Abstract Book

S1086

ESTRO 37

Norway 3 University of Oslo, Department of Physics, Oslo, Norway Purpose or Objective Anal cancers (AC) show pronounced uptake of 18F- fluorodexoyglucose (FDG) in positron emission tomo- graphy (PET). The purpose was to develop a patient- specific tumor control probability (TCP) model employing the PET-based total lesion glycolysis (TLG), to assess its prognostic role and to use the model to estimate the gain in local control from dose escalation (DE). Material and Methods Eighty-eight patients with AC receiving conventional radiotherapy (RT) were prospectively included. Patients were regularly followed up at 3-6 months intervals after therapy, and only local recurrences were scored as events. FDG-PET was done prior to therapy. A TCP model was developed based on 1) published intrinsic radiosensitivity and fractionation sensitivity for AC and 2) TLG reflecting the number of clonogenic cells within the gross tumor volume (GTV). Furthermore, a scaling factor was used for the model to provide a global population- based control level of 80% based on previous literature. The model was thus developed without use of outcome data for the given cohort. The impact of DE from 58 Gy (conventional treatment) to 65 Gy (proposed new treatment) was assessed by the TCP model. Results Fourteen patients had local recurrence. The median and range of the patient-specific TCPs was 0.73 (0.08, 1.00). Dividing patients into two groups with low and high TCPs, the local control levels were 56 % and 91 %, respectively (Figure 1). This difference in recurrence-free survival was highly significant (P=0.001; Cox regression). A compa- rable TCP model based on GTV did not show any association with recurrence rates. The median increase in estimated TCP from DE was 0.52 and 0.23 for the group with low and high TCPs from conventional RT, respectively. Conclusion The patient-specific TCP model incorporating TLG was predictive of local recurrence, and was superior to a comparable model incorporating GTV only. The model estimated a clear benefit of DE for patients with high- pretreatment TLG and thus low TCP from conventional RT dosage. EP-1997 Monte Carlo simulations of direct 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, Division of 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 Purpose or Objective Gold nanoparticles have demonstrated a radiosensiti- zation potential under proton irradiation. Initially the radiosensitization effect was attributed to physical interactions of radiation with the gold and the production of secondary electrons that induce DNA damage. However, experiments have revealed that biological and chemical mechanisms may have significant contribution to the DNA damage and the radiosensitization effect. Material and Methods To understand the underlying physical mechanisms of radiosensitization and DNA damage induction at the cellular level, a computational 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 gold

nanoparticles. A clinically relevant gold concentration (0.7% wt gold) for the gold nanoparticle size of 6, 15, and 30 nm was considered. Protons with linear energy transfer values found in a spread out Bragg peak (1.3- 26.9 keV/µm) were simulated. The event-by-event models available through the Geant4-DNA project were used for accurate calculation of the DNA damage. To quantify the physical contribution to the DNA damage the formation of single (SSB) and double strand breaks (DSB), and break complexity were scored. The locality of the effect, i.e. the existence of higher damage at a location close to the gold distribution, was also addressed by investigating the DNA damage at a chromosomal territory. For a dose fraction of 2 Gy, each scenario was repeated 1000 times to get an average number of SSB and DSB numbers. Results Our model was able to produce SSB and DSB yields similar to the literature. However, for the combinations of gold nanoparticle size and proton energies studied in the present work, no significant increase in the SSB and DSB formation was observed. Conclusion As gold nanoparticles enhanced proton therapy have been proven experimentally, our results allow hypothesizing contribution from alternative mechanisms of radio- sensitization. EP-1998 In silico modelling of the impact of the fractionation for hypofractionated prostate treatments G. Delpon 1,2 , J. N'Guessan 1 , P. Paul-Gilloteaux 3,3 , K. Clément-Colmou 1,2 , V. Potiron 1,2 , S. Supiot 1,2 , F. Paris 1,2 , S. Chiavassa 1,2 1 INSERM, CRCINA U1232, Nantes, France 2 Institut de Cancérologie de l'Ouest, Radiotherapy and Medical Physics, Saint-Herblain, France 3 CNRS UMS 3556- INSERM U16, SFR Santé François Bonamy- Micropicell, Nantes, France Purpose or Objective Due to the improvement of imaging modalities and treatment devices, the concept of hypofractionation is gaining momentum in radiation oncology centres. However the fractionation in terms of total dose and number of fractions (fx) is usually determined according to the linear-quadratic (LQ) model. To derive the hypofractionated schema, the LQ model is used without maintaining the overall duration of the course. In our study, we have used our cellular automata model of tumour response after radiotherapy to study the impact of the number of fractions per week (fx/w) for the different scheme used in international clinical trials. Material and Methods Clinical results published for different moderate or severe hypofractionated prostate international trials were used. For each trial, the automata model was tuned in order to get the Tumor Control Probability (TCP) obtained for the reference arm. a/b was set equal to 3.33Gy. Tuned parameter was the number of cells allowed to divide every day. This methodology allowed to take into account the proliferation rate due to the cancer stage and the associated hormonotherapy when prescribed. Then simulations were run to calculate the TCP for the study arm of each trial according to the number of fx/w, from 2 to 5. For each fractionation, 400 simulations were repeated 5 times to derive an average TCP value. The impact of the number of fx/w was evaluated in terms of computed TCP variations. Results The dose per fx varied from 1.8Gy to 3.1Gy and 2.5Gy to 7.5Gy respectively in the reference and the study arms. Treatment duration varied from 4 weeks (20x3.1Gy) to 7.8 weeks (39x2Gy) and from 2 weeks (5x7.5Gy) to 5.6 weeks (28x2.5Gy) respectively in the reference and the study arms. In order to obtain published TCP values for