Here comes the debate, which patient is the best candidate for TACE? This depends on the residual liver functions and proper assessment of the liver capacity. There have been many prognostic scores that tried to offer a proper TACE-specific prognosis, however, they still lacked validity and TACE specificity.7
Real world clinical data show huge support for TACE as a therapeutic modality for intermediate stage HCC applied in 50%–60% of those class of patients.2,9 It needs to be taken into account that most of the contraindications for TACE lie behind the poor liver functions of the patients and background liver disease progression,10 as the tumor size limit is up to 10 cm, which is not frequently a contraindication. A sub-classification of intermediate stage HCC has been proposed by Bolondi et al.11They sub-classified BCLC stage B into four sub-groups, as shown in Table 1. Later in 2016, Kudo et al proposed another simplified modification named “Kinki criteria”, it sub-classifies BCLC B stage into only three sub-classes according to Child-Pugh score plus Milan and upto-7 criteria, as shown in Table 2.
(To view a larger version of Table 1, click here.)
(To view a larger version of Table 2, click here.)
There are special considerations in various international guidelines regarding treatment allocation in intermediate stage HCC. There is an epidemiological difference in HCC in eastern and western cohorts, and various guidelines have been proposed. HCC originates in middle eastern and Asian countries mostly with a background of viral hepatitis, predominantly HBV or HCV infections. Whereas in western countries, it is mostly due to alcoholic liver disease. Also, there is no well established national HCC screening program in many of the middle eastern and Asian countries, except for highly specialized centers. Here comes the impact of etiology on survival and prognosis, as reported by Piscaglia and Ogasawara.7
The primary background of HCC is cirrhosis, however, the etiology of cirrhosis has been found to impact the prognosis of patients with HCC. This was not considered in all guidelines and prognostic scores. HBV as an etiology accounts for 54.4% of all diagnosed HCC cases globally while HCV accounts for 31.1%, however, around 55% of HCV infected patients were reported as alcoholics.12,13The impact of viral hepatitis on survival was reported by Zhou et al in a meta-analysis that encompassed 4,744 patients where 2,008 were HBV positive and 2,222 were HCV positive, while 514 were HBV and HCV negative. They reported a poor prognosis in patients with viral hepatitis in comparison to patients with negative serology. They also recommended adjuvant antiviral therapy post-HCC treatment to prevent tumor recurrence.14
Waked et al in 2017, reported vascular invasion as another important factor that should be considered in prognostic scoring systems. The authors also validated the parameters of ALBI grade as well as hepatoma arterial-embolization prognostic (HAP) score in 3,030 patients undergoing TACE.15Noteworthy, predictors of poor prognosis in literature included liver functions, vascular invasion, AFP, and tumor size. However, the current available scoring systems lack vascular invasion as a parameter.
RESPONSE EVALUATION AFTER TACE
Overall survival is the primary target of any cancer research. Nevertheless, evaluating the efficacy of response to treatment is usually assessed by imaging which plays a vital role in this process. It has been challenging to have a well established morphologic response criterion for the target lesion, starting from the WHO criteria in 1997 then the Response Evaluation Criteria in Solid Tumors (RECIST) criteria in 2000. Both have standardized methods to assess radiological tumor response to treatment using a quantitative and defined algorithm. They offered a simple way to assess the anatomic tumor size and changes in the target lesion either through bilinear product approach16 or single linear summation (RECIST).
Although both criteria were originally proposed for the assessment of cytotoxic agents, they do not offer ways to evaluate anti-tumor activity, except through the decrease in primary tumor size. However, RECIST criteria addressed that this changes in tumor size only could be misleading when it is applied to tumorous targeted therapeutics or any other interventional therapy. In patients with HCC, it has been frequently reported that there is poor correlation between the clinical benefit and real gain in patient condition and the conventional way of tumor response assessment after locoregional treatments.
Twenty years ago, a commission for HCC considering the decline in residual activity of the tumor using contrast enhanced computed tomography (CT) scanning or magnetic resonance imaging17 was proposed by European Association for the Study of the Liver (EASL) to find a proper way to assess tumor response. This proposal has been subsequently endorsed by the American Association for the Study of Liver Diseases (AASLD). Even the AASLD practice guidelines stated that the decrease in total viable tumorous tissue should be taken into consideration, not only the overall size of the tumor, which further offered a proper assessment of the tumor response to treatment.
In 2008, modification of the RECIST criteria was proposed which focuses on the residual viable tumor tissue to assess the response to locoregional and anti-angiogenic therapies. There have been growing evidence and reports about the prognostic power of the modified RECIST (mRECIST) for patients with HCC in addition to predicting overall survival. A significant degree of concordance has been reported between mRECIST and EASL criteria that has been used for a longer time. Response to TACE and sorafenib has been extensively studied according to RECIST and has been shown to be a proper predictive tool. Table 3 shows, in detail, how to evaluate response according to mRECIST. According to the previously discussed criteria, assessment of response to treatment is the main pillar to declare either success or failure of the treatment. However, identifying the optimal timing to stop TACE cycles is challenging. Of note, declaring TACE failure has been agreed to be after failure of two successive cycles.2,7,18
(To view a larger version of Table 3, click here.)