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

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