Leptomeningeal metastatic disease (LMD), encompassing entities of ‘meningeal carcinomatosis’, neoplastic meningitis’ and ‘leukaemic/lymphomatous meningitis’, arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients. Underdiagnosis and misdiagnosis are common, response assessment remains challenging, and the prognosis associated with this disease of whole neuroaxis remains extremely poor. The dearth of effective therapies is further challenged by the difficulties in studying this dynamic disease state. In this Review, a multidisciplinary group of experts describe the emerging evidence and areas of active investigation in LMD and provide directed recommendations for future research. Drawing upon paradigm-changing advances in mechanistic science, computational approaches, and trial design, the authors discuss domain-specific and cross-disciplinary strategies for optimizing the clinical and translational research landscape for LMD. Advances in diagnostics, multi-agent intrathecal therapies, cell-based therapies, immunotherapies, proton craniospinal irradiation and ongoing clinical trials offer hope for improving outcomes for patients with LMD.

软脑膜转移性疾病 （LMD），包括“脑膜癌病”、“肿瘤性脑膜炎”和“白血病/淋巴瘤性脑膜炎”的实体，继发于癌细胞从颅外和某些颅内恶性肿瘤转移到软脑膜和脑脊液中。LMD 的临床负担一直在增加，继发于更敏感的诊断、对离散脑转移的积极局部治疗以及使用靶向和免疫治疗剂改善颅外疾病的管理，从而提高了生存率。然而，由于药物递送挑战和 LMD 独特的微环境，针对全身性疾病的新疗法尚未转化为改善这些患者的预后。诊断不足和误诊很常见，反应评估仍然具有挑战性，与这种全神经轴疾病相关的预后仍然极差。研究这种动态疾病状态的困难进一步挑战了有效疗法的缺乏。在本综述中，一个多学科专家组描述了 LMD 的新证据和积极研究的领域，并为未来的研究提供了指导性建议。借鉴机制科学、计算方法和试验设计方面改变范式的进步，作者讨论了优化 LMD 临床和转化研究前景的特定领域和跨学科策略。诊断、多药鞘内治疗、基于细胞的疗法、免疫疗法、质子颅脊髓照射和正在进行的临床试验的进步为改善 LMD 患者的预后带来了希望。