Cross-Cancer Circulating Proteins for the Prognosis of Primary and Metastatic Liver Cancer Treated with Local Ablation: Post Hoc Exploratory Analysis of the ESTIMATE Trial.

Purpose To identify a panel based on circulating proteins to predict clinical outcomes after local ablation across patients with primary and metastatic liver cancer to improve patient selection. Materials and Methods This exploratory post hoc analysis is derived from ESTIMATE, a prospective controlled trial (DRKS registration no. 00010587) evaluating progression-free survival and overall survival (OS) after local ablation of liver malignancies between 2017 and 2023. Baseline plasma samples from patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or metastatic breast or colorectal cancer treated with interstitial brachytherapy were profiled using an immunoassay panel. Group comparisons used t tests or Mann-Whitney U tests. Survival was assessed using Kaplan-Meier, log-rank, and Cox regression analyses. Multivariable Cox models were adjusted for tumor type, number of lesions, and treatment response. Model discrimination was assessed using time-dependent areas under the receiver operating characteristic curves (AUCs) for OS, with bootstrap resampling used to estimate optimism-corrected performance. Results In total, 103 patients (62 male; mean age, 67.5 years; range, 36-87 years) were included. Elevated chemokine (C-C motif) ligand 20, interleukin-15, and interleukin-8 levels were associated with poor clinical outcomes across various liver tumors and were therefore incorporated into an immune-inflammatory prognostic model (all P < .05). AUC analysis revealed the predictive accuracy of the model for OS at 6, 12, and 18 months (AUCs: 0.70, 0.72, and 0.74, respectively), and bootstrap optimism-corrected performance ranged from 0.61 to 0.68. Conclusion The findings revealed a cross-cancer panel of circulating proteins that reliably and effectively predicts treatment response and prognosis after local ablation of liver malignancies. Keywords: Prognosis & Prediction, Treatment Response Assessment, Ablation Techniques, Interventional Oncology, Molecular Imaging-Clinical Translation, Molecular Imaging-Cancer, Liquid Biopsy, Abdomen/GI, Decision Analysis, Evidence-based Medicine, Outcomes Analysis, Liver Cancer, Interstitial Brachytherapy, Cross-Cancer Biomarkers, Proximity Extension Assay German Clinical Trials Register no. DRKS 00010587 Supplemental material is available for this article. © RSNA, 2026.