Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study

Abstract

Background and aims: Locoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres.

Approach and results: LEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver.

Conclusions: In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

FIG. 1

Flow diagram of patient study status.

FIG. 2

Waterfall plot of greatest decrease in target lesion size and best overall tumor response by localized mRECIST among evaluable patients in the LEGACY study (n = 143). Abbreviations: CR, complete response; NE, not evaluable; PR, partial response; SD, stable disease.

FIG. 3

Swimmer plot of TTR and DoR by localized mRECIST (confirmed response).

FIG. 4

Detailed spider plot of percent change from baseline in target lesion by localized mRECIST (confirmed response).

FIG. 5

Kaplan‐Meier analysis of TTP (A), PFS (B), and OS (C) by transplantation/resection status.