Dynamic treatment effect (DTE) curves reveal the mode of action for standard and experimental cancer therapies.

Journal Article

We present a method for estimating the empirical dynamic treatment effect (DTE) curves from tumor growth delay (TGD) studies. This improves on current common methods of TGD analysis, such as T/C ratio and doubling times, by providing a more detailed treatment effect and overcomes their lack of reproducibility. The methodology doesn't presuppose any prior form for the treatment effect dynamics and is shown to give consistent estimates with missing data. The method is illustrated by application to real data from TGD studies involving three types of therapy. Firstly, we demonstrate that radiotherapy induces a sharp peak in inhibition in a FaDu model. The height, duration and timing of the peak increase linearly with radiation dose. Second, we demonstrate that a combination of temozolomide and an experimental therapy in a glioma PDX model yields an effect, similar to an additive version of the DTE curves for the mono-therapies, except that there is a 30 day delay in peak inhibition. In the third study, we consider the DTE of anti-angiogenic therapy in glioma. We show that resulting DTE curves are flat. We discuss how features of the DTE curves should be interpreted and potentially used to improve therapy.

Duke Authors

Cited Authors

  • Choudhury, KR; Keir, ST; Ashcraft, KA; Boss, M-K; Dewhirst, MW

Published Date

  • June 2015

Published In

Volume / Issue

  • 6 / 16

Start / End Page

  • 14656 - 14668

PubMed ID

  • 25986925

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

International Standard Serial Number (ISSN)

  • 1949-2553

Language

  • eng