title: Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases.
abstract: OBJECTIVE
  Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥5 melanoma brain metastases.
  
  
  METHODS
  A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model.
  
  
  RESULTS
  The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38-83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01-12.5 cm3). Median follow-up was 6.3 months (range 1-46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume≥0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2-292.6, p<0.0001) and MVA (HR 14.8, 95% CI 3.0-268.5, p=0.0002). Sixteen patients (57.1%) were noted to have distant failure in the brain with a median time to failure of 3 months (range 1-15 months). Nine patients with distant failures received WBRT, and 7 received additional SRS. Median overall survival (OS) was 9.4 and 7.6 months from the date of brain metastases diagnosis and the date of SRS, respectively. The KM OS estimates at 6 and 12 months were 57.8% and 28.2%, respectively, from the time of SRS treatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p=0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1-12.0, p=0.03), and patients who did not receive WBRT prior to SRS had improved OS (HR 0.11, 95% CI 0.02-0.53, p=0.007).
  
  
  CONCLUSIONS
  Stereotactic radiosurgery for ≥5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still have limited efficacy within the central nervous system.
authors.affiliation: Departments of 1 Radiation Oncology.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Frakes
authors.affiliation: University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Figura
authors.affiliation: Departments of 1 Radiation Oncology.
authors.forename: Kamran A
authors.initials: KA
authors.lastname: Ahmed
authors.affiliation: Biostatistics, and.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Juan
authors.affiliation: University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Neha
authors.initials: N
authors.lastname: Patel
authors.affiliation: Departments of 1 Radiation Oncology.
authors.forename: Kujtim
authors.initials: K
authors.lastname: Latifi
authors.affiliation: Departments of 1 Radiation Oncology.
authors.forename: Siriporn
authors.initials: S
authors.lastname: Sarangkasiri
authors.affiliation: Departments of 1 Radiation Oncology.
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Strom
authors.affiliation: Departments of 1 Radiation Oncology.|University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Prakash
authors.initials: P
authors.lastname: Chinnaiyan
authors.affiliation: Departments of 1 Radiation Oncology.|University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Nikhil G
authors.initials: NG
authors.lastname: Rao
authors.affiliation: Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute; and.|University of South Florida, Morsani College of Medicine, Tampa, Florida.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Etame
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D016371:Cranial Irradiation / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D008875:Middle Aged; D010315:Particle Accelerators; D016634:Radiosurgery / Q000295:instrumentation* / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: DC = distant control; GTV = gross tumor volume; KM = Kaplan-Meier; LC = local control; LINAC; LINAC = linear accelerator; MVA= multivariate analysis; OS = overall survival; PTV = planning target volume; RECIST = Response Evaluation Criteria in Solid Tumors; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery; UVA = univariate analysis; WBRT = whole-brain radiotherapy; brain metastases; melanoma; oncology; stereotactic radiosurgery