Newly Diagnosed Non-Small Cell Lung Cancer (NSCLC) With 1-3 Brain Metastases: Validation of the Disease Specific GPA

Abstract

Purpose/Objective(s): Use of the disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool. The survival estimates obtained for this toolmay not reflect the prognosis of patients with brain metastases at the time of NSCLC who are naive to other therapies. Materials/Methods: We identified all patients with newly diagnosed NSCLC with 1-3 brain metastases treated with gamma knife radiosurgery between 1997 and 2011 from an IRB approved registry. We included both patients treated with GK alone or in combination with whole brain radiation therapy (WBRT) for the initial management of brain metastases. We evaluated potential prognostic factors for overall survival including age, treatment modality, Karnofsky Performance Score (KPS), histology, disease burden in the lungs, location of presenting symptoms, and extracranial metastases by Cox Proportional Hazards. Patients were stratified by NSCLC DS-GPA to evaluate the accuracy of survival estimates in patients with newly diagnosed lung cancer. Results: 164 patients were identified with 85 (52%) treated with gammaknife (GK) alone and 79 (48%) treatedwith up front GK andWBRT. Patients treatedwithGK alone had amedian survival of 9.1months versus 8.5months in patients treated with GK and WBRT (p-valueZ 0.093). Neither group demonstrated differences in disease progression, with GK and GK+WBRT median time to disease progression at 6.7 and 6.1 months respectively, pvalueZ 0.52. Significant risk factors for overall survival on univariate analysis were KPS, HR 0.98 (95% CI 0.97-0.99), symptomatic extracranial disease, HR 0.55 (CI 0.36-0.84), presence of extracranial metastases, HR 0.45 (CI 0.34-0.70), and higher number of brain metastases, 1.61 (CI 1.102.35). Neither age,HR1.0 (CI 0.9-1.0) nor up front addition ofWBRT toGK, HR0.76 (CI 0.55-1.05)were significantly associatedwith improved survival. On multivariate analysis only presence of extracranial metastases was significant for disease progression, HR 0.60 (CI 0.39-0.93). Median overall survival stratified byDS-GPAof 0-1, 1.5-2, 2.5-3 and 3.5-4were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with survival estimates for brain metastases in NSCLC as a whole which are 3.0, 6.5, 11.3, and 14.8 months. Conclusion: The prognosis for patients with newly diagnosed NSCLC with synchronous brain metastases is consistent with survival estimates from DS-GPA for NSCLC. In addition to DS-GPA presences of symptoms of systemic disease were associated a worse prognosis. Patients with newly diagnosed NSCLC do not have an improved prognosis compared to what DS-GPA would predict and those with low GPA may not benefit from additional aggressive therapies. Author Disclosure: M. Greer: None. N.M. Woody: None. C.A. Reddy: None.G.M.Videtic:Editor for Thoracic Section ofRed Journal; International Journal of Radiation Oncology. S.T. Chao: Speaker’s Bureau; Varianmedical systems.E.S.Murphy:None.J.H.Suh:Consultant;VarianMedical Systems. L. Angelov: None. G. Barnett: None. M.A. Vogelbaum: Consultant; Neuralstem, Inc., Pharmacokinesis, Inc. Royalty; Infuseon Therapeutics, Inc. Chair and Co-chair; NRG Oncology. K.L. Stephans: None.