5 Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

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

2. INTRODUCTION

The efficacy of brachytherapy (BT) is attributed to the ability of radioactive sources close to or within the target to deliver higher radiation doses more precisely to the target than external beam radiotherapy (EBRT). As in EBRT, the biological effects depend on total dose deliv- ered, administration parameters such as dose rate, fractionation schedule and overall treatment time, and volume parameters such as total volume treated to certain doses and the dose distri- bution within that treated volume BT. In conventional EBRT, the treated volume is usually large. Varia- tion in dose is kept minimal inside the target volume, aiming at a homogeneous distribution of dose. Dose prescription is usually to a point within the target and deviations within a range of only -5% to + 7% of the prescribed dose are considered to be accept- able (ICRU 50 1993, ICRU 62 1999, ICRU 83, 2010). In BT, the dose is prescribed to an isodose encircling a small tar- get volume (either D100 (100 % of the Minimum Target Dose MTD), D98 % or D90 of the MTD. In contrast with EBRT, the dose distribution is very heterogeneous. It is lowest at the pe- riphery of the target, but much higher doses and dose rates are delivered in the vicinity of the sources. The average dose giv- en to the target volume is therefore always significantly higher than the prescribed dose at the periphery of the target. Hence, doses delivered by BT mean significantly higher integral doses than would be delivered by EBRT for the same nominal doses, fraction sizes and dose rates. Such high integral doses delivered by BT are only tolerated because the volumes treated are usually very small as compared to EBRT. Considering only the dose and dose rate at the reference isodose at the periphery of the implant can therefore be very misleading, and information on dose distribution, such as homogeneity or inhomogeneity indices or full 3-dimensional DVH parameters, such as D90 and D98 for CTV, and 2ccm and 0.1ccm for certain OAR, should be provided (see chapter on Reporting in BT) Time-dose factors may also differ widely between EBRT and BT. In EBRT, the total dose is delivered in small daily exposure times of a few seconds or minutes, allowing for full repair between fractions. The overall treatment time is several weeks. In BT, in contrast, the dose is delivered either continuously (LDR, MDR) or discontinuously (PDR, HDR), and overall treatment times tend to be short (several hours to several days). In this chapter we will describe the radiobiological mechanisms, applicable to clinical BT which may explain the differences in biological effects of dose rates and administration schedules between EBRT and BT. We will provide practical examples and solutions to translate treatment rules between different dose rates. For more detailed radiobiological explanations we refer you to the ESTRO course book of Basic Clinical Radiobiology (Joiner and Van der Kogel 2009).

Fig 5.1: Direct and indirect effects of Irradiation on intracellular targets (DNA)

Fig 5.2: Time course of Irradiation on biological objects

3. RADIATION EFFECTS AND TISSUE RESPONSES

Ionizing radiation (IR) – as the name indicates - induces ion- izations in (biological) matter. These can be either distributed in a loose way, as with sparsely IR (e.g. X-, gamma-rays or elec- trons), or in a concentrated way (densely ionizing radiation, e.g. neutrons, heavy ions), depending on the Linear Energy Transfer (LET), i.e. the energy deposited per unit distance of traversal of the beam. In a cell, these ionizations can hit the critical target, i.e. the DNA, either directly, or they can produce radicals, main- ly from water molecules (“radiation hydrolysis”), which are the major component of a cell (Fig 5.1) In the latter case, subsequent radical reaction chains may reach and damage the DNA indi- rectly. In the case of densely IR, direct effects on the DNA are much more likely than with sparsely IR. This accounts for differ- ences in the Relative Biological Effectiveness (RBE) of different radiation qualities. This chapter will deal with sparsely IR, which is usually administered in BT. In terms of the time course of the effect of IR on biological ob- jects, several phases can be distinguished (Fig 5.2): • A extremely short initial physical phase (about 10 -15 - 10 -6 s), during which the above mentioned ionizations occur, • A chemical phase , again very short (about 1 to 10 -3 s), during which the induced radicals interact with any molecule they meet, resulting in “chain reactions.” In this phase there is a com- petition between natural scavenging reactions, e.g. with sulf- hydryl components (glutathione) or other antioxidants, that