Introduction
This topic covers the physical and biological basis of radiotherapy, the use of ionising radiation to destroy tumour cells, and three of its technical forms: the linear accelerator (LINAC), the robotic CyberKnife, and brachytherapy, in which sealed sources are placed inside or next to the tumour. The aim is to deliver a lethal dose to the tumour while sparing the surrounding normal tissue.
Biological basis
Ionising radiation damages cells mainly through the DNA. Direct action breaks the DNA strands when the radiation ionises the molecule itself. Indirect action is more common in tissue: radiolysis of water creates free radicals, mainly the hydroxyl radical, which damage DNA. The most lethal lesion is the double-strand break, and cells that divide while the damage is unrepaired die when they try to divide.
The dose is measured in gray (Gy), where 1 Gy is 1 joule of absorbed energy per kilogram of tissue. Radiotherapy is given in fractions, usually 1.8 to 2 Gy per day, five days a week, to a total of about 45 to 70 Gy. Fractionation exploits the four Rs of radiobiology:
- repair of sublethal damage in normal cells between fractions, which is more efficient in normal tissue than in tumour;
- redistribution of cells into the more radiosensitive phases of the cell cycle, mainly G2 and M;
- reoxygenation of hypoxic tumour cells, which are radioresistant, as the tumour shrinks;
- repopulation of tumour cells during the treatment, which is why overall treatment time matters.