Clinically Useful Pronostic Models in Primar

对皮肤黑色素瘤患者进行前哨淋巴结活检的分期和治疗，以及对高危原发性病变和/或区域淋巴结转移的患者进行全身辅助治疗，近来已变得司空见惯，尽管这两种干预措施均未明确显示出改善总生存率。这些，再加上最近颁布的AJCC分期系统的广泛修订，使其特别及时和重要的进一步开发，验证和出口预后模型，将用于设计有效的临床试验和临床管理的黑色素瘤患者。该项目的总体目标仍然是通过使用一个有充分记录和仔细随访的黑色素瘤患者队列来开发和测试预后模型，从而对黑色素瘤的管理和死亡率产生积极影响。 自1972年以来收集了大约5，000名黑色素瘤患者，并将这些患者的代表性样本的原发性病变的组织块存档。在具体目标1中，我们将通过应用创新的生物统计学方法来建立更好的建模技术和更强大的预后因素，以解决临床和新的免疫组织学生物标志物的候选资格。具体目标2和3旨在继续开发模型，其使用将I）保护患有“最小风险”黑色素瘤的患者免受过度检查和治疗的发病率和成本，和2）通过预测SLN活检揭示黑色素瘤和转移的可能性，更好地校准临床试验者和临床医生对具有转移能力的患者的调查和管理。有或无区域手术分期和治疗的无生存期。优化监测并允许对额外的主要疾病进行早期干预 在后续的黑色素瘤中，在具体目标4中，我们将开发用于预测第二原发性黑色素瘤发生的预后模型。这些新模型最终将整合患者MC 1 R和CDKN 2A基因型的信息。为了促进试验者和从业者使用模型，在所有模型中，我们将开发临床相关事件发生的个体化患者概率，并将与SPORE内部和外部合作者一起完成外部验证。

Staging and therapy of cutaneous melanoma patients with sentinel lymph node biopsies and the use of systemic adjuvant therapy in those with high risk primary lesions and/or regional lymph node metastases lately have become commonplace, although neither intervention has been shown unequivocally to improve overall survival. These, together with the promulgation of the recent extensive revision of the AJCC staging system, make it particularly timely and important to develop further, validate and export prognostic models that will be used for designing efficient clinical trials and for clinical management of patients with melanoma. The overall objective of this project remains to impact positively on melanoma's management and mortality by developing and testing prognostic models using a well documented and carefully followed cohort of approximately 5,000 melanoma patients assembled since 1972 and an archive of tissue blocks of primary lesions for a representative sample these patients. In specific aim 1 we will establish both better modeling techniques and more robust prognostic factors by the application of innovative biostatistical methods to address the candidacy of clinical and new immunohistologic biomarkers. Specific aims 2 and 3 are designed to continue development of models whose use will I) protect patients with "minimal risk" melanomas from the morbidity and cost of excessive investigation and therapy, and 2) better calibrate investigation and management of patients with metastatic capacity by clinical trialists and clinicians by predicting the likelihood of a SLN biopsy revealing melanoma and of metastasis-free survival with and without regional surgical staging and therapy. To optimize surveillance and allow early intervention for additional primary melanomas in follow-up, in specific aim 4 we will develop prognostic models for predicting the occurrence of a second primary melanoma. These new models will ultimately incorporate information on patients' MC1R and CDKN2A genotypes. To promote the use of models by trialists and practitioners, in all models we will develop individualized patient probabilities for the occurrence of clinically relevant events and will accomplish external validation with intra- and extra-SPORE collaborators.