Leptomeningeal metastasis (LM) is one of the most serious complications of non-small cell lung cancer (NSCLC) without standard treatment guidelines and is always accompanied by poor prognosis. Identifying the types of gene mutations is essential to improve the outcome, and an increasing number of rare epidermal growth factor receptor (EGFR) mutations are revealed by next-generation sequencing (NGS). Here, we describe a case of a 56-year-old man who was diagnosed with lung adenocarcinoma and received thoracoscopic resection in May 2015. One year later, LM was confirmed by positive cerebrospinal fluid cytology. Given the existence of EGFR exon 19 deletions, erlotinib was implemented and achieved a short response for 10 months. Then the systemic therapy was changed to osimertinib and obtained clinical remission for 25 months. Owing to the resurgence of violent headache, retching and vomiting, NGS of cerebrospinal fluid was performed and two rare EGFR-SEPT14 fusions were found. Osimertinib combined bevacizumab, chemotherapy (carboplatin and abraxane) and dacomitinib were implemented in turn but ineffective. Thus, osimertinib combined intrathecal chemotherapy with pemetrexed were carried out and gained a complete remission of neurologic symptoms, stable lesions and long-term survival without notable side effects. This study presented the first case of NSCLC-LM harboring particular EGFR-SEPT14 fusions, who showed a durable response to osimertinib and intrathecal pemetrexed, providing a potential therapeutic option for NSCLC-LM patients with this particular mutation.

中文翻译：

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奥希替尼联合培美曲塞鞘内化疗治疗罕见 EGFR-SEPT14 融合的 NSCLC 软脑膜转移完全缓解。

软脑膜转移（LM）是无标准治疗指南的非小细胞肺癌（NSCLC）最严重的并发症之一，且预后不良。识别基因突变类型对于改善结果至关重要，新一代测序 (NGS) 揭示了越来越多的罕见表皮生长因子受体 (EGFR) 突变。在此，我们描述一例56岁男性的病例，他于2015年5月被诊断为肺腺癌并接受胸腔镜切除术。一年后，脑脊液细胞学阳性证实为LM。鉴于EGFR外显子19缺失的存在，实施了厄洛替尼并取得了10个月的短期缓解。随后全身治疗改为奥希替尼，获得25个月的临床缓解。由于剧烈头痛、干呕、呕吐再次出现，进行脑脊液NGS检查，发现两例罕见的EGFR-SEPT14融合。奥希替尼联合贝伐珠单抗、化疗（卡铂和abraxane）和达克替尼依次实施，但效果不佳。因此，奥希替尼联合培美曲塞鞘内化疗，神经症状完全缓解，病灶稳定，长期生存，无明显副作用。这项研究提出了首例携带特定 EGFR-SEPT14 融合的 NSCLC-LM 病例，该病例对奥西替尼和鞘内培美曲塞表现出持久的反应，为具有这种特定突变的 NSCLC-LM 患者提供了潜在的治疗选择。