CORRESPONDENCE
Wait and Transplant for Stage 2 Hepatocellular Carcinoma With Deceased-Donor Liver Grafts: How Long Should We Wait? he method which donor organs are allocated to individuals on the waiting list for transplant is an important topic for research and debate. In recent years, there has been growing interest in applying the concept of utilitarianism to the organ allocation system, seeking the maximum survival benefit of the patient population as a whole, rather than that of an individual patient (1). Ideally, exceptions points were created to allow hepatocellular carcinoma (HCC) patients a fair access to the donor pool. However, the current allocation Model for End-stage Liver Disease exception points seem to overestimate the risk disease progression and dropout in HCC patients, and the likelihood of undergoing a liver transplantation still remains higher for HCC candidates in the United States (2). Therefore, an intention-totreat analysis, such as that published in Transplantation by Chan et al. (3), is a promising tool to optimize organ donation in a more fair way. Tumor size has been associated with the risk of metastasis and HCC progression (4). Whether or not the Milan criteria could be extended without increasing waiting list mortality for non-HCC candidates depends on the availability of organs in each specific region. Thus, an optimal selection of the HCC patients for liver transplantation has an upmost importance in regions with a low donation rate. The wait-and-transplant policy proposed by Chan et al. provided almost the same chances of being transplanted for HCC and non-HCC patients, and the survival rates of those who were transplanted were almost the same in
T
both groups (40.4% vs. 37.9%, respectively). However, most of the HCC patients in the waiting list died (n=18) or had to be excluded because of disease progression (7), and at the end of study, only 5 patients remained in conditions of being transplanted. As a matter of a fact, liver transplantation could not be offered in 48.2% (25/52) of the HCC patients. On the other hand, only 26.2% (27/103) of the non-HCC patients died in the waiting list during the same period, so 34.9% (35/103) of the non-HCC patients still had chances of receiving a liver graft when the study was ended. According to the intention-to-treat analysis, all alive and active patients should be considered as having a potential for long-term survival, regardless if they were transplanted or not. Although the outcomes of the patients who were still alive in the waiting list are unpredictable, a significant fraction of them probably will be transplanted in the following months, increasing the transplant patient rate and, consequently, the overall survival in the non-HCC group. We agree that wait-and-transplant policy is an interesting idea to avoid unnecessary liver transplant for patients at great risk of early tumor progression and recurrence, like the HCC candidates beyond the Milan criteria. The scenario of organ shortage increases even more the need to improve patient selection, but it seems to us that a shorter waiting period policy (3 months) could also combine the selection benefits of the 6-month waitand-transplant policy with a lower dropout and mortality rate on the waiting list. Another argument reinforcing this idea is the fact that HCC patients who
underwent living donor liver transplantation in the same study also achieved excellent postoperative survival outcomes despite a medium waiting time to transplant of 8.5 days. Cleber Rosito Pinto Kruel Aljamir D. Chedid Tomaz J.M. Grezzana-Filho Servi0o de Cirurgia Digestiva Hospital de Clı´nicas de Porto Alegre Ramiro Barcelos, Porto Alegre RS, Brazil The authors declare no funding or conflicts of interest. Address correspondence to: Cleber Rosito Pinto Kruel Capes, Ph.D., Post-doctoral Research Program Rua Ramiro Barcelos, 2350 Sala 600, CEP 90035-003 - Porto Alegre, Brazil. E-mail: [email protected] Each author has reviewed the article, believes it represents valid work, and approves it for submission. All authors participated in the writing, review and preparation of the article. Received 2 October 2013. Accepted 4 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9702-e6 DOI: 10.1097/01.TP.0000437674.24458.6c
REFERENCES 1. 2.
3.
4.
Briceno J, Ciria R, de la Mata M. DonorY recipient matching: myths and realities. J Hepatol 2013; 58: 811. Washburn K, Edwards E, Harper A, et al. Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transplant 2010; 10: 1643. Chan SC, Sharr WW, Chok KS, et al. Wait and transplant for stage 2 hepatocellular carcinoma with deceased-donor liver grafts. Transplantation 2013; 97: e6Ye7. Yao FY, Bass NM, Nikolai B, et al. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl 2003; 9: 684.
Reply to ‘‘Wait and Transplant for Stage 2 Hepatocellular Carcinoma With Deceased-Donor Liver Grafts: How Long Should We Wait?’’ welcome the interest of Dr. Kruel et al. in our article (1) in Transplantation. The bonus Model for End-stage Disease
I
e6
www.transplantjournal.com
score system was devised with an aim to provide patients with hepatocellular carcinoma (HCC) and those without Transplantation
with an equal chance for liver transplantation. This was by and large achieved in this series (40.4% and 37.9%). Such
& Volume 97, Number 2, January 27, 2014
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Correspondence
* 2014 by Lippincott Williams & Wilkins
adjusting of chance is affected by the number of deceased-donor liver grafts available and the number of liver transplant candidates listed. Differences in the proportions of patients transplanted in the two groups are therefore expected, and a constant review of the system is mandatory to reduce the discrepancy. As pointed out by Dr. Kruel et al., 18 (34.6%) of the 52 HCC patients with no suitable living donors died, whereas 27 (26.2%) of the 103 non-HCC patients without suitable living donors died. This would prompt more liberal assignment of bonus Model for End-stage Disease scores to transplant candidates with stage 2 HCC. Overzealous allocation of deceaseddonor liver grafts to HCC patients has been seen in the United States (2). Indeed, this less-than-10% difference could easily be overcorrected.
The 3-month ‘‘wait-and-transplant’’ policy had not been tested in our series. Because imaging of the HCCs was performed every 3 months, there was a high chance that more aggressive tumors were left unidentified. On average, the crosssectional diameter of a HCC doubles in a 4-month period (3). Lesions that have just reached stage 2 (e.g. a solitary 2-cm lesion) most likely will remain at stage 2 in 3 months. This is even more likely to be true when bridging therapies are administered. In a region where deceaseddonor liver grafts are scarce, a very judicious allocation policy should be adopted and adjustments to the bonus score system should be made cautiously. See Ching Chan Department of Surgery The University of Hong Kong Hong Kong, China
e7
The author declares no funding or conflicts of interest. Address correspondence to: See Ching Chan, M.D., Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Rd, Hong Kong, China. E-mail: [email protected] Received 16 October 2013. Accepted 18 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9702-e7 DOI: 10.1097/01.TP.0000438632.98719.69
REFERENCES 1.
2.
3.
Chan SC, Sharr WW, Chok KS, et al. Wait and transplant for stage 2 hepatocellular carcinoma with deceased-donor liver grafts. Transplantation 2013 97: e6Ye7. Washburn K, Edwards E, Harper A, et al. Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transplant 2010; 10: 1643. Yoshino M. Growth kinetics of hepatocellular carcinoma. Jpn J Clin Oncol 1983; 13: 45.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Wait and Transplant for Stage 2 Hepatocellular Carcinoma With Deceased-Donor Liver Grafts: How Long Should We Wait? he method which donor organs are allocated to individuals on the waiting list for transplant is an important topic for research and debate. In recent years, there has been growing interest in applying the concept of utilitarianism to the organ allocation system, seeking the maximum survival benefit of the patient population as a whole, rather than that of an individual patient (1). Ideally, exceptions points were created to allow hepatocellular carcinoma (HCC) patients a fair access to the donor pool. However, the current allocation Model for End-stage Liver Disease exception points seem to overestimate the risk disease progression and dropout in HCC patients, and the likelihood of undergoing a liver transplantation still remains higher for HCC candidates in the United States (2). Therefore, an intention-totreat analysis, such as that published in Transplantation by Chan et al. (3), is a promising tool to optimize organ donation in a more fair way. Tumor size has been associated with the risk of metastasis and HCC progression (4). Whether or not the Milan criteria could be extended without increasing waiting list mortality for non-HCC candidates depends on the availability of organs in each specific region. Thus, an optimal selection of the HCC patients for liver transplantation has an upmost importance in regions with a low donation rate. The wait-and-transplant policy proposed by Chan et al. provided almost the same chances of being transplanted for HCC and non-HCC patients, and the survival rates of those who were transplanted were almost the same in
T
both groups (40.4% vs. 37.9%, respectively). However, most of the HCC patients in the waiting list died (n=18) or had to be excluded because of disease progression (7), and at the end of study, only 5 patients remained in conditions of being transplanted. As a matter of a fact, liver transplantation could not be offered in 48.2% (25/52) of the HCC patients. On the other hand, only 26.2% (27/103) of the non-HCC patients died in the waiting list during the same period, so 34.9% (35/103) of the non-HCC patients still had chances of receiving a liver graft when the study was ended. According to the intention-to-treat analysis, all alive and active patients should be considered as having a potential for long-term survival, regardless if they were transplanted or not. Although the outcomes of the patients who were still alive in the waiting list are unpredictable, a significant fraction of them probably will be transplanted in the following months, increasing the transplant patient rate and, consequently, the overall survival in the non-HCC group. We agree that wait-and-transplant policy is an interesting idea to avoid unnecessary liver transplant for patients at great risk of early tumor progression and recurrence, like the HCC candidates beyond the Milan criteria. The scenario of organ shortage increases even more the need to improve patient selection, but it seems to us that a shorter waiting period policy (3 months) could also combine the selection benefits of the 6-month waitand-transplant policy with a lower dropout and mortality rate on the waiting list. Another argument reinforcing this idea is the fact that HCC patients who
underwent living donor liver transplantation in the same study also achieved excellent postoperative survival outcomes despite a medium waiting time to transplant of 8.5 days. Cleber Rosito Pinto Kruel Aljamir D. Chedid Tomaz J.M. Grezzana-Filho Servi0o de Cirurgia Digestiva Hospital de Clı´nicas de Porto Alegre Ramiro Barcelos, Porto Alegre RS, Brazil The authors declare no funding or conflicts of interest. Address correspondence to: Cleber Rosito Pinto Kruel Capes, Ph.D., Post-doctoral Research Program Rua Ramiro Barcelos, 2350 Sala 600, CEP 90035-003 - Porto Alegre, Brazil. E-mail: [email protected] Each author has reviewed the article, believes it represents valid work, and approves it for submission. All authors participated in the writing, review and preparation of the article. Received 2 October 2013. Accepted 4 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9702-e6 DOI: 10.1097/01.TP.0000437674.24458.6c
REFERENCES 1. 2.
3.
4.
Briceno J, Ciria R, de la Mata M. DonorY recipient matching: myths and realities. J Hepatol 2013; 58: 811. Washburn K, Edwards E, Harper A, et al. Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transplant 2010; 10: 1643. Chan SC, Sharr WW, Chok KS, et al. Wait and transplant for stage 2 hepatocellular carcinoma with deceased-donor liver grafts. Transplantation 2013; 97: e6Ye7. Yao FY, Bass NM, Nikolai B, et al. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl 2003; 9: 684.
Reply to ‘‘Wait and Transplant for Stage 2 Hepatocellular Carcinoma With Deceased-Donor Liver Grafts: How Long Should We Wait?’’ welcome the interest of Dr. Kruel et al. in our article (1) in Transplantation. The bonus Model for End-stage Disease
I
e6
www.transplantjournal.com
score system was devised with an aim to provide patients with hepatocellular carcinoma (HCC) and those without Transplantation
with an equal chance for liver transplantation. This was by and large achieved in this series (40.4% and 37.9%). Such
& Volume 97, Number 2, January 27, 2014
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Correspondence
* 2014 by Lippincott Williams & Wilkins
adjusting of chance is affected by the number of deceased-donor liver grafts available and the number of liver transplant candidates listed. Differences in the proportions of patients transplanted in the two groups are therefore expected, and a constant review of the system is mandatory to reduce the discrepancy. As pointed out by Dr. Kruel et al., 18 (34.6%) of the 52 HCC patients with no suitable living donors died, whereas 27 (26.2%) of the 103 non-HCC patients without suitable living donors died. This would prompt more liberal assignment of bonus Model for End-stage Disease scores to transplant candidates with stage 2 HCC. Overzealous allocation of deceaseddonor liver grafts to HCC patients has been seen in the United States (2). Indeed, this less-than-10% difference could easily be overcorrected.
The 3-month ‘‘wait-and-transplant’’ policy had not been tested in our series. Because imaging of the HCCs was performed every 3 months, there was a high chance that more aggressive tumors were left unidentified. On average, the crosssectional diameter of a HCC doubles in a 4-month period (3). Lesions that have just reached stage 2 (e.g. a solitary 2-cm lesion) most likely will remain at stage 2 in 3 months. This is even more likely to be true when bridging therapies are administered. In a region where deceaseddonor liver grafts are scarce, a very judicious allocation policy should be adopted and adjustments to the bonus score system should be made cautiously. See Ching Chan Department of Surgery The University of Hong Kong Hong Kong, China
e7
The author declares no funding or conflicts of interest. Address correspondence to: See Ching Chan, M.D., Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Rd, Hong Kong, China. E-mail: [email protected] Received 16 October 2013. Accepted 18 October 2013. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9702-e7 DOI: 10.1097/01.TP.0000438632.98719.69
REFERENCES 1.
2.
3.
Chan SC, Sharr WW, Chok KS, et al. Wait and transplant for stage 2 hepatocellular carcinoma with deceased-donor liver grafts. Transplantation 2013 97: e6Ye7. Washburn K, Edwards E, Harper A, et al. Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transplant 2010; 10: 1643. Yoshino M. Growth kinetics of hepatocellular carcinoma. Jpn J Clin Oncol 1983; 13: 45.
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
