| Περίληψη: | The aim of this study is the clinical derivation of the dose-response relations of bladder and prostate regarding PSA progression and urinary complications using patients treated for prostate cancer with both photon and proton beams. Such data are necessary for a prospective estimation of the clinical effectiveness of radiation therapy using combinations of different radiation modalities.
Material
During the period from 2002 until 2006, at the Academic Hospital in Uppsala, Sweden 189 patients underwent radiotherapy for prostate cancer, which combined photon and proton beams therapy. Of these patients, 100 have been included in this study and have been analysed for the prostate. The analyses for urinary complications were made for 72 patients who didn’t have final clinical urinary outcome equal to one . The dose distribution delivered to the prostate, the two regions of the bladder and the clinical treatment outcome, were available for each patient. The patients were given a proton boost of 20 Gy in 4 fractions of 5 Gy in addition to a conventional photon beam treatment, which was prescribed to a dose of 50 Gy in 25 fractions of 2 Gy. In this analysis, the delineated regions of interest were the prostate, the whole urinary bladder and the lower 3 cm part of the bladder. It is known that most urinary complications come from the lower 3cm part of bladder due to its anatomical position near to urethra and prostate. The photon and proton doses were calculated using the BED (biologically effective dose) concept. Furthermore, for the calculation of the proton dose an RBE value of 1.1 was considered. Finally, the combined effective dose was chosen to be the sum of the maximum dose of protons and the mean dose of photons for the whole bladder and the bladder-3cm, while for the prostate, the effective dose was considered as the sum of the mean dose for photons and the minimum dose for protons. The radiobiological parameter acquisition was performed for the Poisson Binomial and Probit models using the Maximum Likelihood method.
Results
Of the 100 patients, 94 had tumor control (94 %), whereas 6 patients had treatment failure (6 %). Of the 72 patients, 15 (21%) showed urinary complications, whereas 57 (79%) were complication-free.. The estimated values of the parameters for tumour are D50= 49.4 Gy (68% CI = 47.90-52.80 Gy) and γ = 2.25 (68% CI = 1.95-2.80) for the Poisson , D50= 49.55Gy (68% CI= 47.56-51.45Gy) and γ = 2.25 (68% CI = 1.95-2.80) for Binomial, whereas for the Probit model the values of D50 and γ50 are 47,27Gy (68% CI = 45.25-50.01 Gy) and 1,33 (68% CI = 1.20-1.37), respectively. The estimated values of the parameters for the whole bladder are D50= 104 Gy (68% CI = 103.12-105.01 Gy) and γ = 0.7 (68% CI = 0.67-0.72) for the Poisson , D50= 108 Gy (68% CI= 106-108.8 Gy) and γ = 0.6 (68% CI = 0.58-0.70) for Binomial, whereas for the Probit model the values of D50 and γ50 are 97 Gy (68% CI = 95.30-97.56 Gy) and 1 (68% CI = 0.94-1.12), respectively. Finally, the estimated values of the parameters for bladder 3cm are D50= 88.4 Gy (68% CI = 85.4-89.5 Gy) and γ = 1.30 (68% CI = 1.18-1.45) for the Poisson , D50= 88.58 Gy (68% CI= 86.21-89.85 Gy) and γ = 1.28 (68% CI = 1.12-1.51) for Binomial, whereas for the Probit model the values of D50 and γ50 are 85.58 Gy (68% CI = 83.23-89.21Gy) and 1.78 (68% CI = 1.56-1.83), respectively. From the derived mean DVHs of the prostate it is concluded that photon and proton therapies contribute the same in the toxicity of the patients and both proton and photon therapy provide the patients with the prescribed dose in the target – prostate gland. From the derived mean DVHs of the bladder and the bladder 3cm, it is observed that photon therapy provides the patients with more dose than the proton therapy, thus it can be assumed that the urinary complications were mainly due to the photon treatment. Bladder 3cm receives more dose both during photon and proton therapy in comparison with the whole bladder for patients with and without complications. Thus, the lower 3cm part of the bladder contributes more in the possibility of urinary complications. In ROC analysis, for the prostate the area under the ROC curve is 0.71. This indicates that the model distinguishes quite well the group of the patients with and without PSA progression. For the whole bladder and the lower 3cm of the bladder, the results are 0.61 and 0.65 respectively; the model does not separate well the two groups (with and without the complications). These results suggest that other factors may also be important for urinary toxicity.
Conclusions
The dose-response relations of bladder and prostate appear to be described well by the estimated parameters of the Poisson, Poisson and Probit models. Future studies incorporating more radiobiological models and more detailed factors describing the combined treatment and endpoint registration will be needed until an accurate prospective estimation of the expected urinary complications is reached.
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