SECONDARY PREVENTION OF LIVER CANCER IN HAIMEN, CHINA

中国海门的肝癌二级预防

• 批准号: 2098292
• 负责人: William Thomas LONDON
• 金额: $ 36.65万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-05 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2098292
• 关键词: China; alpha fetoprotein; blood chemistry; cancer prevention; clinical trials; computed axial tomography; diagnosis design /evaluation; diagnosis quality /standard; early diagnosis; enzyme linked immunosorbent assay; hepatocellular carcinoma; human mortality; human subject; longitudinal human study; mass screening; neoplasm /cancer diagnosis; prognosis; questionnaires; radioimmunoassay; ultrasonography

Secondary Prevention of Primary Liver Cancer in Haimen County, China Primary hepatocellular carcinoma (PHC) causes 250,000 to 1,000,000 deaths annually worldwide and 100,000 to 200,000 per year in China. Five-year survival rates for patients with PHC who are diagnosed after symptoms appear are < 5%. Surgical resection of small, asymptomatic tumors, however, has yielded five-year survival rates as high as 67%. Because other therapies have not changed survival, early detection of small (< 3 cm in diameter) tumors followed by surgical resection is the only available method of improving the outcome of these patients. Chronic hepatitis B virus (HBV) infection is associated with ~80% of liver cancers. Monitoring HBV carriers with serum alpha-fetoprotein (AFP) levels for the detection of early stage PHCs has been used among Alaskan natives and is widely practiced by clinicians in the USA. In Asia, clinicians use real time ultrasonography (US) for screening for PHC. Although US is both a more sensitive and more specific initial screening test than AFP, it is not feasible to apply US screening to large numbers of persons outside of a hospital setting. AFP as the initial screening method followed by US of persons with elevated AFPs is practical. However, there has never been a properly controlled trial of the efficacy of AFP screening alone or in combination with US. Only a controlled clinical trial which prospectively follows both a monitored and unmonitored cohort will be able to discern the ultimate efficacy of these screening modalities. Therefore, we have designed a controlled trial of AFP screening followed by US, for the early detection of PHC, to be carried out in a highly endemic area of China, Haimen County in Jiangsu Province. Two cohorts of 5000 male and 2500 female HBV carriers each, one monitored at six- month intervals, the other unmonitored (usual care) will be studied for five years. The following hypotheses will be tested: 1. The monitored will have a > 50% reduction in mortality from PHC compared with the unmonitored cohort. 2. Decreased mortality from PHC will cause reduction in all-cause mortality of the unmonitored cohort. 3. Among the monitored cohort, > 60% of the screening detected cases of PHC will have solitary resectable tumors. Among the unmonitored cohort < 10% of the PHCs will be solitary resectable lesions. 4. The predictive value positive of the screening program, AFP screening followed by US, will be > 75%. The sensitivity and specificity of the screening program will be > 80%. In addition, the following parameters of the natural history of PHC will be estimated: a. The lead time in diagnosis gained by screening. b. The length of the detectable pre-clinical phase. c. The proportion of screening detected tumors that progress to clinical cancers.

海门县原发性肝癌二级预防 原发性肝细胞癌（PHC）导致25万至100万人死亡 在中国每年有10万到20万人。 五年 症状后确诊的PHC患者的生存率 似乎<5%。 手术切除小的无症状肿瘤， 然而，五年存活率高达67%。 因为 其他疗法没有改变生存率，早期发现小（< 3厘米直径）肿瘤，其次是手术切除是唯一的 改善这些患者预后的有效方法。 慢性B型肝炎病毒（HBV）感染与约80%的 肝癌 血清甲胎蛋白监测乙型肝炎病毒携带者 (AFP)检测早期PHCs的水平已被用于 阿拉斯加本地人，在美国被临床医生广泛使用。 在 在亚洲，临床医生使用真实的超声检查（US）筛查 PHC。 虽然US是一个更敏感、更具体的首字母缩写， 筛查测试比AFP，这是不可行的，适用于美国筛查， 大量的人在医院外。 法新社作为 对AFP升高的人进行超声检查的初步筛查方法是 实用. 然而，从来没有一个适当的对照试验， AFP筛查单独或联合US的有效性。 只有 前瞻性对照临床试验， 未监测的队列将能够辨别 这些筛选模式。 因此，我们设计了一项AFP筛查的对照试验， 由美国，为早期发现PHC，将在一个高度 中国流行区，江苏省海门县。 两个队列 在5000名男性和2500名女性HBV携带者中， 每隔一个月，将研究其他未监测（常规护理） 五年 将检验以下假设： 1. 受监测者的PHC死亡率将降低50%以上 与未监测的队列相比。 2. PHC死亡率的降低将导致全因 未监测队列的死亡率。 3. 在监测的队列中，> 60%的筛查发现病例 的原发性肝癌将有孤立的可切除的肿瘤。 在未受监控的 队列< 10%的PHC将是孤立的可切除病变。 4. 筛查项目AFP阳性预测值 筛选后，美国，将> 75%。 的敏感性和 筛选程序的特异性将> 80%。 此外，下列PHC自然史参数将 估计： a. 通过筛查获得的诊断提前期。 B. 可检测的临床前阶段的长度。 C. 筛查检测到的肿瘤进展到 临床癌症