Fractionated Stereotactic Radiotherapy using CyberKnife for the Treatment of Large Brain Metastases: A Dose Escalation Study

AimsTo 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 methodsBetween 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.ResultsOverall 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.ConclusionsThe 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.