Figure 2. The toxicity of radiotherapy.

Acute effects occur during or shortly after completion of treatment and are usually reversible and not generally considered dose-limiting. They occur in rapidly proliferating tissues, such as skin, gastrointestinal tract and the haematopoietic system. Early reactions tend to be relatively insensitive to changes in the radiation dose per fraction but are sensitive to the time over which radiation is delivered. Protracted treatment reduces acute toxicity but can compromise tumour control. Late effects manifest 6 months to several years after radiotherapy. The long time frame prevents titration of radiation dose against toxicity in individual patients, and the relationship between acute and late effects remains unclear³²,¹³²,¹³³. As late side effects can be permanent, they provide the basis for dose constraints to radiation toxicity. Late effects typically occur in more slowly proliferating tissues, such as kidney, heart and central nervous system. The pathogenesis includes fibrosis, atrophy and vascular damage. Other important late normal tissue side effects include hormone deficiencies, infertility and second malignancies. Late toxicity tends to be more sensitive to changes in the radiation dose per fraction than acute reacting tissues and less sensitive to the overall treatment time.