Expanded Criteria for Liver Transplantation in Patients with Hepatocellular Carcinoma J.M. Kim, C.H.D. Kwon, J.-W. Joh, J.B. Park, J.H. Lee, G.S. Kim, S.J. Kim, S.W. Paik, and S.-K. Lee ABSTRACT Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size 6 cm, 7 tumors, and/or AFP levels 1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size 6 cm, tumor number 7, and/or AFP levels 1000 ng/mL.
L
IVER transplantation (LT) is the only treatment for saving the life of patients with unresectable hepatocellular carcinoma (HCC) with or without end-stage liver disease. The advantage of LT is that the tumor, the tumor margin, and the underlying liver cirrhosis are removed in one step, resulting in the restoration of liver function and a decrease in the risk of de novo HCC [1]. In Eastern Asian countries, such as Korea and Japan, most patients with HCC receive liver allografts from living donors because of the scarcity of deceased donors. Many patients who undergo living donor liver transplantation (LDLT) develop recurrent HCC despite repeated locoregional therapy, but these patients have been found to survive longer than expected after LT [2e5]. Therefore, it seems practical to attempt further reduction of unnecessary dropouts caused by the confined application of limited selection criteria. However, it is also essential to improve the recipient survival rate by excluding high-risk HCC patients from LDLT. Our purpose in this study was to identify pre-LT risk factors for HCC recurrence and to determine how the current criteria for patient selection can be safely extended based on a single-center experience. MATERIALS AND METHODS Between February 2002 and December 2008, 180 patients with HCC underwent LT at Samsung Medical Center (SMC), Seoul, 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.037 726
Korea. Of the 180 patients, a total of 157 patients (87.2%) underwent LDLT using right lobe grafts and 23 (12.8%) patients underwent deceased donor liver transplantation (DDLT). Patients were diagnosed with HCC based on preoperative and postoperative findings. Patients who died within 1 month posttransplantation were excluded. Liver computed tomography (CT) scanning was repeated until 1 month before LDLT to confirm the patient’s suitability for LT with respect to the extent of the HCC and hepatic vasculature. After establishment of our new criteria reported here (we refer to these criteria as the SMC criteria), patients were also classified radiologically and pathologically. All liver transplant recipients were followed up periodically by measuring levels of alpha-fetoprotein (AFP) and performing chest X-rays and liver CT scans. HCC recurrence was diagnosed when imaging studies revealed evidence of new tumors.
From the Department of Surgery (J.M.K., C.H.D.K., J.-W.J., J.B.P., S.J.K., S.-K.L.), Division of Gastroenterology (J.H.L., S.W.P.), Department of Medicine, and Department of Anesthesiology and Pain Medicine (G.S.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Address reprint requests to Jae-Won Joh, MD, PhD, Professor, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong GangnamGu, Seoul, Korea 135-710. E-mail: [email protected] ª 2014 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 726e729 (2014)
EXPANSION OF LT CRITERIA IN HCC
STATISTICAL ANALYSIS
Cut-off value in each variable was calculated using receiver operating characteristics (ROC) curve. Analysis of disease-free survival was performed using the Kaplan-Meier method and survival was compared between groups using the log-rank test. Stepwise Cox proportional hazards regression analysis was used for univariate and multivariate analyses. A ROC curve based on the preoperative imaging study findings was constructed according to the Milan, University of California at San Francisco (UCSF), and Samsung Medical Center (SMC) criteria to compare the efficacy of the various criteria for patient selection. P values 6 cm and an AFP concentration of >1000 ng/mL were significant risk factors in HCC patients with a single tumor. A maximal tumor diameter >6 cm, a tumor number >7, a high total tumor size, AFP values of >1000 ng/mL, low MELD scores, and Child-Turcotte-Pugh (CTP) C class were predisposing factors for HCC recurrence in HCC patients with multiple tumors. Multivariate analysis in single HCC patients revealed that a maximal tumor diameter of >6 cm and an AFP value >1000 ng/mL were independent risk factors for postoperative recurrence. In addition, a maximal tumor diameter >6 cm, a tumor number >7, and an AFP value >1000 ng/mL were independent risk factors for HCC recurrence in HCC patients with multiple tumors. We reanalyzed the predisposing factors for HCC recurrence regardless of tumor number. Univariate and multivariate analysis showed that a maximal tumor diameter of >6 cm, a tumor number of >7, and an AFP value of >1000 ng/mL were closely associated with HCC recurrence (Table 1).
727 Table 1. Risk Factors for HCC Recurrence Regardless of Tumor Number Variables
Univariate Maximal tumor size >6 cm Tumor number >7 AFP (>1000 ng/mL) Multivariate Maximal tumor size >6 cm Tumor number >7 AFP (>1000 ng/mL)
Odds Ratio
95% Confidence Interval
P
11.651 33.157 6.759
3.418e39.706 6.788e161.960 2.952e15.477
L
IVER transplantation (LT) is the only treatment for saving the life of patients with unresectable hepatocellular carcinoma (HCC) with or without end-stage liver disease. The advantage of LT is that the tumor, the tumor margin, and the underlying liver cirrhosis are removed in one step, resulting in the restoration of liver function and a decrease in the risk of de novo HCC [1]. In Eastern Asian countries, such as Korea and Japan, most patients with HCC receive liver allografts from living donors because of the scarcity of deceased donors. Many patients who undergo living donor liver transplantation (LDLT) develop recurrent HCC despite repeated locoregional therapy, but these patients have been found to survive longer than expected after LT [2e5]. Therefore, it seems practical to attempt further reduction of unnecessary dropouts caused by the confined application of limited selection criteria. However, it is also essential to improve the recipient survival rate by excluding high-risk HCC patients from LDLT. Our purpose in this study was to identify pre-LT risk factors for HCC recurrence and to determine how the current criteria for patient selection can be safely extended based on a single-center experience. MATERIALS AND METHODS Between February 2002 and December 2008, 180 patients with HCC underwent LT at Samsung Medical Center (SMC), Seoul, 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.037 726
Korea. Of the 180 patients, a total of 157 patients (87.2%) underwent LDLT using right lobe grafts and 23 (12.8%) patients underwent deceased donor liver transplantation (DDLT). Patients were diagnosed with HCC based on preoperative and postoperative findings. Patients who died within 1 month posttransplantation were excluded. Liver computed tomography (CT) scanning was repeated until 1 month before LDLT to confirm the patient’s suitability for LT with respect to the extent of the HCC and hepatic vasculature. After establishment of our new criteria reported here (we refer to these criteria as the SMC criteria), patients were also classified radiologically and pathologically. All liver transplant recipients were followed up periodically by measuring levels of alpha-fetoprotein (AFP) and performing chest X-rays and liver CT scans. HCC recurrence was diagnosed when imaging studies revealed evidence of new tumors.
From the Department of Surgery (J.M.K., C.H.D.K., J.-W.J., J.B.P., S.J.K., S.-K.L.), Division of Gastroenterology (J.H.L., S.W.P.), Department of Medicine, and Department of Anesthesiology and Pain Medicine (G.S.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Address reprint requests to Jae-Won Joh, MD, PhD, Professor, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong GangnamGu, Seoul, Korea 135-710. E-mail: [email protected] ª 2014 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 726e729 (2014)
EXPANSION OF LT CRITERIA IN HCC
STATISTICAL ANALYSIS
Cut-off value in each variable was calculated using receiver operating characteristics (ROC) curve. Analysis of disease-free survival was performed using the Kaplan-Meier method and survival was compared between groups using the log-rank test. Stepwise Cox proportional hazards regression analysis was used for univariate and multivariate analyses. A ROC curve based on the preoperative imaging study findings was constructed according to the Milan, University of California at San Francisco (UCSF), and Samsung Medical Center (SMC) criteria to compare the efficacy of the various criteria for patient selection. P values 6 cm and an AFP concentration of >1000 ng/mL were significant risk factors in HCC patients with a single tumor. A maximal tumor diameter >6 cm, a tumor number >7, a high total tumor size, AFP values of >1000 ng/mL, low MELD scores, and Child-Turcotte-Pugh (CTP) C class were predisposing factors for HCC recurrence in HCC patients with multiple tumors. Multivariate analysis in single HCC patients revealed that a maximal tumor diameter of >6 cm and an AFP value >1000 ng/mL were independent risk factors for postoperative recurrence. In addition, a maximal tumor diameter >6 cm, a tumor number >7, and an AFP value >1000 ng/mL were independent risk factors for HCC recurrence in HCC patients with multiple tumors. We reanalyzed the predisposing factors for HCC recurrence regardless of tumor number. Univariate and multivariate analysis showed that a maximal tumor diameter of >6 cm, a tumor number of >7, and an AFP value of >1000 ng/mL were closely associated with HCC recurrence (Table 1).
727 Table 1. Risk Factors for HCC Recurrence Regardless of Tumor Number Variables
Univariate Maximal tumor size >6 cm Tumor number >7 AFP (>1000 ng/mL) Multivariate Maximal tumor size >6 cm Tumor number >7 AFP (>1000 ng/mL)
Odds Ratio
95% Confidence Interval
P
11.651 33.157 6.759
3.418e39.706 6.788e161.960 2.952e15.477
