S533
ESTRO 36 2017
_______________________________________________________________________________________________
2
University of Naples Federico II, Department of Physics,
Napoli, Italy
3
Azienda Ospedaliera Universitaria Federico II, Radiation
Oncology Department, Napoli, Italy
4
National Council of Research CNR, Institute of
Biostructures and Bioimaging, Napoli, Italy
Purpose or Objective
The innovative radiotherapy techniques such as Intensity-
Modulated Radiation Therapy (IMRT) and Volumetric-
Modulated Arc Therapy (VMAT) allow for more conformity
of dose to the tumor target and sparing of healthy tissues.
However, these techniques require an increase of monitor
units (MUs) and therefore an increase of
treatment/delivery times for each fraction. In addition, a
higher dose outside the field caused by photons scattering
in the flattening filter (FF) is expected. Flattening Filter-
Free (FFF) photon beams can deliver higher dose rates and
reduce the treatment time by about a factor 4 compared
to conventional photon beams. Additional benefits also
include reduced head scatter, a lower peripheral dose and
neutron contamination. Purpose of the present study is to
compare the radiobiological effects of FFF versus FF
photon beams in mammary epithelial tumor cells (MCF7).
Material and Methods
MCF7 cells were irradiated with conventional and FFF 6MV
photon beams using a TrueBeamSTx (Varian Medical
Systems). Different dose rate values were considered (600
MU/min and 1400 MU/min). The cells were exposed to
0.25, 0.5, 1.0, 2.0 and 4.0 Gy doses. The number of
monitor units required to deliver the desired doses to the
cells was calculated using Pinnacle
3
(Philips) Treatment
Planning System (TPS). Irradiations were performed with
the flasks placed on 5 cm of equivalent water phantom
(RW3) slabs and gantry angle at 180° to deliver
homogeneous dose to the cell layer. A check of the actual
dose delivered to cells was done exposing 9 thermo-
luminescent dosimeters (LiF:Mg,Ti TLD-100) placed on the
bottom of one of the irradiated flask. Clonogenic cell
survival of MCF7 cells was determined. Cell survival data
were fitted to linear-quadratic model.
Results
In the investigated dose range (0-4Gy), no statistically
significant differences on breast cancer cell survival
curves was observed a) with or without flattening filter
(600 MU/min vs. 600 FFF MU/min) and b) at different dose
rates (600 FFF MU/min vs 1400 FFF MU/min). Cell survival
curves are reported in figure 1.
Conclusion
Our preliminary results suggest that the use of FFF beams
does not influence cancer cell survival rate when
compared with standard flattened
beams. The effects of
higher dose per fraction have to be further investigated.
PO-0973 Dimensionality reduction of clonogenic
survival data to identify candidates for
radiosensitization
N. Brix
1
, R. Hennel
1
, C. Belka
1
, K. Lauber
1
1
LMU University Hospital Grosshadern, Department of
Radiation Oncology, Munich, Germany
Purpose or Objective
With approximately 70,000 new cases per year in
Germany, breast cancer is the most common malignancy
in women. Together with surgery and chemotherapy, the
majority of patients is undergoing radiotherapy. While
stratification by clinicopathological parameters – such as
hormone receptor and Her2 expression – is part of the
clinical routine, biomarkers for tumor radioresistance and
targets for radiosensitization are currently not available.
The colony formation assay represents a versatile tool to
analyze cellular radiosensitivity
in vitro
making it
indispensable for the identification of factors involved in
tumor cell radioresistance. As an alternative to the linear-
quadratic model, we propose a novel approach of
dimensionality reduction to fully exploit the information
obtained from clonogenic survival assays which allows, for
instance, correlation with gene expression data.
Material and Methods
Clonogenic survival of 13 breast cancer cell lines and
normal human mammary epithelial cells upon irradiation
with 0-8 Gy was analyzed in colony formation assays. The
data derived thereof were subjected to linear-quadratic
fitting and principal component analysis (PCA) to extract
scores of radioresistance for each cell line.
Next, mRNA expression levels of more than 40 DNA
damage response (DDR) regulators were measured by qRT-
PCR. In order to identify predictors of radioresistance and
potential targets for radiosensitization, mRNA expression
levels were correlated with the PCA-derived
radioresistance scores.