Optimizing chemo-scheduling based on tumor growth rates

We review the classic tumor growth and regression laws of Skipper and Schable based on fixed exponential growth assumptions, and Norton and Simon’s law based on a Gompertzian growth assumption. We then discuss ways to optimize chemotherapeutic scheduling using a Moran process evolutionary game-theory model of tumor growth that incorporates more general dynamical and evolutionary features of tumor cell kinetics. Using this model, and employing the quantitative notion of Shannon entropy which assigns high values to low-dose metronomic (LDM) therapies, and low values to maximum tolerated dose (MTD) therapies, we show that low-dose metronomic strategies can outperform maximum tolerated dose strategies, particularly for faster growing tumors. The general concept of designing different chemotherapeutic strategies for tumors with different growth characteristics is discussed.

Cancer Log-Kill Revisited

INTRODUCTION At the root of science lie basic rules, if we can discover or deduce them. This is not an abstract project but practical; if we can understand the why then perhaps we can rationally intervene. One of the unifying unsolved problems in physics is the hypothetical “Theory of Everything.” In a similar vein, we can ask whether our own field contains such hidden fundamental truths and, if so, how we can use them to develop better therapies and outcomes for our patients. Modern oncology has developed as drugs and translational science have matured over the 50 years since ASCO's founding, but almost from that beginning tumor modeling has been a key tool. Through this general approach Norton and Simon changed our understanding of cancer biology and response to therapy when they described the fit of Gompertzian curves to both clinical and animal observations of tumor growth. The practical relevance of these insights has only grown with the development of DNA sequencing promising a raft of new targets (and drugs). In that regard, Larry Norton's contribution to this year's Educational Book reminds us to always think creatively about the fundamental problems of tumor growth and metastases as well as therapeutic response. Demonstrating the creativity and thoughtfulness that have marked his remarkable career, he now incorporates a newer concept of self-seeding to further explain why Gompertzian growth occurs and, in the process, provides a novel potential therapeutic target. As you read his elegantly presented discussion, consider how this understanding, wisely applied to the modern era of targeted therapies, might speed the availability of better treatments. But even more instructive is his personal model—not only the Norton-Simon Hypothesis—of how to live and approach science, biology, patients and their families, as well as the broader community. He shows that with energy, enthusiasm, optimism, intellect, and hard work we can make the world better. Clifford A. Hudis, MD, FACP, 2013–2014 ASCO President