Optimal Management of Leptomeningeal Carcinomatosis in Breast Cancer Patients-A Systematic Review

Clin Breast Cancer. 2016 Dec;16(6):456-470. doi: 10.1016/j.clbc.2016.07.014. Epub 2016 Jul 28.

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.

Keywords: Neurologic progression; Overall survival; Quality of life; Toxicity; Treatment.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy*
  • Drug Therapy / methods
  • Female
  • Humans
  • Incidence
  • Meningeal Carcinomatosis / mortality
  • Meningeal Carcinomatosis / secondary
  • Meningeal Carcinomatosis / therapy*
  • Observational Studies as Topic*
  • Quality of Life
  • Radiotherapy / methods
  • Randomized Controlled Trials as Topic*
  • Survival Rate
  • Treatment Outcome