title: Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study.
abstract: BACKGROUND
  A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications.
  
  
  METHODS
  Eighty-eight patients with large brain metastases ≥10 cm(3) in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm(3) for individual lesions. Univariate and multivariate analyses were conducted.
  
  
  RESULTS
  As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm(3) (median, 16.2 cm(3)) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10-19.9 cm(3), 2) 20-29.9 cm(3) and 3) ≥30 cm(3). The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm(3) were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection.
  
  
  CONCLUSIONS
  Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction of complications (risk line for hypofractionation), as well as Kjellberg's necrosis risk line used in single-session radiosurgery, is effective and safe for large brain metastases or other lesions in critical areas.
authors.affiliation: Cyber Center, Kanto Neurosurgical Hospital, 1120 Dai, Kumagaya, Saitama, 360-0804, Japan. chair.ino@instno-med.org.|Neurosurgery and Radiation Oncology, Institute of Neural Organization, 1120 Dai, Kumagaya, Saitama, 360-0804, Japan. chair.ino@instno-med.org.
authors.forename: Hiroshi K
authors.initials: HK
authors.lastname: Inoue
authors.affiliation: Cyber Center, Kanto Neurosurgical Hospital, 1120 Dai, Kumagaya, Saitama, 360-0804, Japan. h-sato0808@hotmail.co.jp.
authors.forename: Hiro
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Radiation Oncology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan. ysuzui@fmu.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. junsaito@gunma-u.ac.jp.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Saitoh
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. snoda@gunma-u.ac.jp.
authors.forename: Shin-ei
authors.initials: SE
authors.lastname: Noda
authors.affiliation: Cyber Center, Kanto Neurosurgical Hospital, 1120 Dai, Kumagaya, Saitama, 360-0804, Japan. cyber@kantounouge.com.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Seto
authors.affiliation: Gunma University Heavy-ion Medical Research Center, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. torikai@gunma-u.ac.jp.
authors.forename: Kota
authors.initials: K
authors.lastname: Torikai
authors.affiliation: Proton Medical Research Center, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki, 365-8576, Japan. hsakurai@pmrc.tsukuba.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. cyber@kantounouge.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods / Q000592:standards*; D012307:Risk Factors; D015996:Survival Rate