Thermal Ablation versus Stereotactic Ablative Body Radiotherapy to Treat Unresectable Colorectal Liver Metastases: A Comparative Analysis from the Prospective Amsterdam CORE Registry

Abstract

Thermal ablation and stereotactic ablative radiotherapy (SABR) are techniques to eradicate colorectal liver metastases (CRLM). This study compares the safety, efficacy and long-term oncological outcomes of these treatment methods. All prospectively registered patients (AmCORE registry) treated with thermal ablation or SABR alone for unresectable CRLM between 2007 and 2020 were analyzed using multivariate Cox-proportional hazard regression. In total 199 patients were included for analysis: 144 (400 CRLM) thermal ablation; 55 (69 CRLM) SABR. SABR patients were characterized by older age (p = 0.006), extrahepatic disease at diagnosis (p = 0.004) and larger tumors (p < 0.001). Thermal ablation patients were more likely to have synchronous disease, higher clinical risk scores (p = 0.030) and higher numbers of CRLMs treated (p < 0.001). Mortality was zero and morbidity low in both groups: no serious adverse events were recorded following SABR (n = 0/55) and nine (n = 9/144 [6.3%]; all CTCAE grade 3) after thermal ablation. SABR was associated with an inferior overall survival (OS) (median OS 53.0 months vs. 27.4 months; HR = 1.29, 95% CI 1.12-1.49; p = 0.003), local tumor progression-free survival (LTPFS) per-tumor (HR = 1.24, 95% CI 1.01-1.52; p = 0.044) and local control per-patient (HR = 1.57, 95% CI 1.20-2.04; p = 0.001) and per-tumor (HR = 1.89, 95% CI 1.44-2.49; p < 0.001). In this study thermal ablation was superior to SABR with regard to OS, LTPFS and local control, albeit at the cost of a limited risk of serious adverse events. Further studies are required to assess whether the worse outcomes following SABR were the effect of true differences in ablative treatment or a result of residual confounding.

Keywords: colorectal liver metastases (CRLM); microwave ablation (MWA); radiofrequency ablation (RFA); stereotactic ablative radiotherapy (SABR); thermal ablation.

Figure 1

Flowchart of selected patients from the prospective Amsterdam Colorectal Liver Metastases Registry (AmCORE). CRLM = colorectal liver metastases, RFA = radiofrequency ablation, MWA = microwave ablation, SABR = stereotactic ablative radiotherapy.

Figure 2

Patients treated with SABR (blue) were older, had larger tumors and higher rates of extrahepatic disease. Patients treated with thermal ablation (red) had higher numbers of CRLMs, higher Fong’s clinical risk scores and higher rates of synchronous disease. All other variables were evenly distributed.

Figure 3

Survival curves following thermal ablation (red) and stereotactic ablative radiotherapy (SABR) (blue) for unresectable colorectal liver metastases: overall survival (A), distant progression-free survival (B), local tumor progression free survival, per-patient and per-tumor (C,D) and local control allowing repeat treatment, per-patient and per-tumor (E,F).

Figure 4

Univariate Subgroup Cox Regression Analyses of SABR versus thermal ablation associated with OS.

Figure 5

Follow-up cross-sectional ceCT images of a segment IVa-VIII CRLM treated with SABR. At three months ceCT showed a typical halo sign of hypoattenuation directly surrounding the irradiated, largely necrotic tumor (white arrowheads) and characteristic hyperattenuation of the perilesional liver parenchyma, which correlates with radiation induced hepatic fibrosis (A). At six months a solid ring-enhancing nodular lesion (white arrow) can be appreciated at the right-lateral margin of the irradiated tumor (B). This appearance is highly specific for the presence of local tumor progression post-SABR. Follow-up ceCT at six and 12 months (C,D) further confirmed the local tumor progression.

Figure 6

Follow-up cross-sectional ceCT images of a CRLM treated with thermal ablation. At six months a typical sharply demarcated hypoattenuating scar lesion (white arrowheads) is visible (A). At 12 months a characteristic “incomplete ring sign” (white arrow) at the left margin of the ablation zone can be appreciated (B), which, especially when combined with 18F-FDG avidity, is highly specific for local tumor progression following thermal ablation. Follow-up ceCT at 15 and 18 months (C,D) further confirmed local tumor progression.

Figure 7

Univariate Subgroup Cox Regression Analyses of SABR versus thermal ablation associated with LTPFS per tumor.

Figure 8

Local tumor progression-free survival curves (LTPFS) following thermal ablation (red) and stereotactic ablative radiotherapy (blue) for unresectable colorectal liver metastases according to subgroup analyses: stratified by CRLM < 3 cm versus 3–5 cm (A) and by specific treatment method radiofrequency ablation (RFA), microwave ablation (MWA), conventional stereotactic ablative radiotherapy (SABR) and selective MR-guided ablative radiotherapy (SMART) (B).