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      Comment on a meta-analysis comparing hepatic resection or transarterial chemoembolization as initial treatment for hepatocellular carcinoma

      1 , 2 , 1 , 2 , 1 , 2

      Drug Design, Development and Therapy

      Dove Medical Press

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          Abstract

          Dear editor We read with great interest the meta-analysis by Tian et al1 comparing the efficacy of initial hepatic resection (HR) or transarterial chemoembolization (TACE) for patients with primary hepatocellular carcinoma (HCC). The results from this analysis of eleven cohort studies involving 6,297 patients suggested similar overall survival (OS) and recurrence rate for the two techniques. We believe this conclusion should be treated with caution because it conflicts with much larger original studies2,3 and large systematic reviews.4,5 Potential problems with patient heterogeneity weaken the validity of the meta-analysis by Tian et al. Those authors did not mention explicitly that they selected only studies examining HR or TACE as initial therapy, yet all except one study focused on initial therapy. That one study,6 involving 1,296 patients, compared preoperative TACE plus HR with HR alone. This may have introduced significant clinical heterogeneity into the study population, since preoperative TACE plus HR, HR alone, and TACE alone are associated with substantially different OS. In addition, this meta-analysis included patients with early,7 intermediate,8,9 and advanced HCC.10 This may have introduced additional heterogeneity, since recommended HCC treatments depend on tumor stage.11 Unfortunately, it is impossible to assess tumor stage in this meta-analysis because essential information, including tumor number and incidence of macrovascular invasion, is not reported. For reasons that are unclear, this meta-analysis failed to include several studies comparing initial HR and TACE to treat primary HCC. These include large, propensity score-matched studies;2,12 a large, well-designed retrospective study;13 and a randomized trial.14 All four of these studies reported that initial HR was associated with significantly longer short- and long-term OS in patients with intermediate or advanced HCC. A meta-analysis15 with similar goals to Tian et al but much larger – bringing together 50 studies involving 14,673 patients with primary HCC – found significantly higher 1-, 3-, and 5-year OS after initial HR than initial TACE. Subgroup analyses in that study showed similar results for patients in Barcelona Clinic Liver Cancer (BCLC) stage A, patients in BCLC stage B, and patients with portal vein tumor thrombus. Several methodological issues in the meta-analysis by Tian et al further weaken their conclusions. First, although those authors did acknowledge that HR is considered curative while TACE is only palliative, they nevertheless calculated a recurrence rate for TACE and compared it with recurrence after HR. This may not be valid, since it is unclear whether tumors completely disappear after one or more cycles of TACE. Second, although most studies in this meta-analysis were “high quality” based on the Newcastle–Ottawa Scale, all were low quality based on Cochrane quality assessment standards. Third, those authors did not report intention-to-treat analyses, which meant, among other things, that the same total number of patients in each study was used to calculate survival at 1, 2, 3, 4, and 5 years. The reality is that patients die during follow-up, which intention-to-treat analysis would capture. Fourth, I 2 in most studies in the meta-analysis was >80%, indicating significant heterogeneity and suggesting that meta-analysis may be inappropriate. Though we compliment Tian et al on their effort, and studies like this meta-analysis are necessary to gain a definitive picture of optimal initial treatment, which remains controversial for certain types of HCC patients,11,16 such studies should be conducted in a way that controls for patient heterogeneity.

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          Most cited references 14

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          Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma.

           Tao Peng,  Ping Ye,  Feng Gong (2014)
          The efficacy and safety of hepatic resection (HR) to treat patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC) was retrospectively assessed. Although guidelines from the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease do not recommend HR for treating BCLC stage B/C HCC, several Asian and European studies have come to the opposite conclusions. A consecutive sample of 1259 patients with BCLC stage B/C HCC who underwent HR (n = 908) or transarterial chemoembolization (TACE, n = 351) were included. Moreover, propensity score-matched patients were analyzed to adjust for any baseline differences. In parallel with this retrospective clinical study, the MEDLINE database was searched for studies evaluating the efficacy and safety of HR for BCLC stage B/C HCC. Among our patient sample, the 90-day mortality rate in the HR group was 3.1%. HR provided a survival benefit over TACE at 1, 3, and 5 years (88% vs 81%, 62% vs 33%, and 39% vs 16%, respectively; all P < 0.001). Propensity scoring and subgroup analyses based on tumor size, tumor number, presence or absence of macrovascular invasion, and portal hypertension (PHT) also showed that HR was associated with better long-term survival than TACE. All 36 studies identified in our literature search reported that HR is associated with good long-term survival and low morbidity. Multivariate analyses revealed that alpha-fetoprotein more than or equal to 400 ng/mL, diabetes mellitus, macrovascular invasion, and PHT are independent predictors of poor prognosis in patients with BCLC stage B/C HCC. Our clinical and literature analyses suggest that in patients with HCC with preserved liver function, the presence of large, solitary tumors, multinodular tumors, macrovascular invasion, or PHT are not contraindications for HR.
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            Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT.

            The aim of this randomized comparative trial (RCT) is to compare partial hepatectomy (PH) with transcatheter arterial chemoembolization (TACE) to treat patients with resectable multiple hepatocellular carcinoma (RMHCC) outside of Milan Criteria.
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              Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

              The long-term survival outcomes of hepatic resection (HR) compared with transcatheter arterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are unclear. Between December 2002 and December 2007, 201 consecutive patients diagnosed with resectable HCC with PVTT received HR as an initial treatment in our center. These patients were compared with 402 case-matched controls selected from a pool of 1798 patients (with a 1:2 ratio) who received TACE as an initial treatment during the study period. PVTT was classified to 4 types: PVTT involving the segmental branches of the portal vein or above (type I), PVTT extending to involve the right/left portal vein (type II), the main portal vein (type III), or the superior mesenteric vein (type IV). The 1-, 3-, and 5-year overall survivals for the HR and TACE groups were 42.0%, 14.1%, and 11.1% and 37.8%, 7.3%, and 0.5%, respectively (P 5 cm (P < .001, P = .002, P < .001, P < .001, respectively), but not for type III PVTT, type IV PVTT, multiple tumors, and tumor size <5 cm (P = .541, P = .371, P = .264, P = .338, P = .125, respectively). Multivariate analysis showed the type of PVTT and initial treatment allocation were significant prognostic factors for overall survival. Compared with TACE, HR provided survival benefits for patients with resectable HCC with PVTT, especially for those with a type I PVTT or a type II PVTT. Copyright © 2012 American Cancer Society.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                13 October 2015
                : 9
                : 5623-5624
                Affiliations
                [1 ]Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China
                [2 ]Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China
                Author notes
                Correspondence: Le-Qun Li, Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, He Di Rd #71, Nanning 530021, People’s Republic of China, Tel +86 771 533 0855, Fax +86 771 531 2000, Email xitongpingjia@ 123456163.com
                Article
                dddt-9-5623
                10.2147/DDDT.S96547
                4610782
                © 2015 Zhong et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Letter

                Pharmacology & Pharmaceutical medicine

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