title: Clinical outcomes of biological effective dose-based fractionated stereotactic radiation therapy for metastatic brain tumors from non-small cell lung cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy10. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method.
  
  
  RESULTS
  Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement.
  
  
  CONCLUSIONS
  This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.
authors.affiliation: Department of Radiation Oncology, Kumamoto University, Kumamoto, Japan. matsutomo_llp@yahoo.co.jp
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Kasei
authors.initials: K
authors.lastname: Kogo
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oya
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden