Global landscape of yttrium-90 clinical trials: a systematic registry-based analysis

Background   Yttrium-90 (Y-90) selective internal radiation therapy (SIRT) has emerged as an important locoregional treatment for liver and other malignancies. However, despite its expanding clinical application, the global landscape of Y-90 clinical trials has not been systematically characterized. The objective of this study was to systematically characterize the global portfolio of Y-90 clinical trials, compare liver cancer with non–liver cancer indications, and evaluate patterns of result dissemination.
Methods  We conducted a cross-sectional registry-based analysis of all Y-90 clinical trials registered on ClinicalTrials.gov from 2000 to 2025. Trial characteristics, temporal and geographic patterns, methodological features, and reported outcomes were summarized. Comparative analyses were performed between liver cancer and non–liver cancer trials. Registry entries were linked to PubMed to assess publication output.
Results  A total of 373 eligible trials were identified. Most were interventional (86.9%), treatment-focused (93.1%), and single-center (70.1%), with small sample sizes (54.2% enrolled ≤ 30 participants). Nearly half were phase 1–2 (47.7%) or phase 2–3 (45.8%), with only 6.5% reaching phase 3–4. Randomization was reported in 43.5% of trials, but masking was rare (3.4%). Geographically, studies were concentrated in North America (68.4%), with limited representation from Asia (11.5%) despite its high disease burden. Liver cancer accounted for 44.5% of trials and was more likely than non–liver cancer studies to be randomized, advanced-phase, and Asia-based. Among 93 (24.9%) discontinued trials, accrual difficulties were the leading cause (38.7%). Only 68 trials (18.2%) had published results, with efficacy and safety endpoints more consistently reported in liver cancer studies.
Conclusions  Y-90 research has expanded globally, especially in liver cancer, but trials remain largely small, early phase, and geographically uneven, with limited dissemination. Strengthening methodological rigor through adequately powered multicenter trials, enhancing transparency in result dissemination, and encouraging broader research efforts in high-burden regions such as Asia may help further clarify the optimal role of Y-90 in oncology.
© The Author(s) 2026.