Risk Factors for Venous Thromboembolism in Cancer Patients Receiving Chemotherapy

描述(申请人提供)：血栓栓塞症是癌症治疗的一个主要并发症，特别是使用新的药物，并与癌症患者死亡率和发病率的增加有关。这个问题涉及不同的领域，需要跨学科的方法。这一职业发展奖的目的是为申请者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员。Khorana博士将通过正式的硕士课程、定向阅读、研讨会和支持性机构环境中的指导研究相结合的方式来实现这一目标。一支高素质和敬业的导师团队，具有血栓形成、癌症和流行病学方面的专业知识，并有培训调查人员的历史，将监督这一计划，并确保他实现目标。Khorana博士将研究与化疗期间发生静脉血栓栓塞症(VTE)相关的风险因素。这项建议的具体目的是：1)开发和验证一个风险模型，该模型将确定一组癌症患者发生VTE的高风险；2)前瞻性地确定使用该模型选择的一组高风险患者中无症状和有症状的VTE的发生率；以及3)前瞻性地确定止血和血小板激活的标志物，这些标志物与这一高风险队列中的VTE的发展有关。第一个目标将通过对正在进行的前瞻性观察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。拟议计划的结果将通过帮助在临床环境中识别高危患者而具有直接的临床意义。这些数据还将为未来预防血栓形成的试验设计提供有用的信息。此外，这些研究将使申请人能够提高他在风险评估模型、临床试验的设计和进行以及血栓形成研究方面的专业知识。拟议的研究计划和受指导的职业发展活动将使申请者发展成为“进行严格科学研究的独立调查者。相关性：接受化疗的癌症患者经常会出现血栓或血栓，这可能危及生命或导致并发症。血栓形成可以使用抗凝剂药物预防，但这需要确定哪些患者风险最大。拟议的研究计划将开发和测试风险”模型来识别此类患者，然后招募高危患者参加一项研究，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记物。

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.