Safety margin in irradiation of colorectal liver metastases: assessment of the control dose of micrometastases.

BACKGROUND

Micrometastases of colorectal liver metastases are present in up to 50% of lesions. In this study we sought to determine the threshold dose for local control of occult micrometastases in patients undergoing CT (computed tomography)-guided brachytherapy of colorectal liver metastases.

MATERIALS AND METHODS

Nineteen patients demonstrated 34 local tumor recurrences originating from micrometastases after CT-guided brachytherapy of 27 colorectal liver metastases. We considered a local tumor recurrence as originating from a micrometastasis if tumor regrowth occurred adjacent to a formerly irradiated lesion and the distance of the 3D isocenter of the new lesion was <or= 23.5 mm from the previous tumor margin. Follow-up MRI was fused with the planning-CT and dosimetry data. Two reviewers independently indicated the dose exposure at the isocenter of the micrometastases. Statistical analysis included an analysis of variance (ANOVA) using backward selection. 95% tolerance intervals with coverage of 87.5 and 75% of the data of the normal distribution were calculated.

RESULTS

The median distance of the micrometastases to the margin of the originating colorectal metastases was 8.75 mm (1-21 mm). Dose exposure at the isocenter was 12.25 Gy (7-19.8) in median. We stratified according to the distance from the isocenter to the initial tumor margin: <or= 9 mm, > 9-15 mm and > 15 mm. The median dose in the according isocenters was 13.18, 11.6 and 11.85 Gy. The threshold dose failing to prevent micrometastasis growth was sigificantly higher in a subgroup of lesions with <or= 9 mm distance as compared to > 15 mm (13.18 vs 11.85 Gy). Adjuvant chemotherapy correlated with greater distance of micrometastasis growth to the tumor but not with the threshold dose.

CONCLUSION

To prevent loss of local tumor control by continuous growth of micrometastases a threshold dose of 15,4 Gy (single fraction) should be delivered at a distance of 21 mm to the gross tumor margin.