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PO-0906 HYPOFRACTIONATED PROSTATE RADIOTHERAPY AND RECTAL TOXICITY: DOES RECTAL OUTLINE MATTER?
ESTRO 31
(chemo) radiotherapy and to compare the performance of this model with generally applied dose distribution parameters to predict RP, such as the mean lung dose (MLD) and the V20 of both lungs. Materials and Methods: The study population consisted of 269 NSCLC patients treated with 3D conformal radiation therapy (3D-CRT) alone, or in combination with chemotherapy in three institutions, treated with different fractionation schedules. The total dose ranged from 46 to 94.5 Gy, with fraction doses ranging from 1.5 Gy (b.i.d.) to 2.5 Gy. RP was scored using the SWOG-classification and the primary endpoint was defined as grade II-IV RP in the first 6 months after completion of radiotherapy. In the multivariate analysis, the following candidate predictive factors were included: sex, age, WHO performance, concurrent chemotherapy, T-stage and N-stage. To select the most predictive variables a multivariate logistic regression model with bootstrapping was used. Results: In order to judge possible collinearity between selected variables, and to facilitate the interpretation of the modelling results, we first produced a correlation matrix to identify variables that were strongly correlated (i.e., Spearmans’s correlation coefficient ³ 0.8) A strong correlation was found between most DVH parameters within each OAR. In the univariate analysis only a small proportion of the candidate variables was significantly associated with the endpoint. The average likelihood of bootstrap prediction in the multivariate logistic regression analysis was optimal with a model consisting of two variables: V40 of the ipsilateral lung, and age. Increasing the number of variables to three did not further improve the model. The AUC for this 2-variable model was 0.66 (95% CI: 0.58 – 0.74). A model based on the V40 of the ipsilateral lung and age was most predictive, with odds ratios of 1.03 (95% CI: 1.01-1.06) for each % increase in relative volume, and 1.04 (95% CI: 1.00-1.08), for each year increase in age. The AUC of a model based on the V20 of the ipsilateral lung was 0.61 (95% CI: 0.52-0.70). The AUC of a model based on the mean lung dose the AUC was 0.59 (95% CI: 0.51-0.68) Conclusions: A multivariate NTCP model based including the V40 of the ipsilateral lung and age is more predictive than a model based on the V20 or the mean lung dose, such as currently used in clinical practice. The results of this study show that the development of RP may not only be dependent on dose but also on age. PO-0906 HYPOFRACTIONATED PROSTATE RADIOTHERAPY AND RECTAL TOXICITY: DOES RECTAL OUTLINE MATTER? 1 2 3 1 A. McPartlin , E. Maile , G. Webster , J. Logue , J. Livsey1, T. Elliott1, J. Wylie1, N. Alam1, A. Choudhury1 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom 2Manchester University, Medical School, Manchester, United Kingdom 3 The Christie NHS Foundation Trust, Physics, Manchester, United Kingdom Purpose/Objective: Numerous authors have attempted to establish models to minimise rectal late effects following prostate radiotherapy, most using data from standard fractionation regimes with little agreement as to predictive dosimetric values. This study aimed to establish if there was a link, in patients treated with hypofractionated radiotherapy, between rectal dose-volumes and patient reported late rectal toxicity. It further investigated whether the method used to outline the rectal volume affected calculated dose-volumes. Materials and Methods: 70 of 122 patients treated with radical radiotherapy to the prostate (57Gy in 19 fractions) between 2004-09 completed a validated LENT/SOMA questionnaire. Rectal dose-volume histograms (DVH) were calculated for each patient using standard rectal and rectal wall contouring (ano-rectal to recto-sigmoid junction)and truncated volumes (0.5cm superior/inferior to the PTV, identified as xxx_edit). The data was analysed using Spearmans Rho rank test for associations between rectal toxicity ≥2 and volume receiving a dose up to 55Gy (in 5Gy increments). Results: A maximum score for late rectal-bowel toxicity of ≥2 was reported by 2/3 of patients. No significant correlation was found between this and the volume of rectum receiving any given dose of radiation using each outlining method (p>0.05 in all cases). Non statistically significant trends were identified using differing voluming techniques. Although the normalised volume receiving a high dose (>40Gy) was not significantly influenced by using a standard or truncated technique the normalised volume was consistently higher for low doses (<20Gy) using a truncated volume. The use of standard rectum or rectal wall outlining had no effect on the normalised volume receiving a dose below 40Gy but at higher doses rectal wall
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contouring generated consistantly higher values. This was most apparent at 50Gy with the dose being received by 21% of the volumed rectal wall compared to only 15% of whole rectum.
Conclusions: Patients report notable late GI toxicity following hypofractionated prostate radiotherapy. None of the contouring techniques used found a statistical correlation between toxicity and generated dose volumes. Contouring a truncated rectal volume may be used to reduce planning time without significantly affecting dosevolume values at high doses, suggested by some authors as the principle predictor of late toxicity. Low dose-volumes however are likely to be inaccurate if the rectum is not conventionally outlined. Using rectal wall outlining increases generated dose-volumes at high doses but was not found to have a statistical correlation with toxicity and would not, on these results, justify the extra planning time required. The analysis is of small numbers and may have missed subtle correlations. It shows that the contouring technique used does affect DVH values but not whether this has an effect on predicting late toxicity. Further study of contouring techniques, generated DVH values and toxicity is required. PO-0907 AN RBE MODEL FOR PROTONS: THE TISSUE SPECIFIC PARAMETER A/Þ OF PHOTONS IS A PREDICTOR FOR THE SENSITIVITY TO LET CHANGES M. Wedenberg1, B.K. Lind1, B. Hårdemark2 1 Karolinska Institutet, Oncology-Pathology, Stockholm, Sweden 2 RaySearch Laboratories, Sveavägen 25 11134, Stockholm, Sweden Purpose/Objective: The biological effects of particles are often expressed in relation to that of photons using the concept of relative biological effectiveness, RBE. The proton dose can be multiplied with the RBE to obtain a so called effective dose. In proton radiotherapy, a constant RBE of 1.1 is usually assumed. However, there is experimental evidence that RBE depends on the local energy spectrum, the dose, the cell or tissue type, and the endpoint. The use of a constant RBE has largely been due to the uncertainties in the experimentally obtained RBE values with seemingly non-systematic results between different beam setups and biological systems. In this study, we will investigate if more clear trends in the variation of RBE are revealed if accounting for cell type. The aim of this study is to develop a model to estimate RBE based on linear energy transfer (LET), dose, and cell or tissue type. Cell type is here represented by the tissue specific parameter α/β of the linear-quadratic model for the reference radiation. Moreover, the model should capture the basic features of the RBE using a minimum of assumptions, each supported by experimental data. Materials and Methods: The α and β parameters were studied with respect to their dependence on LET. An expression where the cell sensitivity to LET changes is linked to the αref/βref ratio was proposed so that RBE increases with increasing LET with a slope that decreases with increasing αref/βref. In order to study how RBE vary with LET and cell type, published in vitro clonogenic cell survival data where the LET and cell type are well-defined were chosen. The data selected for model evaluation include 10 cell lines with different αref/βref ratios irradiated with near mono-energetic proton beams giving in total 24 experimental data points. Results: A statistically significant relation between α for protons and LET was found (one-tailed p-value < 0.05). Moreover, the strength of that relation varied statistically significantly with the αref/βref (pvalue < 0.05). No statistically significant relation between β and LET was found. The resulting RBE model estimated experimental RBE values well (r=0.89). The RBE generally increased with decreasing αref/βref, increasing LET, and decreasing dose. Limited RBE variability was observed at high αref/βref. Our results indicate that
(chemo) radiotherapy and to compare the performance of this model with generally applied dose distribution parameters to predict RP, such as the mean lung dose (MLD) and the V20 of both lungs. Materials and Methods: The study population consisted of 269 NSCLC patients treated with 3D conformal radiation therapy (3D-CRT) alone, or in combination with chemotherapy in three institutions, treated with different fractionation schedules. The total dose ranged from 46 to 94.5 Gy, with fraction doses ranging from 1.5 Gy (b.i.d.) to 2.5 Gy. RP was scored using the SWOG-classification and the primary endpoint was defined as grade II-IV RP in the first 6 months after completion of radiotherapy. In the multivariate analysis, the following candidate predictive factors were included: sex, age, WHO performance, concurrent chemotherapy, T-stage and N-stage. To select the most predictive variables a multivariate logistic regression model with bootstrapping was used. Results: In order to judge possible collinearity between selected variables, and to facilitate the interpretation of the modelling results, we first produced a correlation matrix to identify variables that were strongly correlated (i.e., Spearmans’s correlation coefficient ³ 0.8) A strong correlation was found between most DVH parameters within each OAR. In the univariate analysis only a small proportion of the candidate variables was significantly associated with the endpoint. The average likelihood of bootstrap prediction in the multivariate logistic regression analysis was optimal with a model consisting of two variables: V40 of the ipsilateral lung, and age. Increasing the number of variables to three did not further improve the model. The AUC for this 2-variable model was 0.66 (95% CI: 0.58 – 0.74). A model based on the V40 of the ipsilateral lung and age was most predictive, with odds ratios of 1.03 (95% CI: 1.01-1.06) for each % increase in relative volume, and 1.04 (95% CI: 1.00-1.08), for each year increase in age. The AUC of a model based on the V20 of the ipsilateral lung was 0.61 (95% CI: 0.52-0.70). The AUC of a model based on the mean lung dose the AUC was 0.59 (95% CI: 0.51-0.68) Conclusions: A multivariate NTCP model based including the V40 of the ipsilateral lung and age is more predictive than a model based on the V20 or the mean lung dose, such as currently used in clinical practice. The results of this study show that the development of RP may not only be dependent on dose but also on age. PO-0906 HYPOFRACTIONATED PROSTATE RADIOTHERAPY AND RECTAL TOXICITY: DOES RECTAL OUTLINE MATTER? 1 2 3 1 A. McPartlin , E. Maile , G. Webster , J. Logue , J. Livsey1, T. Elliott1, J. Wylie1, N. Alam1, A. Choudhury1 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom 2Manchester University, Medical School, Manchester, United Kingdom 3 The Christie NHS Foundation Trust, Physics, Manchester, United Kingdom Purpose/Objective: Numerous authors have attempted to establish models to minimise rectal late effects following prostate radiotherapy, most using data from standard fractionation regimes with little agreement as to predictive dosimetric values. This study aimed to establish if there was a link, in patients treated with hypofractionated radiotherapy, between rectal dose-volumes and patient reported late rectal toxicity. It further investigated whether the method used to outline the rectal volume affected calculated dose-volumes. Materials and Methods: 70 of 122 patients treated with radical radiotherapy to the prostate (57Gy in 19 fractions) between 2004-09 completed a validated LENT/SOMA questionnaire. Rectal dose-volume histograms (DVH) were calculated for each patient using standard rectal and rectal wall contouring (ano-rectal to recto-sigmoid junction)and truncated volumes (0.5cm superior/inferior to the PTV, identified as xxx_edit). The data was analysed using Spearmans Rho rank test for associations between rectal toxicity ≥2 and volume receiving a dose up to 55Gy (in 5Gy increments). Results: A maximum score for late rectal-bowel toxicity of ≥2 was reported by 2/3 of patients. No significant correlation was found between this and the volume of rectum receiving any given dose of radiation using each outlining method (p>0.05 in all cases). Non statistically significant trends were identified using differing voluming techniques. Although the normalised volume receiving a high dose (>40Gy) was not significantly influenced by using a standard or truncated technique the normalised volume was consistently higher for low doses (<20Gy) using a truncated volume. The use of standard rectum or rectal wall outlining had no effect on the normalised volume receiving a dose below 40Gy but at higher doses rectal wall
S357
contouring generated consistantly higher values. This was most apparent at 50Gy with the dose being received by 21% of the volumed rectal wall compared to only 15% of whole rectum.
Conclusions: Patients report notable late GI toxicity following hypofractionated prostate radiotherapy. None of the contouring techniques used found a statistical correlation between toxicity and generated dose volumes. Contouring a truncated rectal volume may be used to reduce planning time without significantly affecting dosevolume values at high doses, suggested by some authors as the principle predictor of late toxicity. Low dose-volumes however are likely to be inaccurate if the rectum is not conventionally outlined. Using rectal wall outlining increases generated dose-volumes at high doses but was not found to have a statistical correlation with toxicity and would not, on these results, justify the extra planning time required. The analysis is of small numbers and may have missed subtle correlations. It shows that the contouring technique used does affect DVH values but not whether this has an effect on predicting late toxicity. Further study of contouring techniques, generated DVH values and toxicity is required. PO-0907 AN RBE MODEL FOR PROTONS: THE TISSUE SPECIFIC PARAMETER A/Þ OF PHOTONS IS A PREDICTOR FOR THE SENSITIVITY TO LET CHANGES M. Wedenberg1, B.K. Lind1, B. Hårdemark2 1 Karolinska Institutet, Oncology-Pathology, Stockholm, Sweden 2 RaySearch Laboratories, Sveavägen 25 11134, Stockholm, Sweden Purpose/Objective: The biological effects of particles are often expressed in relation to that of photons using the concept of relative biological effectiveness, RBE. The proton dose can be multiplied with the RBE to obtain a so called effective dose. In proton radiotherapy, a constant RBE of 1.1 is usually assumed. However, there is experimental evidence that RBE depends on the local energy spectrum, the dose, the cell or tissue type, and the endpoint. The use of a constant RBE has largely been due to the uncertainties in the experimentally obtained RBE values with seemingly non-systematic results between different beam setups and biological systems. In this study, we will investigate if more clear trends in the variation of RBE are revealed if accounting for cell type. The aim of this study is to develop a model to estimate RBE based on linear energy transfer (LET), dose, and cell or tissue type. Cell type is here represented by the tissue specific parameter α/β of the linear-quadratic model for the reference radiation. Moreover, the model should capture the basic features of the RBE using a minimum of assumptions, each supported by experimental data. Materials and Methods: The α and β parameters were studied with respect to their dependence on LET. An expression where the cell sensitivity to LET changes is linked to the αref/βref ratio was proposed so that RBE increases with increasing LET with a slope that decreases with increasing αref/βref. In order to study how RBE vary with LET and cell type, published in vitro clonogenic cell survival data where the LET and cell type are well-defined were chosen. The data selected for model evaluation include 10 cell lines with different αref/βref ratios irradiated with near mono-energetic proton beams giving in total 24 experimental data points. Results: A statistically significant relation between α for protons and LET was found (one-tailed p-value < 0.05). Moreover, the strength of that relation varied statistically significantly with the αref/βref (pvalue < 0.05). No statistically significant relation between β and LET was found. The resulting RBE model estimated experimental RBE values well (r=0.89). The RBE generally increased with decreasing αref/βref, increasing LET, and decreasing dose. Limited RBE variability was observed at high αref/βref. Our results indicate that