Quantitative Analysis of the Tumor/Metastasis System and its Optimal Therapeutic Control

TL;DR

This paper develops a mathematical model to analyze metastasis development and optimize cancer treatment schedules, demonstrating the advantages of continuous metronomic therapy over traditional dosing methods.

Contribution

It introduces a novel mathematical framework for metastatic progression and derives optimal treatment schedules, highlighting the benefits of metronomic therapy.

Findings

Metronomic therapy reduces overall metastatic burden more effectively.

Optimal scheduling favors continuous drug administration.

The model quantifies surgery's impact on metastasis size distribution.

Abstract

A mathematical model for time development of metastases and their distribution in size and carrying capacity is presented. The model is used to theoretically investigate anti-cancer therapies such as surgery and chemical treatments (cytotoxic or anti-angiogenic), in monotherapy or in combination. Quantification of the effect of surgery on the size distribution of metastatic colonies is derived. For systemic therapies, emphasis is placed on the differences between the treatment of an isolated lesion and a population of metastases. Combination therapy is addressed, in particular the problem of the drugs administration sequence. Theoretical optimal schedules are derived that show the superiority of a metronomic administration scheme (defined as a continuous administration of a given amount of drug spread during the whole therapeutic cycle) on a classical Maximum Tolerated Dose scheme (where the dose is given as a few concentrated administrations at the beginning of the cycle), for the total metastatic burden in the organism.