Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy c... more Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.
Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications, 2001
An inverse treatment planning system based on fast Monte Carlo (MC) dose calculation is presented... more An inverse treatment planning system based on fast Monte Carlo (MC) dose calculation is presented. It allows optimisation of intensity modulated dose distributions in 15 to 60 minutes on present day personal computers. If a multi-processor machine is available, parallel simulation of particle histories is also possible, leading to further calculation time reductions. The optimisation process is divided into two stages. The first stage results in fluence profiles based on pencil beam (PB) dose calculation. The second stage starts with MC verification and post-optimisation of the PB dose and fluence distributions.
In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combin... more In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.
In this study the effects of small systematic MLC misalignments and gravitational errors on the q... more In this study the effects of small systematic MLC misalignments and gravitational errors on the quality of Rapidarc treatment plan delivery are investigated with respect to verification measurements with two detector arrays and the evaluation of clinical significance of the error-induced deviations. Five prostate and six head and neck plans were modified by means of three error types: (1) both MLC banks are opened, respectively, in opposing directions, resulting in larger fields; (2) both MLC banks are closed, resulting in smaller fields; and (3) both MLC banks are shifted for lateral gantry angles, respectively, in the same direction to simulate the effects of gravity on the leaves. Measurements were evaluated with respect to a gamma-index of 3%/3 mm and 2%/2 mm. Dose in the modified plans was recalculated and the resulting dose volume histograms for target and critical structures were compared to those of the unaltered plans. The smallest introduced leaf position deviations which ...
A model for the simulation of the accelerator heads of two identical linear accelerators was desi... more A model for the simulation of the accelerator heads of two identical linear accelerators was designed at the University Hospital of Tübingen, using the BEAM program developed at the National Research Council of Canada. Both linear accelerators are equipped with multileaf collimators (MLCs) and backup jaws (y-direction) with curved leaf-ends. The accelerator models were divided into two parts. The first part consisted of target, primary collimator, flattening filter, monitor chamber, and mirror. After the Monte Carlo simulation of these parts, the phase-space characteristics below the mirror were stored in a file and used as source for the second part of the accelerator head (jaw, MLC). The electron source was assumed to deliver a gaussian energy spectrum, with parallel direction to the beam axis. With this electron source, there was good agreement between the measured and simulated depth dose curves in water, with difference < 2%. A new module was created for the BEAM program to ...
ABSTRACT A model for the simulation of the accelerator heads of two identical linear accelerators... more ABSTRACT A model for the simulation of the accelerator heads of two identical linear accelerators was designed at the University Hospital of Tübingen, using the BEAM program developed at the National Research Council of Canada. Both linear accelerators are equipped with multileaf collimators (MLCs) and backup jaws (y-direction) with curved leaf-ends. The accelerator models were divided into two parts. The first part consisted of target, primary collimator, flattening filter, monitor chamber, and mirror. After the Monte Carlo simulation of these parts, the phase-space characteristics below the mirror were stored in a file and used as source for the second part of the accelerator head (jaw, MLC). The electron source was assumed to deliver a gaussian energy spectrum, with parallel direction to the beam axis. With this electron source, there was good agreement between the measured and simulated depth dose curves in water, with difference &lt; 2%. A new module was created for the BEAM program to simulate backup jaws, while the standard MLCQ module from BEAM was used to simulate a MLC with curved leaf-ends. As a result, MLCs and backup jaws with curved leaf-ends make the shoulder of the y-profile higher than the straight-end MLCs.
Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyos... more Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. The alveolar subtype harbors a translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor prognosis. However, tumor cells have heterogeneous expression for the fusion gene. Using a conditional genetic mouse model as well as human tumor cell lines, we show that that Pax3:Foxo1a expression is enriched in G 2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes tumor cells to clinicallyestablished chemotherapy agents and emerging molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells.
ABSTRACT Purpose: In recent events, our clinic has experienced a soft x‐ray ion chamber calibrati... more ABSTRACT Purpose: In recent events, our clinic has experienced a soft x‐ray ion chamber calibration drift of 8%. For the INTRABEAMTM system which relies on an ion chamber measurement to deduce a dose rate correction factor for treatment, such an ion chamber change results in a large deviation between the planned patient dose and the treatment dose. We present a cross calibration method between an ion chamber and commercially available optically stimulated luminescent dosimeters (OSLDs) to monitor the consistency of the soft x‐ray ion chamber. Methods: Our method uses the INTRABEAM™ system dose rate determined by a PTW soft x‐ray ion chamber (model 23342) under normal quality assurance procedures to produce the counts per dose rate for irradiated nanoDot™ OSLDs. The procedure replaces the ion chamber with an OSLD at the same position which is obtained with a fabricated stage of the same dimension as the ion chamber stage. Upon replacement of the ion chamber, the QA procedure is repeated irradiating a nanoDot™ OSLD for approximately two minutes with low energy kV x‐rays of energy 20 keV with 0.64 mm Al HVL. The QA procedure is repeated three times with a new OSLD for each irradiation. A ten minute waiting period is invoked prior to reading each nanoDot™ OSLD a total of three times. Results: This method produces an average counts per dose rate for all nanoDot™ OSLDs with a 1‐sigma standard deviation of 1.7%. The low standard deviation gives this method the ability to detect an ion chamber measurement change in dose rate greater than 3.5% incorporating the positional uncertainty and sensitivity change. Conclusion: In the advent of complete equipment failure, a system can degrade and report erroneous measurements. Our quick secondary check for equipment drift provides a necessary tool to ensure patient safety.
Implants with high atomic numbers produce star-like artifacts in CT-images. When coupled in pairs... more Implants with high atomic numbers produce star-like artifacts in CT-images. When coupled in pairs, a black window appears in between. The Philips OMAR algorithm approaches these artifacts by post processing the images. In this study, measurements were performed with radiochromic EBT2 films 1 in order to verify, whether the OMAR algorithm contributes to the accuracy of treatment plans in implant regions.
ABSTRACT Purpose: The consistency between the AAA and XVMC algorithm in the treatment planning fo... more ABSTRACT Purpose: The consistency between the AAA and XVMC algorithm in the treatment planning for RapidArc is investigated. While the majority of the radiation field is blocked by the MLC system, multiple small dose islands with MLC opened only slightly can be observed in one control point. This raises questions on how accurate the clinically used AAA algorithm in Eclipse is able to calculate RapidArc dose distributions. The fast Monte Carlo Code XVMC was used as a benchmark to test the AAA algorithm. Methods: RadpidArc plans of 25 patients were calculated with AAA and XVMC. The patient cohort consisted of 4 different cancer sites (H&amp;N, upper abdominal, lung, prostate). Dose distributions, PTV and OAR coverage were compared looking at the PTV mean dose Dmean, the volume V95% of the PTV receiving 95% of the prescribed dose, the dose D95% delivered to 95% of the PTV Volume, the percentage PTV mean dose with respect to the prescribed dose Dmean/prescr and OAR mean dose. Results: The recalculation of RapidArc plans yielded good agreement of both calculation algorithms for treatment plans of all four cancer sites. PTV mean dose differences of AAA and XVMC were found to be in between -0.11% and 4.89% of the prescribed dose. The mean dose difference found was 0.48±0.77 Gy. Local dose differences were found when comparing dose distributions in regions of big mass density differences and in high dose regions. One head and neck plan and one prostate plan revealed significant differences in PTV coverage (ΔDmean=3.25 Gy) and OAR mean dose (prostate mean dose -13.71 Gy) respectively. Conclusions: The vast majority of treatment plans calculated with the AAA algorithm were found to agree within the expected and acceptable tolerances compared to XVMC results. Nevertheless in some cases dose differences were observed that could be of clinical significance. This work was funded by a Varian grant. Wolfram Laub is working in the physics group of CMS.
ABSTRACT Purpose: To quantitatively evaluate effects of image artifacts of hip prostheses on the ... more ABSTRACT Purpose: To quantitatively evaluate effects of image artifacts of hip prostheses on the accuracy of structure delineation and tissue density calculation on kV and MV CT images. Methods: Five hip prostheses made of stainless steel, titanium and cobalt chrome alloys were positioned inside a water tank and scanned respectively on a Philips CT and a Tomotherapy Hi-Art unit. Prostheses were positioned to mimic single and bilateral implantations. Rods of tissue materials of lung, water and bone were placed at locations next and distal to metal implants near femoral head, neck and stem of prostheses. kV and MV CT scans were repeated for each placement. On CT images, cross-sectional outlines of metal implants and tissue rods were delineated. Densities of rod materials were determined and compared to the true values. Results: Metal artifacts were severe on kV CTs and minimal on MV CTs. Cross-sectional outlines of metal implants and tissue rods on kV CTs were severely distorted by artifacts while those on MV CTs remained clearly identifiable. For kV CTs, deviations of measured tissue density from true value were up to 51.3%, 30.6% and 40.9% respectively for lung, bone and solid water. The magnitude of deviation was generally larger at locations closer to metal implants and greater with bilateral implants than single implant. For MV CTs, deviations of measured density from true value were less than 6% for all three tissue materials either with single or bilateral implants. Magnitude of deviation appeared to be uniform and independent of locations relative to metal implants. Conclusions: High Z metal artifacts on kV CTs can have severe impact on the accuracy of structure delineation and tissue density calculation, while on MV CTs, the impact is substantially less and insignificant. MV CTs should be considered for treatment planning on patients with high Z metal implants.
Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy c... more Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.
Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications, 2001
An inverse treatment planning system based on fast Monte Carlo (MC) dose calculation is presented... more An inverse treatment planning system based on fast Monte Carlo (MC) dose calculation is presented. It allows optimisation of intensity modulated dose distributions in 15 to 60 minutes on present day personal computers. If a multi-processor machine is available, parallel simulation of particle histories is also possible, leading to further calculation time reductions. The optimisation process is divided into two stages. The first stage results in fluence profiles based on pencil beam (PB) dose calculation. The second stage starts with MC verification and post-optimisation of the PB dose and fluence distributions.
In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combin... more In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.
In this study the effects of small systematic MLC misalignments and gravitational errors on the q... more In this study the effects of small systematic MLC misalignments and gravitational errors on the quality of Rapidarc treatment plan delivery are investigated with respect to verification measurements with two detector arrays and the evaluation of clinical significance of the error-induced deviations. Five prostate and six head and neck plans were modified by means of three error types: (1) both MLC banks are opened, respectively, in opposing directions, resulting in larger fields; (2) both MLC banks are closed, resulting in smaller fields; and (3) both MLC banks are shifted for lateral gantry angles, respectively, in the same direction to simulate the effects of gravity on the leaves. Measurements were evaluated with respect to a gamma-index of 3%/3 mm and 2%/2 mm. Dose in the modified plans was recalculated and the resulting dose volume histograms for target and critical structures were compared to those of the unaltered plans. The smallest introduced leaf position deviations which ...
A model for the simulation of the accelerator heads of two identical linear accelerators was desi... more A model for the simulation of the accelerator heads of two identical linear accelerators was designed at the University Hospital of Tübingen, using the BEAM program developed at the National Research Council of Canada. Both linear accelerators are equipped with multileaf collimators (MLCs) and backup jaws (y-direction) with curved leaf-ends. The accelerator models were divided into two parts. The first part consisted of target, primary collimator, flattening filter, monitor chamber, and mirror. After the Monte Carlo simulation of these parts, the phase-space characteristics below the mirror were stored in a file and used as source for the second part of the accelerator head (jaw, MLC). The electron source was assumed to deliver a gaussian energy spectrum, with parallel direction to the beam axis. With this electron source, there was good agreement between the measured and simulated depth dose curves in water, with difference < 2%. A new module was created for the BEAM program to ...
ABSTRACT A model for the simulation of the accelerator heads of two identical linear accelerators... more ABSTRACT A model for the simulation of the accelerator heads of two identical linear accelerators was designed at the University Hospital of Tübingen, using the BEAM program developed at the National Research Council of Canada. Both linear accelerators are equipped with multileaf collimators (MLCs) and backup jaws (y-direction) with curved leaf-ends. The accelerator models were divided into two parts. The first part consisted of target, primary collimator, flattening filter, monitor chamber, and mirror. After the Monte Carlo simulation of these parts, the phase-space characteristics below the mirror were stored in a file and used as source for the second part of the accelerator head (jaw, MLC). The electron source was assumed to deliver a gaussian energy spectrum, with parallel direction to the beam axis. With this electron source, there was good agreement between the measured and simulated depth dose curves in water, with difference &lt; 2%. A new module was created for the BEAM program to simulate backup jaws, while the standard MLCQ module from BEAM was used to simulate a MLC with curved leaf-ends. As a result, MLCs and backup jaws with curved leaf-ends make the shoulder of the y-profile higher than the straight-end MLCs.
Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyos... more Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. Most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. The alveolar subtype harbors a translocation-mediated PAX3:FOXO1A fusion gene and has an extremely poor prognosis. However, tumor cells have heterogeneous expression for the fusion gene. Using a conditional genetic mouse model as well as human tumor cell lines, we show that that Pax3:Foxo1a expression is enriched in G 2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. Pax3:Foxo1a also tolerizes tumor cells to clinicallyestablished chemotherapy agents and emerging molecularly-targeted agents. Thus, the surprisingly dynamic regulation of the Pax3:Foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells.
ABSTRACT Purpose: In recent events, our clinic has experienced a soft x‐ray ion chamber calibrati... more ABSTRACT Purpose: In recent events, our clinic has experienced a soft x‐ray ion chamber calibration drift of 8%. For the INTRABEAMTM system which relies on an ion chamber measurement to deduce a dose rate correction factor for treatment, such an ion chamber change results in a large deviation between the planned patient dose and the treatment dose. We present a cross calibration method between an ion chamber and commercially available optically stimulated luminescent dosimeters (OSLDs) to monitor the consistency of the soft x‐ray ion chamber. Methods: Our method uses the INTRABEAM™ system dose rate determined by a PTW soft x‐ray ion chamber (model 23342) under normal quality assurance procedures to produce the counts per dose rate for irradiated nanoDot™ OSLDs. The procedure replaces the ion chamber with an OSLD at the same position which is obtained with a fabricated stage of the same dimension as the ion chamber stage. Upon replacement of the ion chamber, the QA procedure is repeated irradiating a nanoDot™ OSLD for approximately two minutes with low energy kV x‐rays of energy 20 keV with 0.64 mm Al HVL. The QA procedure is repeated three times with a new OSLD for each irradiation. A ten minute waiting period is invoked prior to reading each nanoDot™ OSLD a total of three times. Results: This method produces an average counts per dose rate for all nanoDot™ OSLDs with a 1‐sigma standard deviation of 1.7%. The low standard deviation gives this method the ability to detect an ion chamber measurement change in dose rate greater than 3.5% incorporating the positional uncertainty and sensitivity change. Conclusion: In the advent of complete equipment failure, a system can degrade and report erroneous measurements. Our quick secondary check for equipment drift provides a necessary tool to ensure patient safety.
Implants with high atomic numbers produce star-like artifacts in CT-images. When coupled in pairs... more Implants with high atomic numbers produce star-like artifacts in CT-images. When coupled in pairs, a black window appears in between. The Philips OMAR algorithm approaches these artifacts by post processing the images. In this study, measurements were performed with radiochromic EBT2 films 1 in order to verify, whether the OMAR algorithm contributes to the accuracy of treatment plans in implant regions.
ABSTRACT Purpose: The consistency between the AAA and XVMC algorithm in the treatment planning fo... more ABSTRACT Purpose: The consistency between the AAA and XVMC algorithm in the treatment planning for RapidArc is investigated. While the majority of the radiation field is blocked by the MLC system, multiple small dose islands with MLC opened only slightly can be observed in one control point. This raises questions on how accurate the clinically used AAA algorithm in Eclipse is able to calculate RapidArc dose distributions. The fast Monte Carlo Code XVMC was used as a benchmark to test the AAA algorithm. Methods: RadpidArc plans of 25 patients were calculated with AAA and XVMC. The patient cohort consisted of 4 different cancer sites (H&amp;N, upper abdominal, lung, prostate). Dose distributions, PTV and OAR coverage were compared looking at the PTV mean dose Dmean, the volume V95% of the PTV receiving 95% of the prescribed dose, the dose D95% delivered to 95% of the PTV Volume, the percentage PTV mean dose with respect to the prescribed dose Dmean/prescr and OAR mean dose. Results: The recalculation of RapidArc plans yielded good agreement of both calculation algorithms for treatment plans of all four cancer sites. PTV mean dose differences of AAA and XVMC were found to be in between -0.11% and 4.89% of the prescribed dose. The mean dose difference found was 0.48±0.77 Gy. Local dose differences were found when comparing dose distributions in regions of big mass density differences and in high dose regions. One head and neck plan and one prostate plan revealed significant differences in PTV coverage (ΔDmean=3.25 Gy) and OAR mean dose (prostate mean dose -13.71 Gy) respectively. Conclusions: The vast majority of treatment plans calculated with the AAA algorithm were found to agree within the expected and acceptable tolerances compared to XVMC results. Nevertheless in some cases dose differences were observed that could be of clinical significance. This work was funded by a Varian grant. Wolfram Laub is working in the physics group of CMS.
ABSTRACT Purpose: To quantitatively evaluate effects of image artifacts of hip prostheses on the ... more ABSTRACT Purpose: To quantitatively evaluate effects of image artifacts of hip prostheses on the accuracy of structure delineation and tissue density calculation on kV and MV CT images. Methods: Five hip prostheses made of stainless steel, titanium and cobalt chrome alloys were positioned inside a water tank and scanned respectively on a Philips CT and a Tomotherapy Hi-Art unit. Prostheses were positioned to mimic single and bilateral implantations. Rods of tissue materials of lung, water and bone were placed at locations next and distal to metal implants near femoral head, neck and stem of prostheses. kV and MV CT scans were repeated for each placement. On CT images, cross-sectional outlines of metal implants and tissue rods were delineated. Densities of rod materials were determined and compared to the true values. Results: Metal artifacts were severe on kV CTs and minimal on MV CTs. Cross-sectional outlines of metal implants and tissue rods on kV CTs were severely distorted by artifacts while those on MV CTs remained clearly identifiable. For kV CTs, deviations of measured tissue density from true value were up to 51.3%, 30.6% and 40.9% respectively for lung, bone and solid water. The magnitude of deviation was generally larger at locations closer to metal implants and greater with bilateral implants than single implant. For MV CTs, deviations of measured density from true value were less than 6% for all three tissue materials either with single or bilateral implants. Magnitude of deviation appeared to be uniform and independent of locations relative to metal implants. Conclusions: High Z metal artifacts on kV CTs can have severe impact on the accuracy of structure delineation and tissue density calculation, while on MV CTs, the impact is substantially less and insignificant. MV CTs should be considered for treatment planning on patients with high Z metal implants.
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