Is surgery superior than external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium?

Abstract

Dear Editors, We read with great interest the article by Dr Lee et al1 recently published in the Journal of HepatoBiliaryPancreatic Science. This systematic review and metaanalysis (SRMA) aims to investigate the efficacy and safety of surgery and external beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA). The results suggested that surgery may be associated with a better survival rate, while EBRT is a valid palliative option with lower complication rates. Herein, we would like to raise the following concerns. First, the trials contained in this SRMA were mainly smallsample studies of single armed datasets, with only two retrospective analyses, involving 158 patients, that had direct comparison of outcomes between surgery and EBRT. Therefore, significant methodological and statistical heterogeneity between trials might exist. Combining the results from these heterogeneous datasets will lead to meaningless results. Although the authors had performed I2– test and Cochrane Q statistics for heterogeneity assessment, these methods may fail to identify differences between the effect estimates of single datasets and the majority of trails. In this regard, regression analysis should be applied to investigate the potential effect of each singlearmed dataset on trial outcomes.2 Besides, we also recommend that the network metaanalysis should be applied, as it provides more accurate results by combining results of direct and adjusted indirect comparisons. In fact, network metaanalysis has now been widely used and accepted for mixed treatment comparison.3 Second, in this SRMA, both of the two studies with direct comparisons showed inconsistent results with the final conclusion, as they reported that survival time or median time to progression in radiotherapy group was significantly superior to that in the liver resection group. This is probably because of the fact that the dates of inclusion (1990 to 2018) in the EBRT were wide. In 30 years, progress in radiation oncology techniques has greatly reduced the risk of radiationassociated injury by delivering a high dose accurately to the tumor, with a sharp dose gradient to adjacent regions. Therefore, it is more valuable to investigate treatment outcomes of EBRT using the latest techniques. As a matter of fact, previous SRMA of eight very recent retrospective studies had already concluded that EBRT is a feasible option to HCC with IVC/RA, with a median survival time of 13.2 months.4 It is noteworthy that the first line treatment method for HCC with vascular invasion is sorafenib, which only has a reported median survival time of up to 7 months.5 Considering this as well as its lower complication rate, EBRT might be an optimal treatment method for HCC with IVC/RA. In conclusion, this SRMA by Lee et al is a great work focusing on the treatment method for HCC with IVC/RA. However, the evidence was limited for the significant heterogeneity between trials. Further randomized trials with large sample sizes are in urgent need to determine the best treatment option for advanced HCC with vascular invasion.