本文選題：臨床實踐 + 療效評價��； 參考：《第四軍醫(yī)大學(xué)》2017年博士論文

【摘要】：在實體瘤診治過程中,療效評價是一項非常重要的工作。實體瘤療效評價標(biāo)準(zhǔn)(RECIST)是多年來實體瘤臨床療效判定的最主要的依據(jù)。然而,RECIST標(biāo)準(zhǔn)原本是為了評價抗癌新藥有效性而制定的。RECIST指南明確指出RECIST標(biāo)準(zhǔn)不完全適用于日常工作實踐,只有在腫瘤醫(yī)生認為恰當(dāng)?shù)那闆r下才考慮將其用于日常臨床實踐中的治療決策[1-2]。因此我們考慮,若能應(yīng)用若干新的方法完善實體瘤療效評價體系,可能會對臨床腫瘤醫(yī)生的日常工作實踐有一定幫助。本課題利用沈陽軍區(qū)總醫(yī)院腫瘤科診治的晚期腫瘤患者的臨床資料,分三部分探討實體瘤臨床療效評價的若干新方法。第一部分實體瘤療效評價中的測量變異度:以非小細胞肺癌肺內(nèi)靶病灶為例目的:實體瘤療效評價是以測量靶病灶大小為基礎(chǔ)的,因此需要明確當(dāng)前臨床實踐中對于實體瘤的觀察者變異度。材料和方法:收集2014年1月1日至2014年6月30日在沈陽軍區(qū)總醫(yī)院腫瘤科住院的非小細胞肺癌患者的影像學(xué)資料,預(yù)先選定了78處肺內(nèi)靶病灶。兩名工作經(jīng)驗10年以上的放射科醫(yī)生通過PACS工作站分別獨立測量腫瘤最長徑,其中一名放射科醫(yī)生間隔四周后重復(fù)測量一次。應(yīng)用Bland-Altman法計算觀察者內(nèi)及觀察者間變異度,應(yīng)用組內(nèi)相關(guān)系數(shù)評價相應(yīng)兩組測量結(jié)果的一致性。結(jié)果:Bland-Altman法分析顯示全組病灶觀察者內(nèi)及觀察者間變異度的范圍均近似于RECIST客觀反應(yīng)截斷值的范圍。但剔除測量徑線明顯不一致的病灶后,Bland-Altman散點圖顯示觀察者內(nèi)及觀察者間變異度的范圍均在±10%之間,觀察者測量差異的絕對值的95%的一致性界限在±3mm之間。無論是肺窗還是縱隔窗,每兩組測量值的組內(nèi)相關(guān)系數(shù)均在0.9至1之間。結(jié)論:當(dāng)前臨床實踐中,非小細胞肺癌肺內(nèi)靶病灶靶病灶觀察者變異度相對較低,可能有助于臨床醫(yī)生更敏感的判定腫瘤緩解或進展。第二部分靶病灶緩解深度與患者生存期相關(guān)性的前瞻性觀察研究:以廣泛期小細胞肺癌一線化療患者為例目的:延長患者生存期是晚期腫瘤治療的最主要的目的之一,但化療后腫瘤緩解是否預(yù)示生存期的延長尚有爭議。本研究以廣泛期小細胞肺癌一線化療患者為例,探討腫瘤緩解深度與患者生存期存在怎樣的關(guān)聯(lián)。材料與方法:對2014年9月1日至2016年2月29日在沈陽軍區(qū)總醫(yī)院腫瘤科住院治療的初治的51例廣泛期小細胞肺癌患者進行前瞻性觀察研究。應(yīng)用Spearman秩相關(guān)及線性回歸分析評價靶病灶緩解深度與生存期的相關(guān)性。應(yīng)用log-rank檢驗對影響生存期的相關(guān)因素進行單因素分析,應(yīng)用COX比例回歸模型進行多因素分析。結(jié)果:Spearman秩相關(guān)及線性回歸分析顯示靶病灶緩解深度與PFS及OS均呈中等程度相關(guān)。一線化療腫瘤緩解深度達10%以上、體重減輕5%、ECOG PS評分0-1分、化療周期數(shù)≥4是廣泛期小細胞肺癌PFS的獨立影響因素;體重減輕5%、ECOG PS評分0-1分、化療周期數(shù)≥4以及進行二線治療是廣泛期小細胞肺癌OS的獨立預(yù)后因素,而靶病灶緩解深度與OS的關(guān)系未顯示有統(tǒng)計學(xué)意義。結(jié)論:廣泛期小細胞肺癌一線化療后靶病灶緩解深度達10%以上預(yù)示較長的PFS,但不能預(yù)測OS。第三部分血清腫瘤標(biāo)志物在療效判定中的決策價值的探索性研究:以晚期乳腺癌血清CEA及CA153為例目的:既往研究發(fā)現(xiàn)血清腫瘤標(biāo)志物的改變可預(yù)測化療療效,但RECIST標(biāo)準(zhǔn)不推薦單獨應(yīng)用血清腫瘤標(biāo)志物進行療效評價。本研究通過分析晚期乳腺癌患者血清CEA及CA153與腫瘤影像學(xué)改變的關(guān)系,探討是否可在部分情況下將血清腫瘤標(biāo)志物作為療效評價的決定性指標(biāo)。材料與方法:回顧性分析2011年1月1日至2015年12月31日93例沈陽軍區(qū)總醫(yī)院住院化療的晚期乳腺癌患者的病歷資料,實施療效評價188次,有完整CEA、CA153數(shù)據(jù)的病例分別為105、139例次,將療效評價為CR、PR及SD的情況均定義為“無影像學(xué)進展”,分析血清CEA及CA153連續(xù)且顯著降低對于無影像學(xué)進展的判定效度。結(jié)果:CEA連續(xù)降低且降低總幅度達10%時,判定無影像學(xué)進展的敏感度為54.1%,特異度為95%;CA153連續(xù)降低且降低總幅度達40%時,判定無影像學(xué)進展的敏感度為19.1%,特異度為96.6%。結(jié)論:血清CEA及CA153連續(xù)降低分別達10%與40%以上時可考慮作為晚期乳腺癌患者的療效判定的決定性指標(biāo)。綜上所述,臨床實踐中晚期實體瘤的療效評價不應(yīng)拘泥于RECIST標(biāo)準(zhǔn),而需要結(jié)合臨床實際情況判定腫瘤大小的真實變化,有助于及時調(diào)整治療方案;需要結(jié)合具體臨床因素分析腫瘤緩解深度對延長病人生存期的意義,有助于正確認識腫瘤緩解的臨床價值;可考慮在適當(dāng)情況下應(yīng)用血清標(biāo)志物代替影像學(xué)檢查進行療效評價,節(jié)省醫(yī)療資源及診療時間。
[Abstract]:The evaluation of curative effect is a very important work in the process of diagnosis and treatment of solid tumors. The standard of evaluating the effect of solid tumor (RECIST) is the most important basis for the evaluation of the clinical efficacy of solid tumors for many years. However, the RECIST standard originally developed by the.RECIST guide to evaluate the effectiveness of the new anticancer drug clearly points out that the RECIST standard is not fully applicable to the day. Often working practice, only when the oncologist thinks it is appropriate to consider the treatment decision [1-2]. used in daily clinical practice, so we consider that the application of a number of new methods to improve the evaluation system of solid tumor effect may be helpful to the daily work of the clinical oncologist. The subject takes advantage of the Shenyang army. The clinical data of the advanced tumor patients in the oncology department of the general hospital were divided into three parts to discuss the new methods of evaluating the clinical efficacy of solid tumors. It is necessary to clarify the variability of the observer in the current clinical practice. Materials and methods: the imaging data of non small cell lung cancer patients hospitalized in the oncology department of the General Hospital of Shenyang military region from January 1, 2014 to June 30, 2014 were collected. 78 lung target lesions were selected in advance. Two radiologists with more than 10 years of work experience were used. The longest diameter of the tumor was measured independently by the PACS workstation, and one radiologist was measured repeatedly after four weeks. Bland-Altman method was used to calculate the variability between the observer and the observer, and the correlation coefficient of the group was used to evaluate the consistency of the corresponding two groups of measurements. Results: the Bland-Altman analysis showed the whole group of focus observation. The range of variation between internal and observer was similar to the range of RECIST objective response truncation value. But after eliminating the lesions with different measured diameters, the Bland-Altman scatter plot showed that the range of variation between the observer and the observer was in the range of + 10%, and the 95% of the absolute values of the observer measured the difference between the 3mm. The correlation coefficient in each two group was between 0.9 and 1. Conclusion: in the current clinical practice, the variability of the target focus of non-small cell lung cancer is relatively low, which may help the clinicians more sensitive to determine the tumor remission or progression. The second part of the target focus is in depth and patients. A prospective study of the survival time correlation: for patients with broad stage small cell lung cancer as an example, prolonging the survival period is one of the most important objectives for advanced cancer treatment, but whether chemotherapy after chemotherapy predicts the prolongation of survival is still controversial. To explore the relationship between the depth of tumor remission and the existence of the patient's survival. Materials and methods: a prospective study was conducted in 51 patients with extensive small cell lung cancer from September 1, 2014 to February 29, 2016 in the oncology department of the General Hospital of the Shenyang military general hospital. The Spearman rank correlation and linear regression analysis were used to evaluate the target lesion. The correlation between depth and life period was solved. Single factor analysis was carried out by log-rank test on the related factors affecting the survival time. The COX proportional regression model was applied to multifactor analysis. Results: the Spearman rank correlation and linear regression analysis showed that the target remission depth was related to the moderate degree of PFS and OS. The depth of tumor remission of the first-line chemotherapy was reached. More than 10%, weight loss 5%, ECOG PS score 0-1, and chemotherapy cycle number more than 4 are independent factors of PFS in broad stage small cell lung cancer; weight loss 5%, ECOG PS score 0-1, chemotherapy cycle number > 4, and second line therapy are independent preconditioning factors of OS in the extensive stage of small cell lung cancer, and the relationship between target remission depth and OS is not demonstrated. Study significance. Conclusion: the target remission depth of the target focus of the broad stage small cell lung cancer after the first line chemotherapy is up to 10% of the longer PFS, but it is not possible to predict the decision value of the serum tumor markers in the third part of the third part of the breast cancer serum CEA and CA153 as an example: the previous study found the serum tumor markers The changes in substance can predict the efficacy of chemotherapy, but the RECIST standard does not recommend the evaluation of the efficacy of serum tumor markers alone. In this study, the relationship between serum CEA and CA153 and tumor imaging changes in patients with advanced breast cancer was analyzed, and whether the serum tumor markers could be used as the decisive index of the evaluation of the curative effect in some cases. Materials and methods: retrospective analysis of the medical records of 93 patients with advanced breast cancer hospitalized in Shenyang military area general hospital from January 1, 2011 to December 31, 2015. The curative effect was evaluated 188 times. The cases with complete CEA and CA153 data were 105139 times respectively. The curative effect was evaluated as CR, PR and SD were all defined as "no imaging progress". The determination validity of serum CEA and CA153 was analyzed continuously and significantly. Results: when CEA was continuously reduced and reduced to 10%, the sensitivity of non imaging progress was 54.1% and the specificity was 95%; when CA153 was reduced continuously and the total amplitude was 40%, the sensitivity of the non imaging progress was 19.1% and the specificity was 96. .6%. conclusion: the continuous reduction of serum CEA and CA153 by 10% and more than 40% can be considered as a decisive indicator of the outcome of patients with advanced breast cancer. To sum up, the evaluation of the curative effect of advanced solid tumors in clinical practice should not be restricted to the RECIST standard, but it is necessary to determine the true changes of the size of the tumor in combination with the clinical facts. It is necessary to analyze the significance of the tumor remission depth to the survival period of the patients with specific clinical factors, and help to correctly understand the clinical value of the tumor remission, and consider the application of serum markers instead of imaging examination to evaluate the curative effect and save medical resources and time of diagnosis and treatment.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R734.2
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本文編號：1983627