5 Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

7

THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part I: The Basics of Brachytherapy Version 1 - 22/10/2015

Fig 5.6 : Increasing biological effectiveness with increasing dose rate. Modified from Hall 1964 HeLa cell survival in function of dose rate (Hall). The arrows indicate the separation between the LDR, MDR and HDR dose rates according to the ICRU 38 definitions (ICRU 1985)

Fig 5.4: The Four R’s of Radiobiology : Repair, Redistribution, Reoxygenation , Repopulation in function of Dose Rate or Treatment Time to deliver 2 Gy (after Steel 1986).According to ICRU LDR ranges from 0.6 to 3.3 cGy / minute, HDR starts from dose rates over 20 cGy / min. (ICRU 1985)

Fig 5.7 : Variation of radiobiological effect in function of changes in dose rate. The highest dose rate effect variation is noticed in the MDR range (Van Limbergen 1987)

Fig 5.5. Cell survival according to dose rate. Increasing the dose rate leads to more cell kill for the same Total Dose. Line A corresponds to a dose rate level where no repair of sublethal dam- age is done. Line B corresponds to a dose rate so low that not only repair but also repopulation is possible. The clinical zones of LDR (40- 200 cGy/h) and HDR (> 12 Gy /h) are indicated

the less time is left for recovery, leading to higher tissue effects at higher dose rates (as demonstrated for an in-vitro situation) up to a dose rate where no recovery is possible at all (line A in Fig 5.5). Further increases in dose rates lead to overkill and no further effects. Lowering the dose rate allows for a progressive increase in recovery, down to a dose rate where maximum recov- ery takes place (line B in Fig 5.5). The differences in biological effectiveness according to dose rate effects are also illustrated in an RBE/dose rate plot (Fig 5.6). This dose rate effect leads to a substantial increase in cell kill by a factor of 2- 4when comparing the effect of LDR to HDR. The variation of biological effect with changing dose rate is smaller (with a slower slope) in the LDR and HDR ranges, and signifi- cantly larger (with a steeper slope) in the MDR range (Fig 5.6). Altering dose rate will hence result in a larger dose rate effect in this MDR region in and around a radioactive source (Van Lim- bergen 1987) (Fig 5.7).

Fig 5.8: The effects of sublethal damage, progression in cell cycle, and repopulation on survival rate, according to dose rate.

Repopulation (see above) is the slowest process.

The relative importance of recovery, repopulation, and reoxy- genation is dependent on the dose rate. Repopulation is possible during low dose rate irradiation or in protracted schedules in combination with external beam irradiation, while recovery has a dominant effect in all the dose rate ranges used in BT. In case of very low dose rate, repopulation of clonogenic tumour cells may play an important role. (Fig 5.8)