Improved Local Control with Stereotactic Body Radiation Therapy Compared to Radiofrequency Ablation in the Treatment of Unresectable Intrahepatic Metastases

Abstract

For patients with a limited number of unresectable intrahepatic metastases, stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are appealing focal liver therapies; however, direct comparisons of these modalities are lacking. We hypothesized that both modalities would provide excellent freedom from local progression (FFLP) for small metastases, with an advantage favoring SBRT when treating larger lesions. From 2000 to 2015, 161 patients with 282 pathologically diagnosed unresectable liver metastases were treated with RFA or SBRT at a single institution. Retrospective analysis of these patients was approved through the local institutional review board. The primary outcome, FFLP, was defined as the time from the start of SBRT/RFA until local progression of the treated lesion. Overall survival (OS) was measured at the patient level as the time from treatment start to death from any cause. The effect of treatment and covariates on FFLP was modeled using a mixed-effects Cox model with patient-level random effects to adjust for correlation between multiple lesions in the same patient. We applied inverse probability of treatment weighting to the Kaplan-Meier method and Cox models for FFLP to adjust for potential imbalances in treatment assignment. Sixty-nine patients were treated with RFA to 112 metastases and 92 patients were treated with SBRT to 170 metastases. Median follow-up for all patients was 24.6 months. Patients receiving SBRT had larger tumors than those treated with RFA (2.7 cm vs. 1.8 cm, P < 0.01). The most common histology in both groups was colon/rectal adenocarcinoma (66% overall). On univariate analysis tumor size was associated with worse FFLP for RFA (HR = 1.57, 95% CI = 1.15-2.14, P < 0.01), but not SBRT (HR = 1.38, 95% CI = 0.76-2.51, P = 0.3). The 2-year FFLP for patients treated with SBRT was 88.2% compared to 73.9% for patients receiving RFA, which approached statistical significance (P = 0.06). For tumors larger than 2 cm in diameter, RFA was associated with worse FFLP (HR = 3.54, 95% CI = 1.08-11.6, P < 0.01). 2-year OS was 51.1% and there was no difference between SBRT and RFA (P = 0.81). On multivariate analysis, treatment with SBRT (HR = 0.22, 95% CI = 0.08-0.60, P = 0.003) and decreasing tumor size (HR = 0.64, 95% CI = 0.48-0.85, P < 0.01) were associated with improved FFLP. Grade 3+ treatment related toxicity was rare and there was no difference in toxicity between SBRT (n = 4) and RFA (n = 6). Treatment with SBRT or RFA is well tolerated and provides excellent and similar local control for intrahepatic metastases less than 2 cm in size. For tumors greater than 2 cm in size, treatment with SBRT is associated with improved FFLP, and may be the preferable treatment option.