發(fā)布時(shí)間：2018-01-03 00:07

  本文關(guān)鍵詞：鹽酸�？颂婺嵩谕砥诜西[癌患者中生存分析研究　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 肺鱗癌 肺腺癌 鹽酸�？颂婺� EGFR EGFR-TKI 傾向性評(píng)分匹配

【摘要】：背景與目的表皮生長(zhǎng)因子受體-酪氨酸激酶抑制劑(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)靶向治療被廣泛應(yīng)用于晚期肺腺癌患者中,尤其是伴有EGFR基因突變的肺腺癌患者,而關(guān)于EGFR-TKI在晚期肺鱗癌患者中應(yīng)用仍存在很多爭(zhēng)議。本研究第一章通過回顧性研究分析在未選擇的晚期肺鱗癌患者中服用EGFR-TKI鹽酸�？颂婺嶂委煹臒o進(jìn)展生存時(shí)間(progression free survival,PFS)和總生存時(shí)間(overall survival,OS)。肺鱗癌EGFR突變率遠(yuǎn)遠(yuǎn)低于肺腺癌EGFR突變率,關(guān)于EGFR突變型肺鱗癌患者選擇EGFR-TKI治療較肺腺癌患者療效差異存在爭(zhēng)議,認(rèn)為肺鱗癌患者選擇TKI較腺癌效果差,本研究第二章通過比較EGFR突變型肺鱗癌和肺腺癌患者服用鹽酸�？颂婺嶂委煹纳�存時(shí)間來驗(yàn)證這個(gè)論點(diǎn)。方法回顧性分析2013年6月至2016年6月服用鹽酸埃克替尼治療的肺鱗癌患者,納入標(biāo)準(zhǔn):年齡≥18歲;已簽署知情同意書;病理證實(shí)為肺鱗癌;臨床分期為IIIB或IV期;KPS評(píng)分≥60分;適宜的骨髓、肝腎功能;接受鹽酸埃克替尼治療進(jìn)入慈善贈(zèng)藥范圍。排除標(biāo)準(zhǔn):鹽酸�？颂婺崧�(lián)合化療患者除外;有嚴(yán)重心肺疾病;有習(xí)慣性腹瀉或便秘等影響藥物吸收的胃腸道疾病;妊娠或哺乳。患者治療期間定期復(fù)診行體格檢查、影像學(xué)及常規(guī)實(shí)驗(yàn)室檢查。電話隨訪病人生存時(shí)間,截止日期為2017年4月。主要結(jié)局指標(biāo)為PFS,次要結(jié)局指標(biāo)為OS、客觀緩解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)。生存分析采用Kaplain-Meier法計(jì)算;單因素生存時(shí)間差異采用Log-rank法,多因素分析采用Cox比例風(fēng)險(xiǎn)模型;組間、組內(nèi)比較及不同因素的客觀有效率比較采用卡方比較。檢驗(yàn)水準(zhǔn)確定P0.05為有統(tǒng)計(jì)學(xué)差異(Cox比例風(fēng)險(xiǎn)模型中P0.1)�；仡櫺苑治�2013年6月至2016年6月服用鹽酸埃克替尼治療的肺腺癌患者,納入標(biāo)準(zhǔn):病理證實(shí)為肺腺癌;基因檢測(cè)EGFR為突變型;余同鱗癌。排除標(biāo)準(zhǔn)同鱗癌。隨訪截止日期為2017年4月。選擇合適的肺腺癌患者與EGFR突變型肺鱗癌患者進(jìn)行傾向性評(píng)分1:1比例匹配,匹配因素:年齡、性別、臨床分期、KPS評(píng)分、吸煙情況、EGFR基因突變類型、治療線數(shù),卡鉗值0.03,比較兩組人群的生存時(shí)間。結(jié)局指標(biāo)及統(tǒng)計(jì)方法同鱗癌,檢驗(yàn)水準(zhǔn)確定P0.05為有統(tǒng)計(jì)學(xué)差異。結(jié)果487例肺鱗癌患者服用鹽酸�？颂婺嶂委�,中位無進(jìn)展生存時(shí)間為13.0月(95%CI 12.2-13.8),中位總生存時(shí)間為16.0月(95%CI 14.7-17.3),1年生存率為55.4%,2年生存率為22.8%,客觀緩解率為41.3%,疾病控制率為99.8%。多因素Cox逐步回歸分析中肺鱗癌KPS評(píng)分和治療療效對(duì)無進(jìn)展生存時(shí)間影響有顯著性差異(P=0.063,P=0.001),同時(shí)對(duì)總生存時(shí)間影響亦有顯著性差異(P=0.018,P=0.003)�；颊叩牟涣挤磻�(yīng)以皮疹、腹瀉、肝酶升高為主。156例EGFR突變型肺鱗癌和肺腺癌患者服用鹽酸�？颂婺嶂委�,其中肺鱗癌78例,肺腺癌78例,中位無進(jìn)展生存時(shí)間分別為12.7月(95%CI 10.4-15.0)和15.8月(95%CI 12.4-19.2),差異無統(tǒng)計(jì)學(xué)意義(P=0.275);中位總生存時(shí)間分別為18.5月(95%CI14.4-22.6)和24.2月(95%CI不能計(jì)算),差異無統(tǒng)計(jì)學(xué)意義(P=0.150);1年生存率分別為53.8%和61.5%(P=0.297),2年生存率分別為26.7%和30.9%(P=0.191);客觀緩解率分別為48.7%和59.0%(P=0.199)。肺鱗癌和肺腺癌亞組分析中EGFR-TKI治療線數(shù)對(duì)無進(jìn)展生存時(shí)間和總生存時(shí)間影響有顯著性差異(P=0.024,P=0.018)。結(jié)論鹽酸�？颂婺嵩谕砥诜西[癌患者中療效佳,可延長(zhǎng)肺鱗癌患者生存時(shí)間;EGFR突變型晚期肺鱗癌和肺腺癌患者對(duì)鹽酸�？颂婺嶂委熡行�率無顯著性差異。
[Abstract]:Background and objective: epidermal growth factor receptor tyrosine kinase inhibitors (epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs) targeting has been widely applied in the treatment of patients with advanced lung adenocarcinoma, especially with EGFR gene mutation in patients with lung adenocarcinoma, and on the application of EGFR-TKI in advanced lung squamous cell carcinoma is still controversial in this study. The first chapter by retrospective analysis in unselected patients with advanced lung squamous cell carcinoma with EGFR-TKI icotinib treatment progression free survival time (progression free, survival, PFS) and overall survival (overall, survival, OS). EGFR mutation rate is far lower than that of lung squamous cell carcinoma of lung adenocarcinoma EGFR mutation, EGFR mutation of a dispute variant of squamous cell lung cancer treated by EGFR-TKI with lung adenocarcinoma patients differences, that patients with squamous cell carcinoma of lung adenocarcinoma TKI with poor results, on the second Chapter through the comparison of the EGFR mutant lung cancer patients taking icotinib hydrochloride in the treatment of the survival time to verify this argument. Methods a retrospective analysis from June 2013 to June 2016 taking icotinib hydrochloride in the treatment of lung squamous cell carcinoma patients with inclusion criteria: 18 years of age or older; informed consent; pathology of lung squamous cell carcinoma the clinical stage was IIIB; or IV; KPS score more than 60 points; liver and kidney function for bone marrow; receive icotinib hydrochloride in the treatment of entering the charity donated medicine. Exclusion criteria: icotinib combined with chemotherapy in patients with severe pulmonary disease except; center of gravity; habitual diarrhea or constipation and other gastrointestinal effects of drug absorption tract disease; pregnancy or lactation. Regular follow-up visits for patients during physical examination, imaging and routine laboratory examination. The survival time of patients with telephone follow-up, the deadline for April 2017. The main result indicators for PFS, Secondary outcome measures were OS, objective response rate (objective response, rate, ORR), disease control rate (disease control, rate, DCR). Survival analysis using Kaplain-Meier method; single factor survival difference by Log-rank method, multivariate analysis using Cox proportional hazard model; group, group comparison and different objective factors the efficiency compared with the chi square test level. P0.05 was identified as statistically significant (P0.1 Cox proportional hazard model). A retrospective analysis from June 2013 to June 2016 taking icotinib hydrochloride in the treatment of patients with lung cancer, inclusion criteria: pathology of lung adenocarcinoma; gene detection for EGFR mutant; Yu with squamous cell carcinoma. Exclusion criteria with squamous cell carcinoma. The deadline for follow-up in April 2017. The right lung adenocarcinoma patients with EGFR mutant lung squamous cell carcinoma patients choose the propensity score matched 1:1, match factors: age, gender, clinical Stage, KPS score, smoking status, EGFR gene mutation type, treatment line number, caliper value 0.03, the two groups were compared. The survival time of outcome indicators and statistical methods with squamous cell carcinoma, test the level of P0.05 was determined. Results there were significant differences in 487 cases of lung squamous cell carcinoma patients taking icotinib therapy, the median progression free survival time was 13 months (95%CI 12.2-13.8), the median survival time was 16 months (95%CI 14.7-17.3), the 1 year survival rate was 55.4%, 2 year survival rate was 22.8%, the objective response rate was 41.3%, the disease control rate was 99.8%. multivariate Cox regression analysis of KPS score and curative effect in the treatment of lung squamous cell carcinoma was significant the difference in progression free survival time (P=0.063, P=0.001), influence and impact on the total survival time significantly difference (P=0.018, P=0.003). The adverse reactions of patients with skin rash, diarrhea, liver enzymes increased.156 cases of EGFR mutant lung squamous cell carcinoma and adenocarcinoma of the lung Patients taking icotinib treatment, including 78 cases of lung squamous cell carcinoma, 78 cases of lung adenocarcinoma, the median progression free survival time was 12.7 months (95%CI 10.4-15.0) and 15.8 months (95%CI 12.4-19.2), the difference was not statistically significant (P=0.275); the median overall survival time was 18.5 months (95%CI14.4-22.6) and 24.2 April (95%CI not calculated), the difference was not statistically significant (P=0.150); the 1 year survival rates were 53.8% and 61.5% (P=0.297), the 2 year survival rates were 26.7% and 30.9% (P=0.191); objective remission rates were 48.7% and 59% (P=0.199). Lung squamous cell carcinoma and lung adenocarcinoma subgroup analysis effect EGFR-TKI treatment line number on progression free survival and overall survival time had significant difference (P=0.024, P=0.018). Conclusion icotinib in advanced squamous cell lung cancer patients with good curative effect, can prolong the survival time of patients with lung squamous cell carcinoma; EGFR mutant of hydrochloric acid had advanced squamous cell carcinoma and adenocarcinoma of lung cancer patients There was no significant difference in the rate of efficacy of the treatment of the treatment of the treatment.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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