Photodynamic Therapy - Radiation Damage in Biomolecular Systems - page 447

27.2 Radiotherapy

27.2.1 Conventional and spatially resolved radiotherapy

Radiation therapy with X-rays beams is one of the most common and efficient
technique for cancer treatment. It is the golden standard for many types of cancers.
Currently, radiation delivery techniques are based on external radiotherapy or
internal radiotherapy also known as brachytherapy. Technical innovations in these
fields always aim at improving the dose deposition and distribution to decrease
normal tissue toxicity. The precision of external radiation therapy has been markedly
improved by innovative technical development of various imaging modalities and
irradiation devices. Recently, intensity modulated radiotherapy (IMRT) and volu-
metric modulated arc therapy (VMAT) have shown benefits especially in decreasing
acute treatment-related toxicity in either definitive or palliative re-irradiated cases
[ 7 ]. As a result, since 1994 when the first clinical IMRT with modern delivery
technology was used for head and neck cancers at Baylor College of Medicine [ 8 ],
the tumour control rate by radiation therapy improved significantly. IMRT became
an excellent alternative to surgery for early stage lung cancer, low-risk prostate
cancer and for asymptomatic or mildly symptomatic brain tumours [ 9 ].
However, brain tumours radiotherapy may cause considerable long time scale
healthy tissue damage such as pituitary diseases, hormone depletion, demyelin-
ization and white matter radionecrosis [ 10 - 13 ]. The latter two may lead to severe
cognitive dysfunctions and dementia. Complications of irradiation may also arise as
a consequence of vasogenic oedema following disruption of the blood-brain barrier
[ 14 , 15 ].
Microbeam radiation therapy (MRT) is a spatially fractionated radiotherapy that
uses an array of microscopically thin (25 to

m width) and nearly parallel
synchrotron-generated X-ray beams separated by 100 to

100

m centre-to-centre
distances [ 16 ]. The high flux of synchrotron light allows very high rates of
dose deposition (several hundreds Gy within less than 1 s). MRT was initiated at
the National Synchrotron Light Source (Brookhaven National Laboratory, USA)
[ 16 , 17 ] and then later developed at the European Synchrotron Radiation Facility
(ESRF, Grenoble, France) [ 18 - 20 ]. The properties of microbeams that make them
good candidates for tumour therapy are (a) their sparing effect on normal tissues,
including the central nervous system [ 17 - 22 ], and (b) their preferential damage
to tumours, even when administered from a single direction [ 22 , 23 ]. MRT is
currently considered one of the most exciting applications of synchrotron X-rays in
medical research. Despite MRT potential, such high-intensity microbeams can only
be produced by synchrotron radiation sources, which is a practical limitation for
clinical implementation. Therefore, following the principle of spatial fractionation,
an extension of the MRT method has been proposed by Dilmanian et al. [ 24 ] from
the National Synchrotron Light Source (Brookhaven National Laboratory, USA)
and termed minibeam radiation therapy (MBRT). In MBRT, the beam thickness
ranges from 500 to

200

m with a separation between two adjacent minibeams of
the same magnitude. These aspects are discussed in greater details in Chapter 26.

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