title: Optimal Management of Leptomeningeal Carcinomatosis in Breast Cancer Patients-A Systematic Review.
abstract: The incidence of leptomeningeal carcinomatosis in breast cancer patients (LC-BC) is increasing. Despite significantly affecting patient quality of life (QoL) and overall survival (OS), little is known about its optimal management. A systematic review of treatment strategies for LC-BC was performed. EMBASE, Ovid Medline, Pubmed, and the Cochrane Central Register of Controlled Trials were searched from 1946 to 2015 for trials reporting on treatments for LC-BC. All treatment modalities and study types were considered. The outcome measures of interest included OS, time to neurologic progression (TTNP), QoL, and treatment toxicity. Of 718 unique citations, 173 studies met the prespecified eligibility criteria. Most were not specific to LC-BC patients. Of 4 identified randomized controlled trials (RCTs), 1 was specific to LC-BC patients and compared systemic therapy and involved-field radiotherapy with or without intrathecal (IT) methotrexate (35 patients), and the remaining 3 had compared different IT chemotherapy regimens (58 of 157 with LC-BC). Of the remaining studies, 19 were nonrandomized interventional studies (225 LC-BC patients), 148 were observational studies (3230 LC-BC patients), and 2 systematic reviews. Minimal prospective data were available on OS, TTNP, QoL, and toxicity. Owing to study heterogeneity, meta-analyses of the endpoint data could not be performed. Limited high-quality evidence exists regarding optimal treatment of LC-BC. The identified studies were heterogeneous and often methodologically poor. The only RCT that specifically assessed the role of IT chemotherapy showed no benefit, and, if anything, harm. Further prospective, tumor-specific trials with improved interstudy methodologic consistency and transparently reported data on OS, TTNP, QoL, and toxicity are urgently needed.
authors.affiliation: Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Shaan
authors.initials: S
authors.lastname: Dudani
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Mazzarello
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.affiliation: Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Vandermeer
authors.affiliation: Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Mohammed F K
authors.initials: MF
authors.lastname: Ibrahim
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.affiliation: Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Habeeb
authors.initials: H
authors.lastname: Majeed
authors.affiliation: Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Baimani
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Radiation Medicine, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Caudrelier
authors.affiliation: The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Risa
authors.initials: R
authors.lastname: Shorr
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Medical Oncology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada. Electronic address: mclemons@toh.on.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D055756:Meningeal Carcinomatosis / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D064887:Observational Studies as Topic; D011788:Quality of Life; D011878:Radiotherapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Neurologic progression; Overall survival; Quality of life; Toxicity; Treatment