Is TARE in patients with TACE-refractory HCC safe and effective?

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry

Clinical Question

Does prior transarterial chemoembolization impact outcomes in patients undergoing transarterial Y90 radioembolization in the context of nonresectable liver tumor?

Take Away Point

Outcomes in patients undergoing transarterial SIR-Sphere Y90 radioembolization with and without prior transarterial chemoembolization were similar. This suggests that transarterial radioembolization is a safe and effective treatment option for patients with hepatocellular carcinoma who previously received transarterial chemoembolization treatment.

Reference

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry, Hund et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 12, P2147-2154



Link to abstract

Study Design

Prospective, observational, cohort study

Funding Source

Sirtex Medical

Setting

36 medical centers in the United States



Figure 2

Overall survival (OS) for previous TACE (red line) and TACE-naïve (black line) participants, with a median OS of (95% confidence interval [CI]: 15.4–25.2) and 21.5 months (95% CI: 14.9–29.9), respectively. TACE = transarterial chemoembolization.

Summary

Transarterial chemoembolization is an established treatment for hepatocellular carcinoma, serving as both a bridge to transplantation and as a definitive therapy. For patients whose disease burden is refractory to transarterial chemoembolization, systemic therapy, ablation, and transarterial radioembolization with yttrium-90 may be offered. Two single-center studies have shown radioembolization to be successful after chemoembolization however both studies had a relatively small sample size. This study aimed to analyze the outcomes of radioembolization in a larger multicenter patient population, comparing those with and without prior transarterial chemoembolization.



This study included 262 participants from 36 medical centers throughout the United States, using data obtained from the Radiation-Emitting SIR-Spheres in Nonresectable liver tumor registry. The study cohort included patients with treatment-naïve hepatocellular carcinoma or those who underwent prior transarterial chemoembolization. Patients with previous procedures, ablation, external beam radiation, or systemic therapy were excluded. The chemoembolization and treatment-naive groups consisted of 93 and 169 participants, respectively. There was no significant difference in age, sex, Child-Pugh, or Barcelona Clinic Liver Cancer Stages between the two groups. Both groups had significant proportion of participants with Barcelona Clinic Liver Cancer stages of B and C. The only notable difference between the two groups was that the chemoembolization group had more multifocal disease, while the treatment naïve group had a larger index tumor diameter.



Participants underwent treatment with resin Y90 microspheres and the median delivered activity was similar for two groups. The primary outcome of this study was overall survival, measured in months from date of radioembolization treatment to the date of death, completion of the study, or last follow-up. Secondary outcomes included best tumor response by the modified Response Evaluation Criteria in Solid Tumors and treatment toxicities at 6 months after radioembolization. Objective response rate was defined as the sum of complete and partial responses, while disease control rate further included stable disease.



In this study, the median overall survival for patients in the chemoembolization (22.3 months) and treatment-naive (21.5 months) groups showed no significant difference. Stratifying by Child-Pugh classification or Barcelona Clinic Liver Cancer stages did not change the results. Objective response rate at 6 months showed no significant difference between the two groups, at 49% and 64%, respectively. Disease control rates were achieved in 73% for the chemoembolization group and 86% for the treatment-naive group. Cox Proportional Hazard analysis identified Barcelona Clinic Liver Cancer Stage A, index tumor ≤5 cm, and Child-Pugh Class A as the strongest predictors of overall survival. Solitary lesion and no previous chemoembolization did not predict overall survival. Grade 3 or greater hepatic toxicities were comparable.



Even though radioembolization is gaining popularity as a first-line treatment given the favorable overall survival compared to drug-eluting embolic chemoembolization, as seen in the TRACE and LEGACY trials, transarterial chemoembolization remains the first-line option in many centers given its high profile in multispecialty treatment recommendations. This study has provided more robust evidence for the practice of transitioning patients with chemoembolization refractory hepatocellular carcinoma to radioembolization as the latter can achieve similar rates of overall survival, imaging response, and safety profile in this patient population compared to patients who were treatment naïve.



The study acknowledged the inherent limitations associated with real-world data and registries. As well as differences in practice patterns at some of the institutions and a lack of centralized interpretation of image findings. The authors suggested future research focusing on initiating radioembolization for patients with prior chemoembolization treatments and comparing radioembolization with systemic therapies.

Commentary

The purpose of this study was to assess the impact of prior chemoembolization on outcomes in patients with hepatocellular carcinoma undergoing radioembolization. Given that this area has been previously studied but in small patient populations at single institutions, the current study provided the much-needed supporting evidence from a large multi-institutional patient cohort. The methods and execution of the study were adequate given the data was based on a prospective observational registry. However, as the authors have pointed out, some standardizing measures could have improved the study, such as having independent radiologist(s) re-evaluate the response on imaging. The study comprehensively discussed the statistical analysis methods, which were appropriate for the data collected. The results supported previous findings demonstrating that radioembolization is a safe and effective treatment after chemoembolization. Future research focusing on radioembolization in patients with prior chemoembolization should employ robust study parameters such as an randomized clinical trial for more conclusive evidence. The authors also described that Kudo et al. performed a retrospective matched-pair study that determined overall survival was longer in Lenvatinib (37.9 months) compared with transarterial chemoembolization (21.3 months). Future research comparing radioembolization with systemic therapy and examining the effects of combination therapy may further impact the hepatocellular carcinoma treatment algorithm. Overall, while the study provided evidence that radioembolization is a safe and effective option in patients with chemoembolization refractory hepatocellular, it also highlights research areas in need of comparative data and robust conclusions.

Post Author

Aric Patel, MS
OMS-IV
University of New England
College of Osteopathic Medicine