title: Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control.
abstract: OBJECTIVE
  Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.
  
  
  METHODS
  Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.
  
  
  RESULTS
  Median patient age at first SRS treatment was 58 years (range 37-84 years). The most frequently diagnosed primary tumor was non-small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.
  
  
  CONCLUSIONS
  Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.
authors.affiliation: Division of Neurosurgery, Department of Surgery, and.
authors.forename: Christian
authors.initials: C
authors.lastname: Iorio-Morin
authors.forename: Laurence
authors.initials: L
authors.lastname: Masson-Côté
authors.forename: Youssef
authors.initials: Y
authors.lastname: Ezahr
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Blanchard
authors.forename: Annie
authors.initials: A
authors.lastname: Ebacher
authors.forename: David
authors.initials: D
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary / Q000601:surgery; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control / Q000601:surgery; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality*; D011879:Radiotherapy Dosage; D012086:Reoperation; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
keywords: Gamma Knife; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; brain metastasis; stereotactic radiosurgery; tumor bed