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0.15) as compared with patients with mild (median
fraction of injured lung = 0.06) or no dyspnea (median
fraction of injured lung = 0.04) as seen in the top left panel
of the figure showing boxplots of the overall fraction of
injured lung in the three groups of patients. Similar results
were found when dividing the radiological injuries in
categories based on appearance (see the last three panels
in the figure). Patients with severe dyspnea had a
significant higher fraction of interstitial changes or
ground-glass opacities in the lung as compared with
patients with no dyspnea, while the severe and mild
groups only were borderline different. The fraction of lung
with consolidation injury was low and did not significantly
differ between patient groups.
Conclusion
The fraction of lung with radiological injuries after
radiotherapy was higher in patients with severe dyspnea
as compared to mild or no dyspnea. Dividing the
radiological injury based on appearance did not increase
the association with clinical symptoms. The radiologic
endpoint provides supplementary information in patient
outcome assessment and could be attractive for
radiobiological response modelling as an objective
endpoint disentangled from medical commodities.
Proffered Papers: Understanding RBE and its relevance
in vivo
OC-0242 The oxygen enhancement ratio for carbon
ions is smaller than for photons in R3327-HI prostate
tumors
C. Glowa
1,2,3
, P. Peschke
2,4
, S. Brons
5
, P. Huber
1,2,4
, J.
Debus
1,2
, C. Karger
2,3
1
University Hospital Heidelberg, Department of
Radiotherapy and Radiation Oncology, Heidelberg,
Germany
2
National Center for Radiation Research in Oncology
NCRO, Heidelberg Institute for Radiation Research in
Oncology HIRO, Heidelberg, Germany
3
German Cancer Research Center, Department of
Medical Physics in Radiotherapy, Heidelberg, Germany
4
German Cancer Research Center, Clinical Cooperation
Unit Molecular Radiooncology, Heidelberg, Germany
5
Heidelberg Ion Beam Therapy Center, Heidelberg Ion
Beam Therapy Center, Heidelberg, Germany
Purpose or Objective
Carbon ions (
12
C-ions) show an increase d relative
biological effectiveness (RBE) relative to photons and cell
culture experiments exhibit a higher RBE especially in
hypoxic tumors. The underlying reason for this is that the
oxygen enhancement ratio (OER) is smaller for
12
C-ions
than for photons. However, there is a lack of
in vivo
evidence for a decreased OER of
12
C-ions relative to
photons. To investigate the impact of hypoxia, dose-
response curves for photons and
12
C-ions were determined
for R3327-HI rat prostate adenocarcinomas under ambient
and acute hypoxic conditions.
Material and Methods
Tumor fragments of a Dunning prostate tumor R3327-HI
were transplanted
s.c.
into the distal thigh of male
Copenhagen rats. Tumors were treated with increasing
doses of either
12
C-ions or 6 MeV photons under ambient
or acute hypoxic conditions. Acute hypoxia was induced
by clamping the feeding artery 10 min before and during
treatment. Primary endpoint was local tumor control
within 300 days. OER-values for ambient vs. hypoxic
conditions for both irradiation modalities as well as RBE-
values were calculated based on TCD
50
-values (dose at 50%
tumor control probability) of photons and
12
C-ions,
respectively.
Results
Local tumor control was achieved with
12
C-ions and
photons under normoxic as well as hypoxic conditions,
however, a higher effectiveness was obtained for
12
C-ions.
The RBE for local tumor control after single dose
irradiation increased from ambient conditions (2.08±0.13)
to hypoxic conditions (≈2.5). The OER was significantly
smaller for
12
C-ions than for photons, but both values were
lower than the OER-values measured under cell culture
conditions. Since some animals are within their 300 days
follow-up, precise OER-values are still pending.
Conclusion
The RBE of
12
C-ions increases under hypoxic conditions,
since the OER of
12
C-ions is significantly lower than for
photons. Interestingly, the OER for both radiation qualities
was much lower than measured
in vitro
. This supports the
need of
in vivo
experiments to assess the impact of
hypoxia in patients treated in heavy ion radiotherapy.
OC-0243 Submicron focused proton irradiation –
understanding the RBE of heavy ion irradiation
T.E. Schmid
1,2
, C. Greubel
3
, K. Ilicic
2
, D. Walsh
3
, J.
Reindl
3
, C. Siebenwirth
2
, J.J. Wilkens
2
, G. Multhoff
2
, E.
Schmid
4
, G. Dollinger
3
, S.E. Combs
1,2
1
Helmholtz Zentrum München, Institute of innovative
Radiotherapy, Neuherberg, Germany
2
Klinikum rechts der Isar, Radiooncology, München,
Germany
3
Universität der Bundeswehr München, Applied Physics,
Neubiberg, Germany
4
University of Munich, Department for Anatomy and Cell
Biolog, München, Germany
Purpose or Objective
High LET radiation like heavy ions is well known to induce
a higher relative biological effectiveness (RBE) than low
LET radiation. The dependence of RBE with LET is of
special interest for heavy ion tumor therapy and for
radiation safety issues. Irradiations with low and high LET
particles differ in the spatial dose distribution. Only a few
high LET particles hit a cell nucleus and deposit doses of a
few gray where the dose deposition and thus the DNA
damage concentrates around the few ion trajectories. In
contrast several hundred low LET particle hits are needed
to achieve the same dose resulting in a quasi-
homogeneous damage distribution. The influence of
different spot sizes is studied on the induction of dicentric
chromosomes.
Material and Methods
Human-hamster hybrid (AL) cells were irradiated with
focused 20 MeV protons in a quadratic matrix pattern with
point distances of 5.4×5.4 µm2 and 117 protons per matrix
point at the ion microbeam SNAKE using different spot-
sizes between 0.8 and 2.7 µm (full width at half