CLINICAL CORRELATIVE STUDIES IN GERM CELL TUMORS

生殖细胞肿瘤（GCT）是一种可治愈的恶性肿瘤，其中医生 必须区分好的风险和差的风险属性， 为高风险或低风险患者设计的治疗方案。 虽然好和差风险类别的几个分配标准 存在，目前可用的模型基于患者的预处理 临床特征不精确。 约10%的良好风险 患者仍然死亡，约三分之一的低风险患者存活 尽管预后指标不佳，但仍接受标准治疗。 最近 在我们的机构产生的大部分数据表明，一个或多个 额外的肿瘤标志物可能是更好的，或额外的， 指标 该提案的具体目标是将四个 肿瘤缓解和患者生存预后的推定标志物： (1)甲胎蛋白（AFP）的清除率（半衰期）和/或 开始化疗后的人绒毛膜促性腺激素（HCG） 使用每周标记物测定;（2）在初级细胞中的12 p拷贝数 12 p标记探针检测肿瘤组织中TP 53的表达; 原发性肿瘤;和（4）原发性肿瘤中Hst 1/kFGF的表达。 的 具体的假设是，AFP的半衰期延长， 和/或HCG、高12 p拷贝数、突变型TP 53突变和Hst-1/kFGF 表达是预后不良的结果，这可能是独立的 预后的预测因素。 纪念医院的高风险患者， 西南肿瘤组和来自纪念医院的低风险患者 医院将在前瞻性临床试验中累积， 风险状况。 AFP和HCG的每周测定将在 开始化疗以确定标记物半衰期清除率。 将获得原发性肿瘤并研究12 p拷贝数， 突变型TP 53表达和Hst-1/kFGF表达。 生物统计 将使用逻辑和考克斯回归技术进行分析 为了确定这四个变量中的每一个的重要性， 标准预后变量的存在。 如果其中一个或多个 四个新变量独立预测治疗结果和患者 生存，那么一个更好的算法选择治疗， 可以开发个体患者。

Germ Cell Tumors (GCT) are a curable malignancy in which the physician must discriminate between good risk and poor risk attributes and choose a treatment program designed for good risk or poor risk patients. Although several allocation criteria for good and poor risk categories exist, the currently available models based on a patient's pretreatment clinical characteristics are imprecise. About 10% of good risk patients still die, and about one-third of poor risk patients survive with standard treatment despite poor prognostic indicators. Recent data largely generated at our institution suggest that one or more additional tumor markers may be better, or additional, prognostic indicators. The Specific Aims of this proposal are to relate four putative markers of prognosis to tumor response and patient survival: (1) the rate of clearance (half-life) of alphafetoprotein (AFP) and/or human chorionic gonadotropin (HCG) after initiation of chemotherapy using weekly marker assays; (2) the 12p copy number in the primary tumor determined by 12p painting probes; (3) TP53 expression in the primary tumor; and (4) Hst1/kFGF expression in primary tumors. The specific hypotheses are that a prolonged half-life clearance of AFP and/or HCG, high 12p copy number, mutant TP53 mutation, and Hst-l/kFGF expression are poor prognostic findings which may be independent predictors of prognosis. Good risk patients from Memorial Hospital and the Southwest Oncology Group and poor risk patients from Memorial Hospital will be accrued onto prospective clinical trials specific to risk status. Weekly assays of AFP and HCG will be obtained after the initiation of chemotherapy to determine the marker half-life clearance. Primary tumors will be obtained and studied for 12p copy number, mutant TP53 expression, and Hst-1/kFGF expression. Biostatistical analyses will be performed using logistic and Cox regression techniques to determine the significance of each of these four variables in the presence of standard prognostic variables. If one or more of these four new variables independently predicts treatment outcome and patient survival, then a better algorithm for the selection of treatment for the individual patient can be developed.