title: Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era.
abstract: BACKGROUND
  Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM.
  
  
  METHODS
  Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3.
  
  
  RESULTS
  LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007).
  
  
  CONCLUSIONS
  In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication.
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA; Department of Internal Medicine, University of California Davis School of Medicine; Division of Hematology/Oncology, University of California Davis Cancer Center, Sacramento, CA. Electronic address: jonathan.riess@ucdmc.ucdavis.edu.
authors: Jonathan W
authors: JW
authors: Riess
authors: Division of Neuro-Oncology, Department of Neurology, Stanford University School of Medicine, Stanford, CA.
authors: Seema
authors: S
authors: Nagpal
authors: Department of Radiology, Stanford University School of Medicine, Stanford, CA.
authors: Michael
authors: M
authors: Iv
authors: Department of Radiology, Stanford University School of Medicine, Stanford, CA.
authors: Michael
authors: M
authors: Zeineh
authors: Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors: Matthew A
authors: MA
authors: Gubens
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Kavitha
authors: K
authors: Ramchandran
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Joel W
authors: JW
authors: Neal
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Heather A
authors: HA
authors: Wakelee
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D019786:Gadolinium DTPA; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D055756:Meningeal Carcinomatosis / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D000068437:Pemetrexed; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D012189:Retrospective Studies; D013534:Survival
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D005971:Glutamates; D047428:Protein Kinase Inhibitors; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D005682:Gadolinium; D019786:Gadolinium DTPA
keywords: CNS disease; Chemotherapy; Leptomeningeal carcinomatosis; NSCLC; Targeted therapy