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01-05-2022 | Metastasis | Original Article

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis—a safety analysis and validation of the EANO-ESMO classification

Authors: Sarah Iglseder, Martha Nowosielski, MD PhD, Gabriel Bsteh, Armin Muigg, Johanna Heugenhauser, Elke Mayer, Astrid Grams, Günther Stockhammer, Meinhard Nevinny-Stickel

Published in: Strahlentherapie und Onkologie | Issue 5/2022

Abstract

Background

Although there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology—European Society for Medical Oncology) classification in this unique cohort.

Methods

Treatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to RTOG (Radiation Therapy Oncology Group) toxicity criteria and NCI CTCAE V5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0). Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan–Meier analysis and Breslow test.

Results

In all, 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥grade 3 according to RTOG toxicity criteria; in 22 patients (55%) NCI CTCAE ≥grade 3 were detected. Median overall survival was 124 days. Median time to neurological progression was 52 days. Patients with positive cerebrospinal fluid (CSF) cytology (n = 26) showed worse prognosis compared to patients with negative CSF cytology (n = 14; mOS (median overall survival) 84 days versus 198 days, p = 0.006, respectively). The EANO-ESMO response assessment was significantly associated with survival: “stable” (n = 7) mOS 233 days, “response” (n = 10) mOS 206 days, “progression” (n = 17) mOS 45 days, “suspicion of progression” (n = 6) mOS 133 days; overall, p < 0.001.

Conclusions

In this retrospective analysis, combined treatment of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile and may indicate a trend towards improved efficacy. The EANO-ESMO classification for diagnosis and treatment response predicts survival.

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Title: Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis—a safety analysis and validation of the EANO-ESMO classification
Authors: Sarah Iglseder
Martha Nowosielski, MD PhD
Gabriel Bsteh
Armin Muigg
Johanna Heugenhauser
Elke Mayer
Astrid Grams
Günther Stockhammer
Meinhard Nevinny-Stickel
Publication date: 01-05-2022
Publisher: Springer Berlin Heidelberg
Keywords: Metastasis
Radiotherapy
Published in: Strahlentherapie und Onkologie / Issue 5/2022
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-022-01910-9

At a glance: The STEP trials

Springer Medicine

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis—a safety analysis and validation of the EANO-ESMO classification

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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