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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.