Radiobiological considerations in stereotactic radiosurgery with the Gamma Knife in the treatment of malignancies of the brain

Stereotactic radiosurgery for the treatment of malignancies of the brain can raise difficult radiobiological questions. Radiosurgery is often used to treat malignant brain tumours that have recurred after a course of conventional external beam radiotherapy. In these cases it is necessary to know the capacity for long-term recovery of radiation-induced damage to surrounding normal tissues in order to define the levels of tolerance doses for critical structures in the brain during a retreatment. The second question is about the toxicity and the tolerance of normal tissues when larger volumes (with diameter 3-5 cm) are treated with single high-dose radiotherapy. Larger tumours (correlated to the number of cells) require higher doses which may raise the dose to clonogenic normal tissues up to tolerance (necrosis). The Gamma Knife can only deliver a small number of fractions; for example the total dose is delivered in 2 fractions separated by between 24 and 36 hours; it is difficult, in fact, to prolong the time when the patient has the stereotactic frame fixed on the head. On the basis of the knowledge about the repair kinetics of sublethal lesions in the CNS cells, we investigate in this paper the effectiveness of these fractionated regimens to reduce the radiation toxicity to critical structures without decreasing the local tumour control. The treatment outcome strictly depends on the irradiated tissues (brainstem, cranial nerves) and on the normal-tissue volume included in the high-dose treatment region. The results of different studies are reported here.