Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brain Tumor Center, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Neurotherapeutics. 2022 Oct;19(6):1782-1798. doi: 10.1007/s13311-022-01261-4. Epub 2022 Jul 5.
Leptomeningeal metastases arise from cancer cell entry into the subarachnoid space, inflicting significant neurologic morbidity and mortality across a wide range of malignancies. The modern era of cancer therapeutics has seen an explosion of molecular-targeting agents and immune-mediated strategies for patients with breast, lung, and melanoma malignancies, with meaningful extracranial disease control and improvement in patient survival. However, the clinical efficacy of these agents in those with leptomeningeal metastases remains understudied, due to the relative rarity of this patient population, the investigational challenges associated with studying this dynamic disease state, and brisk disease pace. Nevertheless, retrospective studies, post hoc analyses, and small prospective trials in the last two decades provide a glimmer of hope for patients with leptomeningeal metastases, suggesting that several cancer-directed strategies are not only active in the intrathecal space but also improve survival against historical odds. The continued development of clinical trials devoted to patients with leptomeningeal metastases is critical to establish robust efficacy outcomes in this patient population, define drug pharmacokinetics in the intrathecal space, and uncover new avenues for treatment in the face of leptomeningeal therapeutic resistance.
脑膜转移是癌细胞进入蛛网膜下腔引起的，在多种恶性肿瘤中导致严重的神经发病率和死亡率。在癌症治疗的现代时代，针对乳腺癌、肺癌和黑色素瘤恶性肿瘤的患者，出现了分子靶向药物和免疫介导的治疗策略的爆炸式增长，显著控制了颅外疾病，并提高了患者的生存率。然而，由于此类患者人群相对较少，研究这种动态疾病状态的调查挑战以及疾病进展迅速，这些药物在脑膜转移患者中的临床疗效仍未得到充分研究。然而，在过去二十年中的回顾性研究、事后分析和小型前瞻性试验为脑膜转移患者带来了一线希望，表明几种针对癌症的治疗策略不仅在鞘内空间中有效，而且还提高了生存率，打破了以往的纪录。继续开展针对脑膜转移患者的临床试验对于在该患者人群中建立稳健的疗效结果、确定鞘内空间中的药物药代动力学以及面对脑膜治疗耐药性时发现新的治疗途径至关重要。
