the impact of bed correction on application of the lyman ntcp model

1
Henry Ford Hospital, Detroit, MI Purpose/Objective(s): We report on a retrospective evaluation of 4D-CT images and plans for 7 patients with pancreatic cancer. The aims of this study are to analyze the extent of intrafraction motion of the pancreas, and to evaluate the dosimetric consequences of motion on the planned doses to the target and healthy tissues. Materials/Methods: The 4DCTs were acquired and sorted to generate respiratory correlated datasets at multiple phases of the breathing cycle. An internal target volume (ITV) was derived from a composite union of the GTvs. on each of the datasets. The PTV was formed by a 3 mm uniform expansion of the ITV except in the vicinity of adjacent normal organs, where no margin was used. Optimization was performed on the free-breathing (FB) scan and doses were mapped onto each phase. A weighted com- posite plan containing doses for all breathing phases was created and mapped onto the FB CT scan. Individual phase doses were weighted according to the 60%-10%-20%-10% ratio for Exh-Mid-Inh-Inh-Mid-Exh 1 . Also, a conventional, non-4D plan was designed on the exhale phase using a uniform 1 cm GTV-to-PTV expansion. The dose prescription was typically 30 or 35 Gy delivered in 5 IMRT fractions. Results: Excursion of the pancreas center of mass (COM) was 0.48 ± 0.27 cm (m ± s) with the mean ranging between 0.2 and 0.93 cm. Deformation effects were found to be clearly evident resulting in some regions of the tumor moving more than the COM. For one patient the inferior aspect of the tumor moved 1.2 cm in SI direction while the COM moved 0.93 cm. Analysis of doses to the target indicated that a 1 cm margin expansion of the GTV-to-CTV in the FB-based, non-4D plan, resulted in approximately equiv- alent coverage relative to the composite 4D plan. However, significant volume and dose differences were sometimes observed be- tween the FB-based and 4D plans for the organs at risk. Concerning volume differences, the volume of the liver on the FB scan was anywhere from 7 to 14% lower than on the phase-specific CT images. This resulted in up to 20% higher max. doses to liver as compared to the original FB-based plan, when the plan was mapped onto phase-specific images. Mean liver doses were also under- estimated when on the FB scan by, on average, 25% vs. the composite 4D plan. Relative to plans on the exhale phase, the mean liver dose was up to 28% greater than that in the composite 4D plan (averaged over all phases) suggesting that the exhale plan provides a worst case estimate of liver dose. Conclusions: Analysis of 4DCTs of patients with pancreatic cancer treated with SBRT showed significant intrafraction motion and deformation effects. A non-4D, FB-based plan using a 1 cm PTV margin achieved adequate target dose coverage relative to a com- posite 4D plan. Significant dose differences to surrounding healthy tissues were observed. 1. Lujan et al.: Medical Physics, 26,1999 Author Disclosure: A.K. Reding, None; M. Haley, None; M. Ajlouni, None; I. Chetty, None; T. Nurushev, None. 3129 The Impact of BED Correction on Application of the Lyman NTCP Model B. J. Warkentin 1 , 2 1 Alberta Health Services, Edmonton, AB, Canada, 2 Universtiy of Alberta, Edmonton, AB, Canada Purpose/Objective(s): There has been increasing effort to establish quantitative metrics to characterize the dose-volume response of normal tissues. The Lyman NTCP model has been used to fit a growing number of clinical data sets in recent years. However, large uncertainties remain as to appropriate parameter values for a given normal tissue. Since dose to normal tissues is highly het- erogeneous, one confounding but little-appreciated issue is whether or not, and if so how, to correct dose-volume histograms (DVHs) for biological equivalence. The purpose of this study is to explore the potential significance of such corrections to Lyman model fits. Materials/Methods: The Lyman model describes a dose-response curve as the cumulative normal distribution of the equivalent uniform dose (EUD) with respect to a mean dose D 50 and a SD of m*D 50 . In addition to the position (D 50 ) and slope (m) parameters, a third parameter n describes the tissue-specific dose-volume relationship used in the calculation of the EUD from a differential DVH. In some analyses, DVH doses are first converted bin-by-bin into biologically equivalent doses (BEDs), and in others not. A third option is to modify the dose-volume information by applying a global BED correction based on the prescription dose alone. To test the impact of the type of BED correction, a dose-response data set was fit using the Lyman model and each of these three correction methods (none, global, bin-by-bin). The data was based on a rectal complication study published by Sohn (2007). Since the actual DVH data was not available, hypothetical DVH curves were created that matched the five EUD dose levels in this work. Results: Preliminary fits of the Lyman model to this data set gave parameter values for n, m, and D 50 (Gy) respectively of: 0.044, 0.10, 81.9 without correction; 0.041, 0.10, 80.1 with a global correction; and 5.77, 0.14, 56.2 with a bin-by-bin correction. Thus, in comparison to no correction, a global correction results in a small decrease in D 50 and negligible change to the other parameters. In contrast, a bin-by-bin BED correction substantially decreases D 50 , and significantly alters the value of n. Unlike the other two fits, which suggest a serial response, the implication of this latter result from the bin-by-bin corrected fit is that the rectal response is more closely related to the mean dose, typical of a parallel structure. Conclusions: This fitting exercise suggests that correction of a DVH for biological equivalence can impact the interpretation of Lyman NTCP model fits to clinical data. Such corrections would be even more important for analysis of hypofractionated data. It is critical that the application of model parameters used to predict NTCP is consistent with the DVH correction method performed in the original fits. Author Disclosure: B.J. Warkentin, None. 3130 Application of Multiple Radiobiological Models in Predicting TCP B. Zhao 1 , M. C. Joiner 1 , J. Burmeister 2,1 1 Wayne State University School of Medicine, Detroit, MI, 2 Department of Radiation Oncology, Karmanos Cancer Center, Detroit, MI Proceedings of the 52nd Annual ASTRO Meeting S709

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Page 1: The Impact of BED Correction on Application of the Lyman NTCP Model

Proceedings of the 52nd Annual ASTRO Meeting S709

Henry Ford Hospital, Detroit, MI

Purpose/Objective(s): We report on a retrospective evaluation of 4D-CT images and plans for 7 patients with pancreatic cancer.The aims of this study are to analyze the extent of intrafraction motion of the pancreas, and to evaluate the dosimetric consequencesof motion on the planned doses to the target and healthy tissues.

Materials/Methods: The 4DCTs were acquired and sorted to generate respiratory correlated datasets at multiple phases of thebreathing cycle. An internal target volume (ITV) was derived from a composite union of the GTvs. on each of the datasets.The PTV was formed by a 3 mm uniform expansion of the ITV except in the vicinity of adjacent normal organs, where no marginwas used. Optimization was performed on the free-breathing (FB) scan and doses were mapped onto each phase. A weighted com-posite plan containing doses for all breathing phases was created and mapped onto the FB CT scan. Individual phase doses wereweighted according to the 60%-10%-20%-10% ratio for Exh-Mid-Inh-Inh-Mid-Exh1. Also, a conventional, non-4D plan wasdesigned on the exhale phase using a uniform 1 cm GTV-to-PTV expansion. The dose prescription was typically 30 or 35 Gydelivered in 5 IMRT fractions.

Results: Excursion of the pancreas center of mass (COM) was 0.48 ± 0.27 cm (m ± s) with the mean ranging between 0.2 and 0.93cm. Deformation effects were found to be clearly evident resulting in some regions of the tumor moving more than the COM. Forone patient the inferior aspect of the tumor moved 1.2 cm in SI direction while the COM moved 0.93 cm. Analysis of doses to thetarget indicated that a 1 cm margin expansion of the GTV-to-CTV in the FB-based, non-4D plan, resulted in approximately equiv-alent coverage relative to the composite 4D plan. However, significant volume and dose differences were sometimes observed be-tween the FB-based and 4D plans for the organs at risk. Concerning volume differences, the volume of the liver on the FB scan wasanywhere from 7 to 14% lower than on the phase-specific CT images. This resulted in up to 20% higher max. doses to liver ascompared to the original FB-based plan, when the plan was mapped onto phase-specific images. Mean liver doses were also under-estimated when on the FB scan by, on average, 25% vs. the composite 4D plan. Relative to plans on the exhale phase, the mean liverdose was up to 28% greater than that in the composite 4D plan (averaged over all phases) suggesting that the exhale plan providesa worst case estimate of liver dose.

Conclusions: Analysis of 4DCTs of patients with pancreatic cancer treated with SBRT showed significant intrafraction motion anddeformation effects. A non-4D, FB-based plan using a 1 cm PTV margin achieved adequate target dose coverage relative to a com-posite 4D plan. Significant dose differences to surrounding healthy tissues were observed.1. Lujan et al.: Medical Physics, 26,1999

Author Disclosure: A.K. Reding, None; M. Haley, None; M. Ajlouni, None; I. Chetty, None; T. Nurushev, None.

3129 The Impact of BED Correction on Application of the Lyman NTCP Model

B. J. Warkentin1,2

1Alberta Health Services, Edmonton, AB, Canada, 2Universtiy of Alberta, Edmonton, AB, Canada

Purpose/Objective(s): There has been increasing effort to establish quantitative metrics to characterize the dose-volume responseof normal tissues. The Lyman NTCP model has been used to fit a growing number of clinical data sets in recent years. However,large uncertainties remain as to appropriate parameter values for a given normal tissue. Since dose to normal tissues is highly het-erogeneous, one confounding but little-appreciated issue is whether or not, and if so how, to correct dose-volume histograms(DVHs) for biological equivalence. The purpose of this study is to explore the potential significance of such corrections to Lymanmodel fits.

Materials/Methods: The Lyman model describes a dose-response curve as the cumulative normal distribution of the equivalentuniform dose (EUD) with respect to a mean dose D50 and a SD of m*D50. In addition to the position (D50) and slope (m) parameters,a third parameter n describes the tissue-specific dose-volume relationship used in the calculation of the EUD from a differentialDVH. In some analyses, DVH doses are first converted bin-by-bin into biologically equivalent doses (BEDs), and in othersnot. A third option is to modify the dose-volume information by applying a global BED correction based on the prescriptiondose alone. To test the impact of the type of BED correction, a dose-response data set was fit using the Lyman model and eachof these three correction methods (none, global, bin-by-bin). The data was based on a rectal complication study published bySohn (2007). Since the actual DVH data was not available, hypothetical DVH curves were created that matched the five EUDdose levels in this work.

Results: Preliminary fits of the Lyman model to this data set gave parameter values for n, m, and D50 (Gy) respectively of: 0.044,0.10, 81.9 without correction; 0.041, 0.10, 80.1 with a global correction; and 5.77, 0.14, 56.2 with a bin-by-bin correction. Thus, incomparison to no correction, a global correction results in a small decrease in D50 and negligible change to the other parameters. Incontrast, a bin-by-bin BED correction substantially decreases D50, and significantly alters the value of n. Unlike the other two fits,which suggest a serial response, the implication of this latter result from the bin-by-bin corrected fit is that the rectal response ismore closely related to the mean dose, typical of a parallel structure.

Conclusions: This fitting exercise suggests that correction of a DVH for biological equivalence can impact the interpretation ofLyman NTCP model fits to clinical data. Such corrections would be even more important for analysis of hypofractionated data.It is critical that the application of model parameters used to predict NTCP is consistent with the DVH correction method performedin the original fits.

Author Disclosure: B.J. Warkentin, None.

3130 Application of Multiple Radiobiological Models in Predicting TCP

B. Zhao1, M. C. Joiner1, J. Burmeister2,1

1Wayne State University School of Medicine, Detroit, MI, 2Department of Radiation Oncology, Karmanos Cancer Center,Detroit, MI