本文選題：氣機升降 + 隊列研究��； 參考：《北京中醫(yī)藥大學》2017年碩士論文

【摘要】：目的:觀察花寶金教授運用中西醫(yī)結合治療化療敏感的小細胞肺癌患者,對總生存期(Overall survival,OS)、無進展生存時間(progression-free survival,PFS)的影響,分析中醫(yī)藥在整體治療過程中介入的合適時機,并對應用的方藥進行討論分析,為小細胞肺癌患者的治療提供依據(jù)和幫助。方法:本研究采用探索性的隊列研究模式,納入2013年10月一2015年12月期間就診于中國中醫(yī)科學院廣安門醫(yī)院及中國醫(yī)學科學院腫瘤醫(yī)院的初治的門診小細胞肺癌患者。根據(jù)是否接受中醫(yī)藥治療為暴露因素,分為中西醫(yī)結合隊列和西醫(yī)隊列。研究總共納入70例病例,脫落5例,最終完成治療并納入統(tǒng)計的共65例。其中,中西醫(yī)結合隊列組34例,包括局限期25例,廣泛期9例;西醫(yī)隊列組31例,包括局限期20例,廣泛期11例。西醫(yī)隊列采用EP/CE的一線化療方案,治療至少4-6周期,并結合患者實際情況施行放療及預防性全腦放療,中西醫(yī)隊列西醫(yī)治療同西醫(yī)隊列,中醫(yī)治療依據(jù)辨證要素不同及西醫(yī)治療階段不同予以系列方藥。氣虛證:組方以黃芪、白術、茯苓、陳皮為基礎加減;陰虛證:組方以北沙參、麥冬為基礎加減;痰濕證:組方以瓜蔞、薤白、半夏為基礎加減;血瘀證:組方以桃仁、赤芍、枳殼、桔梗、柴胡、川芎為基礎加減;熱毒證:組方以麻黃、生石膏、杏仁為基礎加減�；熾A段:多選用旋覆花、代赭石、半夏、黃連、熟地、山萸肉、阿膠、鹿角霜等中藥辨證隨癥加減;放療階段:多選用瓜蔞、薤白、北沙參、麥冬、桔梗、荷梗、蘇梗、麻黃、生石膏、杏仁等中藥辨證隨癥加減;維持治療階段:多選用黃芪、白術、茯苓、陳皮、天麻、鉤藤、石決明、酒大黃、姜黃、僵蠶、蟬蛻等中藥辨證隨癥加減。4-6周期化療后進入隨訪階段。研究的主要終點指標包括OS、PFS、1年生存率、2年生存率、半年疾病無進展率、1年疾病無進展率、2年疾病無進展率;次要指標包括實體瘤療效評價、中醫(yī)癥狀評分改善情況、KPS評分變化情況以及NCI不良反應等。另外,本研究將中藥介入的時機對PFS的影響納入也列入觀察,并對應用的方藥進行討論分析。結果:1生存分析:(1)中西醫(yī)隊列組與西醫(yī)隊列組的中位總生存期(Median Survival Time,MST)分別為24和20個月(P=0.221),1年、2年的累計生存率分別為94.1%、64.7%和80.6%、51.6%。經分層研究,局限期中西醫(yī)隊列組與西醫(yī)隊列組的MST分別為25和22個月(P=0.656),1年、2年的累計生存率分別為96.0%、48.0%和85.0%、35.0%;廣泛期中西醫(yī)隊列組與西醫(yī)隊列組的MST分別為21和16個月(P=0.632),1年、2年的累計生存率分別為88.9%、22.2%和72.7%、18.2%。(2)中西醫(yī)隊列組與西醫(yī)隊列組的中位無進展生存時間(Median Progression Free Survival,mPFS)分別為19和14個月(P=0.098),半年、1年、2年無進展率分別為91.2%、70.6%、44.1%和74.2%、51.6%、29.0%。經分層研究,局限期中西醫(yī)結合隊列與西醫(yī)隊列比較,mPFS分別為19和15個月(P=0.421),半年無進展率分別為96.0%、85.0%,1年無進展率分別為80.0%、60.0%,2年無進展率分別為48.0%、35.0%;廣泛期中西醫(yī)結合隊列與西醫(yī)隊列比較,mPFS分別為11和7個月(P=0.289),半年無進展率分別為77.8%、54.5%,1年無進展率分別為44.4%、36.4%,2年無進展率分別為33.3%、18.2%。(3)將中西醫(yī)隊列按照中藥介入時間的不同分組,分為診斷后6個月以內介入中藥組與超過6個月時間介入中藥組。兩組mPFS分別為24和19個月(P=0.809)。(4)以60歲為界,小于60歲與大于60歲的MST分別為25和21個月,差異具有統(tǒng)計學意義(P=0.002)。(5)按性別不同分組,男性和女性的MST分別為22和24個月(P=0.904)。(6)按KPS評分不同分組,KPS70分、80分、90分三組MST分別為12、22和25個月。KPS70分與80分相比,差異具有統(tǒng)計學意義(P=0.000);KPS70分與90分相比,差異具有統(tǒng)計學意義(P=0.001);KPS80分與90分相比,差異不具有統(tǒng)計學意義(P=0.492)。(7)按化療方式不同分組,單純化療、序貫、夾心及同步放化療的MST分別為20、22、24和32個月,單純化療與其他各組比較,差異均具有統(tǒng)計學意義(P值分別為0.038、0.042和0.026)。(8)按施行PCI的情況分組,施行PCI治療與未行PCI治療的MST分別為 32 和 20 個月(P=0.006)。2預后分析:進入Cox比例風險模型的預后因素分別是隊列、年齡、KPS評分、PCI情況,Wald 值分別為 3.643、7.004、4.578、8.811,回歸系數(shù)分別為-0.595、0.859、-1.320、-1.008,相對危險度分別為 0.551、2.361、0.267、0.365,P 值分別為 0.056、0.008、0.032、0.003。3實體瘤療效:療后42天、84天,兩組的總有效率(Overall Response Rate,ORR)無統(tǒng)計學差異(P0.05),但在療后126天,兩組ORR相比P=0.052。療后42天,兩組的腫瘤疾病控制率(Disease Control Rate,DCR)無統(tǒng)計學差異(P0.05),但在療后84天、126天,兩組DCR具有統(tǒng)計學差異(P值分別為0.015和0.031)。4 KPS評分變化:療后42天、84天、126天KPS評分變化情況,中西醫(yī)隊列和西醫(yī)隊列比較,差異均具有統(tǒng)計學意義(P0.05)。5中醫(yī)臨床癥狀療效比較:對治療前后中醫(yī)臨床癥狀療效評價情況作比較,中西醫(yī)隊列組與西醫(yī)隊列組差異具有統(tǒng)計學意義(P=0.0l0),并對癥狀量表進行分析,結果發(fā)現(xiàn)在改善神疲乏力、氣短、食欲不振、自汗盜汗、口干咽燥、胸悶、咳嗽、咯痰、便秘等9個癥狀方面,中西醫(yī)隊列與西醫(yī)隊列相比,差異具有統(tǒng)計學意義(P0.05)6 NCI不良反應分析:在血液系統(tǒng)不良反應方面,白細胞和血小板減少不良反應,兩隊列相比,差異不具有統(tǒng)計學意義(P0.05),在中性粒細胞及血紅蛋白減少不良反應方面,兩隊列相比,差異具有統(tǒng)計學意義(P值分別為0.008和0.008);在消化系統(tǒng)不良反應各方面,兩隊列差異均不具有統(tǒng)計學意義(P0.05);在泌尿系統(tǒng)不良反應方面,肌酐不良反應,差異具有統(tǒng)計學意義(P=0.032)。7研究方藥討論分析:依據(jù)辨證要素不同及西醫(yī)治療階段不同予以的系列方藥,利用了藥物的升降浮沉及性味歸經,在疾病發(fā)展及西醫(yī)治療的不同階段中針對用藥,升清降濁,以使肺癌發(fā)生所涉臟腑順應其各自的生理特性,氣機升降恢復平衡,從而改善機體持續(xù)存在的惡性環(huán)境。結論:1初治的小細胞患者年齡不超過60歲、KPS評分高于70分,施行PCI治療是影響小細胞肺癌生存的3個有益因素。2花寶金教授運用以氣機升降為指導的中藥治療配合西醫(yī)治療較單純西醫(yī)治療,可以改善化療敏感的小細胞肺癌患者體力狀況,緩解臨床癥狀以及減輕血液系統(tǒng)和泌尿系統(tǒng)的不良反應。在延長OS、PFS方面有一定作用,并提示中藥早期介入可能效果更佳,需擴大樣本量以驗證。
[Abstract]:Objective: To observe the effect of the combination of Chinese and Western Medicine on the treatment of chemotherapy sensitive small cell lung cancer patients with chemotherapy sensitive small cell lung cancer, the effect of Overall survival (OS) and progression-free survival, PFS). Methods: This study adopted an exploratory cohort study into the early treatment of small cell lung cancer patients in the Guanganmen Hospital of Chinese Academy of traditional Chinese medicine (Chinese Academy of Chinese Medicine) and the Cancer Hospital of the Chinese Academy of Medical Sciences in December 2015 October 2013. The exposure factors were divided into the combination of Chinese and Western medicine and the western medicine cohort. A total of 70 cases were included, 5 cases were dropped out, and the final treatment was completed in a total of 65 cases. Among them, 34 cases of integrated traditional Chinese and Western medicine group, including 25 cases of limited period, 9 cases extensively, 31 cases in the western medicine cohort, 20 cases in the inclusion Bureau, 11 in the extensive period, and EP/CE in the western medicine cohort. The first line chemotherapy regimen was treated at least 4-6 cycles, combined with the actual situation of the patients to carry out radiotherapy and preventive whole brain radiotherapy. Western medicine and Western medicine were used to treat the same Western medicine cohort. Traditional Chinese medicine treatment was based on different syndrome differentiation factors and different Western medicine treatment stages. Qi deficiency syndrome: the group was based on Astragalus, Atractylodes, Poria, and Pericarpium, and yin deficiency. Syndrome: the group with Radix Ophiopogon and Radix Ophiopogon as basic addition and subtraction, phlegm dampness syndrome: group with Trichosanthes, Allium scallion and Pinellia ternate; blood stasis syndrome: group with peach kernel, radix paeoniae rubra, Fructus aurantii, Radix Bupleuri, Ligusticum chuanxiong as basic addition and subtract; heat toxin syndrome: group with ephedra, gypsum and almond as the basis. The TCM syndrome differentiation and subtraction of Chinese herbal medicine, such as Cornus meat, Ejiao, antler frost, and other TCM syndrome differentiation, and radiotherapy stage: multiple selection of Trichosanthes, Allium macrostemon, Radix Ophiopogon, Rhizoma Ophiopogon, rhizome, ephedra, apricot kernel and other TCM syndrome differentiation and reduction; maintenance treatment stage: more selection of Astragalus, Atractylodes, tuckahoe, Chen peel, Gastrodia elata, rhubarb, rhubarb, turmeric, silkworm, cicada and other Chinese Medicine The main end points of the study were OS, PFS, 1 year survival rate, 2 year survival rate, six year disease progression rate, 1 year disease free progression rate, 1 year disease free progression rate, 2 year disease free progression rate, and secondary indexes including solid tumor evaluation, improvement of TCM symptom score, KPS score, and NCI did not. In addition, the effect of the timing of the intervention of traditional Chinese medicine on PFS was also included, and the application of the prescription was discussed and analyzed. Results: 1 Survival Analysis: (1) the median total survival period (Median Survival Time, MST) of the Chinese and Western medicine cohort group and the western medicine cohort were 24 and 20 months (P=0.221), 1 years, and 2 years' cumulative survival rate. Don't be 94.1%, 64.7%, and 80.6%. 51.6%. was studied by stratification. The MST of the traditional Chinese and Western medicine cohort and the western medicine cohort were 25 and 22 months (P=0.656), 1 years and 2 years were 96%, 48% and 85%, 35%, respectively. The extensive period of Chinese and Western Medicine cohort and the western medicine cohort were respectively 21 and 16 months (P=0.632), 1 years, and the cumulative birth years. The survival rates were 88.9%, 22.2% and 72.7% respectively. 18.2%. (2) the middle and Western medicine queue group and the western medicine queue group were 19 and 14 months (P=0.098), respectively, 19 and 14 months (P=0.098), half a year, 1 years, and 2 years, respectively, 91.2%, 70.6%, 44.1% and 74.2%, 51.6%, 29.0%. through stratified study, limited period and Western medicine team. Compared with the western medicine cohort, mPFS was 19 and 15 months (P=0.421) respectively. The non progress rate of half a year was 96%, 85%, and 1 year progression free rate was 80%, 60% and 35%, respectively, 48% and 35%, respectively. Compared with the western medicine cohort, mPFS was divided into 11 and 7 months (P=0.289), and the half year progression rate was 77.8%, respectively. The rate of no progress in 1 years was 44.4%, 36.4%, and 2 years, respectively, 33.3%. 18.2%. (3) divided the Chinese and Western medicine queues according to the different intervention time of Chinese medicine, divided into 6 months after the diagnosis and more than 6 months to intervene the traditional Chinese medicine group. The two group mPFS was 24 and 19 months (4) respectively. (4) with 60 years as the boundary, less than 60 and greater than those. MST was 25 and 21 months, respectively, and the difference was statistically significant (P=0.002). (5) according to gender differences, the MST of men and women were 22 and 24 months (P=0.904). (6) according to the KPS score, the differences were statistically significant (P=0.000), KPS70, 80, 90 and 25 months.KPS70 and 25 months respectively (P=0.000); KPS70 score. Compared with 90 points, the difference was statistically significant (P=0.001). Compared with 90 points, the difference was not statistically significant (P=0.492). (7) the differences were statistically significant (P value points) compared with other groups according to the different groups of chemotherapy, the MST of simple chemotherapy, sequential, sandwich and concurrent chemoradiotherapy were 20,22,24 and 32 months respectively. 0.038,0.042 and 0.026). (8) groups according to the implementation of PCI, the MST of the PCI treatment and the non PCI treatment was 32 and 20 months (P=0.006).2, respectively. The prognostic factors of the Cox proportional hazard model were the cohort, the age, the KPS score, the PCI, the Wald was 3.643,7.004,4.578,8.811, and the regression coefficients were respectively 95,0.859, -1.320, -1.008, relative risk was 0.551,2.361,0.267,0.365, P value was 0.056,0.008,0.032,0.003.3 solid tumor respectively: 42 days, 84 days after treatment, the total effective rate of two groups (Overall Response Rate, ORR) was not statistically significant (P0.05), but 126 days after the treatment, two groups of ORR compared with the two group of cancer control 42 days after treatment. Disease Control Rate (DCR) had no statistical difference (P0.05), but at 84 days and 126 days after treatment, the two groups of DCR had statistical difference (P value 0.015 and 0.031).4 KPS score changes: 42 days after treatment, 84 days, 126 days KPS score changes, the difference was statistically significant (P0.05).5 traditional Chinese medicine clinical symptoms (P0.05). Comparison of curative effect: the comparison of the clinical symptoms and symptoms of traditional Chinese medicine before and after treatment, the difference between the Chinese and Western medicine queue group and the western medicine queue group had statistical significance (P=0.0l0), and the symptom scale was analyzed. The results were found in the improvement of fatigue, shortness of breath, loss of appetite, sweating and sweating, dry mouth dryness, chest tightness, cough, phlegm, constipation, and other 9 symptoms. Compared with the western medicine cohort, the difference was statistically significant (P0.05) 6 NCI adverse reaction analysis: in the side effects of the blood system, leukocytes and thrombocytopenia decreased adverse reactions, and the differences were not statistically significant (P0.05). The two teams decreased the adverse reactions in neutrophils and hemoglobin. The difference was statistically significant (P value was 0.008 and 0.008), and the differences in the adverse reactions of the digestive system were not statistically significant (P0.05); the adverse reaction of the urinary system, the adverse reaction of the creatinine, was statistically significant (P=0.032) the analysis of the.7 research prescription: according to the differentiation of syndrome differentiation factors and the West A series of prescriptions which are different at the stage of medical treatment have made use of the rise and fall of the drugs and the sexual taste to the meridian. In the different stages of the disease development and the different stages of the western medicine treatment, the medicine should be raised to reduce the turbidity, so that the organs involved in the lung cancer should conform to their respective physiological characteristics, the Qi and the Qi can be restored and balanced, so as to improve the persistent malignant environment of the body. The age of 1 primary treatment of small cell patients is not more than 60 years old, KPS score is higher than 70. PCI treatment is the 3 beneficial factor affecting the survival of small cell lung cancer..2 Hua Bao Jin is treated with western medicine treatment in combination with western medicine, which is guided by the lifting of air machine, and can improve the physical condition of patients with chemotherapy sensitive small cell lung cancer. Alleviate the clinical symptoms and reduce the adverse reactions of the blood system and the urinary system. It has a certain role in prolonging the OS and PFS, and suggests that the early intervention of Chinese medicine may be better, and the sample size should be expanded to verify.

【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2

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