Jun Chen, Tianyou Shao, Bi Sheng
In this retrospective comparative analysis, the addition of CT/ultrasound-guided 125I seed implantation to Atezo/Bev was associated with improved tumor response and survival outcomes compared to Atezo/Bev alone in patients with recurrent HCC after hepatectomy, with a manageable safety profile. These findings suggest a potential benefit of combining local brachytherapy with systemic immunotherapy, but causality cannot be established due to the observational design. Prospective randomized trials are warranted to confirm these results.
PURPOSE: This study evaluated whether combining Iodine-125 (125I) seed implantation with atezolizumab and bevacizumab (Atezo/Bev) improves outcomes compared to Atezo/Bev alone in patients with recurrent HCC after hepatectomy.
METHODS: This retrospective comparative analysis included patients with recurrent HCC after hepatectomy treated between January 2020 and December 2025. Patients were divided into a Combination Group (125I seed implantation plus Atezo/Bev, n=79) and a Control Group (Atezo/Bev alone, n=94). To minimize selection bias, propensity score matching (PSM) was performed using a 1:1 nearest-neighbor algorithm, yielding 62 matched pairs. A 14-day landmark analysis was conducted to address immortal-time bias. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Tumor response was assessed by RECIST 1.1. Treatment effects were estimated using stratified Cox proportional hazards models with matched pairs as strata, and a multivariable stratified Cox model was performed as a sensitivity analysis.
RESULTS: After propensity score matching, 62 matched pairs were obtained with satisfactory covariate balance (all SMDs < 0.1). The Combination Group showed significantly higher objective response rate (63.3% vs 46.8%, P = 0.03) and disease control rate (81.0% vs 63.8%, P = 0.012). In the matched cohort, median PFS was significantly longer in the Combination Group (16.0 months vs 8.0 months; HR = 0.49, 95% CI: 0.35-0.68, P < 0.001), as was median OS (31.0 months vs 16.0 months; HR = 0.53, 95% CI: 0.38-0.74, P < 0.001). Stratified Cox regression confirmed treatment modality as an independent prognostic factor for both OS and PFS, with consistent results in multivariable sensitivity analyses. Grade 3-4 treatment-related adverse events occurred in 22.8% (18/79) of the Combination Group and 20.2% (19/94) of the Control Group (P = 0.68). Liver-related AEs and hepatic decompensation events were comparable between groups (all P > 0.05), with no radiation-induced liver disease observed. Procedural complications from seed implantation were minimal (pneumothorax in 2.5%, self-limited hematoma in 1.3%), with no procedure-related mortality.
CONCLUSION: In this retrospective comparative analysis, the addition of CT/ultrasound-guided 125I seed implantation to Atezo/Bev was associated with improved tumor response and survival outcomes compared to Atezo/Bev alone in patients with recurrent HCC after hepatectomy, with a manageable safety profile. These findings suggest a potential benefit of combining local brachytherapy with systemic immunotherapy, but causality cannot be established due to the observational design. Prospective randomized trials are warranted to confirm these results.