Biomarkers of Prostate Cancer Radiation Outcome

前列腺癌放射结果的生物标志物

• 批准号: 7253362
• 负责人: Mark A Ritter
• 金额: $ 26.68万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-06 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7253362
• 关键词: Ablation; Accounting; Adjuvant; Androgens; Archives; Biochemical; Biological Markers; Biopsy Specimen; Cancer Patient; Categories; Cities; Clinical; Clinical Markers; Clinical Trials; Computer Assisted; Computer-Assisted Image Analysis; Correlative Study; Count; Databases; Diagnosis; Diagnostic; Enrollment; Failure; Freedom; Future; Hospitals; Immunohistochemistry; Intervention; Laboratory Finding; Link; Localized; Malignant neoplasm of prostate; Manuals; Measures; Molecular; Neoadjuvant Therapy; Numbers; Outcome; PSA screening; Pathway interactions; Patients; Pilot Projects; Predictive Value; Prevalence; Prostate; Radiation; Radiation Therapy Oncology Group; Radiation therapy; Randomized Controlled Clinical Trials; Range; Relative (related person); Research Personnel; Resistance; Risk; Role; Sampling; Score; Sodium Chloride; Specimen; Staging; Staining method; Stains; System; TP53 gene; Testing; Tissues; Today; Translational Research; Treatment Failure; Upper arm; Work; base; cellular imaging; deprivation; design; insight; interest; prognostic; programs; repository; resistance mechanism; response; tissue resource; tumor

DESCRIPTION (provided by applicant): There is increasing evidence that prostate cancers have molecular alterations that render them poorly responsive to radiation therapy and that are associated with a significant proportion of treatment failures. Certain biomarkers for these alterations have been identified as being prognostic for clinical outcome in high grade, locally advanced prostate cancer, but there is far less such information available for favorable or intermediate risk patients, the type of patient most frequently diagnosed today. The Radiation Therapy Oncology Group's multi-institutional randomized trial RTOG 94-08, focused primarily upon this important favorable-to-intermediate risk group of patients, comparing radiation therapy with or without 4 months of androgen ablation therapy. Diagnostic tumor specimens from 875 patients from this trial have been archived by RTOG and will be made available for the study proposed here. This provides a unique opportunity to carry out correlative studies between appropriately selected biomarkers and clinical outcome, with a statistical power not previously available. Study biomarkers have been selected based upon prognostically useful prevalence ranges and pathways linked to radiation and/or androgen deprivation response. The specific aims of this proposed study are to: 1) immunohistochemically measure the levels of p53, Bcl-2, bax, mdm2 and Ki-67 in pre-treatment diagnostic biopsy specimens from the RTOG clinical trial 94-08; 2) analyze correlations between these markers and clinical outcomes (freedom from biochemical and metastatic failure) in univariate and multivariate fashion, taking conventional prognosticators such as stage, grade and PSA into account; and 3) examine whether the predictive value of these molecular markers is influenced by the use of short term androgen deprivation therapy in one of the two treatment arms. Both manual and computer assisted analyses of immunohistochemical staining will be employed. If successful, this proposed study will define biomarkers that are clinically useful in predicting response to radiation with or without androgen deprivation therapy in the important group of early-to-intermediate risk prostate cancer patients, will provide insight into mechanisms of resistance to radiation or androgen deprivation and will guide the design of future clinical trials that could include biologic/molecular interventions directed against these biomarker-associated pathways.

描述（由申请人提供）：有越来越多的证据表明前列腺癌具有分子改变，使它们对放射治疗的反应不佳，并且与相当一部分治疗失败有关。这些改变的某些生物标志物已被确定为对高级，局部晚期前列腺癌的临床结果的预后，但是对于有利或中级风险的患者，当今最常见的患者类型的类型较少。 放射疗法肿瘤学组的多机构随机试验RTOG 94-08主要集中于这一重要的有利对中间风险的患者，将放射疗法与有或没有4个月的雄激素消融疗法进行比较。 RTOG已存档了来自该试验的875名患者的诊断性肿瘤标本，并将在此处提出的研究提供。这提供了一个独特的机会，可以在适当选择的生物标志物和临床结果之间进行相关研究，而以前没有统计能力。 研究生物标志物是基于预后有用的患病率范围和与辐射和/或雄激素剥夺反应相关的途径的选择。这项拟议的研究的具体目的是：1）从RTOG临床试验的预处理诊断活检标本中，免疫组织化学测量p53，Bcl-2，BAX，MDM2和KI-67的水平94-08； 2）分析这些标记和临床结果（从生化和转移性失败的自由）中的单变量和多变量方式之间的相关性，并考虑了常规的预后剂，例如舞台，等级和PSA； 3）检查这些分子标记的预测值是否受到在两个治疗臂之一中使用雄激素剥夺疗法的使用影响。将采用手动和计算机辅助分析免疫组织化学染色的分析。 如果成功，这项提出的研究将定义在重要的早期到中间风险前列腺癌患者中预测有或没有雄激素剥夺治疗的疗法的生物标志物，将提供对辐射耐药性或雄激素剥夺的抗性机制的见解，并将指导未来的临床试验，包括对这些临床疗法的设计，包括对这些生物学的互动 - 对这些互动式介绍这些互动。