BMET-13CSF PROFILES AS PROGNOSTIC MARKER OR PREDICTIVE MARKER FOR INTRAVENTRICULAR CHEMOTHERAPY IN PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS FROM SOLID CANCERS

Abstract

One of difficulties in intra-CSF chemotherapy for leptomeningeal carcinomatosis (LMC) is a lack of quantitative measure for the treatment response. Previous studies evaluated CSF profiles to predict treatment response or to correlate with prognosis. However, the results were inconsistent mainly due to small number of patients and heterogeneous treatment. We analyzed 283 patients with LMC from solid cancer, who underwent intraventricular chemotherapy at National Cancer Center from 2003 to 2013. CSF parameters were cytology, cell count and protein level. Control of intracranial pressure (ICP) was reviewed as an objective indicator of symptom improvement. CSF profiles before the treatment were significantly different according to sample sites (p < 0.001) in both cell count (lumbar vs. ventricular is mean 23 ± 44 vs. 8 ± 30) and protein level (mean 124 ± 168 vs. 33 ± 66 mg/dL). Initial lumbar CSF protein level was correlated with development of increased ICP (p = 0.059), hydrocephalus (HCP) (p = 0.049), and cauda equine syndrome (CES) (p< 0.001). But, initial ventricular CSF profiles did not reflect LMC disease activity. Decrease of CSF protein level after treatment was associated with increased ICP control (p = 0.017) while cell count change or cytology conversion is not predictive. Patients with low initial protein level (≤ 50mg/dL), or cell count (≤15) show prolonged survival (p = 0.001 and 0.015, respectively). But, decrease of either protein level or cell count after the treatment and cytology response did not significantly affect the patients OS. We suggest that CSF cell count is too low to reflect disease activity or treatment response especially those from ventricle. Initial CSF protein is in accordance with LMC symptoms and the decrease of protein level after the treatment is predictive of treatment response. We need new quantitative pharmacodynamic markers for LMC treatment to improve efficacy of intraventricular chemotherapy.