Validation of a risk model for stage I lung adenocarcinoma

I 期肺腺癌风险模型的验证

• 批准号: 8386244
• 负责人: Prasad S. Adusumilli
• 金额: $ 24.19万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-10 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8386244
• 关键词: Adjuvant Therapy; Aftercare; Cessation of life; Characteristics; Chest; Clinical; Complex; Data; Databases; Development; Diagnosis; Disclosure; Early Diagnosis; Excision; Formalin; Foundations; Goals; Hematoxylin and Eosin Staining Method; Hospitals; Individual; Intervention; Lung Adenocarcinoma; Malignant neoplasm of lung; Methods; MicroRNAs; Modeling; Nomograms; Non-Small-Cell Lung Carcinoma; Oncologist; Operative Surgical Procedures; Outcome; Paraffin Embedding; Pathologic; Patients; Performance; Prognostic Factor; Prognostic Marker; Protocols documentation; Publications; Publishing; Recurrence; Research Personnel; Research Proposals; Risk; Screening procedure; Slide; Specimen; Staging; Surgeon; Testing; Thoracic Surgeon; Tissue Sample; Tissues; Validation; Variant; X-Ray Computed Tomography; cohort; cost effective; experience; high risk; improved; instrument; lung cancer screening; prognostic; tissue processing; tool; tumor

DESCRIPTION (provided by applicant): Development and validation of a prognostic model for predicting recurrence in stage I lung adenocarcinoma. With the recent disclosure of results from the National Lung Cancer Screening Trial, suggesting that annual chest CT scans can reduce 20% of lung cancer deaths in high-risk individuals, the number of early stage LACs detected by screening CT scans and their resection is expected to increase. While the 5-year recurrence rate following curative-intent surgical resection in stage I LAC is 18% - 29%, there is substantial individual variation in post-resection recurrence free survival. Currently, the only accepted prognostic factor guiding treatment decisions for both surgeons and oncologists is tumor size, and its prognostic performance remains unclear. Better prognostic tools are needed to provide good quality individual risk prediction, identify patients at high risk of recurrence and help to guide treatment decisions by both oncologists and thoracic surgeons. In an attempt to identify prognostic markers that accurately predict the risk of unfavorable outcome; our group has performed extensive clinical and pathological examination of the largest cohort of stage I LAC to date. We have developed a prediction score that uses combined clinical, histological and cytological criteria that can be assessed routinely on an H&E slide in any hospital, and predicts the risk of recurrence or death with high accuracy. In this proposal, we aim to further improve the predictive ability of our score by microRNA analysis (miRNA). The potential of using microRNAs for prognostication of early lung cancer has been established by several investigators independently including our group. We have developed a microRNA signature capable of prognostication of early lung cancer. A distinct advantage of our methods is the use of formalin-fixed paraffin-embedded (FFPE) tissue, similar to our clinico-pathologic criteria, thus avoiding the requirement of complex tissue processing protocols. We hypothesize that the comprehensive clinico-pathological score, enriched with miRNA expression data, can be combined into a simple, cost-effective predictive instrument that will accurately determine the risk of recurrence or death following curative-intent surgical resection for stage I LAC, and will identify those patients who are primary candidates for aggressive surveillance and adjuvant therapy. In this proposal, we seek to validate and refine our existing miRNA signature for LAC and examine its ability to enrich the predictive quality of our clinico-pathological score. As the model is built upon simple clinical, pathological characteristics (assessed on H&E slide) and miRNA analysis from FFPE, the results of our proposal are immediately implementable, timely and are of high translational significance. PUBLIC HEALTH RELEVANCE: Detection of early stage lung cancer is anticipated to increase necessitating more accurate predictive instruments to identify patients at higher risk for recurrence. In this proposal, we combine our expertise of pathological, cytological and microRNA analyses to develop and validate a comprehensive risk model to identify patients at a higher risk for recurrence for aggressive surveillance or intervention.

描述（由申请人提供）：预测模型的开发和验证，用于预测I期肺腺癌中复发。 随着国家肺癌筛查试验结果最近披露结果，这表明每年的胸部CT扫描可以减少高危个体中肺癌死亡的20％，通过筛查CT扫描检测到的早期lac的数量，预计切除将增加。虽然I lac的治愈性手术切除后的5年复发率为18％-29％ 切除后复发无生存的个体变化。目前，为外科医生和肿瘤学家指导治疗决策的唯一公认的预后因素是肿瘤的大小，其预后表现尚不清楚。需要更好的预后工具来提供高质量的个人风险预测，识别出高风险复发的患者，并有助于指导肿瘤学家和胸外科医生的治疗决策。 试图确定准确预测不利结果风险的预后标记；我们的小组对迄今为止最大的I级lac群进行了广泛的临床和病理检查。我们开发了一种预测评分，该评分使用了临床，组织学和细胞学标准组合，可以在任何医院的H＆E幻灯片上进行常规评估，并以高准确性预测复发或死亡的风险。在此提案中，我们旨在通过microRNA分析（miRNA）进一步提高分数的预测能力。几位研究人员独立于包括我们的小组，已经建立了使用microRNA进行早期肺癌预后的潜力。我们已经开发了一种能够预测早期肺癌的microRNA签名。我们方法的一个明显优势是使用福尔马林固定石蜡包裹（FFPE）组织，类似于我们的临床病理标准 避免需要复杂的组织加工方案。 我们假设，富含miRNA表达数据的综合临床病理分数可以合并为一种简单，成本效益的预测仪器，该工具将准确地确定I级治愈性手术切除后，可以确定复发性或死亡的风险，并将确定那些是主要候选者进行侵略性表现和辅助疗法的患者。在此提案中，我们试图验证和完善我们现有的miRNA签名，以实现LAC，并研究其丰富我们诊所病理评分的预测质量的能力。 作为 模型建立在简单的临床，病理特征（根据H＆E幻灯片评估）和FFPE的miRNA分析建立，我们的建议的结果可以立即实施，及时且具有很高的翻译意义。 公共卫生相关性：预计对早期肺癌的检测将增加，因此需要更准确的预测工具来识别出更高复发风险的患者。在此提案中，我们结合了病理，细胞学和microRNA分析的专业知识，以开发和验证一种综合风险模型，以识别具有更高风险重新出现的积极监测或干预措施风险的患者。