Dose, volume, and tumor-control predictions in radiotherapy

Tumor volume has a profound influence on the dose required to control a given type of tumor. The most obvious explanation for this is related to the larger number of stem cells which must be sterilized, leading to a more stringent requirement on cell survival. There are, however, other mechanisms by which volume may influence tumor control, such as clonogenic fraction, oxygenation or inter-cellular communication. We investigate the question of whether the effect of volume on tumor control is, in general, predictable on the basis solely of the differing number of stem cells.

We investigate whether the effect of volume on tumor control in four sites can be predicted, using the linear-quadratic formalism, based on the assumption that the number of cells that must be sterilized is directly proportional to the tumor volume. We require that the biological parameters in the model should have plausible values.

We find that the results of four clinical data sets, exhibiting a wide range of doses, volumes, and tumor control rates, are consistent with the hypothesis that the number of potential stem cells which must be sterilized is proportional to the tumor volume.

If these considerations are correct, the potential exists that realistic radiobiologically-based dose corrections for tumor size could be routinely made. This applies both to an entire treatment, and also between fractions, as the tumor shrinks. Such an approach may contribute towards optimized radiotherapy.