放疗为主的综合方案治疗脑膜转移瘤Ⅱ期临床研究

目的 前瞻性分析脑膜转移瘤以放疗为主的综合治疗方案的有效性及安全性。方法 纳入2014-2017年中国医学科学院肿瘤医院收治的93例脑膜转移瘤患者,接受螺旋断层放疗技术实施的全脑放疗、局部推量和/或全脊髓照射为基础的综合治疗,记录临床症状、磁共振检查、脑脊液细胞学、液体活检变化情况及不良反应。主要研究终点为总生存(OS),次要研究终点为局部控制(LC)、颅内无进展生存(IPFS)及脑转移专项生存(BMSS)及不良反应。结果 主要原发病为非小细胞肺癌。全组接受全脑放疗±局部推量(中位剂量分别为40Gy分20次、60Gy分20次)或全脑、全脊髓照射(中位剂量分别为40Gy分20次或50Gy分25次、36Gy分20次)。20例找到肿瘤细胞并行鞘注化疗;63例接受靶向治疗。中位随访时间33.8个月,1年OS、LC及IPFS分别为62%、77%及53%。中位生存时间15.9个月,中位BMSS时间42.2个月。3-4级不良反应少见,仅观察到8例3级血液学不良反应。结论 精准放疗结合鞘注化疗或靶向治疗的综合治疗方法,可有效延长脑膜转移瘤患者的生存时间,且不良反应可耐受。

A phase Ⅱ trial of comprehensive treatment based on radiotherapy in leptomeningeal metastasis

Objective To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study. Methods A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS),the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity. Results The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months.Treatment-related grade 3–4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity. Conclusion Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.