SIR Today

Y-90 Glass Microsphere Treatment for Intrahepatic Cholangiocarcinoma: Final Results from the Largest Prospective Real-World Study (PROACTIF)

E. Garin, B. Guiu, T. Ghoufrane, I. Brenot-Rossi, C. Bailly, J. Roux, J. Blanc, B. Chanez, Y. Touchefeu, J. Edeline, J. Chalaye, H. Regnault, L. Tselikas, J. Tasu, E. Vibert, A. Rode, P. Chevallier, S. Renaud, J. Goupil, A. Bouvier, M. Greget, G. Sergent, S. Manfredi, A. Dieudonné, E. Vicaut 

Intra‑hepatic cholangiocarcinoma (iCCA) remains one of the most aggressive liver cancers, with limited therapeutic options and poor prognosis. The final results from PROACTIF, a large‑scale, prospective French registry now provides compelling real‑world evidence that trans‑arterial radio‑embolization (TARE) with yttrium‑90 (Y‑90) glass microspheres (TheraSphere™) can extend survival while maintaining an acceptable safety profile.

PROACTIF is the largest prospective, real-world study of the impact of Y-90 on primary liver cancer. Over 1,000 patients with primary liver cancer have been enrolled across 34 French institutions. Researchers have previously released data exploring the beneficial impact of personalized dosimetry on hepatocellular carcinoma patients, as well as interim data.

PROACTIF builds on the DOSISPHERE-01 trial, an SIR 2023 Abstract of the Year, which showed that increasing the tumor dose while controlling normal tissue dose—rather than a standardized dose to perfused volume—improves survival outcomes for patients with HCC.

“The use of personalized dosimetry has been validated by DOSISPHERE-01, but that was a relatively smaller study,” said lead author Etienne Garin, MD, PhD. “The next step is to document the use of personalized dosimetry in wider use, not just at a few centers of excellence in France, but across the country and eventually worldwide.”

The registry study reflects the outcomes of patients who are treated per standard of care with guidance to perform pre-treatment dosimetry according to treatment goals (complete response, disease control, bridge to surgery) and to perform posttreatment dosimetry. 

While over 80% of the study population had HCC, 15% of patients had iCCa, providing a substantial cohort. In total, 207 patients with iCCA were enrolled. Within the cohort, a third (32%) had underlying liver fibrosis or cirrhosis and 53% presented with a solitary tumor. Patients were either treatment‑naïve (52%) or had received prior systemic (34%) or locoregional (7%) therapy; a third received concurrent gemcitabine‑cisplatin chemotherapy.

According to researchers, median overall survival for the full cohort was 21.9 months. Further analysis indicated that overall survival was longer in those with single tumor disease, had not previously been treated and did not have cirrhosis or fibrosis. They also found that patients who later underwent surgery (resection or transplantation) enjoyed the greatest benefit.
These findings cement Y‑90 glass microsphere radio‑embolization as a key therapeutic pillar for iCCA, capable of delivering meaningful survival gains across diverse patient subsets, including those with cirrhosis. Moreover, the 13% rate of subsequent curative surgery or transplantation highlights its role as a bridge to definitive treatment, building a pathway that allowed a significant number of patients to cross over from being inoperable to becoming eligible for life-saving surgery.