Fractionated high dose rate versus low dose rate regimens for intracavitary brachytherapy of the cervix. I. General considerations based on radiobiology

Abstract

Intracavitary brachytherapy at low dose rate (LDR), often with the addition of external-beam radiotherapy, has long been considered the treatment of choice for carcinoma of the cervix, maximizing acute damage in the treatment volume, whilst minimizing late effects. In recent years, primarily for reasons of convenience and cost, there has been a move towards treatments involving a few fractions at high dose rate (HDR). Using data from cells of human origin cultured in vitro, we make estimates of the doses that, delivered in 2-12 HDR fractions, produce tumour control and early effects equivalent to intracavitary treatments at LDR. We also show that, for situations where the normal-tissue dose responsible for late effects is significantly smaller than the tumour dose, HDR schemes may be devised which, while yielding early killing comparable with that of LDR, should not result in worse late effects. We suggest that this scenario probably applies to treatment of carcinoma of the cervix.

External beam techniques to boost cervical cancer when brachytherapy is not an option—theories and applications

“…For patients receiving SBRT, a similar fractionation scheme was proposed; therefore, negligible radiobiologic differences could be expected when 30 Gy in 5 fractions is delivered with either HDR BT or SBRT (setting aside the dose distribution variation with each technique that is clearly advantageously hotter in brachytherapy). Comparable to more protracted regimens (as in LDR), the hypofractionated schedules (adopted in HDR BT or SBRT) maybe as forgiving regarding the sparing of normal tissue refuting initial claims of lower rate of interfraction repair of sublethal damage at high dose per fraction (>5 Gy) (23). Indeed, full repair is expected when appropriate interfraction interval is allowed thus accounting for the late-reacting normal tissue repair half time averaging about 2.5 hours (24).…”

Constraints in the use of repair half times and mathematical modelling for the clinical application of HDR and PDR treatment schedules as an alternative for LDR brachytherapy

“…In the design of new fractionation schedules for high dose rate (HDR) and/or pulsed dose rate (PDR) brachytherapy as compared to low dose rate (LDR) brachytherapy [4][5][6]13,16], it is important to realise the impact of the assumed values of the repair factors in the calculations of isoeffective doses. Experimental and clinical data show a reasonable consistency in the repair capacity (alp ratio) for both the acute (tumor) and late responding tissues under the conditions of complete re pair.…”

Biological equivalance of low dose rate to multifractionated high dose rate irradiations: investigations in mouse lip mucosa

“…Currently the LQ model provides an increasingly applied method of comparing the relative radiobiological efficacy of different time dose prescriptions to result in an equivalent biological endpoint. Although repair capacities and kinetics are known to vary greatly in different tissues some pub lished equivalence calculations apply average values for repair parameters [7][8][9]28]. Based on otfft ratios and repair times of 36 sets of survival curves of human cells in vitro, Brenner and Hall [7] concluded that a 10-min pulse, repeated at hourly intervals, would produce a biological effect, virtually indistinguishable from LDR at 0.5 Gy/h.…”