Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2026
Update on the management of leptomeningeal disease in solid organ malignancy: Systemic, intrathecal and novel therapies.
СтатьяСистематический обзорНазвание и аннотация: Перевод в очереди
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Fisher Sanlin, Topp Monique, Airth Angus, Campbell Bethany, Stylli Stan, Hovens Chris, Dimou James
Аннотация
BACKGROUND: Leptomeningeal disease (LMD) is an increasingly recognised late-stage complication of solid tumours (primarily melanoma, lung and breast cancers). It involves dissemination to the leptomeninges surrounding the brain and spinal cord and carries a poor prognosis ranging from 2-6 months. Recent advances in emerging therapies such as CNS-active targeted therapy, intrathecal agents, and early-phase immunotherapy necessitate an updated appraisal of prospective data.
METHODS: A systematic search of MEDLINE, Embase, Scopus and CENTRAL (January 2020-July 2025) was undertaken according to PRISMA 2020 guidelines (PROSPERO CRD420251181223). Prospective clinical studies evaluating systemic, intrathecal, or novel therapies for adult solid-tumour LMD were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), response rates, neurological function, quality of life (QoL) and safety. Risk of bias was assessed using the Newcastle-Ottawa Scale or Cochrane RoB-2 as appropriate.
RESULTS: Ten prospective trials (n = 520) met study inclusion criteria. Two Korean phase II studies demonstrated consistent intracranial activity of osimertinib in EGFR-mutant NSCLC-LMD, with median OS 13-15 months and intracranial ORR 51.6% by blinded RANO-LMD review. Three phase I/II Chinese trials of IT pemetrexed showed reproducible disease-control signals (ORR 43.5-80.3%, median OS 9-12 months) with frequent neurological improvement and predominantly reversible myelosuppression. In breast-cancer LMD, IT liposomal cytarabine improved LM-PFS (3.8 vs 2.2 months) without a significant OS or QoL advantage. IT trastuzumab produced modest responses with acceptable tolerability, while combined IT/IV nivolumab in melanoma LMD showed feasibility and manageable toxicity. BLOSSOM was the only study to demonstrate QoL improvement, while DEPOSEIN collected EORTC-based QoL data but found no between-arm differences; QoL reporting in other trials was minimal or absent.
CONCLUSIONS: Contemporary prospective evidence suggests incremental outcome gains in solid-tumour LMD, driven by CNS-active targeted therapy (osimertinib) and, in selected cases, IT pemetrexed. However, reliance on single-arm designs, heterogeneous endpoints, and sparse QoL data reduces confidence in the findings. Standardised LMD-specific outcomes and controlled comparative trials are needed to define best practice.
METHODS: A systematic search of MEDLINE, Embase, Scopus and CENTRAL (January 2020-July 2025) was undertaken according to PRISMA 2020 guidelines (PROSPERO CRD420251181223). Prospective clinical studies evaluating systemic, intrathecal, or novel therapies for adult solid-tumour LMD were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), response rates, neurological function, quality of life (QoL) and safety. Risk of bias was assessed using the Newcastle-Ottawa Scale or Cochrane RoB-2 as appropriate.
RESULTS: Ten prospective trials (n = 520) met study inclusion criteria. Two Korean phase II studies demonstrated consistent intracranial activity of osimertinib in EGFR-mutant NSCLC-LMD, with median OS 13-15 months and intracranial ORR 51.6% by blinded RANO-LMD review. Three phase I/II Chinese trials of IT pemetrexed showed reproducible disease-control signals (ORR 43.5-80.3%, median OS 9-12 months) with frequent neurological improvement and predominantly reversible myelosuppression. In breast-cancer LMD, IT liposomal cytarabine improved LM-PFS (3.8 vs 2.2 months) without a significant OS or QoL advantage. IT trastuzumab produced modest responses with acceptable tolerability, while combined IT/IV nivolumab in melanoma LMD showed feasibility and manageable toxicity. BLOSSOM was the only study to demonstrate QoL improvement, while DEPOSEIN collected EORTC-based QoL data but found no between-arm differences; QoL reporting in other trials was minimal or absent.
CONCLUSIONS: Contemporary prospective evidence suggests incremental outcome gains in solid-tumour LMD, driven by CNS-active targeted therapy (osimertinib) and, in selected cases, IT pemetrexed. However, reliance on single-arm designs, heterogeneous endpoints, and sparse QoL data reduces confidence in the findings. Standardised LMD-specific outcomes and controlled comparative trials are needed to define best practice.