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Radiation therapy uses ionizing radiation (X photons, electrons, protons, or heavy ions) to destroy tumor cells by damaging DNA. The central mechanism is DNA double-strand breaks (DSBs): unrepaired DSBs lead to cell death in the following mitosis. The linear-quadratic (LQ) model quantifies cell survival: the linear term ·d represents direct DSBs (repair impossible); the quadratic term ·d² represents the DSB due to the interaction of two sublethal lesions.

The / ratio is the key tissue parameter of the LQ model: late responding tissues (spinal cord, lung, kidney) have / 3 Gy and are more sensitive to large doses per fraction; rapid response tumors and tissues have / 10 Gy. This difference justifies conventional fractionation (1.82 Gy/fraction): it protects late normal tissues more than the tumor. Hypofractionated radiotherapy (SBRT: 520 Gy/fraction) exploits the low / of certain tumors (prostate: / 1.5 Gy) to be equivalent in 5 fractions to the conventional treatment of 39 fractions.

The TCP (probability of tumor control) is calculated with Poisson statistics: if even one clonogenic cell remains, the tumor can recur. To obtain TCP = 0.95 with N = 10 initial clonogenic cells, SF 5×10¹ is needed, which is equivalent to a BED of ~80100 Gy (/ = 10). The NTCP (complication in normal tissues) must be maintained < 5% (TD, m of each organ at risk).

The oxygen effect (OER 2.53) explains why hypoxic tumors (pO < 5 mmHg) are radioresistant: O fixes DNA lesions induced by radiation ('fixation hypothesis'). Intratumoral hypoxia may require a 2.53× higher dose for the same tumor control. Strategies to overcome hypoxic radioresistance include: hypoxic radiosensitizers (nimorazol), hypofractionation (partially overcomes repair), and heavy ion therapy (less dependence on O).

The dose distribution in the irradiated volume is calculated by convolution of the energy deposition kernel K(r) with the beam fluence (r). Modern planning systems (TPS) calculate the optimal plan (IMRT, VMAT) that maximizes the TCP while keeping the NTCP of each risk organ below the tolerance limit. 4D-CT planning tomography and online verification systems allow anatomical changes to be corrected in real time during treatment.

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