MULTIPLEXED PROTEIN BIOMARKER-BASED ASSAY FOR THE DETECTION OF BLADDER CANCER

用于检测膀胱癌的多重蛋白质生物标志物检测

• 批准号: 10672214
• 负责人: Charles J Rosser
• 金额: $ 65.13万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672214
• 关键词: Adjuvant; Adjuvant Therapy; Age; Algorithms; BCG Live; Biological Assay; Biological Markers; Bladder; Blood; Cancer Detection; Cancer Patient; Caring; Clinic; Clinical; Cohort Studies; Cost Analysis; Cost Savings; Cost utility; Costs and Benefits; Cystectomy; Cystoscopy; Cytology; Data; Diagnosis; Disease; Effectiveness; Ensure; Evaluation; Excision; Funding; Gender; General Population; Guidelines; Health Care Costs; Hematuria; Image; Immunoassay; Institution; Invasive Lesion; Laboratories; Life; Malignant neoplasm of urinary bladder; Manuscripts; Measures; Medicine; Methodology; Microscopic; Molecular Profiling; Muscle; Newly Diagnosed; Parents; Patient Care; Patients; Performance; Prediction of Response to Therapy; Predictive Value; Prospective cohort; Publishing; Recommendation; Recording of previous events; Recurrence; Research; Residual Neoplasm; Retrospective cohort; Risk; Sampling; Schedule; Specificity; Survival Rate; Technology; Technology Transfer; Testing; Time; Tobacco; Translating; Translations; Transurethral Resection; Tumor stage; Urine; Validation; Weight; cancer biomarkers; cancer diagnosis; clinically relevant; cohort; cost effective; cost effectiveness; detection assay; detection method; diagnostic assay; diagnostic signature; high risk; improved; intravesical; markov model; multiplex assay; muscle invasive bladder cancer; patient response; patient stratification; predicting response; predictive modeling; preservation; prospective; protein biomarkers; response; risk stratification; treatment response; tumor; tumorigenesis; urinary; Adjuvant; Adjuvant Therapy; Age; Algorithms; BCG Live; Biological Assay; Biological Markers; Bladder; Blood; Cancer Detection; Cancer Patient; Caring; Clinic; Clinical; Cohort Studies; Cost Analysis; Cost Savings; Cost utility; Costs and Benefits; Cystectomy; Cystoscopy; Cytology; Data; Diagnosis; Disease; Effectiveness; Ensure; Evaluation; Excision; Funding; Gender; General Population; Guidelines; Health Care Costs; Hematuria; Image; Immunoassay; Institution; Invasive Lesion; Laboratories; Life; Malignant neoplasm of urinary bladder; Manuscripts; Measures; Medicine; Methodology; Microscopic; Molecular Profiling; Muscle; Newly Diagnosed; Parents; Patient Care; Patients; Performance; Prediction of Response to Therapy; Predictive Value; Prospective cohort; Publishing; Recommendation; Recording of previous events; Recurrence; Research; Residual Neoplasm; Retrospective cohort; Risk; Sampling; Schedule; Specificity; Survival Rate; Technology; Technology Transfer; Testing; Time; Tobacco; Translating; Translations; Transurethral Resection; Tumor stage; Urine; Validation; Weight; cancer biomarkers; cancer diagnosis; clinically relevant; cohort; cost effective; cost effectiveness; detection assay; detection method; diagnostic assay; diagnostic signature; high risk; improved; intravesical; markov model; multiplex assay; muscle invasive bladder cancer; patient response; patient stratification; predicting response; predictive modeling; preservation; prospective; protein biomarkers; response; risk stratification; treatment response; tumor; tumorigenesis; urinary

Project Summary/Abstract Background Microscopic hematuria (blood in urine) may occur in up to 10% of the general population and results in costly evaluation to ensure it is of no consequence, i.e., no bladder cancer (BCa) is present since hematuria is typically the initial sign of BCa. Furthermore, 75% of patients with newly diagnosed BCa have non- muscle-invasive disease (NMIBC), which has a very high recurrence rate (>70%). Because of this, it is recommended that the patients have adjuvant intravesical bacillus Calmette-Guerin (BCG) instillation to reduce this risk. Despite BCG treatment, up to 50% of patients fail to respond and 20% progress to muscle invasive bladder cancer (MIBC) mandating more radical treatment (i.e., cystectomy - removal of the urinary bladder). Moreover, the delay in radical treatment can negatively impact survival rates, hence, a test that could predict treatment response to intravesical BCG, ensuring the right patient, gets the right treatment at the right time is urgently required. To date, no such test is available. There exists an unmet clinical need for reliable biomarkers to a) ‘rule out’ which patients with microscopic hematuria do not require further evaluation and b) predict which patients will respond to BCG. Hypothesis Our central hypothesis is that a molecular profile exists that is specifically associated with BCa that a) can be utilized to indicate the presence of BCa in non-invasively obtained urine samples and b) can be utilized to predict response to BCG. This hypothesis will be tested by completing the following Specific Aims: 1) To validate the multiplex immunoassay for BCa detection in subjects presenting with microscopic hematuria, 2) To evaluate the cost benefit, cost utility and cost effectiveness of the multiplex immunoassay in subjects with hematuria and a history of BCa on tumor surveillance and 3) To validate prospectively the urine-based multiplex immunoassay to predict BCG response in subjects with intermediate/high risk NMIBC. Significance This research will open the door for improving on the non-invasive methods for detecting BCa and predicting treatment response as such it will have a marked impact on patient care. Methodology Our group has developed and tested a multiplex immunoassay towards a BCa signature with extremely encouraging results in subjects evaluated for gross hematuria and a history of BCa on tumor surveillance. In the current proposal, we now seek to test the multiplex assay in two additional independent cohorts: intermediate/high-risk patients (AUA microscopic hematuria guidelines 2020) presenting with microscopic hematuria for early BCa detection and patients with intermediate/high risk NMIBC treated with intravesical BCG to predict treatment response. Furthermore, we will generate Markov models and using data collected from the parent R01 to assess cost benefit, cost utility and cost effectiveness of the multiplex immunoassay. Expected Results The validation of the multiplex immunoassay will reduce the need to subject large numbers of patients who do not have BCa to frequent, uncomfortable and expensive cystoscopic examinations. Specifically, we would anticipate a reduction in the number of cystoscopies/year by 500,000, which would translate into cost savings of $225 million/year.

项目摘要/摘要 背景微观血尿（尿液中的血液）可能发生在多达10％的一般人群中，并且 导致昂贵的评估以确保没有后果，即没有膀胱癌（BCA），因为 血尿通常是BCA的初始征兆。此外，有75％的新诊断为BCA患者的患者非 - 肌肉侵入性疾病（NMIBC），复发率很高（> 70％）。因此，是 建议患者具有可调节的静脉内芽孢杆菌塞莱特 - 甘酸盐（BCG）滴注以减少 这个风险。尽管BCG治疗，但多达50％的患者无法反应，有20％的肌肉侵入性进展 膀胱癌（MIBC）要求更自由基治疗（即膀胱切除术 - 去除尿道膀胱）。 此外，自由基治疗的延迟会对生存率产生负面影响，因此可以预测 确保正确患者的静脉内BCG的治疗反应在正确的时间进行正确的治疗是 迫切需要。迄今为止，尚无此类测试。对可靠的生物标志物的临床需求未满足 a）“排除”微观血尿患者不需要进一步评估，b）预测 患者将对BCG做出反应。假设我们的中心假设是存在分子谱 特别与BCA相关的是a）可以用来指示非侵入性中BCA的存在 获得的尿液样品和b）可用于预测对BCG的反应。该假设将通过 完成以下特定目的：1）验证多重免疫测定以进行BCA检测 出现微观血尿的受试者，2）评估成本收益，成本效用和成本 多重免疫测定在血尿和BCA病史上的有效性 监视和3）验证前瞻性的基于尿液的多重免疫测定以预测BCG响应 在具有中间/高风险NMIBC的受试者中。意义这项研究将为改进开辟大门 用于检测BCA和预测治疗反应的非侵入性方法这样将具有 对患者护理的影响明显。我们小组开发并测试了多重免疫测定方法 迈向BCA签名，在评估总血尿和A BCA在肿瘤监测中的历史。在当前的提案中，我们现在试图在两个中测试多重测定 其他独立人群：中级/高风险患者（AUA微观血尿指南2020） 出现早期BCA检测的微观血尿和中等/高风险NMIBC的患者 用静脉内BCG治疗以预测治疗反应。此外，我们将生成马尔可夫模型和 使用父母R01收集的数据来评估成本收益，成本效用和成本效益 多重免疫测定。预期结果多重免疫测定的验证将减少需求 对没有BCA经常，不舒服且昂贵的大量患者进行 膀胱镜检查。具体而言，我们预计通过 500,000，这将转化为每年节省2.25亿美元的成本。