title: Radiobiological rationale for compensation for gaps in radiotherapy regimens by post-gap acceleration of fractionation.
abstract: It is now recognized that clonogenic tumour cells may repopulate vigorously during radiotherapy. Gaps in treatment schedules which lead to prolongation of overall treatment time may therefore cause sparing of tumour. Acute-responding normal tissues will also be spared if repopulation by surviving stem cells takes place. However, it is unlikely that stem cells in late-responding normal tissues repopulate significantly over the time-scale of a conventional treatment regime; these tissues will therefore experience little or no sparing as a result of a gap. This poses a dilemma since tumour cell repopulation implies that an increased therapeutic effect in the post-gap phase of treatment may be necessary to compensate for any prolongation of treatment time, but it is difficult to achieve increased tumour effect without also increasing damage to late-responding normal tissues. Neither increased total dose nor increased fraction size is able to achieve this. A possible solution is provided if total treatment time can be held constant, with unchanged total dose and fraction size, by use of twice-daily conventionally sized dose fractions administered after the gap. Provided the twice-daily fractions are sufficiently spaced (not less than 6-8 h apart), the result will be to offset repopulation in tumour and acute-responding normal tissues without additional impairment of late-responding normal tissues. The feasibility of the approach depends on being able to complete treatment by the time originally intended; it is therefore more readily applicable to gaps occurring early rather than late in a treatment schedule. The strategy should be especially advantageous for tumours with rapid repopulative potential in sites where risk of damage to late-responding normal tissues imposes limitation of dose.
authors.affiliation: Radiation Oncology Research Group, Beatson Oncology Centre, Western Infirmary, Glasgow.
authors.forename: T E
authors.initials: TE
authors.lastname: Wheldon
authors.forename: A
authors.initials: A
authors.lastname: Barrett
mesh_terms: D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D013997:Time Factors