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Monday, July 3, 2017

Segmental Y90 vs Segmental TACE for Localized HCC


Summary

Embolotherapies play an important role in the management of hepatocellular carcinoma (HCC), but the optimal modality remains controversial. Transarterial chemoembolization (TACE) remains the most widely accepted option for HCC, but some studies have suggested that transarterial radioembolization (TARE) may have superior outcomes. Padia et al present a single center retrospective series comparing segmental TARE versus TACE for HCC. Due to inherent biases in the use of these modalities over time (i.e. preferential use of TACE to bridge for liver transplantation), there were baseline differences in the patient population including higher ECOG performance scores in the TACE group (p=0.003), larger tumor size in the TARE group (mean diameter 3.2 versus 2.6 cm, p<0.001), higher volume of tumor infiltration in the TARE group (23% versus 9%, p=0.01), and greater incidence vascular invasion in the TARE group (18% versus 1%, p<0.001). Recognizing the potential for bias from these baseline differences, the authors used a propensity score adjustment approach for the analyses. TARE was performed with glass microspheres (Therasphere) in all cases, with target doses of >200 Gy for ablative intent (median administered dose: 1.59 GBq). TACE was performed using drug eluting beads (100-300 um LC beads loaded with doxorubicin) or conventional ethiodized oil, doxorubicin emulsion following by 300-500 um microspheres. Tumor responses were assessed in the index lesion as well as whole liver per RECIST 1.1. TARE demonstrated significantly higher complete response rate, both by index lesion (TARE 92% versus TACE 74%, p=0.001) and overall liver (TARE 84% versus TACE 58%, p<0.001), with statistical significance in both unadjusted and propensity-score adjusted analyses. Survival analysis from the time of first embolotherapy demonstrated significantly longer median progression-free survival (PFS) in the TARE group (564 days) compared to TACE (271 days), p=0.02, with significance maintained on inverse probability of treatment weighting (IPTW) propensity score adjustment. Overall survival (OS) was; however, not significantly different between the two groups. At 1 year, the local tumor recurrent rate was significantly lower following TARE (8%) compared to TACE (30%). A significantly higher proportion of patients receiving TARE achieved optimal response after 1 treatment compared to TACE (93% versus 79%, p=0.012). Both modalities had low rates of clinical and biochemical toxicities (Common Terminology Criteria for Adverse Events grade 3 or higher), with no significant difference in the overall rate of complications, although there was a higher rate of pain in the TARE group (7.6% versus 1%), and higher rate of post-embolization syndrome in the TACE group (8.8% versus 2.3%).



Commentary

In HCC, extensive experience with TACE has cemented the modality as the mainstay choice for many providers and institutions, but there is a growing body of evidence supporting TARE. Comparisons between embolotherapy modalities are inherently challenging due to variations in patient selection and technical approach, particularly in retrospective studies, which contribute bias and limit generalizability of results. To circumvent some of these challenges, Padia et al focused on only cases of segmental TARE and TACE and applied propensity score adjustment to their outcomes analysis. The findings of improved index lesion and whole liver complete response rates and longer median PFS following segmental TARE using an “ablative” dose suggest that this approach may be superior to TACE. These results were echoed by findings of the PREMIERE trial (a prospectively randomized controlled trial comparing TARE [lobar and selective] with conventional TACE, Salem et al. Gastroenterology 2016) that also demonstrated significantly longer median time to progression in the TARE group, although no difference in imaging response rate was shown. In this study, additional benefits of TARE included lower 1-year local recurrence rates, which were similar to rates reported following thermal ablation or surgery, and ability to achieve optimal response after 1 treatment in a higher percentage of patients compared to TACE. There are several limitations to consider when evaluating these results, in addition to the inherent biases of retrospective approach. Although the authors used a sound statistical approach to reduce the impact of baseline differences in treatment populations, there may still be residual bias in the results. Furthermore, it is never stated whether the patients in the study were embolotherapy na├»ve, or the degree of treatment crossover that occurred following the first treatment, which could confound the survival analysis. Nonetheless, this study provides convincing support for the use of segmental TARE over TACE for HCC to achieve better local tumor control. Many institutions preferentially use TACE as a bridge to liver transplantation, and results like these suggest that TARE could potentially be the superior modality for reducing the rate of waitlist drop-out.

Click here for abstract

Padia SA, Johnson GE, Horton KJ, et al. Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score-Matched Study. J Vasc Interv Radiol 2017; 28:777-85 e1.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
University of Michigan Health Systems

James X. Chen, MD
Resident in Radiology
Hospital of the University of Pennsylvania

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