ESTRO 36 Abstract Book

S460 ESTRO 36 2017 _______________________________________________________________________________________________

PO-0855 Use of the LKB model to fit urethral strictures for prostate patients treated with HDRB V. Panettieri 1 , E. Onjukka 2 , T. Rancati 3 , R. Smith 1 , J. Millar 1 1 Alfred Hospital, Alfred Health Radiation Oncology, Melbourne, Australia 2 Karolinska University Hospital, Dept of Hospital Physics, Stockholm, Sweden 3 Fondazione IRCCS- Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy Purpose or Objective High-Dose-Rate brachytherapy (HDRB) is widely used in combination with external beam radiotherapy in the treatment of prostate cancer. Despite providing biochemical control similar to other techniques, due to the variety of fractionation regimes used there is no clear consensus on the dose limits for the organs-at-risk, in particular the urethra. The aim of the work has been to fit the Lyman-Kutcher- Burman (LKB) Normal Tissue Complication Probability model to clinical outcome on urethral strictures data collected at a single institution. Material and Methods Dose-volume histograms and clinical records of 262 patients were retrospectively analysed. The patients had follow-up 6, 12, 18, 24 months and then every year until 10 years after the treatment. Clinical and toxicity data were collected prospectively. The end-point was the time of the first urethrotomy, a follow-up cut-off time of 4 years was chosen and the average stricture rate was about 12.6%. The LKB NTCP model was fitted using the maximum likelihood method and used simulated annealing to find a stable solution. Since the patients were treated with 3 different fractionation regimes (18 Gy in 3, 19 Gy in 2 and 18 Gy in 2 fractions) doses were converted into EQD2 with α/β = 5 Gy. Results For this cohort of patients the risk of urethral stricture could be modelled by means of a smooth function of EUD (see Fig 1). Using the LKB model the risk of complication could be represented by a TD50 of 220 Gy, a steepness parameter m of 0.55 and a volume-effect parameter n of 2.7. The fitted model showed good correlation with the observed toxicity rates with the largest deviation shown at higher doses. The large value of n could suggest a parallel behaviour of the urethra, however further validation is required with an independent dataset.

within a 200 times iterated 5-fold cross-validation approach. One additional analysis was performed with the lowest MIO over the three follow-up times as response variable (referred to as “3-12 months”; observed at the 3/6 months follow-ups in 60% of the cases). Candidate predictors from UVA, i.e. with a median two-sided p- value≤0.05 over all iterations, qualified for multivariate linear regression analysis (MVA) applying the same cross- validation approach. Predictability was assessed using coefficient of determination (r 2 ), and Spearman’s rank correlation coefficient (Rs); both given as the median over all iterations. Results Of 5-12 variables that presented with p≤0.20 on UVA ( Table ), trismus status pre-RT was an independent predictor for post-RT trismus (p=0.01-0.02 for all response variables) as was the mean dose to the ipsilateral masseter (p=0.05 at 3, 6, and 3-12 months). The combination of these two candidate predictors generated MVA models with increased predictability compared to the corresponding UVA models (r 2 =0.35-0.40 vs. 0.20-0.32; Rs=0.59-0.63 vs. 0.44-0.57), and consequently steeper response curves with 11-13 mm and 15-16 mm MIO difference between the least and the most risky quintile for the UVA and MVA models, respectively ( Figure ). A tendency of trismus recovery was noted for longer follow- up with a lower pre-RT normalized MIO difference at 12 months compared to that of the two earlier assessments; median (range): 0.14 (-0.67, 0.62) vs. 0.17 (-1.07, 0.66) at 3 months, and 0.16 (-1.33, 0.64) at 6 months.

Conclusion A temporally robust dose-response relationship for radiation-induced trismus, quantified as a millimeter mouth-opening decrease, could be observed within the first year after completed radiotherapy. Our results suggest that the dose-response for trismus within this period relies on the mean dose to the ipsilateral masseter, as well as the underlying pre-treatment mouth-opening ability. Up to ten additional variables presented with p- values in the interval p=0.06-0.19 and may prove to be of importance if investigated in larger/pooled cohorts with diversified treatment approaches where potential effects can be thoroughly investigated.

Conclusion In this work we have fitted the LKB model to clinical outcome on urethral strictures data for patients treated with HDRB collected at a single institution. The results show that the fitted model provides a good representation of the observed data, however further analysis and independent validation are necessary to confirm its behaviour and parameters.

Poster: Physics track: Intra-fraction motion management