Leptomeningeal Carcinomatosis from Solid Tumor Malignancies: Treatment Strategies and Biomarkers

Abstract

Leptomeningeal metastases/diseases (LMDs) are a late-stage complication of solid tumor or hematologic malignancies. LMD is spread of cancer cells to the layers of the leptomeninges (pia and arachnoid maters) and subarachnoid space seen in 3 to 5% of cancer patients. It is a disseminated disease which carries with it significant neurologic morbidity and mortality. Our understanding of disease pathophysiology is currently lacking; however, advances are being made. As our knowledge of disease pathogenesis has improved, treatment strategies have evolved. Mainstays of treatment such as radiotherapy have changed from involved-field radiotherapy strategies to proton craniospinal irradiation which has demonstrated promising results in recent clinical trials. Systemic treatment strategies have also improved from more traditional chemotherapeutics with limited central nervous system (CNS) penetration to more targeted therapies with better CNS tumor response. Many challenges remain from earlier clinical detection of disease through improvement of active treatment options, but we are getting closer to meaningful treatment.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors

“…The primary outcome measure was the univariable hazard ratio (HR) for survival as predicted by CSF-TC density. On an exploratory basis, other independent variables were tested without multiple comparison correction, and a multivariable model was constructed using CSF-TC density and variables previously identi ed as prognostic in LMD: KPS, CSF protein, systemic disease status, and age [8][9][10][11]. Assumptions of proportional hazards and non-linearity were tested.…”