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Simplifying planning and delivery of IMRT using direct aperture optimization
S178
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
approaches are not currently practical for clinical use. In contrast, prenyltransferase inhibitors, which represent an alternative approach to inhibiting Ras, are in clinical trials. In this study, we assessed the ability of the prenyltransferase inhibitor L-778,123 as well as the novel prenyltransferase inhibitor AZD3409 to radiosensitize a panel of oncogenic K-ras expressing human pancreatic cancer cell lines. Both compounds promoted radiosensitization of ASPC-1, Capan-1, MiaPaCa-2, Panc-1 and PSN-1 cell lines, with dose modifying effects ranging from 1.3–1.5 at 2 Gy. Neither compound radiosensitized the wild-type K-ras expressing BxPC-3 and Hs 766T cell lines. Finally, we have found that L778,123 radiosensitizes xenografts of ASPC-1 and PSN-1 in mice. These experiments reveal that L778,123 is able to radiosensitize oncogenic K-ras expressing pancreatic tumors in vivo. Conclusions: Activated K-Ras signaling promotes decreased radiosensitivity in pancreatic cells. Prenylatransferase inhibitors radiosensitize oncogenic K-ras expressing pancreatic carcinoma cell lines both in vitro and in vivo. This preclinical study suggests that oncogenic K-Ras is an important cellular target for prenyltransferase inhibitor mediated radiosensitization in pancreatic cancer cells and that the use of prenyltransferase inhibitors in combination with radiation may represent a promising approach to treatment of pancreatic carcinoma.
80
Simplifying Planning and Delivery of IMRT Using Direct Aperture Optimization
D. M. Shepard, Z. Jiang, M. Earl, C. Yu Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD Purpose/Objective: The purpose of this study is to examine the extent to which IMRT planning and delivery can be simplified through the use of Direct Aperture Optimization (DAO). The key feature of DAO is that it optimizes the segment shapes and weights directly rather than optimizing the intensity patterns. All of the constraints imposed by the multileaf collimator are directly incorporated into the IMRT optimization. DAO allows the user to specify the number of apertures per beam angle in the prescription. The DAO algorithm is then able to find the optimal treatment plan for that number of apertures. The user is thus provided with control of the complexity of the plan delivery. Materials/Methods: Prior to clinical implementation, the DAO algorithm was benchmarked through a systematic study of the degree to which IMRT treatment plans can be simplified (using a small number of apertures) without sacrificing the dosimetric quality of the plans. For three patient cases, IMRT plans were first generated with two commercial inverse planning systems (Pinnacle and CORVUS). A series of optimizations were then performed with DAO. Each optimization used identical beam angles and optimization constraints. The only variable that was changed from one optimization to the next was the number of apertures per beam direction. The optimized treatment plans were analyzed through comparisons of the resulting objective function values and the corresponding DVHs. Thereby we obtain 1) the minimum number of apertures required by DAO to produce a plan with comparable dose conformity with beamlet-based treatment planning systems; and 2) the asymptotic limits of the number of apertures required for different sites when using DAO. After the benchmarking was complete, DAO was implemented clinically at the University of Maryland School of Medicine using the Prowess treatment planning system. Initial treatment sites include head-and-neck, prostate, and pancreas. For each patient, the pencil beam and final dose calculation are performed using a convolution/superposition based dose engine, and the treatments are delivered on an Elekta SL20 linear accelerators. Results: The results indicate that the required number of apertures per beam direction is dependant upon the complexity of the case. For simple cases with a convex tumor volume and a separation between the tumor and the organs at risk, there is little improvement in the objective function and the corresponding DVHs beyond three apertures per beam direction. However, for large and complex tumor volumes, the objective function and its DVHs are converge more slowly as the number of apertures is increased. This is particularly true if the target is concave in nature or if the treatment seeks to simultaneously treat multiple target volumes. For these most complex cases, it has been observed that nine or more apertures per beam angle are often necessary to achieve an IMRT treatment plan of the highest quality. Overall, the benchmarking study revealed that for the majority of IMRT patient cases, there is little dosimetric gain in increasing the number of apertures per beam angle beyond six. In comparison with beamlet-based inverse planning systems, the number of segments was reduced between 50 and 90 percent. Initial clinical results are consistent with the benchmarking studies. For all cases, between 21 and 45 apertures have been used for the optimized treatment plan. This allows the patients to be treated in a traditional fifteen minute time slot. Consequently, there are few if any negative consequences in terms of patient throughput as compared with 3D conformal treatments. Conclusions: Pre-clinical benchmark studies along with clinical patient deliveries at the University of Maryland have demonstrated that Direct Aperture Optimization produces highly conformal IMRT treatment plans comparable to beamlet-based IMRT while using a small number of apertures per beam angle. DAO addresses many of the issues associated with the increased complexity of IMRT treatment plans including reduced patient throughput, increased staffing requirements, and additional wear-and-tear on treatment machines.
81
The Relationship Between Parotid Gland-PTV Overlap and the Ability to Achieve Dosimetric Sparing of the Parotid Using Intensity Modulated Radiation Therapy
M. Hunt,1 A. Jackson,1 A. Narayana,2 N. Lee2 1 Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, 2Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY Purpose/Objective: To determine the relationship between the volume of the parotid gland, the volume of parotid-PTV overlap, PTV coverage and dosimetric sparing of the parotid gland when using intensity modulated (IMRT) dose-painting techniques. Materials/Methods: Data were collected retrospectively for 20 patients treated with 7–9 field IMRT for whom dosimetric sparing of the parotid (mean dose ⱕ26 Gy) was attempted in at least one gland. All patients were treated using “dose-painting” techniques (simultaneous boost), delivering doses of either 54 or 59.4 Gy to sub-clinical disease and 70 Gy to gross disease.
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
approaches are not currently practical for clinical use. In contrast, prenyltransferase inhibitors, which represent an alternative approach to inhibiting Ras, are in clinical trials. In this study, we assessed the ability of the prenyltransferase inhibitor L-778,123 as well as the novel prenyltransferase inhibitor AZD3409 to radiosensitize a panel of oncogenic K-ras expressing human pancreatic cancer cell lines. Both compounds promoted radiosensitization of ASPC-1, Capan-1, MiaPaCa-2, Panc-1 and PSN-1 cell lines, with dose modifying effects ranging from 1.3–1.5 at 2 Gy. Neither compound radiosensitized the wild-type K-ras expressing BxPC-3 and Hs 766T cell lines. Finally, we have found that L778,123 radiosensitizes xenografts of ASPC-1 and PSN-1 in mice. These experiments reveal that L778,123 is able to radiosensitize oncogenic K-ras expressing pancreatic tumors in vivo. Conclusions: Activated K-Ras signaling promotes decreased radiosensitivity in pancreatic cells. Prenylatransferase inhibitors radiosensitize oncogenic K-ras expressing pancreatic carcinoma cell lines both in vitro and in vivo. This preclinical study suggests that oncogenic K-Ras is an important cellular target for prenyltransferase inhibitor mediated radiosensitization in pancreatic cancer cells and that the use of prenyltransferase inhibitors in combination with radiation may represent a promising approach to treatment of pancreatic carcinoma.
80
Simplifying Planning and Delivery of IMRT Using Direct Aperture Optimization
D. M. Shepard, Z. Jiang, M. Earl, C. Yu Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD Purpose/Objective: The purpose of this study is to examine the extent to which IMRT planning and delivery can be simplified through the use of Direct Aperture Optimization (DAO). The key feature of DAO is that it optimizes the segment shapes and weights directly rather than optimizing the intensity patterns. All of the constraints imposed by the multileaf collimator are directly incorporated into the IMRT optimization. DAO allows the user to specify the number of apertures per beam angle in the prescription. The DAO algorithm is then able to find the optimal treatment plan for that number of apertures. The user is thus provided with control of the complexity of the plan delivery. Materials/Methods: Prior to clinical implementation, the DAO algorithm was benchmarked through a systematic study of the degree to which IMRT treatment plans can be simplified (using a small number of apertures) without sacrificing the dosimetric quality of the plans. For three patient cases, IMRT plans were first generated with two commercial inverse planning systems (Pinnacle and CORVUS). A series of optimizations were then performed with DAO. Each optimization used identical beam angles and optimization constraints. The only variable that was changed from one optimization to the next was the number of apertures per beam direction. The optimized treatment plans were analyzed through comparisons of the resulting objective function values and the corresponding DVHs. Thereby we obtain 1) the minimum number of apertures required by DAO to produce a plan with comparable dose conformity with beamlet-based treatment planning systems; and 2) the asymptotic limits of the number of apertures required for different sites when using DAO. After the benchmarking was complete, DAO was implemented clinically at the University of Maryland School of Medicine using the Prowess treatment planning system. Initial treatment sites include head-and-neck, prostate, and pancreas. For each patient, the pencil beam and final dose calculation are performed using a convolution/superposition based dose engine, and the treatments are delivered on an Elekta SL20 linear accelerators. Results: The results indicate that the required number of apertures per beam direction is dependant upon the complexity of the case. For simple cases with a convex tumor volume and a separation between the tumor and the organs at risk, there is little improvement in the objective function and the corresponding DVHs beyond three apertures per beam direction. However, for large and complex tumor volumes, the objective function and its DVHs are converge more slowly as the number of apertures is increased. This is particularly true if the target is concave in nature or if the treatment seeks to simultaneously treat multiple target volumes. For these most complex cases, it has been observed that nine or more apertures per beam angle are often necessary to achieve an IMRT treatment plan of the highest quality. Overall, the benchmarking study revealed that for the majority of IMRT patient cases, there is little dosimetric gain in increasing the number of apertures per beam angle beyond six. In comparison with beamlet-based inverse planning systems, the number of segments was reduced between 50 and 90 percent. Initial clinical results are consistent with the benchmarking studies. For all cases, between 21 and 45 apertures have been used for the optimized treatment plan. This allows the patients to be treated in a traditional fifteen minute time slot. Consequently, there are few if any negative consequences in terms of patient throughput as compared with 3D conformal treatments. Conclusions: Pre-clinical benchmark studies along with clinical patient deliveries at the University of Maryland have demonstrated that Direct Aperture Optimization produces highly conformal IMRT treatment plans comparable to beamlet-based IMRT while using a small number of apertures per beam angle. DAO addresses many of the issues associated with the increased complexity of IMRT treatment plans including reduced patient throughput, increased staffing requirements, and additional wear-and-tear on treatment machines.
81
The Relationship Between Parotid Gland-PTV Overlap and the Ability to Achieve Dosimetric Sparing of the Parotid Using Intensity Modulated Radiation Therapy
M. Hunt,1 A. Jackson,1 A. Narayana,2 N. Lee2 1 Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, 2Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY Purpose/Objective: To determine the relationship between the volume of the parotid gland, the volume of parotid-PTV overlap, PTV coverage and dosimetric sparing of the parotid gland when using intensity modulated (IMRT) dose-painting techniques. Materials/Methods: Data were collected retrospectively for 20 patients treated with 7–9 field IMRT for whom dosimetric sparing of the parotid (mean dose ⱕ26 Gy) was attempted in at least one gland. All patients were treated using “dose-painting” techniques (simultaneous boost), delivering doses of either 54 or 59.4 Gy to sub-clinical disease and 70 Gy to gross disease.