title: Radiosurgery for non-small cell lung carcinoma metastatic to the brain: long-term outcomes and prognostic factors influencing patient survival time and local tumor control.
abstract: OBJECTIVE
  Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non-small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival.
  
  
  METHODS
  A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival. The overall median patient survival time was 15 months (range 1-116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time. Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis.
  
  
  CONCLUSIONS
  Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, Pennsylvania, USA. jps2f@virginia.edu
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Sun
authors.forename: Douglas
authors.initials: D
authors.lastname: Kondziolka
authors.forename: John
authors.initials: J
authors.lastname: Flickinger
authors.forename: L Dade
authors.initials: LD
authors.lastname: Lunsford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D018288:Carcinoma, Small Cell / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D016634:Radiosurgery; D016019:Survival Analysis; D016896:Treatment Outcome