ESTRO 36 Abstract Book

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S860 ESTRO 36 2017
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ensures that differences between the trials such as use of
hormones and outcome metrics are accounted for. It was
assumed that the dose response was linear between trial
arms. In 3 of the trials, the hypofractionated schedule was
compared to 2 Gy per fraction, in the RTOG 0415 study the
standard fractionation was 1.8 Gy per fraction. A grid
search approach was used to minimise the error for EQD2.
Repopulation was included in the model using the term
OTT-Tk where OTT is the overall treatment time and Tk is
the number of days from the start of treatment when
repopulation is assumed to begin. A proliferation rate of
0.31 Gy/day was used [1]. The CHHiP trial had two
hypofractionated arms and these were fitted separately.
Results
Figure 1 is a representative example of the grid search
results to minimise the squared difference in EQD2
corrected for outcome between the trial arms. Varying the
Tk parameter has 3 distinct phases; i) Tk less than the OTT
of the hypofractionated arm, where the α/β ratio varies
little ii) Tk between the OTT of the hypofractionated and
standard arms, where the α/β ratio transitions steeply and
iii) Tk greater than the OTT of the standard arm. This last
case reduces to equating the two fractionation schedules.
The best fit parameter values for α/β ratio and Tk are
shown in Table 1 along with the best fit values for the α/β
ratio when repopulation is not considered. For all trials,
the overall best fit parameters included a value of Tk that
was less than the overall treatment time of the standard
arm, indicating an improvement when compared to a
model which considered the α/β ratio only.
Figure 1
Table 1
Conclusion
The estimation of α/β ratio for prostate cancer presented
here included two unknown parameters in the model, as
such, no definitive conclusion was reached. However,
including Tk in the model consistently reduced the
squared difference and increased the α/β ratio.
References
1. Vogelius, I.R., et al., Int J Radiat Oncol Biol Phys, 2013.
85(1): p. 89-94.
2. Dearnaley, D., et al., Lancet Oncol, 2016. 17(8): p.
1047-60.
3. Incrocci, L., et al., Lancet Oncol, 2016. 17(8): p. 1061-
9.
4. Catton, C., J Clin Oncol, 2016. 34(suppl).
5. Lee, W.R., et al., J Clin Oncol, 2016. 34(20): p. 2325-
32.
EP-1613 Modelling DNA damage on gold nanoparticle
enhanced proton therapy
M. Sotiropoulos 1, N.T. Henthorn1, J.W. Warmenhoven1,
R.I. Mackay2, K.J. Kirkby1,3, M.J. Merchant1,3
1University of Manchester, Faculty of Biology Medicine
and Health Division of Molecular & Clinical Cancer
Sciences, Manchester, United Kingdom
2The Christie NHS Foundation Trust, Christie Medical
Physics and Engineering, Manchester, United Kingdom
3The Christie NHS Foundation Trust, Manchester, United
Kingdom
Purpose or Objective
Gold nanoparticles have demonstrated a
radiosensitization potential under photon and proton
irradiation. Most existing studies have attributed the
effect to the increased local dose delivered by electrons
generated from interactions of the beam protons with the
gold nanoparticles. However, the mechanism leading to an
increase in the cell killing is yet not clear.
Material and Methods
To further understand the underlying mechanisms of the
radiosensitization at the cellular level, a cell model with
detailed nuclear DNA structure was implemented in the
Geant4 Monte Carlo simulation toolkit. A realistic gold
nanoparticle distribution was incorporated, allowing for
the formation of clusters of vesicles filled with the gold
nanoparticles. A clinically relevant gold concentration was
simulated for the gold nanoparticle size of 6, 15, and 30
nm. Protons with linear energy transfer values found in a
spread out Bragg peak (1.3-4.8 keV/µm) were simulated.
The event-by-event models available through the Geant4-
DNA were used for accurate calculations of DNA damage.
Damage to the DNA inducing either single (SSB) or double
strand breaks (DSB) was used for the quantification of the
radiosensitization effect, for a dose fraction of 2 Gy. Each
case was repeated 100 times to get an average number of
SSB or DSB numbers.
Results
For the combinations of gold nanoparticle size and proton
energies studied in the present work, no statistically
significant increase in the single or double strand break
formation was observed. The DSBs induced for the 4.8
kev/µm protons were 14.93 ± 0.38 for the control while
ranged from 15.09 ± 0.39 to 15.76 ± 0.41 when the gold
nanoparticles were present, depending on the gold
nanoparticle size. Similarly, for the 1.3 keV/µm protons
the control value was 12.21 ± 0.34 DSBs and in the
presence of gold nanoparticle was 11.94 ± 0.36 to 12.48 ±
0.33 DSBs depending on the gold nanoparticle size.
Conclusion
As gold nanoparticles enhanced proton therapy have been
proven experimentally, our results allow hypothesizing
contribution from alternative mechanisms of
radiosensitization.
EP-1614 Uncertainty of dose-volume constraints
obtained from radiation pneumonitis dose-response
analysis
C.M. Lutz1, D.S. Møller2, L. Hoffmann2, A.A. Khalil1, M.M.
Knap1, M. Alber1,3
1Aarhus University Hospital, Department of Oncology,
Aarhus C, Denmark
2Aarhus University Hospital, Department of Medical