ESTRO 36 Abstract Book

S13 ESTRO 36 2017 _______________________________________________________________________________________________

[1] Aerts et al. Nat Commun 2014;5:4006. doi:10.1038/ncomms5006. [2] Parmar C, et al. Sci Rep 2015;5:11044. doi:10.1038/srep11044.

OC-0036 Does androgen deprivation therapy result in lowering the alpha / beta values in prostate cancers? N.R. Datta 1 , E. Stutz 1 , S. Rogers 1 , S. Bodis 1 1 Kantonsspital Aarau, Radio-Onkologie, Aarau, Switzerland Purpose or Objective Reports indicate that prostate cancers exhibit fractionation sensitivity with low α/β values similar to those of late-responding normal tissues. This has resulted in a number of hypofractionated (HRT) randomized clinical trials being undertaken in prostate cancer. Some of these have been reported to be isoeffective in terms of identical biochemical and/or clinical failure (BCF) rates. This allows estimation of the α/β values using the specified RT dose parameters, thus avoiding any uncertainty in choice of values for additional variables pertaining to tumour kinetics, repair and tumour control probability. The present study has been undertaken to estimate the α/β values for prostate cancer from randomized clinical trials of conventional (CRT) vs. HRT radiotherapy (RT) reporting similar 5-year BCF. The influence of various tumour and treatment variables on the α/β estimates was also examined. Material and Methods Randomized clinical trials with similar BCF following CRT or HRT for prostate cancer were collated following a detailed database search as per the PRISMA guidelines. The α/β value from each trial was derived using the linear- quadratic (L-Q) expression, α/β (Gy) = (d HRT D HRT – d CRT D C- RT )/(D CRT – D HRT ) where, 'd” and 'D” indicate the dose/fraction and the total dose respectively of the corresponding HRT and CRT schedules (represented by subscripts). Prostate cancers being slow growing tumours, a time factor was not included in these calculations. RT dose/fraction (1.8-2Gy for CRT; 2.4-3.4Gy for HRT), total RT dose (73.8-80Gy in CRT; 60-72Gy in HRT), use of androgen deprivation therapy (ADT) and tumour risk categories were considered as possible covariates in a multivariate regression analysis for the estimated α/β value. Results Seven randomized trials including 5,916 patients treated with CRT (n=2,949) or HRT (n=2,967) were available from 156 citations searched. Three trials recruited patients in a single risk category (one for each of low, intermediate or high-risk), 2 trials included both intermediate and high- risk patients and 2 trials included all risk categories. One study in low-risk patients did not use ADT while in others, 21%-100% patients were treated with ADT. The estimated α/β values ranged from 1.33-11.1Gy (5.41+4.0) (Table, Fig). On multivariate analysis, only %patients receiving ADT predicted the estimated α/β values (model R 2 : 0.992; coefficient = -0.096, p<0.001).

Figure 1: Exponential fit of radiomics signature score versus overall survival for different datasets.

Figure 2: Risk group identification based on the radiomics signature score for each dataset. Conclusion The radiomics signature model is able to predict two-year survival above the chance level in every validation cohort. Furthermore, the radiomics signature allows the identification of low, medium and high risk group patients. These findings indicate that the signature is robust and transferable across hospitals. References