Y90: Year in Review

At the 2025 Symposium on Clinical Interventional Oncology (CIO) in Miami, Florida, Robert J. Lewandowski, MD, FSIR, presented “Y90: Year in Review,” a comprehensive update on advances in yttrium-90 (Y-90) radioembolization across hepatocellular carcinoma (HCC), cholangiocarcinoma, and metastatic liver disease. The session highlighted major regulatory milestones, comparative efficacy data, and prospective trials shaping the interventional oncology landscape.

The session began with the landmark DOORwaY⁹⁰ study, the first prospective, multicenter, open-label US trial supporting FDA approval of SIR-Spheres Y-90 for unresectable HCC. Conducted across 18 centers and enrolling 100 patients (median tumor size 2.7 cm), the study achieved a 98.5% overall response rate and 92.2% complete response rate by mRECIST criteria, with 100% local tumor control and a median response duration of 300.5 days. The safety profile was favorable, with 85% mild-to-moderate adverse events and more than 95% of patients achieving stable liver function.

Dr Lewandowski featured several studies emphasizing the potential of radiation segmentectomy (RadSeg) to achieve complete pathologic necrosis (CPN) in patients with HCC. A 2025 study published in the European Journal of Nuclear Medicine and Molecular Imaging showed that tumors treated with specific absorbed-dose thresholds were correlated with higher predictive CPN in early-stage HCC.¹ Comparative data from the Journal of Vascular and Interventional Radiology demonstrated CPN rates by tumor of 83.3% for transarterial radioembolization (TARE) vs 29% for transarterial chemoembolization (TACE).² A March 2025 Journal of Hepatocellular Carcinoma report found RadSeg achieved a faster (1 vs 7 months), more complete (97% vs 83%) response, and better 1-year local control (97% vs 93%) than external-beam radiotherapy. The CPN was also higher in the RadSeg group (76% vs 33%).³

Outside HCC, Dr Lewandowski highlighted a Clinical Nuclear Medicine 2025 series showing that mean tumor doses ≥ 400 Gy,  margin mean absorbed dose ≥350 Gy, and stereotactic tumor irradiation ≥300 Gy were associated with prolonged local-tumor progression-free survival in colorectal liver metastases.⁴ Preliminary results published in Transplant International also suggested that sequential systemic therapy plus TARE (SYS-TARE) could enable liver transplantation in selected patients with intrahepatic cholangiocarcinoma.⁵

The ROWAN trial, a global, open-label, Phase II multicenter study evaluating Y-90 plus durvalumab and tremelimumab, completed enrollment in August 2025. With 100 patients and up potentially 50 sites, it has been called “one of the most significant efforts to explore the synergy between [TARE] and checkpoint blockade immunotherapy.”⁶ Results are expected in 2026 to 2027. Additionally, Dr Lewandowski presented data from the interim analysis of the prospective, real-world PROACTIF registry, which demonstrated a median overall survival of 21.1 months in intermediate and advanced HCC when contemporary multicompartment dosimetry and selective administration were used (873 patients, 32 sites).

The 2025 data reinforce Y-90’s role as a front-line modality in multiple stages of liver cancer and an effective bridging therapy to transplant. The clear dose-response relationship supports individualized dosimetry, while ongoing trials may extend indications beyond HCC. For clinicians, patient selection, dosimetry precision, and integration with systemic therapy remain central to optimizing outcomes.

Dr Lewandowski’s presentation at CIO 2025 highlighted a transformative year for Y-90 radioembolization. Future data from ROWAN and PROACTIF are anticipated to further refine treatment algorithms.

1. Montazeri SA, De la Garza-Ramos C, Silver C, et al. Achieving complete pathologic necrosis in hepatocellular carcinoma treated with radiation segmentectomy before liver transplantation: a comprehensive glass microsphere analysis. Eur J Nucl Med Mol Imaging. 2025;52(9):3145-3150. doi:10.1007/s00259-025-07179-1
2. Sher A, Todd RI, Shilo D, Garcia-Reyes KI, Bishay VL, Patel RI, Patel RS, Fischman AM, Nowakowski FS, Lookstein RA, Tabrizian P, Kim E. Histopathologic response and oncologic outcomes after segmental and subsegmental transarterial chemoembolization and radioembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2025;36(8):1285-1295.e2. doi:10.1016/j.jvir.2025.05.009
3. De la Garza-Ramos C, Montazeri SA, LeGout JD, et al. Radiation segmentectomy or ablative external beam radiation therapy as initial treatment for solitary hepatocellular carcinoma: a multicenter experience. J Hepatocell Carcinoma. 2025;12:553-559. doi:10.2147/JHC.S507267
4. Dimopoulos PM, Sotirchos VS, Dunne-Jaffe C, et al. Voxel-based dosimetry predicts local tumor progression post 90 Y radiation segmentectomy of colorectal liver metastases. Clin Nucl Med. 2025;50(2):133-142. doi:10.1097/RLU.0000000000005565
5. Maspero M, Sposito C, Bongini MA, et al. Liver transplantation for intrahepatic cholangiocarcinoma after chemotherapy and radioembolization: an intention-to-treat study. Transpl Int. 2024;37:13641. doi:10.3389/ti.2024.13641
6. ROWAN study of TheraSphere with durvalumab and tremelimumab in HCC completed enrollment. OncoDaily. August 27, 2025. Accessed November 12, 2025. https://oncodaily.com/oncolibrary/immune-oncology/rowan-study-enrol-complet