Risk Factors for Venous Thromboembolism in Cancer Patients Receiving Chemotherapy

描述（由申请人提供）：血栓栓塞是癌症治疗的主要并发症，尤其是新药物治疗，并且与癌症患者死亡率和发病率增加有关。这个问题涉及不同的领域，需要跨学科的方法。该职业发展奖项的目的是为申请人Alok Khorana博士提供必要的经验和知识，使其成为癌症相关血栓形成的独立临床研究者。Khorana博士将通过在一个支持性的机构环境中结合正式的硕士课程、指导阅读、研讨会和指导研究来实现这一目标。一支在血栓、癌症和流行病学方面具有专业知识并具有培训调查人员经验的高素质和敬业的导师团队将监督这一计划，并确保他实现目标。Khorana博士将检查与化疗期间静脉血栓栓塞（VTE）发展相关的危险因素。本提案的具体目的是：1)建立并验证一个风险模型，以确定一组具有静脉血栓栓塞高风险的癌症患者；2)在使用该模型选择的高风险患者队列中，前瞻性地确定无症状和有症状的静脉血栓栓塞发生率；3)前瞻性地确定与该高风险队列中静脉血栓栓塞发生相关的止血和血小板活化标志物。第一个目标将通过对正在进行的前瞻性观察性研究进行二次分析来实现，后两个目标将通过前瞻性队列研究来实现。该计划的结果将通过在临床环境中帮助识别高危患者而具有直接的临床意义。这些数据也将为今后预防血栓形成试验的设计提供有用的信息。此外，这些研究将允许申请人提高他在风险评估模型、设计和实施临床试验以及血栓研究方面的专业知识。拟议的研究计划和指导的职业发展活动将使申请人发展成为“进行严谨科学研究的独立研究者”。相关性：接受化疗的癌症患者经常会形成血块或血栓，这可能危及生命或导致并发症。血栓形成可以使用抗凝药物预防，但这需要确定哪些患者的风险最大。拟议的研究计划将开发和测试一个“风险”模型来识别这类患者，然后将高风险患者纳入一项研究，在化疗期间筛查血栓形成，并测试可能与血栓形成相关的血液标志物。

DESCRIPTION (provided by applicant): Thromboembolism is a major complication of cancer therapy, particularly with newer agents, and is associated with increased mortality and morbidity in cancer patients. This problem involves disparate fields, and requires an interdisciplinary approach. The objective of this career development award is to provide the applicant, Dr. Alok Khorana, with the experience and knowledge necessary to become an independent clinical investigator in cancer-associated thrombosis. Dr. Khorana will accomplish this objective through the combination of a formal Master's program, directed reading, seminars and mentored research in a supportive institutional environment. A highly qualified and dedicated team of mentors with expertise in thrombosis, cancer and epidemiology, and with a history of training investigators, will supervise this plan and ensure that he achieves his goals. Dr. Khorana will examine risk factors related to the development of venous thromboembolism (VTE) during chemotherapy. The specific aims of this proposal are: 1) to develop and validate a risk model that will identify a group of cancer patients at high risk for development of VTE, 2) to prospectively identify the rate of asymptomatic and symptomatic VTE in a cohort of high-risk patients selected using this model, and 3) to prospectively identify markers of hemostatic and platelet activation that are associated with the development of VTE in this high-risk cohort. The first aim will be accomplished by conducting a secondary analysis of an ongoing prospective observational study, and the latter two aims through a prospective cohort study. Results from the proposed plan will have direct clinical significance by helping identify high-risk patients in a clinical setting. These data will also provide useful information for the design of future trials for prevention of thrombosis. Further, these studies will allow the applicant to enhance his expertise in risk assessment models, design and conduct of clinical trials, and studies of thrombosis. The proposed research plan and mentored career development activities will allow the applicant to develop into" an independent investigator conducting rigorous scientific research. Relevance: Cancer patients on chemotherapy can often develop blood clots, or thrombosis, which can be life-threatening or lead to complications. Thrombosis can be prevented using anticoagulant drugs, but this requires identifying which patients are most at risk. The proposed research plan will develop and test a risk" model to identify such patients, and then enroll high risk patients on a study to be screened during chemotherapy for thrombosis as well as test blood markers that may correlate with its development.