间变性淋巴瘤激酶阳性的非小细胞肺癌的临床分析

发布时间：2018-07-03 15:15

  本文选题：间变性淋巴瘤激酶 + 非小细胞肺癌　； 参考：《浙江大学》2017年博士论文

【摘要】：目的:分析ALK融合基因阳性的NSCLC患者的临床和影像学特征,探讨克唑替尼靶向治疗在ALK阳性NSCLC患者中的疗效和安全性,为这一特殊亚型的NSCLC的临床诊疗提供参考依据。方法:收集浙江大学医学院附属第一医院2013年1月1日至2017年2月1日期间收治的经病理学或细胞蜡块确诊的、基因检测为ALK融合基因阳性的NSCLC患者,回顾性总结其临床特征并对比其与EGFR突变NSCLC患者的影像学差异。通过分别比较一线克唑替尼靶向治疗和一线培美曲塞联合铂类化疗及一线克唑替尼和非一线克唑替尼靶向治疗的PFS和ORR,评估克唑替尼在ALK阳性NSCLC患者中的疗效。同时收集克唑替尼相关的不良事件,评价其安全性。结果:129例ALK阳性的NSCLC患者的中位发病年龄为52岁,既往无吸烟史的患者占72.1%。96.1%的患者的病理类型为腺癌。其中71例患者同时进行了 EGFR基因检测,未发现共阳患者。静脉血栓栓塞事件在ⅢB/Ⅳ期患者中的发生率为9.7%。ALK阳性患者的肺部CT影像多表现为周围型的(62.7%)、实性密度的(87.3%)、边缘为细毛刺或分叶状(94.1%)的团块影。相较于EGFR突变的NSCLC患者,Ⅳ期ALK阳性患者中多区域淋巴结转移更常见(67.1%vs.45.0%,P=0.003),磨玻璃或半实性密度(6.8%vs.29.4%,P0.001)和双肺多发转移(30.1%vs.51.4%,P=0.005)更少见。在治疗上,一线克唑替尼治疗的患者的PFS和ORR均显著高于一线培美曲塞联合铂类化疗的患者(PFS:12.7个月vs.5.6个月,P0.001;ORR:68.2%vs.26.1%,P=0.001),但与非一线克唑替尼治疗相比无显著差异(PFS:12.7个月 vs.12.8 个月,P=0.954;ORR:68.2%vs.60.5%,P=0.470)。在 38 例 ALK 阳性NSCLC伴脑转移的患者中,克唑替尼靶向治疗联合头颅放疗的中位cPFS为7.2个月。放疗、基线脑转移是cPFS的独立保护因素。神经系统症状是cPFS的独立危险因素。在84例接受克唑替尼靶向治疗的患者中共发生不良事件203起,其中NCICTCAE3级及以上的严重不良事件23起,包括1起罕见的剥脱性食管炎。所有发生不良事件的患者中仅2例患者因间质性肺炎终止了克唑替尼治疗。结论:ALK阳性的NSCLC患者多为年轻、不吸烟的、EGFR突变阴性的腺癌患者,易合并发生VTE。肺部CT上常表现为周围型的、边缘为毛刺或分叶状的实性密度影和多区域的淋巴结肿大,磨玻璃或半实性密度病灶和双肺多发转移灶相对少见。一线克唑替尼靶向治疗的疗效显著优于一线培美曲塞联合铂类化疗,但与非一线克唑替尼靶向治疗的疗效无显著差异。克唑替尼联合头颅放疗可有效控制颅内转移灶。克唑替尼具有较好的安全性,除极少数发生间质性肺炎的患者,绝大部分患者均能耐受克唑替尼靶向治疗。
[Abstract]:Objective: to analyze the clinical and imaging features of NSCLC patients with ALK fusion gene positive, and to explore the efficacy and safety of cetinib targeted therapy in patients with ALK positive NSCLC, so as to provide reference for the clinical diagnosis and treatment of this special subtype of NSCLC. Methods: from January 1, 2013 to February 1, 2017, NSCLC patients with positive ALK fusion gene were collected from the first affiliated Hospital of Zhejiang University School of Medicine from January 1, 2013 to February 1, 2017. The clinical features of NSCLC were retrospectively summarized and the imaging differences between NSCLC patients with EGFR mutation and those with EGFR mutation were compared. To evaluate the efficacy of kezoltini in patients with ALK-positive NSCLC, the PFS and ORR of first-line and first-line pemetrexide combined with platinum chemotherapy and first-line and non-first-line targeted therapy were compared, respectively, to evaluate the efficacy of ceczoltini in patients with ALK-positive NSCLC. At the same time, safety was evaluated by collecting adverse events associated with cetatinib. Results the median onset age of 129 patients with ALK-positive NSCLC was 52 years old. 72.1% of the patients with no smoking history had adenocarcinoma. EGFR gene was detected simultaneously in 71 patients, and no co-positive patients were found. The incidence of venous thromboembolism in patients with stage 鈪，

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