The role of biologically effective dose (BED) in clinical oncology.

There are many clinical situations in which radiobiological considerations can be usefully applied and all clinicians should be aware of the potential benefits of developing a quantitative radiobiological approach to their practice. The concept of biologically effective dose (BED) in particular is useful for quantifying treatment expectations, but clinical oncologists should recognize that careful interpretation of modelling results is required before clinical decisions can be made and that there is a lack of reliable human parameters for application in some situations. Correct use of the BED concept will, in more complex treatment situations, sometimes involve the use of multiple parameters and BED calculations. Examples include: 1. Where the dose per fraction is being altered and it is possible that normal tissue tolerance may be compromised, calculations should include two or more alpha/beta ratio values, some being less than 3 Gy, in order to estimate the 'worst case scenario'. 2. A single one-point BED calculation will not be representative of the biological effect throughout a large planning target volume where there are significant 'hot spots'. Multiple BED evaluations are then indicated. 3. Where there are combinations of radiotherapy treatments or phases of treatments, these can be quantitatively assessed by the addition of BEDs, although the volume of tissue is not inherently included in the BED calculation and any high-dose region needs to be separately assessed as in point 2. 4. Allowance for tumour clonogen repopulation during therapy is required for some tumour types. 5. Different histological classes of cancers require the use of different alpha/beta ratios. Where there is reasonable doubt regarding this parameter, a suitable range should be used. The principles involved are illustrated by worked examples. Attention to detail and the examination of ranges of possible results should offer a safer guide to alternative dose fractionation schedules, although the ultimate choice will be tempered by clinical circumstances.