Abstract
BACKGROUND: To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. METHODS: Twenty patients with liver metastases were treated repeatedly (2 - 4 times) at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion), and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy) for different alpha/beta values (2, 3, 10, 20, 100) based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. RESULTS: The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on alpha/beta in the clinically relevant range of alpha/beta = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p < 0.05), and to the number of interventions. In addition, we observed a significant inverse correlation (p = 0.037) between D90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. CONCLUSIONS: Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (alpha/beta ~ 5 Gy). This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD). Repeated small volume irradiation may be applied safely within the limits of this study.