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. 2021 Jul 1;23(7):1100-1112.
doi: 10.1093/neuonc/noaa298.

Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors

Emilie Le Rhun  1   2   3   4   5 , Patrick Devos  6 , Johannes Weller  7 , Katharina Seystahl  4 , Francesca Mo  8 , Annette Compter  9 , Anna S Berghoff  10 , Joost L M Jongen  11 , Fabian Wolpert  4 , Roberta Rudà  8 , Dieta Brandsma  9 , Martin van den Bent  11 , Matthias Preusser  10 , Ulrich Herrlinger  7 , Michael Weller  4
Affiliations

Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors

Emilie Le Rhun et al. Neuro Oncol. .

Erratum in

Abstract

Background: The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes.

Patients and methods: We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test.

Results: Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (P = 0.020) or systemic pharmacotherapy (P = 0.0004) was associated with improved outcome in type I LM, but not in type II LM.

Conclusion: The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

Keywords: cerebrospinal; fluid; intrathecal; meningitis; neoplastic.

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Figures

Fig. 1
Fig. 1
Survival correlates of the EANO ESMO classification. Survival stratified by level of evidence of the LM diagnosis (confirmed, probable, possible) (A), by presence vs absence of tumor cells in the CSF (B), by pattern of neuroimaging (C), by absence vs presence of nodular disease in type I (D) and type II (E) patients, and by the most common primary tumor (F).
Fig. 2
Fig. 2
Survival associations with intrathecal and systemic pharmacotherapy per LM subtype. Numbers of patients treated with intrathecal (A,C) or systemic (E,G) pharmacotherapy per LM subtype and corresponding survival (B,D,F,H) (Type I: A, B, E, F; Type II: C, D, G, H).
Fig. 2
Fig. 2
Survival associations with intrathecal and systemic pharmacotherapy per LM subtype. Numbers of patients treated with intrathecal (A,C) or systemic (E,G) pharmacotherapy per LM subtype and corresponding survival (B,D,F,H) (Type I: A, B, E, F; Type II: C, D, G, H).
Fig. 3
Fig. 3
Outcome per LM type and primary tumor. Distribution per EANO ESMO subtype (A) and survival per subtype (B) in patients with LM from breast cancer, lung cancer or melanoma. Comparisons of subgroups were performed with the log-rank test.
See this image and copyright information in PMC

Comment in

  • Prognostic factors in leptomeningeal metastases.
    Le Rhun E, Devos P, Weller J, Seystahl K, Mo F, Compter A, Berghoff AS, Jongen JLM, Wolpert F, Rudà R, Brandsma D, van den Bent M, Preusser M, Herrlinger U, Weller M. Le Rhun E, et al. Neuro Oncol. 2021 Jul 1;23(7):1208-1209. doi: 10.1093/neuonc/noab051. Neuro Oncol. 2021. PMID: 33830220 Free PMC article. No abstract available.
  • The relevance of surgical status in nodular leptomeningeal metastasis patient outcomes.
    Dankner M, Maritan SM. Dankner M, et al. Neuro Oncol. 2021 Jul 1;23(7):1207. doi: 10.1093/neuonc/noab035. Neuro Oncol. 2021. PMID: 33830265 Free PMC article. No abstract available.
  • Lepto mets: loads of data.
    Junck L. Junck L. Neuro Oncol. 2021 Jul 1;23(7):1044-1045. doi: 10.1093/neuonc/noab089. Neuro Oncol. 2021. PMID: 33940636 Free PMC article. No abstract available.

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