The prognostic role of ventricular size and its dynamics in patients with leptomeningeal metastases from solid tumors.
Authors: Le Rhun Emilie , Devos Patrick , Seystahl Katharina , Jongen Joost , Gramatzki Dorothee , Roth Patrick , Van Den Bent Martin J. , Brandsma Dieta , Weller Michael 
Published: June 2023

2033

Background: Hydrocephalus is a common radiological sign in patients with leptomeningeal metastasis (LM) from solid tumors and can be assessed using the Evans index (EI) with high interrater agreement. Normal ranges of EI values have been defined as 0.27 ± 0.05 for females and 0.28 ± 0.06 for males aged 65-69 for the diagnostic work-up of dementia. Methods: We retrospectively assembled a cohort of 113 adult patients with a diagnosis of LM from solid extra-central nervous system tumors and explored the association of ventricular size assessed by the EI at diagnosis, of its modification between diagnosis and evaluation at first follow-up ( > 21 days after diagnosis), and at first progression, with outcome. Results: Median age was 58.2 years (interquartile range (IQR) 46.1-65.7), 41 patients (36%) were male, the most frequent cancers were lung cancer (n = 39, 35%), breast cancer (n = 36, 32%) and melanoma (n = 23, 20). The median EI at baseline was 0.28 (IQR 0.26-0.31) and the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI was increased in 19 of 47 patients (40%), including 9 of 47 patients (30%) and 10 of 47 patients (59%), respectively, without and with LM progression at first follow-up. At LM progression, an increase of EI was noted in 18 of 34 patients (53%). The median LM-specific progression-free (LM-PFS) survival was 1.8 months (IQR 0.8-3.7). The baseline EI was not significantly associated with LM-PFS (numerical values: p = 0.299). Median LM-PFS was 2.7 months (IQR 1.2-5.0) with an EI of 0.26 or less versus 1.3 months (IQR 0.6-3.1) with an EI of 0.27 or more (p = 0.296). It was 2.5 months (IQR 0.9-6) with an EI of 0.29 or less versus 1.1 months (IQR 0.5-2.4) with an EI of 0.30 or more (p = 0.147). An increase of 0.01 or more of the baseline EI first evaluation was associated with inferior LM-PFS (p = 0.007). The median overall survival was 2.9 months (IQR 1-7.2). The baseline EI was not associated with survival (p = 0.067), however, patients with a baseline EI of 0.26 or less had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, versus 1.3 months, IQR 0.6-4.1) (p = 0.006). Median survival was 3.7 months (IQR 1.4-8.3) with an EI of 0.29 or less versus 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (p = 0.109). Among patients with follow-up scans available, median overall survival was 9.7 months (IQR 5.6-21.4) for patients with stable or decreased EI at first follow-up as opposed to 6.4 months (IQR 3.2-10.5) for those with an increase in the EI (p = 0.292). Conclusions: The EI at baseline is prognostic in LM on univariate analysis. An increase of EI during the follow-up is associated with inferior LM-PFS. Expanding the sample size and evaluation of confounding factors such as prior or concurrent treatment will help to better define the role of EI assessments in LM.