title: Dose escalation of whole-brain radiotherapy for brain metastases from melanoma.
abstract: OBJECTIVE
  The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the "standard" regimen 30 Gy in 10 fractions (10x3 Gy).
  
  
  METHODS
  Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class.
  
  
  RESULTS
  At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC.
  
  
  CONCLUSIONS
  Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.
authors.affiliation: Department of Radiation Oncology, University Hospital Schleswig-Holstein, Lubeck, Germany. Rades.Dirk@gmx.net
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Christine
authors.initials: C
authors.lastname: Heisterkamp
authors.forename: Stefan
authors.initials: S
authors.lastname: Huttenlocher
authors.forename: Guenther
authors.initials: G
authors.lastname: Bohlen
authors.forename: Juergen
authors.initials: J
authors.lastname: Dunst
authors.forename: Tiina
authors.initials: T
authors.lastname: Haatanen
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
mesh_terms: D000367:Age Factors; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D016371:Cranial Irradiation / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012737:Sex Factors; D012878:Skin Neoplasms; D016019:Survival Analysis