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 <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.

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EClinicalMedicine
Published
2026-04-17
DOI
https://doi.org/10.1016/j.eclinm.2026.103884
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
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article
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article

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

Raphaël Dautry, Emmanuel Durand, Inna Dygai‐Cochet, Massih Ningarhari et al.
EClinicalMedicine
Hepatocellular Carcinoma Treatment and Prognosis
article

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

Raphaël Dautry, Emmanuel Durand, Inna Dygai‐Cochet, Massih Ningarhari, Boris Guiu, Ghoufrane Tlili, Olivier Meyrignac, Christian Sengel, J. Farce, Olivier Rosmorduc, Hélène Regnault, Laëtitia Vercellino, Vincent Habouzit, P. Chevallier, Julie Pellegrinelli, Panteleimon Papadopoulos, Clara Prud’homme, Antoine Boizet, Vincent Di Martino, Romaric Loffroy, Thomas Aparicio, François Ghiringhelli, Éveline Boucher, Anthony Dohan, Xavier Palard-Novello, Sibel Isal, Binal Patel, Maxime Barat, Samuel Lesourd, F. Khemissa Akouz, Arnaud Muller, Aymeric Guibal, Romain Popoff, Thomas Decaens, Julien Edeline, Géraldine Sergent, Haytham Derbel, Frédéric Oberti, Paul Calame, C. Baillet, Julia Chalaye, Thierry Yzet, Julien Ghelfi, Xavier Orry, Yann Touchefeu, Pacôme Fosse, Hicham Kobeiter, Étienne Garin, F. Hubelé, Charles Mastier, Hatem Boulahdour, Y. Rolland, Michel Greget, Jean Frédéric Blanc, I. Brenot-Rossi, Elodie Chevalier, Thierry Debaere, Antoine Bouvier, Claude Somma, Denis Mariano-Goulart, Mohamed Abdel-Rehim, Chalabia Fergani, Jean Romain Risson, Agnès Rode, Eric Vibert, François Godard, Eric Nguyen-Khac, Stéphane Renaud, Clément Bailly, Valérie Laurent, Stéphanie Becker, Julie Roux, Vandici Ovidiu-Florian, Sylvain Manfredi, Eric Vicaut, Gilles Grimon, Guillaume Guthier, Ronan Abral, Arnaud Dieudonné, Lambros Tselikas, Anton Pachev, Olivier Durieux, Kirk Fowers
article en

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.

EClinicalMedicineVol. 95
Centre Hospitalier Universitaire de Grenoble (FR), Institut Gustave Roussy (FR), Boston Scientific (United States) (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Hôpital de la Croix-Rousse (FR), Centre Hospitalier de Perpignan (FR), Hôpital Cochin (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Centre Eugène Marquis (FR), Hôpital Fernand-Widal (FR), Centre Hospitalier Universitaire d'Angers (FR), CHU Dijon Bourgogne (FR), Hôpital Lariboisière (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Hôpital Saint Eloi (FR), Institut Paoli-Calmettes (FR), Hôpital Claude Huriez (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Hôpital de la Timone (FR), Bicêtre Hospital (FR), Hôpital Paul-Brousse (FR), Centre Henri Becquerel (FR)
Boston Scientific Corporation, Sirtex Medical
Good health and well-being
Openalex Percentile: Top 27%
Hepatocellular Carcinoma Treatment and Prognosis
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