title: Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial.
abstract: OBJECTIVE
  To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence.
  
  
  METHODS
  Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board-approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator-based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS).
  
  
  RESULTS
  Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non-small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed.
  
  
  CONCLUSIONS
  SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate.
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina; Department of Surgery, Duke University, Durham, North Carolina. Electronic address: john.kirkpatrick@dm.duke.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina; Department of Surgery, Duke University, Durham, North Carolina.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University, Durham, North Carolina.
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University, Durham, North Carolina.
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Allen
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Eileen
authors.initials: E
authors.lastname: Duffy
authors.affiliation: Department of Radiology, Duke University, Durham, North Carolina.
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Hoang
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: David S
authors.initials: DS
authors.lastname: Yoo
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Kelsey
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Yin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D003071:Cognition / Q000528:radiation effects; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011788:Quality of Life; D011832:Radiation Injuries / Q000473:pathology; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D047368:Tumor Burden