实体瘤临床疗效评价若干新方法的探索性研究

发布时间：2018-06-05 22:23

  本文选题：临床实践 + 疗效评价　； 参考：《第四军医大学》2017年博士论文

【摘要】：在实体瘤诊治过程中,疗效评价是一项非常重要的工作。实体瘤疗效评价标准(RECIST)是多年来实体瘤临床疗效判定的最主要的依据。然而,RECIST标准原本是为了评价抗癌新药有效性而制定的。RECIST指南明确指出RECIST标准不完全适用于日常工作实践,只有在肿瘤医生认为恰当的情况下才考虑将其用于日常临床实践中的治疗决策[1-2]。因此我们考虑,若能应用若干新的方法完善实体瘤疗效评价体系,可能会对临床肿瘤医生的日常工作实践有一定帮助。本课题利用沈阳军区总医院肿瘤科诊治的晚期肿瘤患者的临床资料,分三部分探讨实体瘤临床疗效评价的若干新方法。第一部分实体瘤疗效评价中的测量变异度:以非小细胞肺癌肺内靶病灶为例目的:实体瘤疗效评价是以测量靶病灶大小为基础的,因此需要明确当前临床实践中对于实体瘤的观察者变异度。材料和方法:收集2014年1月1日至2014年6月30日在沈阳军区总医院肿瘤科住院的非小细胞肺癌患者的影像学资料,预先选定了78处肺内靶病灶。两名工作经验10年以上的放射科医生通过PACS工作站分别独立测量肿瘤最长径,其中一名放射科医生间隔四周后重复测量一次。应用Bland-Altman法计算观察者内及观察者间变异度,应用组内相关系数评价相应两组测量结果的一致性。结果:Bland-Altman法分析显示全组病灶观察者内及观察者间变异度的范围均近似于RECIST客观反应截断值的范围。但剔除测量径线明显不一致的病灶后,Bland-Altman散点图显示观察者内及观察者间变异度的范围均在±10%之间,观察者测量差异的绝对值的95%的一致性界限在±3mm之间。无论是肺窗还是纵隔窗,每两组测量值的组内相关系数均在0.9至1之间。结论:当前临床实践中,非小细胞肺癌肺内靶病灶靶病灶观察者变异度相对较低,可能有助于临床医生更敏感的判定肿瘤缓解或进展。第二部分靶病灶缓解深度与患者生存期相关性的前瞻性观察研究:以广泛期小细胞肺癌一线化疗患者为例目的:延长患者生存期是晚期肿瘤治疗的最主要的目的之一,但化疗后肿瘤缓解是否预示生存期的延长尚有争议。本研究以广泛期小细胞肺癌一线化疗患者为例,探讨肿瘤缓解深度与患者生存期存在怎样的关联。材料与方法:对2014年9月1日至2016年2月29日在沈阳军区总医院肿瘤科住院治疗的初治的51例广泛期小细胞肺癌患者进行前瞻性观察研究。应用Spearman秩相关及线性回归分析评价靶病灶缓解深度与生存期的相关性。应用log-rank检验对影响生存期的相关因素进行单因素分析,应用COX比例回归模型进行多因素分析。结果:Spearman秩相关及线性回归分析显示靶病灶缓解深度与PFS及OS均呈中等程度相关。一线化疗肿瘤缓解深度达10%以上、体重减轻5%、ECOG PS评分0-1分、化疗周期数≥4是广泛期小细胞肺癌PFS的独立影响因素;体重减轻5%、ECOG PS评分0-1分、化疗周期数≥4以及进行二线治疗是广泛期小细胞肺癌OS的独立预后因素,而靶病灶缓解深度与OS的关系未显示有统计学意义。结论:广泛期小细胞肺癌一线化疗后靶病灶缓解深度达10%以上预示较长的PFS,但不能预测OS。第三部分血清肿瘤标志物在疗效判定中的决策价值的探索性研究:以晚期乳腺癌血清CEA及CA153为例目的:既往研究发现血清肿瘤标志物的改变可预测化疗疗效,但RECIST标准不推荐单独应用血清肿瘤标志物进行疗效评价。本研究通过分析晚期乳腺癌患者血清CEA及CA153与肿瘤影像学改变的关系,探讨是否可在部分情况下将血清肿瘤标志物作为疗效评价的决定性指标。材料与方法:回顾性分析2011年1月1日至2015年12月31日93例沈阳军区总医院住院化疗的晚期乳腺癌患者的病历资料,实施疗效评价188次,有完整CEA、CA153数据的病例分别为105、139例次,将疗效评价为CR、PR及SD的情况均定义为“无影像学进展”,分析血清CEA及CA153连续且显著降低对于无影像学进展的判定效度。结果:CEA连续降低且降低总幅度达10%时,判定无影像学进展的敏感度为54.1%,特异度为95%;CA153连续降低且降低总幅度达40%时,判定无影像学进展的敏感度为19.1%,特异度为96.6%。结论:血清CEA及CA153连续降低分别达10%与40%以上时可考虑作为晚期乳腺癌患者的疗效判定的决定性指标。综上所述,临床实践中晚期实体瘤的疗效评价不应拘泥于RECIST标准,而需要结合临床实际情况判定肿瘤大小的真实变化,有助于及时调整治疗方案;需要结合具体临床因素分析肿瘤缓解深度对延长病人生存期的意义,有助于正确认识肿瘤缓解的临床价值;可考虑在适当情况下应用血清标志物代替影像学检查进行疗效评价,节省医疗资源及诊疗时间。
[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.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R734.2
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本文编号：1983627