Comparative Assessment of Screening Strategies for Melanoma

项目概述：本资助提案围绕恶性黑色素瘤早期检测中出现的研究问题，重点关注黑色素瘤早期诊断中的性别差异。主要研究领域包括：(i)调查黑色素瘤的自然历史，并开发黑色素瘤早期检测的随机模型；（ii）评估潜在筛查项目在普通人群和高危人群中的死亡率效益；（iii）建立黑色素瘤高危人群的试点数据库，并评估与黑色素瘤和致命黑色素瘤风险相关的因素。在过去的30年里，美国恶性黑色素瘤的发病率一直在稳步上升，目前还没有基于人群的指南来筛查这种相对常见和致命的癌症。虽然年龄、性别和种族是一般人群的危险因素，但黑素瘤的自然史尚不清楚。男性和女性之间发病率和诊断阶段模式的根本不同表明疾病进展过程可能具有性别特异性。已知的患病风险因素包括黑色素瘤的个人病史、非典型痣的存在、痣数量增加、先天性大痣的存在、非黑色素瘤皮肤癌的病史、光化损伤、黑色素瘤的家族史和疾病易感基因。本研究的第一个主要目的是建立一个随机模型来评估黑色素瘤在临床前疾病状态下的进展过程和停留时间分布。该模型将利用来自美国监测流行病学和最终结果（SEER）和东部肿瘤合作组织（ECOG）黑色素瘤研究的数据。第二个目标是比较各种筛查方案的有效性，使用筛查降低死亡率作为效益的衡量标准。将评估由开始/停止年龄和筛查间隔以及基于风险的时间表定义的筛查计划。第三个目标是建立黑色素瘤高风险受试者的数据库。该数据库将利用ECOG/西南肿瘤小组（SWOG）黑色素瘤预防工作组（MPWG）和色素病变小组委员会（PLS）成员的患者数据。将评估发生黑色素瘤的多种危险因素。发生黑色素瘤和致死性黑色素瘤的危险因素之间的关系也将被调查。总的来说，拟议的研究为制定黑色素瘤早期检测计划的实用指南提供了至关重要的基础。针对普通人群以及患黑色素瘤风险较高的个体的项目将被调查。

DESCRIPTION (provided by applicant): Comparative Assessments of Screening Strategies for Melanoma Project Summary This grant proposal is centered around research problems arising in the early detection of malignant melanoma with an emphasis on sex-based differences in the early diagnosis of melanoma. The principal research areas include: (i) Investigate the natural history of melanoma and develop stochastic models for early detection of melanoma, (ii) Evaluate the mortality benefit of potential screening programs in the general and high-risk populations, (iii) Establish a pilot database of individuals at high-risk of developing melanoma and evaluate the factors associated with the risk of developing melanoma and of fatal melanoma. The incidence of malignant melanoma in the U.S. has been steadily rising over the last 30 years and there are no population-based guidelines to screen for this relatively common and lethal cancer. The natural history of melanoma is not well-understood although age, sex, and race are risk factors in the general population. Radically different incidence rates and stage at diagnosis patterns between men and women suggest the disease progression process may be sex-specific. Known risk factors for developing the disease include personal history of melanoma, presence of atypical nevi, increased nevus count, presence of large congenital nevi, history of non-melanoma skin cancer, actinic damage and family history of melanoma and disease susceptibility genes. The first main aim of this research is to develop a stochastic model to evaluate the melanoma progression process and the sojourn time distribution in the preclinical disease state. This model will utilize data from the U.S. Surveillace Epidemiology and End Results (SEER) and Eastern Cooperative Oncology Group (ECOG) melanoma studies. The second aim compares the effectiveness of various screening scenarios, using mortality reduction from screening as a measure of benefit. Screening programs defined by starting/stopping ages and screening intervals as well as risk-based schedules will be evaluated. The third aim establishes a database of subjects at high-risk of developing melanoma. This database will utilize de-identified data from patients followed by members of the ECOG/Southwest Oncology Group (SWOG) Melanoma Prevention Working Group (MPWG) and Pigmented Lesion Subcommittee (PLS). Multiple risk factors for developing melanoma will be evaluated. Associations between the risk factors for developing melanoma and for fatal melanoma will also be investigated. Overall, the proposed research provides a foundation that is crucial in order to develop practical guidelines for early detection programs in melanoma. Programs for the general population as well as among individuals at higher risk of developing melanoma will be investigated.