A1.1 Radiobiology

Topic

When ionizing radiation passes through living matter, it transfers energy capable of altering its molecular structure; this interaction between ionizing radiation and living matter forms the fundamental physical basis for the entire A1 block and underpins the three modules derived from it—external beam radiotherapy, particle radiotherapy, and brachytherapy—which differ from one another only in how they distribute that same dose across space and time within the living matter.

Within living matter, the target most sensitive to this alteration is the genetic material contained in each cell: ionizing radiation damages genetic material directly, and this damage manifests primarily as double-strand breaks—lesions where both strands of the genetic material are severed simultaneously, a type of damage the cell cannot repair as easily as a single-strand break.

In response to a double-strand break, the cell reacts in one of three ways: it activates repair mechanisms to restore the genetic material to its original state; it halts its division cycle while repair is underway; or, when the damage exceeds its repair capacity, it undergoes apoptosis and self-destructs. The combination of these three pathways, applied to the population of irradiated cells, determines cell survival: the more cells that successfully repair their genetic material or survive the cell-cycle arrest, the higher the cell survival rate; conversely, the more cells that cross this threshold and enter apoptosis, the lower the survival rate.

The linear-quadratic model is the tool used to quantify this cell survival in relation to the radiation dose received by the living matter: when the dose delivered in a single fraction is low, the loss of cell survival increases in approximate proportion to the dose, as the linear component of the model dominates; As the dose per fraction increases, the loss of cell survival grows more rapidly than the dose itself because the quadratic component comes into play; consequently, the response ceases to be merely proportional and instead accelerates. For this reason, the linear-quadratic model serves as a bridge between the physics of dosimetry—which determines the magnitude and temporal distribution of the dose received by living tissue—and the clinical practice of fractionation, which dictates how that dose is distributed over time.

Clinical fractionation exploits precisely this difference in behavior between low and high doses: rather than delivering the entire dose at once, it is split into smaller doses separated by intervals of hours. This allows living tissue, between one fraction and the next, to regain its inherent repair capacity, restore damaged genetic material, and return to its original state—thereby becoming resilient enough to withstand subsequent exposure to ionizing radiation and completing the cycle of dose delivery and repair. In tumor tissue, however, this repair capacity is less efficient; tumor cells accumulate double-strand breaks that they fail to resolve in the time available between fractions.

Taken together, this chain—extending from ionizing radiation to genetic material, then to cell survival (governed by the linear-quadratic model), and finally to clinical fractionation—forms the shared physical foundation for the three modules dependent on block A1: external beam radiotherapy, particle radiotherapy, and brachytherapy. While these three modalities differ in where and when ionizing radiation delivers its dose to living tissue—whether from outside the body, via particles, or from within the tumor tissue itself—they all rely, without exception, on the same genetic damage, cellular response, and linear-quadratic model described here. These elements allow for the prediction and control of cell survival, which ultimately determines whether the treatment achieves its goal: destroying the tumor tissue while preserving the surrounding living tissue.

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