体现个体动态信息综合价值的中医药防治肿瘤辅助疗效评价方法

The development of a scientific evaluation tool is a prerequisite to reflecting the effectiveness of Traditional Chinese Medicine (TCM) as an adjuvant therapy for cancer. Currently, issues such as the lack of attention on an individual's dynamic information and the fact that quality of life and time of survival represent different aspects of the global efficacy largely underscored the objectiveness of the clinical evaluation of TCM. Inspired by the quality-adjusted survival (QAS), we developed a TIO (two-in-one) evaluation tool that highlighted the value of an individual's comprehensive and dynamic information for use in clinical assessment of the adjuvant role of TCM for cancer. With this tool, dynamic information on the patient's quality of life is incorporated with patient or physician reported quality of life, and finally a one-dimensional quality-adjusted survival time (QAST) will be gained. In this study of the Zilingjin tablets for middle and late stage non-small cell lung cancer, we measured QAST and the traditionally used indicator TST (total survival time) as efficacy outcomes, and analyzed the survival curves and survival rates. Comparisons of QAST with previously used outcomes were conducted both within group and between group, in order to test sensitivity and feasibility of the TIO tool and examine the global efficacy of Zijinling tablets for adjuvant cancer treatment. We believe that the introduction of the TIO evaluation tool will provide methodological aids for the assessment of the global efficacy of TCM therapy for adjuvant cancer treatment.

肿瘤的中医药辅助治疗效果需要科学的临床评价方法彰显。现阶段存在未充分利用个体动态信息、生存质量和生存时间属性、维度不同等关键问题，影响了肿瘤中医药辅助疗效的客观评价。鉴于此，本课题借鉴生存质量校正法(QAS)的思想，以生存时间为基础，充分利用患者生存质量动态变化的个体信息，结合患者自身和医生对患者生存质量状态的评价，获得一个单维的生存质量校正的生存时间(QAST)，探索构建体现个体动态信息综合价值的中医药辅助治疗肿瘤"二维一体(Two-in-One,TIO)"评价方法。该课题以中晚期非小细胞肺癌为疾病模型，紫龙金片作为干预措施，以QAST和传统的总生存时间(TST)为疗效指标，生存曲线和生存率作为分析内容，进行组内、组间QAST与传统评价指标的横向比较，评价TIO法的敏感性、可行性和紫龙金片辅助治疗肿瘤的综合疗效。二维一体法的提出将为中医药辅助治疗肿瘤的综合疗效评价提供方法学支持。

中医药辅助治疗肿瘤具有一定临床优势。多成分、多靶点的特点使得中医药在改善患者生存时间、生存质量等多方面均有一定疗效，这些疗效信息来源多样、强弱动态变化，同时还受到化疗、放疗等措施的影响。如何评价中医药辅助治疗肿瘤的疗效是亟待解决的关键科学问题。 . 针对上述关键科学问题，本课题完成了以下3个方面的工作：（1）本课题通过文献的系统分析结合专家意见，借鉴生存质量校正法的思想，探索建立了体现个体动态信息综合价值的中医药辅助治疗肿瘤“二维一体（TIO）”评价方法，并制定了TIO法的标准化操作流程，共包括七个步骤。（2）本课题以紫龙金片治疗晚期非鳞非小细胞肺癌的临床试验为载体，验证了TIO法的可行性和敏感性。结果显示，以实体瘤客观疗效评价指标为终点指标，以稳定或进展为生存分界点，校正前的卡方值=2.817，P=0.093，校正后的卡方值=15.996，P<0.001。恶心呕吐和中医证候积分指标也显示出相似的结果。未调整前，两组生存曲线几乎呈平行直线，无法有效识别不同时点的组间差异。调整后生存曲线的斜率明显增大，生存曲线更加平滑，模型拟合更好。二维一体（TIO）法能够充分利用患者疗效变化的动态信息，改善不同组间生存曲线区分度，提高组间指标比较的灵敏性，为评价中医药辅助治疗肿瘤的疗效提供重要的方法学支持。（3）本课题开展了中医药辅助治疗晚期非小细胞肺癌随机对照临床试验指标的系统评价研究，结果显示，实体瘤疗效评价指标和毒副反应指标是目前中医药辅助治疗晚期非小细胞肺癌随机对照临床试验所使用的核心报告指标。TIO法可以将实体瘤疗效评价指标、毒副反应等指标合理整合，是中医药辅助治疗肿瘤疗效评价核心指标体系的重要方法，具有较好的应用前景。