Hypofractionated image-guided breath-hold SABR (stereotactic ablative body radiotherapy) of liver metastases--clinical results

Abstract

Purpose: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR.

Patients and methods: 19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold) were analysed regarding overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC), acute and late toxicity.

Results: PTV (planning target volume)-size was 108 ± 109cm3 (median 67.4 cm3). BED2 (Biologically effective dose in 2 Gy fraction) was 83.3 ± 26.2 Gy (median 78 Gy). Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months). Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999). Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08) when a volume cut-off of 67 cm3 was used.No local relapse was observed at PTV-sizes < 67 cm3 and BED2 > 78 Gy. No acute clinical toxicity > °2 was observed. Late toxicity was also ≤ °2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C-reactive protein.

Conclusions: A trend to statistically significant correlation of local progression was observed for BED2 and PTV-size. Dose-levels BED2 > 78 Gy cannot be reached in large lesions constituting a significant fraction of this series. Image-guided SABR (igSABR) is therefore an effective non-invasive treatment modality with low toxicity in patients with small inoperable liver metastases.

Figure 1

Daily positioning with BAT®. Before (A-B) and after (C-D) position correction. Surrogate structures and PTV are marked with colors: orange, liver; green, PTV; blue, portal vein; red, liver veins. E-F: Alternative repeat breath-hold positioning with CBCT. Green, CBCT; magenta, planning-CT.

Figure 2

Kaplan-Meier-curves for all patients.A.) Overall-survival. B.) Progression-free-survival. C.) Local control.

Figure 3

A) Local control of patients with BED2 ≥ 78 Gy (red) and <78 Gy (black), p = 0.0999 (trend to significance; Kaplan-Meier log-rank test).B) Local control of patients with PTV < 67 cm³ (red) and ≥67 cm³ (black), p = 0.2412, not significant.

Figure 4

Radiation plan, pretreatment- and posttreatment MRI of a patient with two small liver metastases of a melanoma treated with 1x26Gy in 1 PTV. The lesions remain locally controlled (follow-up of 4 years).