title: Breast cancer leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal cytarabine as intra-cerebrospinal fluid chemotherapy.
abstract: BACKGROUND
  This was a prospective observational study to assess the results of the treatment of patients with breast cancer leptomeningeal metastasis (LM) and to compare the efficacy of methotrexate and liposomal cytarabine in patients treated intrathecally by lumbar puncture.
  
  
  METHODS
  In this prospective observational study, 149 consecutive patients with breast cancer and LM treated between the years 1999 and 2011 were assessed. Multimodality treatment methods were used: systemic therapy in 77 patients, radiotherapy in 92 patients, intrathecal methotrexate in 81 patients, and intrathecal liposomal cytarabine in 15 patients.
  
  
  RESULTS
  The median survival of all patients was 4.2 months. The median survival of patients in whom systemic intravenous/oral treatment was used was 6 months, in those who did not have systemic treatment, the median survival was 2 months (P < .001). The median survival of patients treated with intrathecal methotrexate was 4.2 months; in patients treated with intrathecal liposomal cytarabine, the median survival was 4.6 months, and in patients who did not receive intrathecal treatment, the median survival was 3.7 months (P = .717). Median survival after whole-brain radiotherapy was 4.6 months and with no radiotherapy, it was 3.2 months (P = .028). Multivariate analysis revealed a Karnofsky performance status (KPS) of > 70. Systemic intravenous/oral treatment and bone as a site of metastasis were factors prolonging survival from LM.
  
  
  CONCLUSIONS
  Among treatment methods, only systemic therapy prolonged survival in patients with LM. Neither radiotherapy nor lumbar intrathecal therapy influenced survival in those patients; however, both methods alleviated signs and symptoms of LM. No difference in survival was observed in patients treated intrathecally with methotrexate and those treated with liposomal cytarabine. Treatment with both drugs was comparable.
authors.affiliation: Department of Breast Cancer and Reconstructive Surgery, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. Electronic address: annaniwinska@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Niwińska
authors.affiliation: Department of Breast Cancer and Reconstructive Surgery, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Rudnicka
authors.affiliation: Department of Biostatistics, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Murawska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D018270:Carcinoma, Ductal, Breast / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D018275:Carcinoma, Lobular / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D008081:Liposomes; D003561:Cytarabine; D008727:Methotrexate
keywords: Carcinomatous meningitis; Intra-CSF treatment; Leptomeningeal metastasis; Liposomal cytarabine; Systemic treatment