【作者】 柳剑；

【导师】 郭卫；

【作者基本信息】 北京大学 ， 外科学， 2008， 博士

【摘要】 背景:骨肉瘤是来源于间叶组织最常见的儿童及青少年原发恶性骨肿瘤。30年前,骨肉瘤采用单纯手术治疗,大部分病人在1年内死亡,5年生存率不足20%。采用联合化疗以及手术的综合治疗后患者的5年生存率提高到60-70%。化疗成为提高骨肉瘤患者预后的关键因素。但是在联合化疗的引入取得了巨大的成功后,骨肉瘤患者的生存率没有得到进一步的提高,就诊时没有转移的患者5年生存率在60-70%,即仍有30-40%的患者对目前的化疗不敏感,就诊时就存在转移的患者5年生存率仅有20%左右。如何早期区分出这些高危患者成为各国学者研究的焦点。目的:通过分析骨肉瘤患者临床、影像、病理等特点,找出影响骨肉瘤患者预后的相关因素。从而早期区分出高危患者,给予特殊的治疗。方法:研究2003年6月至2007年6月间就诊于北京大学人民医院骨与软组织肿瘤治疗中心的72例原发初治无转移的四肢成骨肉瘤患者。对他们进行了术前化疗+手术切除+术后化疗的标准治疗。所有切除标本进行坏死率分析。术后继续对患者进行化疗并进行随访。对临床、影像、病理三方面的多个因素进行观测。观察的临床项目包括:患者的年龄、性别、身高、体重、血型、疾病部位、就诊时关节活动度、是否存在骨折、化疗前后的碱性磷酸酶水平、乳酸脱氢酶的水平、血沉、化疗后疼痛是否减轻、关节活动是否改善、皮温是否降低、顺铂的注入方式共16项指标。观察的影像学项目包括:X线判断:病变成溶骨改变,化疗后边界是否清晰,骨外钙化是否增加。MRI判断:瘤周水肿是否减少,骨内T1、T2信号变化,骨外T1、T2信号变化,肿瘤化疗前的体积,化疗前后肿瘤的体积变化。共10项影像学指标。观察的病理学项目包括:肿瘤亚型和肿瘤坏死率。将上述临床、影像、病理因素与肿瘤坏死率和患者预后相比较。通过统计学方法找出相关的预后因素。先应用χ2检验进行单因素相关分析,得出各因素与肿瘤坏死率的关系,再应用logistic回归进行多因素分析,得出各因素与肿瘤坏死率的关系。应用Kaplan-meier生存分析,进行单因素生存分析,并应用log-rank检验判断各个因素与患者生存率的关系;再应用cox多因素生存分析筛选出与预后相关的因素。结果:单因素分析:男性患者、化疗后肿瘤体积变小、肿瘤边界变清晰、骨外T2信号增强提示肿瘤坏死率高(P<0.05);多因素分析:化疗后体积变小,提示肿瘤坏死率高(P<0.05);单因素生存分析显示:化疗后碱性磷酸酶水平正常,骨外T2信号增高,肿瘤坏死率高,提示患者的生存率较高(P<0.05)。多因素生存分析提示:肿瘤坏死率高的患者生存率高(P<0.05)。结论:肿瘤坏死率高则患者的预后较好,通过临床、影像等多项指标综合判断,可以间接预测肿瘤坏死率,推测患者的预后。更多还原

【Abstract】 Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Years ago, all patients with osteosarcoma were treated by amputation but the cure rate was under 10% and almost all patients died within a year from diagnosis. Today, for localized osteosarcoma at onset treated in specialized bone tumour centres with pre- and postoperative chemotherapy associated with surgery, the percentage of patients cured varies between 60% and 70%. Surgery is conservative (limb salvage) in more than 90% of patients. Prognosis is more severe (cure rate about 30%) for tumours located in the axial skeleton and in patients with metastasis at onset and in patients with recurrent disease. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event free survival (EFS). The advantages of systemic chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. Thus, how to distinguish poor responders from good responders before the end of chemotherapy is very important. This research contribute to monitoring and evaluation the effect of chemotherapy in patients with osteosarcoma.Objective:To determine the prognostic factors that influence survival of patients with nonmetastatic, high-grade, osteosarcoma of the extremities in China. Materials and Methods:A homogeneous group of 72 patients treated at Peking University People’s Hospital Muscularskeletal tumor center between June 2003 and June 2007, were retrospectively evaluated in relation to gender, age, height, tumor site and size, blood type, serum levels of alkaline phosphatase, X-ray and MRI changes, histological response to preoperative treatment.Results:Upon Univariate analysis, tumor necrosis was significantly related to gender, tumor volume change, tumor margin and T2 signal intensity of the extraosseous component of bone sarcomas. Multivariate analysis, tumor necrosis was only related to tumor volume change. Upon multivariate analysis, good histological response to treatment maintained independent prognostic values on the outcome of patients with nonmetastatic osteosarcoma of the extremities.Conclusion:Event free survival (EFS) was related to the tumor necrosis, the level of alkaline phosphatase (AKP) and the change of T2 signal of the extraosseous component. Tumor necrosis was related to the volume change after preoperative chemotherapy. These factors must be considered when deciding risk-adapted treatments for osteosarcoma patients.更多还原