How we treat patients with leptomeningeal metastases

Abstract

The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease-related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for patients with breast cancer with newly diagnosed leptomeningeal metastasis. Safety and efficacy of intrathecal administration of new agents such as trastuzumab are under evaluation. Systemic therapy using targeted agents and immunotherapy has also improved outcome in patients with brain metastasis, and its emerging role in the management of leptomeningeal metastasis needs to better studied in prospective series. Focal radiotherapy is commonly indicated for the treatment of macroscopic disease such as meningeal nodules or clinically symptomatic central nervous system structures, for example, base of skull with cranial nerve involvement or cauda equine syndrome. The role of whole brain radiotherapy is decreasing. An individualised combination of different therapeutic options should be used considering the presentation of leptomeningeal metastasis, as well as the histological and molecular tumour characteristics, the presence of concomitant brain and systemic metastases, and prior cancer-directed treatments.

Keywords: carcinomatous; cerebrospinal; chemotherapy; intrathecal; meningitis; radiotherapy; targeted.

Figure 1

EANO ESMO Therapeutic approach to LM. +, recommended; (+), optional; -, not recommended; BM, brain metastases; CSF, cerebrospinal fluid; ECD, extracranial disease; IT, intrathecal; LM, leptomeningeal metastases; RT, radiotherapy; WBRT, whole brain radiotherapy.