of AFP (P = 0.018) and the greatest diameter of a nodule (P < 0.001). There were no significant differences in the distribution of etiology between the BCLC stage 0 and BCLC stage A groups (P = 0.822). There were 111 patients (38 in the BCLC stage 0 group and 73 in the BCLC stage A group) who showed evidence of cirrhosis in this study. (Table 1)
Findings of CT and TACE
An analysis of CT and TACE imaging revealed that 115 patients had 1 nodule, 10 patients had 2 nodules, and 4 patients had 3 nodules. Tumors were located in the left lobe of the liver in 18 patients, in the right lobe in 103 patients, and in both the left and right lobes in 8 patients. The greatest tumor diameter was 2.4 cm 1.1. In 4 patients, the nodule was associated with a capsule in the CT scan. The amounts of doxorubicin and lipiodol used were 26.2 mg 12.5 and 6.1 mL 3.5, respectively. Complete lipiodol uptake was observed in 101 patients, and a gelatin sponge was used in 56 patients. Ninety-four patients had 1 feeding vessel, 5 patients had 2 feeding vessels, and 30 patients had more than 3 feeding vessels. Eighteen patients had arterio-venous shunting, while 3 patients presented with an extra-hepatic collateral blood supply.
Risk factors of mortality
In the univariate analysis, the Child-Pugh score, BCLC class, number of TACE procedures, and amount of lipiodol used were correlated with mortality in patients with BCLC stage 0 and stage A HCC (P < 0.050). The other variables were not associated with mortality, as shown in Table 2.
In the Cox regression analysis, the Child-Pugh score > 5 (n = 67, P = 0.005, and OR 3.86), the presence of an arterio-venous shunt (n = 18, P = 0.032, and OR 4.41), the amount of lipiodol used (> 7 cc; n = 32, P = 0.013, and OR 3.51) during TACE, and female gender (n = 92, P = 0.008, and OR 3.47) were risk factors for mortality. (Table 3) There was a positive correlation between nodule diameter and the amount of lipiodol used (r = 0.343, P < 0.001).
Survival of patients
The mean overall survival time and 1, 5, and 10-year survival rates were 80.6 4.9 mo and 91%, 63%, and 49%, respectively (Figure 2). Of the risk factors studied, only a Child-Pugh score of 5 was a statistically significant predictor of survival (P = 0.002). Other risk factors were not associated with a survival difference between groups (p > 0.050; Figure 3).
The mean survival times of patients with 0, 1, 2, and 3 risk factors were 107.1 7.0, 78.0 7.2, 61.1 7.4, and 26.6 10.3 mo, respectively. The 1, 5, and 10-year survival rates according to the number of risk factors were 96%, 87%, and 87%, respectively, for patients with no risk factors (n = 29). For patients with 1 risk factor (n = 67), the corresponding rates were 89%, 65%, and 35%, respectively; and for patients with 2 risk factors (n = 25), the survival rates were 96%, 48%, and not available. For patients with 3 risk factors (n = 8), the 1-, 5-, and 10-year survival rates were 63%, 17%, and 0%, respectively (P < 0.001; Figure 4).
The 1-year survival rates classified according to the Child-Pugh sc o r e ( 5 o r e" 6 ) w e r e s i m i l a r . P a t i e n t s w i t h a C h i l d - P u g h s c o r e o f 5 h a d 1 - y e a r s u r v i v a l r a t e s o f 9 6 % , 9 4 % , a n d 6 7 % f o r p a t i e n t s w i t h n o , 1 , a n d 2 r i s k f a c t o r s , r e s p e c t i v e l y ; h o w e v e r , p a t i e n t s w i t h a C h i l d - P u g h s c o r e e" 6 h a d 1 - y e a r s u r v i v a l r a t e s o f 9 2 % , 9 4 % , and 62% for patients with no, 1, and 2 risk factors, respectively (Figure 5).
Response after TACE in patients with BCLC stage 0 and stage A HCC
Follow-up CT after the first TACE showed that the numbers of CR, PR, SD and PD were as follows: 4, 7, 107, and 0, respectively, according to the RECIST criteria; 99, 12, 4, and 3, respectively, according to the EASL criteria; and 100, 14, 3, and 2, respectively, according to the mRECIST criteria. Follow-up CT after the last TACE showed that the numbers of CR, PR, SD and PD were 16, 65, 16, and 10, respectively, according to the RECIST criteria; 40, 15, 17, and 40, respectively, according to the EASL criteria; and 49, 7, 7, and 44, respectively, according to the mRECIST criteria.
Forty-four patients (34.1%) had disease progression at the time of the follow-up CT scan. The average time to progression was 77.3 (5.1) mo, and the progressionfree survival time was 33.8 (30.6) mo (Table 4).
DISCUSSION
TACE is a widely used primary treatment for unresectable HCC and significantly delays tumor progression and vascular invasion ADDIN EN.CITE Bruix200426262617Bruix, J.Sala, M.Llovet, J. M.BCLC Group, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. bruix@ub.eduChemoembolization for hepatocellular carcinomaGastroenterologyGastroenterologyGastroenterologyGastroenterologyGastroenterologyGastroenterologyS179-881275 Suppl 12004/10/28Carcinoma, Hepatocellular/*therapyChemoembolization, Therapeutic/adverse effects/*methodsHumansLiver/physiologyLiver Neoplasms/*therapyNeoplasm InvasivenessNeoplasm StagingPatient SelectionPrognosisSurvival Analysis2004Nov0016-5085 (Print)
0016-5085 (Linking)15508083Research Support, Non-U.S. Gov't
Reviewhttp://www.ncbi.nlm.nih.gov/pubmed/15508083eng[HYPERLINK \l "_ENREF_26" \o "Bruix, 2004 #26"26]. For early-stage HCC, TACE is not indicated as a first-line option. In this study, which evaluated the efficacy of TACE as a first-line therapy for patients with BCLC stage 0 and stage A HCC, TACE had overall 1-, 5-, and 10-year survival rates of 91%, 63%, and 49%, respectively; these results are comparable to the results of other curative therapies (5-year survival of 50-70 %), including resection, transplantation, or percutaneous treatment ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_15" \o "Llovet, 2003 #15"15, HYPERLINK \l "_ENREF_27" \o "Kudo, 2010 #27"27, HYPERLINK \l "_ENREF_28" \o "Llovet, 2005 #28"28]. Kinugasa et al ADDIN EN.CITE Kinugasa201129292917Kinugasa, H.Nouso, K.Takeuchi, Y.Yasunaka, T.Onishi, H.Nakamura, S. I.Shiraha, H.Kuwaki, K.Hagihara, H.Ikeda, F.Miyake, Y.Takaki, A.Yamamoto, K.Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan, gyacy14@gmail.com.Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinomaJ GastroenterolJournal of gastroenterologyJ GastroenterolJournal of gastroenterologyJ GastroenterolJournal of gastroenterology2011/11/042011Nov 31435-5922 (Electronic)
0944-1174 (Linking)22048256http://www.ncbi.nlm.nih.gov/pubmed/2204825610.1007/s00535-011-0492-9Eng[HYPERLINK \l "_ENREF_29" \o "Kinugasa, 2011 #29"29] suggested that palliative TACE could be effective for treating HCC with 3 tumors or fewer (each up to 3 cm in diameter). Other data have also suggested that TACE provides a survival benefit for patients with early stage HCC ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_21" \o "Hsu, 2011 #21"21, HYPERLINK \l "_ENREF_22" \o "Bargellini, 2011 #22"22]. Therefore, the efficacy of TACE in the treatment of BCLC stage 0 and stage A HCC might be comparable to that of other curative treatments.
Our data also suggest that improvements in TACE technique, early diagnosis using precise imaging modalities, and a regular follow-up schedule according to standard guidelines could improve the survival rate of patients with BCLC stage 0 and stage A HCC.
In general, resection, transplantation, and ablation have been considered superior to TACE for very-early-stage or early-stage HCC. However, few studies comparing TACE and other curative therapies in patients with early-stage HCC are available. Therefore, prospective studies comparing the efficacy of TACE, surgery, and ablation are needed in the future.
Although this study provides a rationale for the use of TACE in the treatment of patients with BCLC stage 0 and stage A HCC (particularly in patients in whom surgery or ablation is risky due to tumor location), further research comparing the efficacy of TACE with curative therapies is needed because these retrospective data do not provide enough evidence to fully support a potential survival benefit.
Previously reported risk factors for mortality following TACE in patients with intermediate or advanced HCC include the extent of lipiodol uptake, tumor location, number, and size, tumor marker levels, viral marker levels, patient age, and liver function ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_29" \o "Kinugasa, 2011 #29"29-31]. The present study examined risk factors for mortality in patients with early-stage HCC and demonstrated that the Child-Pugh score, presence of arterio-venous shunt, amount of lipiodol used during TACE, and female gender were correlated with mortality.
The present study is the first report that discusses the outcome of TACE classified by the number of clinical risk factors among patients with BCLC stage 0 and stage A HCC. In the study, the number of risk factors was shown to be negatively correlated with survival. Overall, it seems likely that TACE could be a curative therapy for patients with fewer than 2 risk factors because our data showed that the 5-year survival rate in suc h p a t i e n t s w a s m o r e t h a n 5 0 % . H o w e v e r , t h e r e s u l t s o f t h i s s t u d y s u g g e s t t h a t T A C E s h o u l d r e m a i n a p a l l i a t i v e t r e a t m e n t o p t i o n f o r p a t i e n t s w i t h e" 2 r i s k f a c t o r s ; t h e s e p a t i e n t s s h o u l d b e t r e a t e d w i t h a n o t h e r c u r a t i v e - i n t e n t t r e a t m e n t f o l l o w i n g t h e f i r s t TACE.
Child-Pugh scores were a major risk factor for mortality in this study. Survival in patients with a Child-Pugh score of 5 was excellent (1, 5, and 10-year survival rates of 95%, 76%, and 70%, respectively). Twenty-eight patients (70%) who died had a Child-Pugh score > 5. Sala et al ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_32" \o "Sala, 2004 #32"32] reported that Child-Pugh class A was the strongest prognostic variable in patients undergoing percutaneous treatments. Shi et al ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_33" \o "Shi, 2010 #33"33] showed that the Child-Pugh class was significantly correlated with survival following TACE in patients with unresectable HCC. In addition, another study documented that the degree of Child-Pugh class was a risk factor for mortality ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_34" \o "Ikai, 2004 #34"34]. However, among patients undergoing transplantation, the presence o f a s i n g l e H C C d" 5 c m o r u p t o 3 n o d u l e s <