title: Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis.
abstract: OBJECTIVE
  Following resection of a brain metastasis, stereotactic radiosurgery (SRS) to the cavity is an emerging alternative to postoperative whole-brain radiation therapy (WBRT). This approach attempts to achieve local control without the neurocognitive risks associated with WBRT. The authors aimed to report the outcomes of a large patient cohort treated with this strategy.
  
  
  METHODS
  A retrospective review identified 91 patients without a history of WBRT who received Gamma Knife (GK) SRS to 96 metastasis resection cavities between 2007 and 2013. Patterns of intracranial control were examined in the 86 cases with post-GK imaging. Survival, local failure, and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were tested by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses.
  
  
  RESULTS
  Common primary tumors were non-small cell lung (43%), melanoma (14%), and breast (13%). The cases were predominantly recursive partitioning analysis Class I (25%) or II (70%). Median preoperative metastasis diameter was 2.8 cm, and 82% of patients underwent gross-total resection. A median dose of 16 Gy was delivered to the 50% isodose line, encompassing a median treatment volume of 9.2 cm(3). Synchronous intact metastases were treated in addition to the resection bed in 43% of cases. Patients survived a median of 22.3 months from the time of GK. Local failure developed in 16 cavities, for a crude rate of 18% and 1-year actuarial local control of 81%. Preoperative metastasis diameter ≥ 3 cm and residual or recurrent tumor at the time of GK were associated with local failure (p = 0.04 and 0.008, respectively). Distant intracranial failure occurred in 55 cases (64%) at a median of 7.3 months from GK. Salvage therapies included WBRT and additional SRS in 33% and 31% of patients, respectively. Leptomeningeal carcinomatosis developed in 12 cases (14%) and was associated with breast histology and infratentorial cavities (p = 0.024 and 0.012, respectively).
  
  
  CONCLUSIONS
  This study bolsters the existing evidence for SRS to the resection bed. Local control rates are high, but patients with larger preoperative metastases or residual/recurrent tumor at the time of SRS are more likely to fail at the cavity. While most patients develop distant intracranial failure, an SRS approach spared or delayed WBRT in the majority of cases. The risk of leptomeningeal carcinomatosis does not appear to be elevated with this strategy.
authors.affiliation: Departments of 1 Radiation Oncology and.
authors.forename: Eric
authors.initials: E
authors.lastname: Ojerholm
authors.forename: John Y K
authors.initials: JY
authors.lastname: Lee
authors.forename: Jayesh P
authors.initials: JP
authors.lastname: Thawani
authors.forename: Denise
authors.initials: D
authors.lastname: Miller
authors.forename: Donald M
authors.initials: DM
authors.lastname: O'Rourke
authors.forename: Jay F
authors.initials: JF
authors.lastname: Dorsey
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Geiger
authors.forename: Suneel
authors.initials: S
authors.lastname: Nagda
authors.forename: James D
authors.initials: JD
authors.lastname: Kolker
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lustig
authors.forename: Michelle
authors.initials: M
authors.lastname: Alonso-Basanta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery; D001943:Breast Neoplasms / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016371:Cranial Irradiation / Q000379:methods; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary / Q000601:surgery; D055756:Meningeal Carcinomatosis / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008577:Meningeal Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy / Q000401:mortality; D012878:Skin Neoplasms / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
keywords: GK = Gamma Knife; GTR = gross-total resection; Gamma Knife; LMC = leptomeningeal carcinomatosis; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; leptomeningeal; resection bed; resection cavity; stereotactic radiosurgery