本文選題：間變性淋巴瘤激酶 + 非小細(xì)胞肺癌　； 參考：《浙江大學(xué)》2017年博士論文

【摘要】：目的:分析ALK融合基因陽性的NSCLC患者的臨床和影像學(xué)特征,探討克唑替尼靶向治療在ALK陽性NSCLC患者中的療效和安全性,為這一特殊亞型的NSCLC的臨床診療提供參考依據(jù)。方法:收集浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院2013年1月1日至2017年2月1日期間收治的經(jīng)病理學(xué)或細(xì)胞蠟塊確診的、基因檢測為ALK融合基因陽性的NSCLC患者,回顧性總結(jié)其臨床特征并對比其與EGFR突變NSCLC患者的影像學(xué)差異。通過分別比較一線克唑替尼靶向治療和一線培美曲塞聯(lián)合鉑類化療及一線克唑替尼和非一線克唑替尼靶向治療的PFS和ORR,評估克唑替尼在ALK陽性NSCLC患者中的療效。同時收集克唑替尼相關(guān)的不良事件,評價其安全性。結(jié)果:129例ALK陽性的NSCLC患者的中位發(fā)病年齡為52歲,既往無吸煙史的患者占72.1%。96.1%的患者的病理類型為腺癌。其中71例患者同時進(jìn)行了 EGFR基因檢測,未發(fā)現(xiàn)共陽患者。靜脈血栓栓塞事件在ⅢB/Ⅳ期患者中的發(fā)生率為9.7%。ALK陽性患者的肺部CT影像多表現(xiàn)為周圍型的(62.7%)、實性密度的(87.3%)、邊緣為細(xì)毛刺或分葉狀(94.1%)的團(tuán)塊影。相較于EGFR突變的NSCLC患者,Ⅳ期ALK陽性患者中多區(qū)域淋巴結(jié)轉(zhuǎn)移更常見(67.1%vs.45.0%,P=0.003),磨玻璃或半實性密度(6.8%vs.29.4%,P0.001)和雙肺多發(fā)轉(zhuǎn)移(30.1%vs.51.4%,P=0.005)更少見。在治療上,一線克唑替尼治療的患者的PFS和ORR均顯著高于一線培美曲塞聯(lián)合鉑類化療的患者(PFS:12.7個月vs.5.6個月,P0.001;ORR:68.2%vs.26.1%,P=0.001),但與非一線克唑替尼治療相比無顯著差異(PFS:12.7個月 vs.12.8 個月,P=0.954;ORR:68.2%vs.60.5%,P=0.470)。在 38 例 ALK 陽性NSCLC伴腦轉(zhuǎn)移的患者中,克唑替尼靶向治療聯(lián)合頭顱放療的中位cPFS為7.2個月。放療、基線腦轉(zhuǎn)移是cPFS的獨立保護(hù)因素。神經(jīng)系統(tǒng)癥狀是cPFS的獨立危險因素。在84例接受克唑替尼靶向治療的患者中共發(fā)生不良事件203起,其中NCICTCAE3級及以上的嚴(yán)重不良事件23起,包括1起罕見的剝脫性食管炎。所有發(fā)生不良事件的患者中僅2例患者因間質(zhì)性肺炎終止了克唑替尼治療。結(jié)論:ALK陽性的NSCLC患者多為年輕、不吸煙的、EGFR突變陰性的腺癌患者,易合并發(fā)生VTE。肺部CT上常表現(xiàn)為周圍型的、邊緣為毛刺或分葉狀的實性密度影和多區(qū)域的淋巴結(jié)腫大,磨玻璃或半實性密度病灶和雙肺多發(fā)轉(zhuǎn)移灶相對少見。一線克唑替尼靶向治療的療效顯著優(yōu)于一線培美曲塞聯(lián)合鉑類化療,但與非一線克唑替尼靶向治療的療效無顯著差異。克唑替尼聯(lián)合頭顱放療可有效控制顱內(nèi)轉(zhuǎn)移灶。克唑替尼具有較好的安全性,除極少數(shù)發(fā)生間質(zhì)性肺炎的患者,絕大部分患者均能耐受克唑替尼靶向治療。
[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，

本文編號：2094078