Applications of Smoothing Splines to Assessing Antitumor Activity in Xenograft Models

• Activity Number: 57
• Type: Topic Contributed
• Date/Time: Sunday, August 1, 2010 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Maiying Kong*+
• Companies: University of Louisville
• Keywords: Mixed effects model ; Smoothing spline ; Subject-specific curve ; Tumor growth curve ; Xenograft model

Abstract

Human tumor xenograft models are often used in preclinical study to select dosing level and dosing schedule, and to evaluate the therapeutic efficacy of certain compound or combination of certain compounds. In a typical human tumor xenograft model, tumor volumes are measured over the duration of the experiment. Generally, tumor growth during treatment period is quite complex, thus, the usage of parametric model is limited. We propose using cubic smoothing splines to describe tumor growth for each treatment group and for each subject, respectively. We adopt the scaled chi- squares test statistics to examine the overall treatment effect and group differences based on the fitted group-level growth curves. By using the current procedure, we can examine tumor growth and growth rate for each treatment group and for each subject, thus providing important information for future studies.