ESTRO 36 Abstract Book

S871 ESTRO 36 _______________________________________________________________________________________________

Material and Methods The α/β ratio for prostate was derived independently for each of the CHHiP[2], HYPRO[3], PROFIT [4]and RTOG 0415 studies[5] by comparing the outcomes in the standard and hypofractionated trial arms. This approach 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.

‘Radiation-induced urgency syndrome’ consists of different self-reported bowel symptoms. To combine the symptoms, factor analyses was used. Dose-response relationships were estimated fitting the data to the Probit model. ROC curve analyses were used to identify which organ at risk is correlated the most with the clinical outcome. Results The maximum likelihood estimates of the dose-response parameters for Probit model, the three organs at risk and ‘radiation induced urgency syndrome’, the Log Likelihood (LL) value and the AUC are: D 50 = 51.3 (48.3-54.6), γ 50 = 1.19 (0.98-1.42), α/β=0.59 (0.034-1.56), LL = -50.2 and AUC=0.63 for rectum, D 50 = 51.6 (48.7-54.9) Gy, γ 50 = 1.20 (0.98- 1.44), α/β =2.02 (0.85-4.73), LL = -51.0 and AUC=0.66 for the sigmoid and D 50 = 61.4 (56.4-67.5) Gy, γ 50 = 0.90 (0.73- 1.08), α/β = 10.3 (2.1- 1e+06 Gy), LL = - 51.4 and AUC=0.60 for small intestines.

Figure 1

Conclusion For the studied organs at risk, the dose to the sigmoid is the best predictor of ‘radiation-induced urgency syndrome’ among gyneocological cancer survivors. Dose planners having the ambition to eliminate the syndrome may consider to delineate the sigmoid as well as rectum in order to incorporate the dose-response results. EP-1612 Estimates of the α/β ratio for prostate using data from recent hypofractionated RT trials. S. Gulliford 1 , C. Griffin 2 , A. Tree 3 , J. Murray 4 , U. Oelfke 1 , I. Syndikus 5 , E. Hall 2 , D. Dearnaley 3 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Joint Department of Physics, London, United Kingdom 2 The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom 3 Royal Marsden NHS Foundation Trust, Academic Urology Unit, London, United Kingdom 4 Guy’s & St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London, United Kingdom 5 Clatterbridge Cancer Centre, Department of Clinical Oncology, Wirral, United Kingdom Purpose or Objective The α/β ratio for prostate cancer has been widely studied with growing evidence for a value significantly lower than the standard value for tumours of 10 Gy. Previous studies have also indicated that there may be a time factor whereby tumour repopulation should be considered during the course of radiotherapy[1]. Recent reporting from 4 separate phase III clinical trials comparing hypofractionated schedules with standard schedules for prostate radiotherapy allow for further exploration of the α/β value.

Table

1