title: What is the optimal treatment of large brain metastases? An argument for a multidisciplinary approach.
abstract: OBJECTIVE
  Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity.
  
  
  METHODS
  We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method.
  
  
  RESULTS
  The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity.
  
  
  CONCLUSIONS
  Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.
authors.affiliation: Department of Neurosurgery, Stanford University Medical Center, Stanford, CA 94305-5847, USA.
authors.forename: Clara Y H
authors.initials: CY
authors.lastname: Choi
authors.forename: Steven D
authors.initials: SD
authors.lastname: Chang
authors.forename: Iris C
authors.initials: IC
authors.lastname: Gibbs
authors.forename: John R
authors.initials: JR
authors.lastname: Adler
authors.forename: Griffith R
authors.initials: GR
authors.lastname: Harsh
authors.forename: Banu
authors.initials: B
authors.lastname: Atalar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lieberson
authors.forename: Scott G
authors.initials: SG
authors.lastname: Soltys
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery*; D003131:Combined Modality Therapy / Q000379:methods; D016371:Cranial Irradiation / Q000379:methods; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016634:Radiosurgery / Q000379:methods*; D018714:Radiotherapy, Adjuvant / Q000379:methods; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult