Laboratory of Applied PK/PD, Department of Clinical Pharmacology and Therapeutics, The Children's Hospital of Philadelphia, Colket Translational Research Building, Room 4012, 3501 Civic Center Blvd, Philadelphia, PA 19104, USA.
J Pharmacokinet Pharmacodyn. 2013 Aug;40(4):527-36. doi: 10.1007/s10928-013-9327-z. Epub 2013 Jul 12.
Semi-parametric and parametric survival models in patients with pancreatic adenocarcinoma (PC) using data from Surveillance, Epidemiology, and End Result (SEER) registry were developed to identify relevant covariates affecting survival, verify against external patient data and predict disease outcome. Data from 82,251 patients was extracted using site and histology codes for PC in the SEER database and refined based on specific cause of death. Predictors affecting survival were selected from SEER database; the analysis dataset included 2,437 patients. Survival models were developed using both semi-parametric and parametric approaches, evaluated using Cox-Snell and deviance residuals, and predictions were assessed using an external dataset from Saint Louis University (SLU). Prediction error curves (PECs) were used to evaluate prediction performance of these models compared to Kaplan-Meier response. Median overall survival time of patients from SEER data was 5 months. Our analysis shows that the PC data from SEER was best fitted by both semi-parametric and the parametric model with log-logistic distribution. Predictors that influence survival included disease stage, grade, histology, tumor size, radiation, chemotherapy, surgery, and lymph node status. Survival time predictions from the SLU dataset were comparable and PECs show that both semi-parametric and parametric models exhibit similar predictive performance. PC survival models constructed from registry data can provide a means to classify patients into risk-based subgroups, to predict disease outcome and aide in the design of future prospective randomized trials. These models can evolve to incorporate predictive biomarker and pharmacogenetic correlates once adequate causal data is established.
使用来自监测、流行病学和最终结果 (SEER) 登记处的数据,为胰腺腺癌 (PC) 患者开发了半参数和参数生存模型,以确定影响生存的相关协变量,与外部患者数据进行验证,并预测疾病结局。使用 SEER 数据库中的 PC 部位和组织学代码从数据库中提取了 82251 名患者的数据,并根据特定的死亡原因进行了细化。从 SEER 数据库中选择影响生存的预测因素;分析数据集包括 2437 名患者。使用半参数和参数方法开发了生存模型,使用 Cox-Snell 和偏差残差进行评估,并使用圣路易斯大学 (SLU) 的外部数据集进行预测评估。预测误差曲线 (PEC) 用于评估这些模型与 Kaplan-Meier 反应相比的预测性能。来自 SEER 数据的患者的中位总生存时间为 5 个月。我们的分析表明,SEER 的 PC 数据最好由半参数和对数逻辑分布的参数模型拟合。影响生存的预测因素包括疾病分期、分级、组织学、肿瘤大小、放疗、化疗、手术和淋巴结状态。来自 SLU 数据集的生存时间预测结果相当,PEC 表明半参数和参数模型均具有相似的预测性能。从登记处数据构建的 PC 生存模型可用于将患者分为基于风险的亚组,预测疾病结局,并有助于设计未来的前瞻性随机试验。一旦建立了足够的因果数据,这些模型就可以发展为纳入预测生物标志物和药物遗传学相关性。