Abstract
BACKGROUND: Selective Internal Radiation Therapy with yttrium-90 (Y90) has been used for decades, yet guideline recommendations remain inconsistent. High-quality real-world data is needed to guide practice. The objectives of this study were to evaluate effectiveness, safety, and patient quality of life (QoL) with TheraSphere™ treatment in real-world clinical practice, and to identify clinical and dosimetric factors associated with survival. METHODS: PROACTIF was a prospective, open label, non-interventional, all-comers cohort study that recruited patients who received Y90 glass microspheres (TheraSphere™) per local standard of care across 34 French sites (January 2019–January 2024). Co-primary endpoints were overall survival (OS) and QoL. Secondary endpoints included safety, conversion to surgery, and factors associated with OS. OS and time-to-deterioration in QoL (Functional Assessment of Cancer Therapy-Hepatobiliary) were assessed by Kaplan–Meier analysis. Adverse events were descriptively summarized using Common Terminology Criteria for Adverse Events, version 5. Trial registration: ClinicalTrials.gov Identifier, NCT04069468. FINDINGS: Amongst 989 HCC patients, 13·3%/18·9%/57·9%/5·8% were Barcelona Clinic Liver Cancer (BCLC) A/B/C/D, respectively; 35·3% had portal-vein tumor thrombosis (PVT); 74·4% were treated using multicompartment dosimetry, and 53·6% with selective Y90 administration. Mean index lesion dose was 435·4 Gy. For all patients, median OS (mOS) [95% CI] was 21·8 months (M) [20·1–23·3]. mOS was 27·0 M [20·7–31·4] for BCLC B, 21·1 M [18·0–22·8] for BCLC C; 23·1 M [21·6–27·0] without PVT, 24·8 M [19·3–30·3] for patients with Vp1/Vp2; 16·8 M mOS for patients with a pretreatment absorbed dose to the index lesion <200 Gy versus 26·0 M with ≥200 Gy (p < 0·001); 19·7 M for <400 Gy and 30·7 M for ≥400 Gy (p < 0·001). After Y90, 106/989 (10·7%) underwent curative-intent surgery, resulting in a mOS of 48·6 M [40·6-not evaluable], versus 20·1 M [17·7–21·7] without surgery. Median time-to-deterioration in QoL was 10·6 M [9·6–11·7]. Serious adverse events occurred in 7·5% patients; serious treatment-related events in 3·7%. INTERPRETATION: In this large real-world cohort, treatment with Y90 glass microspheres demonstrated favorable effectiveness and safety with meaningful outcomes, especially in PVT patients and following subsequent surgery. PROACTIF showed a strong dose-survival relationship as demonstrated in previous studies, and highlights the potential of a tumor absorbed dose ≥400 Gy to further increase survival. These findings support dosimetry-guided Y90 across all BCLC stages, and should inform future guideline recommendations. FUNDING: Boston Scientific Corporation.