ESTRO 36 Abstract Book

S860 ESTRO 36 2017 _______________________________________________________________________________________________

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.

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. Henthorn 1 , J.W. Warmenhoven 1 , R.I. Mackay 2 , K.J. Kirkby 1,3 , M.J. Merchant 1,3 1 University of Manchester, Faculty of Biology Medicine and Health Division of Molecular & Clinical Cancer Sciences, Manchester, United Kingdom 2 The Christie NHS Foundation Trust, Christie Medical Physics and Engineering, Manchester, United Kingdom 3 The Christie NHS Foundation Trust, Manchester, United Kingdom 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. Lutz 1 , D.S. Møller 2 , L. Hoffmann 2 , A.A. Khalil 1 , M.M. Knap 1 , M. Alber 1,3 1 Aarhus University Hospital, Department of Oncology, Aarhus C, Denmark 2 Aarhus University Hospital, Department of Medical Purpose or Objective Gold nanoparticles have demonstrated a

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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.