title: Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).
abstract: OBJECTIVE
  Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials.
  
  
  OBJECTIVE
  To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA.
  
  
  METHODS
  This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index.
  
  
  METHODS
  The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups.
  
  
  RESULTS
  The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-molGPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years.
  
  
  CONCLUSIONS
  In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.
authors.affiliation: Minneapolis Radiation Oncology, Minneapolis, Minnesota2University of Minnesota Gamma Knife Center, Minneapolis.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sperduto
authors.affiliation: Sloan Kettering Cancer Center, New York, New York.
authors.forename: T Jonathan
authors.initials: TJ
authors.lastname: Yang
authors.affiliation: Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hubert
authors.initials: H
authors.lastname: Pan
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: University of Minnesota, Masonic Cancer Center, Biostatistics, Minneapolis.
authors.forename: Ananta
authors.initials: A
authors.lastname: Bangdiwala
authors.affiliation: University of Minnesota, Masonic Cancer Center, Biostatistics, Minneapolis.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shanley
authors.affiliation: University of Denver, Denver, Colorado.
authors.forename: Norman
authors.initials: N
authors.lastname: Yeh
authors.affiliation: University of Denver, Denver, Colorado.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.affiliation: University of California, San Francisco.
authors.forename: Steve
authors.initials: S
authors.lastname: Braunstein
authors.affiliation: University of California, San Francisco.
authors.forename: Penny
authors.initials: P
authors.lastname: Sneed
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Boyle
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Mak
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
authors.affiliation: University of Maryland, Baltimore.
authors.forename: Alex
authors.initials: A
authors.lastname: Engelman
authors.affiliation: University of Montreal Health Centre, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Roberge
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Nils D
authors.initials: ND
authors.lastname: Arvold
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Brian
authors.initials: B
authors.lastname: Alexander
authors.affiliation: Yale University, New Haven, Connecticut.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Awad
authors.affiliation: Yale University, New Haven, Connecticut.
authors.forename: Joseph
authors.initials: J
authors.lastname: Contessa
authors.affiliation: Yale University, New Haven, Connecticut.
authors.forename: Veronica
authors.initials: V
authors.lastname: Chiang
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: John
authors.initials: J
authors.lastname: Hardie
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ma
authors.affiliation: University of Minnesota, Department of Hematology Oncology, Minneapolis.
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: William
authors.initials: W
authors.lastname: Sperduto
authors.affiliation: University of Maryland, Baltimore.
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D003131:Combined Modality Therapy; D004812:Epidemiologic Methods; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000628:therapy; D008297:Male; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases