Fractionated stereotactic radiotherapy using CyberKnife for the treatment of large brain metastases: a dose escalation study.

AIMS

To evaluate the toxicity and efficacy of fractionated stereotactic radiotherapy (FSRT) with doses of 18-30 Gy in three fractions and 21-35 Gy in five fractions against large brain metastases.

MATERIALS AND METHODS

Between 2005 and 2012, 61 large brain metastases (≥ 2.5 cm in maximum diameter) of a total of 102 in 54 patients were treated with FSRT as a first-line therapy. Neurological symptoms were observed in 47 of the 54 patients before FSRT. Three fractions were applied to tumours with a maximum diameter ≥ 2.5 cm and <4 cm, and five fractions were used for brain metastases ≥ 4 cm. After ensuring that the toxicities were acceptable (≤ grade 2), doses were escalated in steps. Doses to the large brain metastases were as follows: level I, 18-22 Gy/three fractions or 21-25 Gy/five fractions; level II, 22-27 Gy/three fractions or 25-31 Gy/five fractions; level III, 27-30 Gy/three fractions or 31-35 Gy/five fractions. Level III was the target dose level.

RESULTS

Overall survival rates were 52 and 31% at 6 and 12 months, respectively. Local tumour control rates of the 102 total brain metastases were 84 and 78% at 6 and 12 months, respectively. Local tumour control rates of the 61 large brain metastases were 77 and 69% at 6 and 12 months, respectively. Grade 3 or higher toxicities were not observed.

CONCLUSIONS

The highest dose levels of 27-30 Gy/three fractions and 31-35 Gy/five fractions seemed to be tolerable and effective in controlling large brain metastases. These doses can be used in future studies on FSRT for large brain metastases.