Prognostic role of the EANO ESMO classification of leptomeningeal metastases

Background The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear + nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the correlation between EANO ESMO subtypes of LM and outcome to assess their clinical utility. Methods We collected data from 254 patients with newly diagnosed LM from different primary solid tumors. Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. Results Median age at LM diagnosis was 56.5 years (range 20-82 years). The main primary tumors were breast cancer (n = 98, 45%), lung cancer (n = 65, 25.5%) and melanoma (n = 51, 13.5%). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n = 33, 13%), C (n = 54, 21%) and D (n = 50, 19.5%) were less common. Tumor cells were observed in the CSF in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Assignment to EANO ESMO classes was as follows: type IA 86 (34%), IB 19 (7.5%), IC 39 (15.5%), ID 45 (17.5%), IIA 28 (11%), IIB 13 (5%), IIC 16 (6.5%), IID 8 (3%). LM was confirmed in 189 (74.5%), probable in 51 (20%) and possible in 14 (5.5%) patients. The median overall survival (OS) was 2.75 months (range 0.09-220 months). OS was inferior in type I compared with type II LM patients (p = 0.0024). EANO ESMO subtype IIA patients had the longest survival (p = 0.0103). Patients with MRI patterns A and D pooled had poorer survival than B and C patients pooled in the presence of tumor cells in the CSF (type I) (p = 0.0402), but longer survival in the absence of tumor cells in the CSF (type II) (p = 0.0273). Conclusions The presence of tumor cells in the CSF appears to have a greater prognostic role than the neuroimaging presentation. EANO ESMO LM subtypes are prognostic and should be considered in the design of clinical trials. Legal entity responsible for the study University Hospital of Zurich. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.