S504
ESTRO 36 2017
_______________________________________________________________________________________________
For Elekta accelerators, all the calculation results show a
deviation from the reference values lower than 3%. For
Siemens and Varian accelerators, the resulting
calculations for fields larger than 2×2 cm
2
differ less than
4%. For 2×2 cm
2
large fields formed by Siemens and Varian
MLC, the differences between the calculated and
measured output factors often exceed 5%, but still are
below 10%.
Conclusion
The RPC measured values provide a consistent dataset for
small field output factors that can be used as a redundant
QA check of a treatment planning system dosimetry data
for small-field treatments. The results of the audit are
very useful for the participants who should carefully
investigate any detected discrepancies between the
standard dataset and calculated values, with attention to
the specific beam model.
PO-0918 Radiotherapy and Her2 targeting agents:
synergism and antagonism in clonogenic and confluence
assays
N. Suchowerska
1
, J. Toohey
2
, S. Carroll
2
, L. Rogers
2
, G.
Lyons
3
, J. Beith
4
, A. Dos Santos Esteves
2
, D.R. McKenzie
5
1
Chris O'Brien Lifehouse, Radiation Oncology,
Camperdown- Sydney, Australia
2
Chris O'Brien Lifehouse, Radiation Oncology,
Camperdown Sydney, Australia
3
Royal Prince Alfred Hospital, Dermatology Cancer,
Sydney, Australia
4
Chris O'Brien Lifehouse, Medical Oncology, Camperdown
Sydney, Australia
5
University of Sydney, School of Physics, Sydney,
Australia
Purpose or Objective
Her2 amplified cancers, comprising 15-20% of patients
presenting with breast cancer, are now routinely
prescribed Trastuzumab (Herceptin), a monoclonal
antibody targeting Her2 receptors, leading to a significant
improvement in outcomes in this previously high risk
breast cancer subtype. Such targeting agents are rapidly
being introduced into the clinic, based on trials showing a
survival advantage. Now combination therapies with drug
conjugates have emerged. The biological interactions of
combined targeting agents, when given concurrently with
radiation, are not well described. Our aim is to identify
whether there is a synergistic or antagonistic interaction
between targeting agents and ionising radiation for two
distinct Her2+ subtypes.
Material and Methods
Two molecular subtypes of HER2+ breast cancer cell lines
were used: HCC-1954, which is ER and PR hormone
negative and BT-474, a luminal B which is ER negative and
PR positive. Both cell lines were treated to Her2 targeting
agents (Trastuzumab and T-DM1) and radiation (6MV
photons, 0 to 4Gy), individually and in combination to
identify whether the response was synergistic, additive or
antagonistic. The alpha/beta ratio was experimentally
determined for each cell line. Synergy (
S
) is defined as the
fractional difference between the observed (
S
o
) and the
predicted survival for each treatment given alone (
S
1
x
S
2
):
The observed response was determined using two assays:
the clonogenic assay and the confluence assay.
Results
The alpha/beta ratio for HCC-1954 (ER-/PR-/Her2+) and
BT474 (Luminal B ER-/PR+/Her2+) are found to be 35 Gy
and 5 Gy respectively, highlighting a heterogeneous
treatment response. The survival of HCC-1954 was not
affected by Trastuzumab alone, but when combined with
radiation, a synergistic interaction was observed. BT-474
showed a 20% decrease in survival when exposed to
Trastuzumab alone, but a combined treatment with
radiation did not yield the expected decrease in survival,
indicating an antagonistic interaction.
Conclusion
Our results show that before starting clinical trials, the
combination of radiation therapy and combined targeting
agents needs to be closely examined for each sub-type
under consideration. The assumption that a combination
of treatments will result in a synergistic response is clearly
not always true.
Acknowledgements
We acknowledge funding from the Sydney Breast Cancer
Foundation
PO-0919 Stereotactic radiotherapy for brain
metastases : Cyberknife versus VersaHD / ExacTrac
M. Perdrieux
1
, M. Celeste
1
, I. Lecouillard
1
, E. Nouhaud
1
,
C. Blay
1
, F. Jouyaux
1
, N. Delaby
1
, J. Bellec
1
, C. Lafond
1
1
Centre Eugène Marquis, Radiotherapy, Rennes CEDEX,
France
Purpose or Objective
The aim of this study was to compare dosimetric and
geometric performances of the CyberKnife (Accuray) and
VersaHD (Elekta) with the ExacTrac system (BrainLab) in
stereotactic radiotherapy for brain metastases.
Material and Methods
This study was conducted on 10 patients for Cyberknife M6
v10.6 with Iris collimator and VersaHD equipped with
ExacTrac v6.1 and the Frameless system (BrainLab). The
prescribed dose was 27 Gy in 3 fractions with 1mm margin
between CTV and PTV for both modalities. The dosimetric
study was also conducted with 2 mm margin for VersaHD
plans in accordance to our clinical practices.
Plans have been computed for CyberKnife with non-
isocentric non-coplanar beams generated by inverse
optimization on Multiplan v5.3 (Accuray) with the
RayTracing dose calculation algorithm. For VersaHD, 4
non-coplanar arcs (VMAT) have been generated b y inverse
optimization on Pinnacle v9.10 (Philips ) with the
Adaptative Convolution algorithm. For each case, plans
were normalized to obtain the same PTV co verage at +/-
0.2 %.
The comparison was based on the brain volume outside
PTV receiving 23.1 Gy. The volume of isodoses 6 Gy, 2.7
Gy and 1 Gy have been reported as well as the Paddick’s
Gradient Index to characterize the dose gradient around
PTV and the spread of low doses.
Quality controls have been performed with Gafchromic
EBT3 films (Ashland) and with an ionization chamber
(Pinpoint 31014 /PTW) in an anthropomorphic phantom
(STEEV/CIRS). The measured dose with film has been
compared to the calculated dose according to the gamma
index method with a 3% (local) / 2 mm criteria (analytical
threshold : 30% of the maximum dose). The geometric shift
between the measured and calculated dose distribution
has been also reported.
Results
Table 1 shows that dosimetric criteria for plan validation
were reached for both modalities and both margins.
Compared to VersaHD, dose gradients obtained with
Cyberknife were greater and lower volumes of healthy
tissue received doses below 6 Gy.
Ionization chamber measurements showed mean
differences with the calculated dose of 2.53% and 0.03%
for Cyberknife and VersaHD respectively. The mean value
of the gamma index was 0.42 for the Cyberknife and 0.38
for the VersaHD. The mean geometric shifts between the
measured and calculated dose distributions were 0.87 mm
and 0.84 mm for Cyberknife and VersaHD respectively.