title: Fractionated stereotactic radiotherapy using CyberKnife for the treatment of large brain metastases: a dose escalation study.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Radiation Oncology, Yokohama Cyberknife Center, Yokohama, Japan. Electronic address: taro8864@yahoo.co.jp.
authors: T
authors: T
authors: Murai
authors: Nagoya Proton Therapy Center, Nagoya, Japan.
authors: H
authors: H
authors: Ogino
authors: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Y
authors: Y
authors: Manabe
authors: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: M
authors: M
authors: Iwabuchi
authors: Department of Neurosurgery, Tsushima City Hospital, Tsushima, Japan.
authors: T
authors: T
authors: Okumura
authors: Department of Neurosurgery, Tsushima City Hospital, Tsushima, Japan.
authors: Y
authors: Y
authors: Matsushita
authors: Department of Neurosurgery, Tsushima City Hospital, Tsushima, Japan.
authors: Y
authors: Y
authors: Tsuji
authors: Department of Radiology, Tsushima City Hospital, Tsushima, Japan.
authors: H
authors: H
authors: Suzuki
authors: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Y
authors: Y
authors: Shibamoto
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary* / Q000601:surgery*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D016634:Radiosurgery / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D011879:Radiotherapy Dosage
keywords: Cyberknife; fractionated stereotactic radiotherapy; large brain metastases; stereotactic radiosurgery