title: Impact of the radiosurgery prescription dose on the local control of small (2 cm or smaller) brain metastases.
abstract: OBJECTIVE The impact of the stereotactic radiosurgery (SRS) prescription dose (PD) on local progression and radiation necrosis for small (≤ 2 cm) brain metastases was evaluated. METHODS An institutional review board-approved retrospective review was performed on 896 patients with brain metastases ≤ 2 cm (3034 tumors) who were treated with 1229 SRS procedures between 2000 and 2012. Local progression and/or radiation necrosis were the primary end points. Each tumor was followed from the date of radiosurgery until one of the end points was reached or the last MRI follow-up. Various criteria were used to differentiate tumor progression and radiation necrosis, including the evaluation of serial MRIs, cerebral blood volume on perfusion MR, FDG-PET scans, and, in some cases, surgical pathology. The median radiographic follow-up per lesion was 6.2 months. RESULTS The median patient age was 56 years, and 56% of the patients were female. The most common primary pathology was non-small cell lung cancer (44%), followed by breast cancer (19%), renal cell carcinoma (14%), melanoma (11%), and small cell lung cancer (5%). The median tumor volume and median largest diameter were 0.16 cm3and 0.8 cm, respectively. In total, 1018 lesions (34%) were larger than 1 cm in maximum diameter. The PD for 2410 tumors (80%) was 24 Gy, for 408 tumors (13%) it was 19 to 23 Gy, and for 216 tumors (7%) it was 15 to 18 Gy. In total, 87 patients (10%) had local progression of 104 tumors (3%), and 148 patients (17%) had at least radiographic evidence of radiation necrosis involving 199 tumors (7%; 4% were symptomatic). Univariate and multivariate analyses were performed for local progression and radiation necrosis. For local progression, tumors less than 1 cm (subhazard ratio [SHR] 2.32; p < 0.001), PD of 24 Gy (SHR 1.84; p = 0.01), and additional whole-brain radiation therapy (SHR 2.53; p = 0.001) were independently associated with better outcome. For the development of radiographic radiation necrosis, independent prognostic factors included size greater than 1 cm (SHR 2.13; p < 0.001), location in the corpus callosum (SHR 5.72; p < 0.001), and uncommon pathologies (SHR 1.65; p = 0.05). Size (SHR 4.78; p < 0.001) and location (SHR 7.62; p < 0.001)-but not uncommon pathologies-were independent prognostic factors for the subgroup with symptomatic radiation necrosis. CONCLUSIONS A PD of 24 Gy results in significantly better local control of metastases measuring < 2 cm than lower doses. In addition, tumor size is an independent prognostic factor for both local progression and radiation necrosis. Some tumor pathologies and locations may also contribute to an increased risk of radiation necrosis.
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center,.|Departments of 2 Neurosurgery and.
authors.forename: Alireza M
authors.initials: AM
authors.lastname: Mohammadi
authors.affiliation: Department of Neurosurgery, University of Toledo Medical Center, Toledo, Ohio.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Schroeder
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center,.|Departments of 2 Neurosurgery and.
authors.forename: Lilyana
authors.initials: L
authors.lastname: Angelov
authors.affiliation: Radiation Oncology, and.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Chao
authors.affiliation: Radiation Oncology, and.
authors.forename: Erin S
authors.initials: ES
authors.lastname: Murphy
authors.affiliation: Radiation Oncology, and.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Radiation Oncology, and.
authors.forename: Gennady
authors.initials: G
authors.lastname: Neyman
authors.affiliation: Quantitative Health Science, Neurological Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland; and.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Radiation Oncology, and.
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center,.|Departments of 2 Neurosurgery and.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center,.|Departments of 2 Neurosurgery and.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
mesh_terms: D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016634:Radiosurgery / Q000379:methods; D012189:Retrospective Studies; D016019:Survival Analysis; D047368:Tumor Burden
keywords: Gamma Knife; KPS = Karnofsky Performance Scale; MTD = maximum tolerated dose; PD = prescription dose; RTOG = Radiation Therapy Oncology Group; SHR = subhazard ratio; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; brain metastases; local progression; oncology; predictive factors; radiation necrosis; stereotactic radiosurgery; tumor volume