胃食管（GE）恶性肿瘤中的软脑膜转移（LM）极为罕见。从历史上看，LM 的治疗包括类固醇、放疗、化疗和鞘内 (IT) 化疗。然而，GE 恶性肿瘤合并 LM 的结果仍然很差。不幸的是，GE 恶性肿瘤的临床试验传统上排除了 LM 患者，限制了治疗策略的进展。鉴于 LM 可能造成毁灭性的神经和心理后遗症，迫切需要更有效的治疗方法。 患者 1 是一名 44 岁女性，患有局限性食管腺癌，接受新辅助放化疗，随后接受食管切除术。手术后七个月，她出现共济失调、虚弱和恶心/呕吐。磁共振成像（MRI）显示颅内疾病，随后成功切除并用伽马刀（GK）放射治疗。病理学证实转移。三个月后，她被发现患有LM。她接受姑息性全脑放射治疗以及脊柱局部放射治疗。此后，她转为同时使用 IT 托泊替康加静脉注射 (IV) 伊匹鲁单抗/纳武单抗，并获得了超过 14 个月的持久缓解。患者 2 是一名 71 岁男性，患有新发转移性食管腺癌，对 5-氟尿嘧啶加伊立替康有持久反应。在初次诊断并接受 GK 治疗 2 年后，通过监测扫描发现无症状颅内转移瘤。后续 MRI 发现新的 LM。因此，为了治疗 LM，他改用 IT 拓扑替康和静脉注射派姆单抗，效果良好，持续 6 个月，直至因胃肠道出血死亡。我们介绍了两例 GE 腺癌患者的 LM 病例，其生存期比报道的要长。他们接受了 IT 拓扑替康和 IV 检查点抑制联合治疗。评估中枢神经系统肿瘤免疫微环境的进一步研究可以帮助我们加深对这种组合如何在患者中发挥良好作用以及如何护理其他具有类似情况的人的理解。2024 年胃肠肿瘤学杂志。版权所有。

Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments.Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed.We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.2024 Journal of Gastrointestinal Oncology. All rights reserved.