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How we treat patients with leptomeningeal metastases.

ABSTRACT: The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease-related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for patients with breast cancer with newly diagnosed leptomeningeal metastasis. Safety and efficacy of intrathecal administration of new agents such as trastuzumab are under evaluation. Systemic therapy using targeted agents and immunotherapy has also improved outcome in patients with brain metastasis, and its emerging role in the management of leptomeningeal metastasis needs to better studied in prospective series. Focal radiotherapy is commonly indicated for the treatment of macroscopic disease such as meningeal nodules or clinically symptomatic central nervous system structures, for example, base of skull with cranial nerve involvement or cauda equine syndrome. The role of whole brain radiotherapy is decreasing. An individualised combination of different therapeutic options should be used considering the presentation of leptomeningeal metastasis, as well as the histological and molecular tumour characteristics, the presence of concomitant brain and systemic metastases, and prior cancer-directed treatments.

SUBMITTER: Le Rhun E

PROVIDER: S-EPMC6555600 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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How we treat patients with leptomeningeal metastases.

Le Rhun Emilie E Preusser Matthias M van den Bent Martin M Andratschke Nicolaus N Weller Michael M

ESMO open 20190521 Suppl 2

The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease-related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for ...[more]

PMID: 31231573

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Project description:IMPORTANCE:Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. OBJECTIVE:To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. DESIGN:Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. SETTING:Monocentric, retrospective, real-life cohort of patients with LM from melanoma. PARTICIPANTS:All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. EXPOSURE:Impact of new systemic therapies and radiotherapy. RESULTS:Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM "confirmed" or "probable" after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09-1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25-6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. CONCLUSION:Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

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How we treat patients with leptomeningeal metastases.

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How we treat patients with leptomeningeal metastases.

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