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S527
ESTRO 36 2017
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In the present study we examined the relative sensitivity
of various tumor cells in vivo and in vitro to alpha radiation
and the role of DNA damage control in this effect.
Material and Methods
Implanted murine tumors were treated with a single
224
Ra-
loaded source, and tumor progression and survival were
recorded. Intratumoral alpha particle distribution was
measured by the spread of
212
Pb. The sensitivity of the
various cancer cells was determined by their ability to
form colonies after irradiation in vitro with alpha
particles. The formation and disappearance of
g
amma-
H2AX foci (DSBs indicators), and activation of non-
homologous end joining following recruitment of Ku70 into
the nucleus, served to evaluate DNA damage control and
repair.
Results
- DaRT caused significant damage in vivo to squamous cell
tumors (SQ2) but not to pancreatic (Panc02) and breast
adenocarcinoma (4T1).
- Tissue necrosis and tumor growth retardation were in
correlation with the intratumoral distribution of released
alpha emitting isotopes.
- SQ2 cells were the most radiosensitive to alpha particles
(mean lethal dose required to reduce cell viability to 37%;
D
0
=0.57) while the pancreatic (D
0
=1.1) and breast cancer
cells (D
0
=1.05) were less radiosensitive.
- The three cell lines exhibited different damage
accumulation and repair kinetics. The radio-resistant cell
line 4T1 had the lowest number of double strand breaks
(DSBs) and a fast recruitment of nuclear Ku70, indicating
a quick and efficient repair process. The relatively radio-
resistant Panc02 cells, had an intermediate number of
DSBs, and fast damage repair. SQ2 cells exhibited high DNA
damage and a low and very slow Ku70 nuclear
recruitment, indicating a slow and not efficient repair
process that consequently resulted in cell death.
Conclusion
The radiosensitivity of tumors to alpha radiation was in
correlation with their ability to avoid or repair double
strand breaks. Identifying the mechanism(s) responsible
for the resistance of various tumor cells to alpha radiation
may open the possibility to block this mechanism(s) and
render the cells more susceptible to alpha particles. This
may have practical implications for the treatment of solid
tumors by DaRT.
PO-0962 Proton minibeam irradiation leads to reduced
acute side effects in an in-vivo mouse ear model
E. Zahnbrecher
1
, M. Sammer
2
, J. Reindl
2
, C. Greubel
2
, B.
Schwarz
2
, C. Siebenwirth
1,2
, D.W.M. Walsh
1,2
, K. Ilicic
1
,
J.J. Wilkens
1,3
, S.E. Combs
1,3
, G. Dollinger
2
, T.E.
Schmid
1,3
1
Klinikum rechts der Isar, Technische Universität
München, Munich, Germany
2
Institut für angewandte Physik und Messtechnik,
Universität der Bundeswehr München, Neubiberg,
Germany
3
Institute of Innovative Radiotherapy, Helmholtz
Zentrum München, Neuherberg, Germany
Purpose or Objective
In Radiation Oncology, the maximum dose which can be
delivered to a certain tumor is often limited by the
radiation induced damage in normal tissue surrounding the
actual tumor. Proton minibeam radiotherapy aims to
minimize normal tissue damage, especially in the entrance
channel. Due to beam widening with increasing track
length, it leads to a homogeneous dose distribution in the
tumor area, which permits tumor control as in
conventional proton therapy. Acute side effects of proton
minibeam irradiation were examined in an in-vivo mouse
ear model to account for immune system, vasculature and
higher complexity. In this study, the effect of partially
widened proton minibeams was investigated as occurring
at different depths on their way through the irradiated
volume.
Material and Methods
A total of six different minibeam sizes were applied to the
ear of Balb/c mice using 20 MeV protons. The average dose
of 60 Gy was distributed in 4x4 minibeams with beam sizes
of σ = 0.09, 0.2, 0.31, 0.45, 0.56 and 0.9 mm and a beam-
to-beam distance of 1.8 mm. Inflammatory response, i.e.
ear swelling and skin reactions, were observed for 90 days
after irradiation.
Results
The results show a link between the applied beam sizes
and the dimension of acute side effects after irradiation.
The largest beam sizes lead to significant inflammatory
reactions such as ear swelling, erythema and
desquamation within 3-4 weeks after irradiation. The
maximum skin reactions were reduced with decreasing
beam sizes until almost no ear swelling or other visible
skin reactions to the irradiation could be detected.
Conclusion
Our results show that the tissue sparing effect of proton
minibeams is highest for the smallest beam sizes as
occurring in the superficial layers of an irradiated volume.
The positive effect decreases with increasing beam size
and is therefore smallest for the biggest beam size which
is equivalent to a homogeneous dose as desired in the
target volume. However, since all minibeams have
significantly reduced acute side effects compared to
broad beam irradiation, proton minibeam radiotherapy
may offer various possibilities for new approaches in
clinical proton radiotherapy.
Supported by the DFG Cluster of Excellence: Munich-
Centre for Advanced Photonics.
PO-0963 RBE variations along the Bragg curve of a 200
MeV proton beam
C. Vandevoorde
1
, A. Baeyens
2
, A. Vral
2
, J. Slabbert
3
1
iThemba LABS, Radiation Biophysics, Cape Town, South
Africa
2
Ghent University, Basic Medical Sciences, Ghent, Belgium
3
iThemba LABS, Medical Directorate, Cape Town, South
Africa
Purpose or Objective
A lack of strong radiobiological datasets has resulted in
the clinical adoption of a fixed, generic relative biological
effectiveness (RBE) of 1.1 in current proton therapy (PT).
However, in the distal area of the spread-out Bragg peak
(SOBP), the RBE is certainly higher than 1.1 due to the
rapid decrease in proton energy, resulting in an increased
linear energy transfer (LET). Therefore, the RBE was
quantified at different positions of the depth-dose profile
for the 200 MeV clinical proton beam at iThemba LABS.
Material and Methods
V-79 fibroblasts were irradiated as monolayers at the
plateau, proximal, middle and distal positions, as well as
in the distal edge (32% of the maximum dose) of a 7 cm
SOBP. At the same time, V-79 cells were also irradiated
with
60
Co γ-rays as reference radiation. α and β values
were determined from the cell survival curves and the 95%
confidence ellipses of these covariant parameters were
compared in the analysis. Mean inactivation dose (MID)
values were calculated and used for the RBE calculations.
Results
A large overlap in the 95% confidence ellipses was
observed for proton plateau and
60
Co γ-rays, so there is no
statistical significant difference in radiation quality. The
MID decreases with depth from 3.65 Gy at the entrance
plateau, to 3.52 Gy, 3.40 Gy and 3.15 Gy for the proximal,
middle and distal position along the SOBP respectively.
Since the entrance plateau results were not significantly
different from
60
Co γ-rays, RBE was calculated based on
the plateau MID as a reference. This resulted in RBE values
of 1.04, 1.07 and 1.16 for the proximal, middle and distal
positions respectively. Furthermore, a clear separation