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Conclusion
Using RBE
1.1
makes proton therapy dose and dose-
dependent predictions less accurate. Our results using a
RBE calculation model show that decreased accuracy may
have clinical implications, which agrees with published
literature (Jones 2012; Jones, 2014), and may affect
secondary cancer risk and normal tissue complication
probability calculations as well.
PO-0961 DNA damage and repair influence tumor
sensitivity to diffusing alpha emitters radiation therapy
Y. Keisari
1
, R. Etzyoni
1
, H. Bittan
2
, E. Lazarov
2
, M. Efrati
1
,
M. Schmidt
2
, T. Cooks
1
, L. Arazi
2
, I. Kelson
2
1
Tel-Aviv University / Faculty of Medicine, Clinical
Microbiology and Immunology, Tel-Aviv, Israel
2
Tel Aviv University, School of Physics and Astronomy-
Sackler Faculty of Exact sciences, Tel Aviv, Israel
Purpose or Objective
We developed an alpha radiation based brachytherapy,
which provides efficient ablation of solid tumors by alpha
radiation. This treatment termed,
Diffusing Alpha
emitters Radiation Therapy
(DaRT) utilizes radium-224
loaded wires, which when inserted into the tumor release
by recoil short-lived alpha-emitting atoms. These atoms
disperse in the tumor, and spray it with highly destructive
alpha radiation.
DaRT achieved substantial tumor growth retardation,
extended survival, and reduced lung metastases in mice
bearing various mouse and human derived tumors. Better
tumor control was achieved when DaRT was applied with
chemotherapy. Furthermore, tumor ablation by DaRT
boosted anti-tumor immune responses.
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