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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part I: The Basics of Brachytherapy
Version 1 - 22/10/2015
Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy
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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).
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
Fig 5.1: Direct and indirect effects of Irradiation on intracellular targets (DNA)
Fig 5.2: Time course of Irradiation on biological objects