克唑替尼对ALK 阳性NSCLC 患者CNS 的影响

Clinical impact of Crizotinib on CNS progression in patients with ALK-positive NSCLC

摘要:

目的 探讨克唑替尼对间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）患者中枢神经 系统（CNS）的影响。方法 回顾性分析在河北大学附属医院接受治疗的59 例ALK 阳性NSCLC 患者的临 床资料，应用荧光原位杂交、逆转录聚合酶链反应或免疫组织化学法评估ALK 基因重组的状态，利用实体肿 瘤反应评估标准客观评估肿瘤情况。结果 患者克唑替尼的客观缓解率为66%，无进展生存期中值为9.7 个月。 24 例患者中CNS 是常见的初始进展位点，18 例患者有单独的CNS 进展。BM 阳性与阴性的患者的无进展生 存率比较有差异（P <0.05）。多变量分析显示，较差的体能状态（脑转移≥ 2）或未治疗的BM 阳性患者与 PFS 有关（P <0.05）。给予克唑替尼治疗后26 个月，BM 阳性与阴性患者CNS 进展发生率比较有差异（P <0.05）。 结论 克唑替尼治疗的ALK 阳性患者中，常见进展部位是CNS，其进展与低渗透性有关。

Abstract:

Objective To investigate the clinical effect of Crizotinib on central nervous system (CNS) in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) and provide scientific evidence for clinical researches. Methods The clinical data of 59 patients with ALK-positive NSCLC treated in our hospital were retrospectively analyzed. The status of ALK gene recombination was evaluated by fluorescence in situ hybridization (FISH). Results The objective remission rate of Crizotinib was 66% and the median progressionfree survival (PFS) was 9.7 months. Of the 59 patients, CNS was a common initial progression site in 24 patients, including 18 patients with isolated CNS progression. The PFS was significantly different between the ALK-positive patients with brain metastasis (BM) and those without BM (P < 0.05). Multivariate analysis showed that poorer physical status (PS) ( ≥ 2) or untreated BM was associated with PFS duration (P < 0.05). In the 26th month after Crizotinib treatment, there was a significant difference in the incidence of CNS progression between the patients with BM and those without BM (P < 0.05). Conclusions Among the ALK-positive patients treated with Crizotinib, the common site of progress is the central nervous system, and this progression is associated with low permeability.