Highlights
- •Around 20% of the patients with leptomeningeal disease (LMD) received no treatment.
- •The presence of a BRAF mutation seems to be higher in patients with LMD.
- •At diagnosis of LMD, most of the patients had concomitant brain metastases.
- •The prognosis of LMD remains poor with a median overall survival of 2.9 months.
Abstract
Objective
The development of leptomeningeal disease (LMD) among melanoma patients is associated
with short survival. Unspecific clinical symptoms and imprecise diagnostic criteria
often delay diagnosis. Because melanoma patients with LMD have been excluded from
most clinical trials, the efficacy of immune checkpoint blockade (ICB) and targeted
therapies (TTs) has not been adequately investigated among these patients.
Methods
We performed a retrospective study in two tertiary-referral skin cancer centres to
evaluate the clinical characteristics, diagnostics, treatments, and overall survival
(OS) of melanoma patients with LMD between June 2011 and March 2019.
Results
In total, 52 patients were included. The median age at LMD diagnosis was 58 years.
Most patients (n = 30, 58%) were men. The median time from the first diagnosis of
unresectable disease to the first diagnosis of LMD was 8.5 months (range 0–91.5 months).
Most patients (65%, n = 34) were BRAF V600 mutated. Sixteen patients (31%) presented with LMD only, whereas 36 patients
(69%) presented with concomitant brain metastases at LMD diagnosis. Eleven patients
(21%) showed no evidence of extracranial disease. Forty-four patients (85%) had clinical
symptoms at LMD diagnosis. Forty-two patients (81%) had received at least one prior
therapy. Forty patients (77%) received at least one treatment after LMD diagnosis,
including TT (n = 17), ICB (n = 13), bevacizumab (n = 1), radiotherapy (n = 3), and
intrathecal chemotherapy (n = 1); five patients received both TT and ICB. Twelve patients
(23%) received no treatment because of rapid progression of LMD. The median OS for
the entire cohort was 2.9 months (95% confidence interval [CI] 1.7–4.1). Among patients
receiving systemic therapy, OS was 3.7 months (95% CI 2.4–4.9).
Conclusions
Systemic treatment with TT or ICB seems to improve OS among patients with LMD. However,
despite new therapy modalities, the prognosis of LMD remains poor.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
CI (confidence interval), CR (complete response), CSF (cerebrospinal fluid), ctDNA (circulating tumor DNA), DCR (disease control rate), ECOG (Eastern Cooperative Oncology Group), HR (hazard ratio), ICB (immune checkpoint blockade), LDH (lactate dehydrogenase), LMD (leptomeningeal disease), MRI (magnetic resonance imaging), ORR (overall response rate), OS (overall survival), PD (progressive disease), PD-1 (anti-programmed cell death 1), PFS (progression-free survival), PR (partial response), RANO (Response Assessment in Neuro-Oncology), SD (stable disease), TT (targeted therapy)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 28, 2021
Accepted:
February 3,
2021
Received in revised form:
February 1,
2021
Received:
November 13,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
