Tumour control probability in cancer stem cells hypothesis

The tumour control probability (TCP) is a formalism derived to compare various treatment regimens of radiation therapy, defined as the probability that given a prescribed dose of radiation, a tumour has been eradicated or controlled. In the traditional view of cancer, all cells share the ability to divide without limit and thus have the potential to generate a malignant tumour. However, an emerging notion is that only a sub-population of cells, the so-called cancer stem cells (CSCs), are responsible for the initiation and maintenance of the tumour. A key implication of the CSC hypothesis is that these cells must be eradicated to achieve cures, thus we define TCPS as the probability of eradicating CSCs for a given dose of radiation. A cell surface protein expression profile, such as CD44high/CD24low for breast cancer or CD133 for glioma, is often used as a biomarker to monitor CSCs enrichment. However, it is increasingly recognized that not all cells bearing this expression profile are necessarily CSCs, and in particular early generations of progenitor cells may share the same phenotype. Thus, due to the lack of a perfect biomarker for CSCs, we also define a novel measurable TCPCD+, that is the probability of eliminating or controlling biomarker positive cells. Based on these definitions, we use stochastic methods and numerical simulations parameterized for the case of gliomas, to compare the theoretical TCPS and the measurable TCPCD+. We also use the measurable TCP to compare the effect of various radiation protocols.