ESTRO 36 Abstract Book

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S87 ESTRO 36
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SP-0169 A small animal tumour model for low-energy
laser-accelerated particles
J. Pawelke1,2, K. Brüchner3,4, M. Krause4,5,6, E. Leßmann2,
M. Schmidt5, E. Beyreuther2
1 OncoRay - National Center for Radiation Research in
Oncology- Faculty of Medicine and University Hospital
Carl Gustav Carus-Technische Universität Dresden,
Department of Medical Physics- Laser Radiooncology
Group, Dresden, Germany
2 Helmholtz-Zentrum Dresden - Rossendorf, Institute of
Radiation Physics, Dresden, Germany
3 Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Experimental
Center, Dresden, Germany
4 Helmholtz-Zentrum Dresden - Rossendorf, Institute of
Radiooncology, Dresden, Germany
5 OncoRay - National Center for Radiation Research in
Oncology- Faculty of Medicine and University Hospital
Carl Gustav Carus-Technische Universität Dresden,
Department of Radiation Oncology, Dresden, Germany
6 German Consortium for Translational Cancer Research
DKTK and German Cancer Research Center DKFZ,
Dresden Site, Dresden, Germany
Introduction: The long-term aim of decveloping laser-
based acceleration of protons and heavier ions towards
clinical radiation therapy application requires not only
substantial technological progress, but also the
radiobiological characterization of the resulting ultra-
short and ultra-intensive particle beam pulses. Recent in
vitro data showed similar effects of laser-accelerated
versus conventional proton beams on clonogenic cell
survival and DNA double-strand breaks. As the proton
energies currently achieved for radiobiological
experiments by laser-driven acceleration are too low to
penetrate standard tumour models on mouse legs, a small
animal tumour model allowing for the penetration of low
energy protons (~20 MeV) was developed to further verify
the effects in vivo.
Methods: The mouse ear tumour model was established
for human HNSCC FaDu and human glioblastoma LN229
cells. For this, cells were injected subcutaneously in the
right ear of NMRI nude mice and the growing tumours were
characterized with respect to growth parameters and
histology. After optimizing the number of injected cells
and used medium (PBS, Matrigel) the radiation response
was studied by 200 kV X-ray irradiation. Furthermore, a
proof-of-principle full scale experiment with laser-
accelerated electrons was performed to validate the FaDu
tumour model under realistic, i.e. harsh, conditions at
experimental laser accelerators.
Results: Both human tumour models showed a high take
rate and continuous tumour growth after reaching a
volume of ~5 – 10 cubic millimetres. Moreover,
immunofluorescence analysis revealed that already the
small tumours interact with the surrounding tissue and
activate endothelial cells to form vessels. By analysing the
dose dependent tumour growth curves after 200 kV X-ray
treatment a realistic dose range, i.e. for inducing tumour
growth delay but not tumour control, was defined for both
tumour entities under investigation. Beside this basic
characterization, the comparison of the influence of laser-
driven and conventional (clinical Linac) electron beams on
the growth of FaDu tumours reveal no significant
difference in the radiation induced tumour growth delay.
Conclusion: The mouse ear tumour model was successfully
established and optimized providing stable tumour growth
with high take rate for two tumour entities (HNSCC,
glioblastoma) which are of interest for patient treatment
with protons. Experiments comparing laser-driven and
conventional proton beams in vivo as the next step
towards clinical application of laser-driven particle
acceleration are under way.
Acknowledgement: The work was supported by the
German Government, Federal Ministry of Education and
Research, grant nos. 03ZIK445 and 03Z1N511.
SP-0170 Novel models in particle biology research
P. Van Luijk1
1van Luijk Peter, Department of Radiation Oncology,
Groningen, The Netherlands
The unique behaviour of particles that causes them to
reach maximum dose deposition at the end of their track
makes them useful for facilitating both treatment
intensification and reduction of normal tissue damage. On
a macroscopic scale particles facilitate reducing normal
tissue dose and irradiated volume. Though it has been
known for a long time that reducing the amount of
irradiated normal tissue reduces toxicity, the increased
precision of particles also makes sparing of substructures
possible and offers more flexibility in choosing how to
distribute inevitable excess dose over the normal tissues.
However, it is also these unique properties that limit the
information in available clinical data that can be used to
guide optimal use of particles. Filling this gap is an
important topic of particle radiobiology that has been
approached with various in vivo models.
On a microscopic scale particles deposit dose with a higher
ionization density, especially near the end of the particle
track, usually positioned in the target volume. Increased
ionization density has been demonstrated to change
response, both in terms of severity and potentially even in
type. These effects have been studied mostly in 2D in vitro
models. However, even though in 2D cell cultures
differential effects between high- and low-LET radiation
are observed, these models seem to be more
radiosensitive than one would expect based on clinical
data. Interestingly it has been observed that cells respond
markedly different when irradiated in a more tissue-
equivalent 3D culture system.
Moreover, recent insights from stem cell biology indicate
a potentially critical role of stem cells both in tumour and
normal tissue response. Taken together, 3D culture
systems based on tissue-specific stem cells may offer new
opportunities to better understand the response of
tumours and normal tissues to particle irradiation.
Proffered Papers: Prostate 1
OC-0171 Multiparametric MRI margin characterization
for focal brachytherapy in low-grade prostate cancer