title: Large intracranial metastatic tumors treated by Gamma Knife surgery: outcomes and prognostic factors.
abstract: OBJECTIVE
  The use of radiosurgery has been well accepted for treating small to medium-size metastatic brain tumors (MBTs). However, its utility in treating large MBTs remains uncertain due to potentially unfavorable effects such as progressive perifocal brain edema and neurological deterioration. In this retrospective study the authors evaluated the local tumor control rate and analyzed possible factors affecting tumor and brain edema response.
  
  
  METHODS
  The authors defined a large brain metastasis as one with a measurement of 3 cm or more in at least one of the 3 cardinal planes (coronal, axial, or sagittal). A consecutive series of 109 patients with 119 large intracranial metastatic lesions were treated with Gamma Knife surgery (GKS) between October 2000 and December 2012; the median tumor volume was 16.8 cm(3) (range 6.0-74.8 cm(3)). The pre-GKS Karnofsky Performance Status (KPS) score for these patients ranged from 70 to 100. The most common tumors of origin were non-small cell lung cancers (29.4% of cases in this series). Thirty-six patients (33.0%) had previously undergone a craniotomy (1-3 times) for tumor resection. Forty-three patients (39.4%) underwent whole-brain radiotherapy (WBRT) before GKS. Patients were treated with GKS and followed clinically and radiographically at 2- to 3-month intervals thereafter.
  
  
  RESULTS
  The median duration of imaging follow-up after GKS for patients with large MBTs in this series was 6.3 months. In the first follow-up MRI studies (performed within 3 months after GKS), 77 lesions (64.7%) had regressed, 24 (20.2%) were stable, and 18 (15.1%) were found to have grown. Peritumoral brain edema as defined on T2-weighted MRI sequences had decreased in 79 lesions (66.4%), was stable in 21 (17.6%), but had progressed in 19 (16.0%). In the group of patients who survived longer than 6 months (76 patients with 77 MBTs), 88.3% of the MBTs (68 of 77 lesions) had regressed or remained stable at the most recent imaging follow-up, and 89.6% (69 of 77 lesions) showed regression of perifocal brain edema volume or stable condition. The median duration of survival after GKS was 8.3 months for patients with large MBTs. Patients with small cell lung cancer and no previous WBRT had a significantly higher tumor control rate as well as better brain edema relief. Patients with a single metastasis, better KPS scores, and no previous radiosurgery or WBRT were more likely to decrease corticosteroid use after GKS. On the other hand, higher pre-GKS KPS score was the only factor that showed a statistically significant association with longer survival.
  
  
  CONCLUSIONS
  Treating large MBTs using either microsurgery or radiosurgery is a challenge for neurosurgeons. In selected patients with large brain metastases, radiosurgery offered a reasonable local tumor control rate and favorable functional preservation. Exacerbation of underlying edema was rare in this case series. Far more commonly, edema and steroid use were lessened after radiosurgery. Radiosurgery appears to be a reasonable option for some patients with large MBTs.
authors.affiliation: Departments of Radiation Oncology and.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Lee
authors.forename: Chun-Po
authors.initials: CP
authors.lastname: Yen
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.forename: Jason
authors.initials: J
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001929:Brain Edema / Q000209:etiology*; D001932:Brain Neoplasms / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016634:Radiosurgery / Q000009:adverse effects* / Q000295:instrumentation; D012189:Retrospective Studies; D016896:Treatment Outcome