Radiation therapy is usually divided or “fractionated” over a treatment course lasting multiple weeks. Fractionation in the context of radiotherapy is the process of dividing a dose of radiation into multiple “fractions”. This practice seeks to maximize the destruction of malignant cells while minimizing damage to healthy tissues. Several of the mechanisms which represent the rationale behind fractionation are outlined below.
Redistribution
The radiosensitivity of cells depends on their stage in the cell cycle. Cells are most sensitive to radiation in the M and late G2 phase of their cycle and most resistant in the late S phase.
Since a group of malignant cells are at various points in their cell cycle, delivering the entire dose of radiation in a single fraction is ineffective against a proportion of the tumor cells. Dividing the total dose of radiation into multiple fractions maximizes the probability of irradiating cells when they are in the most radiosensitive period of their cell cycle.
Re-oxygenation
When tumor cells are hypoxic they are less susceptible to the indirect effects of radiation. Fractionating radiotherapy allows cells which are closer to sources of oxygen to be killed first, and the intervening time between fractions allows the relatively hypoxic cells to improve their oxygen supply. These cells are then more sensitive to subsequent doses of radiation.
Repair
Fractionation increases the destructive effect on tumor cells while minimizing damage to healthy cells due to the different ability of normal cells and malignant cells to repair DNA damage. Healthy cells have a greater ability to repair DNA damage than malignant cells. As such, splitting the total radiation dose allows healthy cells an opportunity to repair this sublethal damage between fractions. Meanwhile, malignant with impaired DNA repair pathways are less able to recover from radiation damage to their DNA.
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