Chapter 7
Radiotherapy and Chemotherapy
Together with neurosurgery, radiotherapy and chemotherapy form the fundamental keystones of (pri-
marily malignant) brain tumour management, and of almost all malignancies overall. In this chapter, a
brief overview of the basic principles of radiotherapy and chemotherapy is given, as well as (EANO)
guidelines concerning the role of these two modalities in PBT management.
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7.1 Basic principles of radiotherapy
Radiotherapy (RT) is the irradiation of (malignant) tissues with ionising radiation (X-rays, gamma rays,
and elementary atomic particles, such as protons, neutrons, and electrons). Upon impact on (live) tis-
sues, ionising radiation ionises (dislodges electrons) atoms of these tissues. This may either have direct
effects on the structural characteristics of essential biomolecules, such as deoxyribonucleic acid (DNA).
Additionally, ionising radiation may act indirectly on these structures by producing so-called free radicals.
These are highly reactive ions—requiring the presence of oxygen for fixation in these radicals—which
may in turn damage essential biomolecules. These effects impair the cellular stability, and may subse-
quently lead to cell death, primarily in mitotic cells which are in the checkpoint 2 phase (CH2 or G2M, that
is, the phase between cell cycle phase G2 and the actual mitotic cell division, phase M) of the cell cycle.
In contrast, cells in the synthesis (S) phase of the cell cycle are most radioresistant. Additionally, mitotic
cells affected by the ionising radiation lose (some of their) replicability. The basic unit of absorbed radia-
tion dose by tissues is expressed in Grays (Gy), which corresponds with energy (in Joules, J) per mass
(in kilogrammes, kg). Ionising radiation may be administered in two ways: external beam radiotherapy
(EBRT, or teletherapy), or brachytherapy (where a radioactive source is placed within patient tissues to
deliver short-distance ionising radiation). Because of the absence of (scientific evidence advocating)
the use of brachytherapy in PBT management, it will not be furtherly discussed in this thesis.
Prior to treatment, a therapy simulation and planning must be designed. First, a pretreatment CT or MR
image is made. On these images, the radiation oncologist may identify tumour and normal tissues. Ad-
ditionally, PET-CT images may be made to help the radiation oncologist in identifying a tumour “hot spot”
which may represent high metabolic activity, to determine the treatment isocentre. This has become a
gold standard in lung tumours, for instance. After pretreatment diagnostic imaging, the patient is sent for
a therapy simulation. Here, a diagnostic CT simulates the actual treatment unit. On the produced simu-
lation images (coregistred with MR images in case of brain tumours), the tumour volumes may be delin-
eated by a radiation oncologist. Radiotherapy technicians put skin marks or tattoos on the patient’s skin
after simulation, to aid patient placement during treatment using laser guides, and may give the radiation
oncologist insight in previous treatment fields in case of additionally needed treatments. After proper
simulation and tumour delineation, physicists and dosimetrists aid the radiation oncologist in designing
the optimal treatment plan (such as number of beams and their respective angles of incidence). This is
the treatment planning. Multiple plans are made; the radiation oncologist may choose a plan with optimal
dose distribution for both tumour tissues and normal tissues.
