Radiotherapy (RT) is the mainstay of treatment of primary brain tumours which are not resectable and is the only treatment modality which has been demonstrated to prolong survival in patients with malignant gliomas. It is a potentially toxic treatment and therefore adequate controls must be in place to monitor the dose administered. This chapter describes the basic physical principles underlying the cellular and molecular mechanisms of RTinduced cell death and then discusses the harmful effects of radiation on the nervous system.

Physical principles of radiation

Radiotherapy is the use of electromagnetic radiation usually in the form of photons to produce cell damage and thereby destroy tumours. Electromagnetic radiation acts principally by ionizing molecules in irradiated tissues. Radiation energy is either absorbed directly into the DNA or indirectly via the generation of free radicals in the aqueous cytosol which produce further molecular damage. The end result of irradiation is DNA damage in the form of inter- and intrastrand cross-links, strand breaks and damage to nucleotide bases. The cellular repair capacity may not be sufficient to repair all DNA lesions, particularly double strand breaks and these may ultimately lead to cell death. The majority of human cells that sustain DNA damage die a mitotic rather than an apoptotic cell death.

The principal biological effect of radiation at tissue level is to inhibit cell proliferation thereby affecting dividing tumour cells rather than non-proliferating normal tissue cells. This results in tumour control, which equates with cure in some tumours, but only minimal damage of normal brain at conventional doses. The balance between tumour control and normal tissue damage is described as the therapeutic ratio. Maximum therapeutic ratio is achieved through exploiting biological differences between tumours and normal tissue (largely by fractionation) and by physically focusing high radiation doses to tumour while sparing surrounding normal brain.

In conventional external beam radiotherapy, radiation is usually given in the form of high energy X-rays (photons) generated by a linear accelerator or as gamma rays (also photons) from an external cobalt source. Radiation can also be delivered by insertion of small radioactive sources directly into a tumour and this is described as brachytherapy or interstitial radiotherapy. Electrons, generated by linear accelerators, are particularly useful for the treatment of superficial lesions and are rarely used for the treatment of CNS tumours.