The necessity of intrathecal chemotherapy for the treatment of breast cancer patients with leptomeningeal metastasis: A systematic review and pooled analysis

Abstract

Leptomeningeal carcinomatosis is a devastating disease. Despite its numerous complications, intrathecal (IT) chemotherapy remains a longstanding treatment for leptomeningeal carcinomatosis. Using case studies with internationally reported results, we attempted to determine the necessity of IT chemotherapy in treating leptomeningeal carcinomatosis. We conducted a systematic review and pooled analysis to compare hormone therapy, chemotherapy, and IT therapy. We excluded articles on IT trastuzumab therapy. We performed our literature search without language restriction. We retrieved articles that were published by as late as July 19, 2016. The present study was performed in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The Cox proportional hazard regression model was performed to examine the effects of prognostic variables. A total of 34 patients from 32 studies were considered eligible. The median age of the patients in the hormone treatment, chemotherapy, and IT therapy groups was 46, 51.5, and 51 years, respectively. The median overall survival (OS) of the patients in the hormone treatment, chemotherapy, and IT therapy groups was 65, 52, and 41 weeks, respectively. One patient who received hormone therapy exhibited the longest survival of approximately 8.5 years. Only magnetic resonance imaging response was associated with OS (hazard ratio = 0.05, 95% confidence interval 0.00-0.74; p = 0.03). Hormone status, HER2 status, age, central nervous system radiation therapy, IT therapy, metastasis sites (central nervous system only vs. others), and cerebrospinal fluid responses were all not associated with OS. Given its obvious side effects and lack of evidence of effectiveness from prospective randomized clinical trials, IT chemotherapy should be used with caution in the treatment of leptomeningeal metastasis breast cancer patients.

Keywords: Breast cancer; Cerebrospinal fluid (CSF); Hormone therapy; Intrathecal chemotherapy; Leptomeningeal; Magnetic resonance imaging (MRI).