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Fractionation - Spreading

For a similar total dose, the biological efficiency EBR varies according to the dose per session, the total number of sessions (fractionation) and the total duration of treatment (spreading).

For example:

22 Gy delivered for analgesic purposes during 6 sessions spread over 9 days will be more efficient than 22 Gy delivered in 11 sessions spread over two weeks.

However, the late toxicity of irradiation seems to be related to the dose per fraction, many protocols of hypofractionated radiotherapy are employed only for patients with a short life expectancy (radiotherapy for metastases for instance), who will not live long enough to develop such toxicities.

Interest of fractionation

Fractionation allows:

• Repair of sublethal lesions i.e. lesions which become lethal by accumulating. The repair of sublethal lesions is far easier for normal cells than for tumour cells: thus fractionation increases the differential effect of ionising radiation.
  
• Repopulation, i.e. cell proliferation between fractions, which is beneficial when it concerns normal cells and is a way of reducing toxic effects, but which is detrimental when involving tumour cells. Hyperfractionated schedules generally include an increased total dose which compensates the tumour repopulation phenomenon.
  
• Reoxygenation of tumour tissue: well oxygenated cells are radiosensitive and are eliminated (apoptosis) after irradiation; hypoxic cells can then benefit from improved oxygenation and again become radiosensitive.
  
• Redistribution of cells in the cell cycle: radiation generally blocks cells in G2, which is the most sensitive cell cycle phase.
  
• Recently, many studies have involved accelerated hyper-fractionated schedules (noticeably in head and neck cancer) in order to increase the tolerance by normal tissue, to increase the total dose for improved tumour control and to diminish the tumour repopulation phenomenon.
  
• In daily practice, it is necessary to compare treatment modalities with atypical fractionation or spreading with standard treatment 'or equivalent dose' which is generally carried out with fractions of 1.8 Gy to 2.0 Gy five times per week.