title: Validation of Recursive Partitioning Analysis and Diagnosis-Specific Graded Prognostic Assessment in patients treated initially with radiosurgery alone.
abstract: OBJECTIVE
  Brain metastases present a therapeutic challenge because patients with metastatic cancers live longer now than in the recent past due to systemic therapies that, while effective, may not penetrate the blood-brain barrier. In the present study the authors sought to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account the histological characteristics of the primary tumor, and the Radiation Therapy Ontology Group Recursive Partitioning Analysis (RPA) system by using a single-institution database of patients who were treated initially with stereotactic radiosurgery (SRS) alone for brain metastases.
  
  
  METHODS
  Investigators retrospectively identified adult patients who had undergone SRS at a single institution, MD Anderson Cancer Center, for initial treatment of brain metastases between 2003 and 2010 but excluded those who had undergone craniotomy and/or whole-brain radiation therapy at an earlier time; the final number was 251. The Leksell Gamma Knife was used to treat 223 patients, and a linear accelerator was used to treat 28 patients. The patient population was grouped according to DS-GPA scores as follows: 0-0.5 (7 patients), 1 (33 patients), 1.5 (25 patients), 2 (63 patients), 2.5 (14 patients), 3 (68 patients), and 3.5-4 (41 patients). The same patients were also grouped according to RPA classes: 1 (24 patients), 2 (216 patients), and 3 (11 patients). The most common histological diagnoses were non-small cell lung cancer (34%), melanoma (29%), and breast carcinoma (16%). The median number of lesions was 2 (range 1-9) and the median total tumor volume was 0.9 cm(3) (range 0.3-22.9 cm(3)). The median radiation dose was 20 Gy (range 14-24 Gy). Stereotactic radiosurgery was performed as the sole treatment (62% of patients) or combined with a salvage treatment consisting of SRS (22%), whole-brain radiation therapy (12%), or resection (4%). The median duration of follow-up was 9.4 months.
  
  
  RESULTS
  In this patient group the median overall survival was 11.1 months. The DS-GPA prognostic index divided patients into prognostically significant groups. Median survival times were 2.8 months for DS-GPA Scores 0-0.5, 3.9 months for Score 1, 6.6 months for Score 1.5, 12.9 months for Score 2, 11.9 months for Score 2.5, 12.2 months for Score 3, and 31.4 months for Scores 3.5-4 (p < 0.0001). In the RPA groups, the median overall survival times were 38.8 months for Class 1, 9.4 months for Class 2, and 2.8 months for Class 3 (p < 0.0001). Neither the RPA class nor the DS-GPA score was prognostic for local tumor control or new lesion-free survival. A multivariate analysis revealed that patient age > 60 years, Karnofsky Performance Scale score ≤ 80%, and total lesion volume > 2 cm(3) were significant adverse prognostic factors for overall survival.
  
  
  CONCLUSIONS
  Application of the DS-GPA to a database of patients with brain metastases who were treated with SRS appears to be valid and offers additional prognostic refinement over that provided by the RPA. The DS-GPA may also allow for improved selection of patients to undergo initial SRS alone and should be studied further.
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Likhacheva
authors.forename: Chelsea C
authors.initials: CC
authors.lastname: Pinnix
authors.forename: Neil
authors.initials: N
authors.lastname: Parikh
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Allen
authors.forename: Nandita
authors.initials: N
authors.lastname: Guha-Thakurta
authors.forename: Mary
authors.initials: M
authors.lastname: McAleer
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.forename: Anita
authors.initials: A
authors.lastname: Mahajan
authors.forename: Almon
authors.initials: A
authors.lastname: Shiu
authors.forename: Dershan
authors.initials: D
authors.lastname: Luo
authors.forename: Max
authors.initials: M
authors.lastname: Chiu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Prabhu
authors.forename: Eric L
authors.initials: EL
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016634:Radiosurgery / Q000295:instrumentation* / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome