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A Serial-imaging Based 4D Dose Computation System for Prostate Implant Dosimetry
Proceedings of the 51st Annual ASTRO Meeting
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A Serial-imaging Based 4D Dose Computation System for Prostate Implant Dosimetry
Z. Chen, J. Deng, D. Carlson, K. Roberts, R. Decker, S. Rockwell, R. Nath Yale-New Haven Hospital, New Haven, CT Purpose/Objective(s): Accurate dosimetry for prostate seed implant has remained a challenge because of the inevitable occurrence of post-surgical prostate edema, which forces the tumor volume and seed locations to vary with time during the dose delivery. The purpose of this work is to develop a serial-imaging based 4D dose computation system for patient-specific implant dosimetry and for comprehensive validation of edema models. Materials/Methods: Post-implant CT scans, acquired at t = 2 hr, 1 day, 7 ± 1 days, 10 ± 2 days, 16 ± 4 days, 30 ± 4 days, and 42 ± 6 days after the seed implantation, were used to characterize the temporal evolution of prostate edema in three-dimensional space. CT acquisitions were performed in accordance to an in-house research protocol approved by the human investigation committee. Deformable image registration on each successive pair of CT scans was used to track the temporal movements of seed position and tumor sub-volume. The deformable image registration was performed using the non-rigid registration function of the BioImage Suite package. For t falls in between two CT scans, the location of a seed or a tumor sub-volume was reconstructed from its positions on the two CT images using linear interpolation. At t $ 42 days, seed locations and tumor volume were assumed stationary. Instantaneous dose rate produced by the implant at any given tumor sub-volume was calculated using the AAPM TG-43 pointsource dosimetry formalism. The total dose delivered to a given tumor sub-volume was obtained by integrating the dose rates using the tracked seed locations and tumor sub-volume over the entire treatment time. Results: The serial-imaging based dose computation system was implemented on a Pentium-4 dual processor desktop computer workstation with two functional modules: a position tracking and reconstruction module and a dose computation module. The performance of the position tracking module was validated by using a set of simulated serial CT images with known isotropic edema expansion and resolution. Visual examination of the tracked sources on patient CT images was performed to further validate the tracking module. Good but not perfect tracking was seen at seed locations with large partial volume effect. Non-exponential temporal evolution of prostate volume and mean inter-source distance were found in some patients up to t = 6 days post-implant. This non-exponential behavior was found to affect the calculated dose more for implants using short-lived radionuclide. Conclusions: A serial-imaging based 4D dose computation system has been developed which allows comprehensive study of the quantitative effects of prostate edema on implant dosimetry. It also provides a platform for comprehensive validation of the isotropic-exponential edema resolution model used previously by many investigators. Author Disclosure: Z. Chen, None; J. Deng, None; D. Carlson, None; K. Roberts, None; R. Decker, None; S. Rockwell, None; R. Nath, None.
2374
Tumor Repopulation during Radiation Therapy
Stage Dependency of Onset Time for Prostate Cancer
M. Gao1, Z. Huang2, N. A. Mayr2, J. Z. Wang2 1
Loyola University Medical Center, Maywood, IL, 2The Ohio State University, Columbus, OH
Purpose/Objective(s): Prostate cancer is a slowly growing tumor. However, once radiotherapy starts, accelerated repopulation may occur as suggested by many studies showing that tumor control probability (TCP) decreased with prolongation of the external-beam radiotherapy (EBRT) course. The onset time of prostate tumor repopulation is poorly understood, and is assumed to be independent of tumor stage. However, clinical observations indicate that the detrimental effect of tumor repopulation may be associated with tumor stage. The purpose of this study is to analyze published clinical data and evaluate the dependency of repopulation onset time on prostate cancer stage. Materials/Methods: We used data published by Perez et al. (Cancer J 2004; 10:349-56), who reported that treatment course protraction from # 7 weeks to . 9 weeks increased the pelvic failure rate significantly for low-risk patients (from 4% to 10% for T1c stage and from 5% to 35% for T2 stage), but not for high-risk patients (ranged from 25% to 32% for T3 stage). Similar findings were reported by D’Ambrosio et al. (IJROBP 2008; 72:1402-07). The extended Linear-Quadratic (LQ) model was adopted to analyze the clinical data. TCP was calculated by TCP = exp (-K$S) and S = exp (-a$D-b$D2/n +ln(2)/Td$(T-TK)), where T is total treatment time; Td is the effective clonogen doubling time; TKi and Ki (i = 1,2,3) are the onset time of accelerated repopulation and the number of tumor clonogens for stage T1c, T2 and T3 respectively. LQ parameters of a = 0.15 Gy-1 & a/b = 3.1 Gy were adopted from literature. The least c2 method was used to fit the clinical data and determine the doubling time and the onset time. Results: A fit with five free parameters (Td, TK, Ki), i.e. assuming constant onset time and doubling time for all stages, did not fit the data well (c2min=18). The data was better described by a LQ model with seven free parameters (Td, TKi, Ki), leaving only the doubling time Td as a constant for all stages (c2min=4). Best fit was achieved with Td = 12 days; TK1 = 30 days, TK2 = 35 days, TK3 = 69 days; K1= 3.1 105, K2 = 8.4 105, K3 = 5.7 106. Conclusions: Our results indicate that the onset time of prostate cancer repopulation is stage dependent and suggest that large advanced tumors may require higher radiation dose and longer time to improve blood/nutrient supply and to trigger accelerated repopulation. This provides a plausible explanation for the observation that tumor repopulation effects are not observed for high-stage tumors because repopulation would not start until after the completion of the EBRT course (10 weeks). More comprehensive analysis of available clinical data is needed to confirm our preliminary findings and whether they are applicable to other type of cancers. Such information will be very helpful for the biologically-based optimization of radiotherapy. Author Disclosure: M. Gao, None; Z. Huang, None; N.A. Mayr, None; J.Z. Wang, None.
2375
Multiple Frame 18F-Fluorocholine or 11C-Acetate PET/CT Compared with Multi-modality MRI in Prostate Cancer Patients after Curative RT without Evidence of Relapse
H. Vees1, F. Buchegger1, H. G. Khan2, M. Wissmeyer1, C. Steiner1, O. Ratib1, R. Miralbell1,3 1 University Hospital Geneva, Switzerland, 2Institute of Radiology Jean Violette, Geneva, Switzerland, 34Servei de Radio-oncologia, Instituto Oncolo´gico Teknon, Barcelona, Spain
Purpose/Objective(s): To investigate the value of MRI and PET studies with either 18F-Fluorocholine (FCH) or 11C-acetate in patients with long term low and stable PSA levels after curative radiotherapy (RT) for prostate cancer. We aimed to test the ability
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2373
A Serial-imaging Based 4D Dose Computation System for Prostate Implant Dosimetry
Z. Chen, J. Deng, D. Carlson, K. Roberts, R. Decker, S. Rockwell, R. Nath Yale-New Haven Hospital, New Haven, CT Purpose/Objective(s): Accurate dosimetry for prostate seed implant has remained a challenge because of the inevitable occurrence of post-surgical prostate edema, which forces the tumor volume and seed locations to vary with time during the dose delivery. The purpose of this work is to develop a serial-imaging based 4D dose computation system for patient-specific implant dosimetry and for comprehensive validation of edema models. Materials/Methods: Post-implant CT scans, acquired at t = 2 hr, 1 day, 7 ± 1 days, 10 ± 2 days, 16 ± 4 days, 30 ± 4 days, and 42 ± 6 days after the seed implantation, were used to characterize the temporal evolution of prostate edema in three-dimensional space. CT acquisitions were performed in accordance to an in-house research protocol approved by the human investigation committee. Deformable image registration on each successive pair of CT scans was used to track the temporal movements of seed position and tumor sub-volume. The deformable image registration was performed using the non-rigid registration function of the BioImage Suite package. For t falls in between two CT scans, the location of a seed or a tumor sub-volume was reconstructed from its positions on the two CT images using linear interpolation. At t $ 42 days, seed locations and tumor volume were assumed stationary. Instantaneous dose rate produced by the implant at any given tumor sub-volume was calculated using the AAPM TG-43 pointsource dosimetry formalism. The total dose delivered to a given tumor sub-volume was obtained by integrating the dose rates using the tracked seed locations and tumor sub-volume over the entire treatment time. Results: The serial-imaging based dose computation system was implemented on a Pentium-4 dual processor desktop computer workstation with two functional modules: a position tracking and reconstruction module and a dose computation module. The performance of the position tracking module was validated by using a set of simulated serial CT images with known isotropic edema expansion and resolution. Visual examination of the tracked sources on patient CT images was performed to further validate the tracking module. Good but not perfect tracking was seen at seed locations with large partial volume effect. Non-exponential temporal evolution of prostate volume and mean inter-source distance were found in some patients up to t = 6 days post-implant. This non-exponential behavior was found to affect the calculated dose more for implants using short-lived radionuclide. Conclusions: A serial-imaging based 4D dose computation system has been developed which allows comprehensive study of the quantitative effects of prostate edema on implant dosimetry. It also provides a platform for comprehensive validation of the isotropic-exponential edema resolution model used previously by many investigators. Author Disclosure: Z. Chen, None; J. Deng, None; D. Carlson, None; K. Roberts, None; R. Decker, None; S. Rockwell, None; R. Nath, None.
2374
Tumor Repopulation during Radiation Therapy
Stage Dependency of Onset Time for Prostate Cancer
M. Gao1, Z. Huang2, N. A. Mayr2, J. Z. Wang2 1
Loyola University Medical Center, Maywood, IL, 2The Ohio State University, Columbus, OH
Purpose/Objective(s): Prostate cancer is a slowly growing tumor. However, once radiotherapy starts, accelerated repopulation may occur as suggested by many studies showing that tumor control probability (TCP) decreased with prolongation of the external-beam radiotherapy (EBRT) course. The onset time of prostate tumor repopulation is poorly understood, and is assumed to be independent of tumor stage. However, clinical observations indicate that the detrimental effect of tumor repopulation may be associated with tumor stage. The purpose of this study is to analyze published clinical data and evaluate the dependency of repopulation onset time on prostate cancer stage. Materials/Methods: We used data published by Perez et al. (Cancer J 2004; 10:349-56), who reported that treatment course protraction from # 7 weeks to . 9 weeks increased the pelvic failure rate significantly for low-risk patients (from 4% to 10% for T1c stage and from 5% to 35% for T2 stage), but not for high-risk patients (ranged from 25% to 32% for T3 stage). Similar findings were reported by D’Ambrosio et al. (IJROBP 2008; 72:1402-07). The extended Linear-Quadratic (LQ) model was adopted to analyze the clinical data. TCP was calculated by TCP = exp (-K$S) and S = exp (-a$D-b$D2/n +ln(2)/Td$(T-TK)), where T is total treatment time; Td is the effective clonogen doubling time; TKi and Ki (i = 1,2,3) are the onset time of accelerated repopulation and the number of tumor clonogens for stage T1c, T2 and T3 respectively. LQ parameters of a = 0.15 Gy-1 & a/b = 3.1 Gy were adopted from literature. The least c2 method was used to fit the clinical data and determine the doubling time and the onset time. Results: A fit with five free parameters (Td, TK, Ki), i.e. assuming constant onset time and doubling time for all stages, did not fit the data well (c2min=18). The data was better described by a LQ model with seven free parameters (Td, TKi, Ki), leaving only the doubling time Td as a constant for all stages (c2min=4). Best fit was achieved with Td = 12 days; TK1 = 30 days, TK2 = 35 days, TK3 = 69 days; K1= 3.1 105, K2 = 8.4 105, K3 = 5.7 106. Conclusions: Our results indicate that the onset time of prostate cancer repopulation is stage dependent and suggest that large advanced tumors may require higher radiation dose and longer time to improve blood/nutrient supply and to trigger accelerated repopulation. This provides a plausible explanation for the observation that tumor repopulation effects are not observed for high-stage tumors because repopulation would not start until after the completion of the EBRT course (10 weeks). More comprehensive analysis of available clinical data is needed to confirm our preliminary findings and whether they are applicable to other type of cancers. Such information will be very helpful for the biologically-based optimization of radiotherapy. Author Disclosure: M. Gao, None; Z. Huang, None; N.A. Mayr, None; J.Z. Wang, None.
2375
Multiple Frame 18F-Fluorocholine or 11C-Acetate PET/CT Compared with Multi-modality MRI in Prostate Cancer Patients after Curative RT without Evidence of Relapse
H. Vees1, F. Buchegger1, H. G. Khan2, M. Wissmeyer1, C. Steiner1, O. Ratib1, R. Miralbell1,3 1 University Hospital Geneva, Switzerland, 2Institute of Radiology Jean Violette, Geneva, Switzerland, 34Servei de Radio-oncologia, Instituto Oncolo´gico Teknon, Barcelona, Spain
Purpose/Objective(s): To investigate the value of MRI and PET studies with either 18F-Fluorocholine (FCH) or 11C-acetate in patients with long term low and stable PSA levels after curative radiotherapy (RT) for prostate cancer. We aimed to test the ability
S349