Effectiveness and safety of selective internal radiation therapy using yttrium-90 glass microspheres for hepatocellular carcinoma: real-world results from the multi-center prospective PROACTIF cohort of 989 patients
Mené en France sur 989 patients atteints d'un carcinome hépatocellulaire, cet essai multicentrique évalue l'efficacité, du point de vue de la survie globale et de la qualité de vie, d'une radiothérapie interne sélective utilisant des microsphères en verre marquées à l'yttrium-90
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.
eClinicalMedicine , article en libre accès, 2026