title: Relation between local result and total dose of radiotherapy for brain metastases.
abstract: OBJECTIVE
  Some studies published recently focused on the improvement of the treatment results of patients with brain metastases who underwent radiation therapy. They evaluated survival as a measure for the expected improvement, but failed to demonstrate a significant benefit from an increased total dose of radiotherapy. This study was targeted to investigate the effect of dose escalation with a different endpoint, the local response.
  
  
  METHODS
  As a first step, a retrospective analysis of 164 patients treated with a standard regimen of 10 x 3 Gy was performed to find factors correlating with the local result. All patients were systematically followed and underwent regular computed tomography (CT) examinations of the brain after irradiation. The second step was to compare, with respect to local control and survival, 39 patients treated with a total dose of 40-60 Gy with 39 patients treated with the standard regimen selected by means of a matched cohort pairs method.
  
  
  RESULTS
  The retrospective analysis showed a dependence of the local result after irradiation on three parameters: diameter of brain metastases, primary tumor, and tumor histology. Small-cell and adenocarcinoma were found to be more radiosensitive than squamous-cell carcinoma. The highest radiosensitivity was found in breast cancer metastases. The matching procedure was performed with respect to those parameters and also the number of brain metastases and total cerebral tumor volume. The resulting groups were absolutely equivalent and differed only with regard to the total dose applied. The local response (complete or partial remission) was 48-52% after 30 Gy vs. 77% after 40-60 Gy (p < or = 0.05). Survival was not significantly different. A further analysis of the dose-response relationships showed the tendency of control probability to increase with total dose.
  
  
  CONCLUSIONS
  This study suggests that there is a rationale for dose escalation in the treatment of brain metastases with radiotherapy, when local control is the aim. However, it seems questionable whether an improvement in survival results.
authors.affiliation: Department of Radiotherapy, University Hospital of the Saarland, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Nieder
authors.forename: W
authors.initials: W
authors.lastname: Berberich
authors.forename: U
authors.initials: U
authors.lastname: Nestle
authors.forename: M
authors.initials: M
authors.lastname: Niewald
authors.forename: K
authors.initials: K
authors.lastname: Walter
authors.forename: K
authors.initials: K
authors.lastname: Schnabel
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016555:Matched-Pair Analysis; D011879:Radiotherapy Dosage; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis