Department of Oncology, The Second Affiliated Hospital of Nanchang University, No.1 Minde Street, Nanchang, Jiangxi Province, 330000, People's Republic of China.
Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, 330000, People's Republic of China.
BMC Cancer. 2023 Apr 11;23(1):333. doi: 10.1186/s12885-023-10806-5.
Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. There is currently no standard treatment for LM, and the efficacy of traditional intravenous drug treatment is low, making refractory LM a difficult problem. In this study, we evaluated the efficacy and safety of intrathecal chemotherapy (IC)-based regimens in patients with refractory LM.
We retrospectively enrolled NSCLC patients with confirmed LM who received IC and systemic therapy at the Second Affiliated Hospital of Nanchang University from December 2017 to July 2022. We analysed overall survival (OS), intracranial progression-free survival (iPFS), clinical response, and safety in these patients.
A total of 41 patients were enrolled. The median number of IC treatments was seven (range: 2-22). Seven patients received intrathecal methotrexate, and 34 patients received intrathecal pemetrexed. Clinical manifestations related to LM improved after IC and systemic therapy in 28 (68.3%) patients. The median iPFS in the whole cohort was 8 months (95% confidence interval [CI]: 6.4-9.7 months), and the median OS was 10.1 months (95% CI: 6.8-13.4 months). Multivariate analysis of the 41 patients with LM using a Cox proportional risk model showed that bevacizumab was an independent prognostic factor in patients treated with combination therapy (p = 0.002; hazard ratio [HR] 0.240; 95% CI: 0.097-0.595). Poor ECOG performance status remained a significant predictor of poor prognosis for survival (p = 0.048; HR 2.560; 95% CI: 1.010-6.484). Myelosuppression was the major adverse event over all IC dose levels. There were 18 cases of myelosuppression, 15 cases of leukopenia, and nine cases of thrombocytopenia. Eleven patients had myelosuppression above grade 3, including four with thrombocytopenia and seven with leukopenia.
Combination therapy based on IC had good curative effects, was safe to use, and was associated with prolonged survival in NSCLC patients with LM. The use of bevacizumab is a good prognostic factor for NSCLC LM patients with combination therapy.
脑膜转移（LM）是非小细胞肺癌（NSCLC）最具破坏性的并发症之一，其发病率正在上升。目前，LM 没有标准的治疗方法，传统静脉药物治疗的疗效较低，使难治性 LM 成为一个难题。在这项研究中，我们评估了鞘内化疗（IC）为基础的方案在难治性 LM 患者中的疗效和安全性。
我们回顾性纳入了 2017 年 12 月至 2022 年 7 月在南昌大学第二附属医院接受 IC 和全身治疗的 NSCLC 伴 LM 患者。我们分析了这些患者的总生存期（OS）、颅内无进展生存期（iPFS）、临床反应和安全性。
共纳入 41 例患者。IC 治疗的中位数为 7 次（范围：2-22 次）。7 例患者接受了鞘内甲氨蝶呤治疗，34 例患者接受了鞘内培美曲塞治疗。28 例（68.3%）患者在 IC 和全身治疗后 LM 相关临床表现得到改善。全队列的中位 iPFS 为 8 个月（95%置信区间[CI]：6.4-9.7 个月），中位 OS 为 10.1 个月（95%CI：6.8-13.4 个月）。采用 Cox 比例风险模型对 41 例 LM 患者进行多因素分析显示，贝伐珠单抗是联合治疗患者的独立预后因素（p=0.002；风险比[HR]0.240；95%CI：0.097-0.595）。ECOG 表现状态差仍是生存预后不良的显著预测因素（p=0.048；HR 2.560；95%CI：1.010-6.484）。骨髓抑制是所有 IC 剂量水平的主要不良事件。18 例出现骨髓抑制，15 例白细胞减少，9 例血小板减少。11 例患者出现 3 级以上骨髓抑制，其中 4 例血小板减少，7 例白细胞减少。
以 IC 为基础的联合治疗对 NSCLC 伴 LM 患者具有良好的疗效，使用安全，可延长患者的生存时间。贝伐珠单抗的使用是 NSCLC LM 患者联合治疗的良好预后因素。
