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Harald Paganetti - One of the best experts on this subject based on the ideXlab platform.
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Brain Necrosis in Adult Patients After Proton Therapy: Is There Evidence for Dependency on Linear Energy Transfer?
International journal of radiation oncology biology physics, 2020Co-Authors: Andrzej Niemierko, Drosoula Giantsoudi, Jan Schuemann, Maximilian Niyazi, Genevieve Maquilan, Helen A. Shih, Harald PaganettiAbstract:Purpose To investigate if radiographic imaging changes defined as necrosis correlate with regions in the brain with elevated Linear Energy Transfer (LET) for proton radiation therapy treatments with partial brain involvement in central nervous system and patients with head and neck cancer. Methods and Materials Fifty patients with head and neck, skull base, or intracranial tumors who underwent proton therapy between 2004 to 2016 with a minimum prescription dose of 59.4 Gy (relative biological effectiveness) and with magnetic resonance imaging changes indicative of brain necrosis after radiation therapy were retrospectively reviewed. Each treatment plan was recalculated using Monte Carlo simulations to provide accurate dose distributions as well as 3-dimensional distributions of LET. To assess the effect of LET on radiographic imaging changes several voxel-based analyses were performed. Results In this patient cohort, LET adjusted for dose was not found to be associated with risk of brain necrosis. Conclusions A voxel-based analysis of brain necrosis as an endpoint is difficult owing to uncertainties in the origin of necrosis, timing of imaging, variability in patient specific radiosensitivity, and the simultaneous effect of dose and LET. Even though it is expected that the LET and thus relative biological effectiveness increases at the end of range, effects in patients might be small compared with interpatient variability of radiosensitivity and might be obscured by other confounding factors.
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can differences in Linear Energy Transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity modulated proton therapy as compared to passively scattered proton therapy
Acta Oncologica, 2018Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose: To investigate the effect of differences in Linear Energy Transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pe...
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can differences in Linear Energy Transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity modulated proton therapy as compared to passively scattered proton therapy
Acta Oncologica, 2018Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose: To investigate the effect of differences in Linear Energy Transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-bea...
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proton treatment techniques for posterior fossa tumors consequences for Linear Energy Transfer and dose volume parameters for the brainstem and organs at risk
International Journal of Radiation Oncology Biology Physics, 2017Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose In proton therapy of posterior fossa tumors, at least partial inclusion of the brainstem in the target is necessary because of its proximity to the tumor and required margins. Additionally, the preferred beam geometry results in directing the field distal edge toward this critical structure, raising concerns for brainstem toxicity. Some treatment techniques place the beam's distal edge within the brainstem (dose-sparing techniques), and others avoid elevated Linear Energy Transfer (LET) of the proton field by placing the distal edge beyond it (LET-sparing techniques). Hybrid approaches are also being used. We examine the dosimetric efficacy of these techniques, accounting for LET-dependent and dose-dependent variable relative biologic effectiveness (RBE) distributions. Methods Six techniques were applied in ependymoma cases: (a) 3-field dose-sparing; (b) 3-field LET-sparing; (c) 2-field dose-sparing, wide angles; (d) 2-field LET-sparing, wide angles; (e) 2-field LET-sparing, steep angles; and (f) 2-field LET-sparing with feathered distal end. Monte Carlo calculated dose, LET, and RBE-weighted dose distributions were compared. Results Decreased LET values in the brainstem by LET-sparing techniques were accompanied by higher, not statistically significant, median dose: 53.6 Gy(RBE), 53.4 Gy(RBE), and 54.3 Gy(RBE) for techniques (b), (d), and (e) versus 52.1 Gy(RBE) for technique (a). Accounting for variable RBE distributions, the brainstem volume receiving at least 55 Gy(RBE) increased from 72.5% for technique (a) to 80.3% for (b) ( P P P =.03 and .004). Conclusions Extending the proton range beyond the brainstem to reduce LET results in clinically comparable maximum radiobiologic effective dose to this sensitive structure. However this method significantly increasing the brainstem volume receiving RBE-weighted dose higher than 55 Gy(RBE) with possible consequences based on known dose-volume parameters for increased toxicity.
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reoptimization of intensity modulated proton therapy plans based on Linear Energy Transfer
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Jan Unkelbach, P Botas, Bram L Gorissen, Drosoula Giantsoudi, Harald PaganettiAbstract:Purpose We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of Linear Energy Transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.
Drosoula Giantsoudi - One of the best experts on this subject based on the ideXlab platform.
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Brain Necrosis in Adult Patients After Proton Therapy: Is There Evidence for Dependency on Linear Energy Transfer?
International journal of radiation oncology biology physics, 2020Co-Authors: Andrzej Niemierko, Drosoula Giantsoudi, Jan Schuemann, Maximilian Niyazi, Genevieve Maquilan, Helen A. Shih, Harald PaganettiAbstract:Purpose To investigate if radiographic imaging changes defined as necrosis correlate with regions in the brain with elevated Linear Energy Transfer (LET) for proton radiation therapy treatments with partial brain involvement in central nervous system and patients with head and neck cancer. Methods and Materials Fifty patients with head and neck, skull base, or intracranial tumors who underwent proton therapy between 2004 to 2016 with a minimum prescription dose of 59.4 Gy (relative biological effectiveness) and with magnetic resonance imaging changes indicative of brain necrosis after radiation therapy were retrospectively reviewed. Each treatment plan was recalculated using Monte Carlo simulations to provide accurate dose distributions as well as 3-dimensional distributions of LET. To assess the effect of LET on radiographic imaging changes several voxel-based analyses were performed. Results In this patient cohort, LET adjusted for dose was not found to be associated with risk of brain necrosis. Conclusions A voxel-based analysis of brain necrosis as an endpoint is difficult owing to uncertainties in the origin of necrosis, timing of imaging, variability in patient specific radiosensitivity, and the simultaneous effect of dose and LET. Even though it is expected that the LET and thus relative biological effectiveness increases at the end of range, effects in patients might be small compared with interpatient variability of radiosensitivity and might be obscured by other confounding factors.
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can differences in Linear Energy Transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity modulated proton therapy as compared to passively scattered proton therapy
Acta Oncologica, 2018Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose: To investigate the effect of differences in Linear Energy Transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pe...
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can differences in Linear Energy Transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity modulated proton therapy as compared to passively scattered proton therapy
Acta Oncologica, 2018Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose: To investigate the effect of differences in Linear Energy Transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-bea...
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proton treatment techniques for posterior fossa tumors consequences for Linear Energy Transfer and dose volume parameters for the brainstem and organs at risk
International Journal of Radiation Oncology Biology Physics, 2017Co-Authors: Drosoula Giantsoudi, Judith Adams, Shannon M Macdonald, Harald PaganettiAbstract:Purpose In proton therapy of posterior fossa tumors, at least partial inclusion of the brainstem in the target is necessary because of its proximity to the tumor and required margins. Additionally, the preferred beam geometry results in directing the field distal edge toward this critical structure, raising concerns for brainstem toxicity. Some treatment techniques place the beam's distal edge within the brainstem (dose-sparing techniques), and others avoid elevated Linear Energy Transfer (LET) of the proton field by placing the distal edge beyond it (LET-sparing techniques). Hybrid approaches are also being used. We examine the dosimetric efficacy of these techniques, accounting for LET-dependent and dose-dependent variable relative biologic effectiveness (RBE) distributions. Methods Six techniques were applied in ependymoma cases: (a) 3-field dose-sparing; (b) 3-field LET-sparing; (c) 2-field dose-sparing, wide angles; (d) 2-field LET-sparing, wide angles; (e) 2-field LET-sparing, steep angles; and (f) 2-field LET-sparing with feathered distal end. Monte Carlo calculated dose, LET, and RBE-weighted dose distributions were compared. Results Decreased LET values in the brainstem by LET-sparing techniques were accompanied by higher, not statistically significant, median dose: 53.6 Gy(RBE), 53.4 Gy(RBE), and 54.3 Gy(RBE) for techniques (b), (d), and (e) versus 52.1 Gy(RBE) for technique (a). Accounting for variable RBE distributions, the brainstem volume receiving at least 55 Gy(RBE) increased from 72.5% for technique (a) to 80.3% for (b) ( P P P =.03 and .004). Conclusions Extending the proton range beyond the brainstem to reduce LET results in clinically comparable maximum radiobiologic effective dose to this sensitive structure. However this method significantly increasing the brainstem volume receiving RBE-weighted dose higher than 55 Gy(RBE) with possible consequences based on known dose-volume parameters for increased toxicity.
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reoptimization of intensity modulated proton therapy plans based on Linear Energy Transfer
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Jan Unkelbach, P Botas, Bram L Gorissen, Drosoula Giantsoudi, Harald PaganettiAbstract:Purpose We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of Linear Energy Transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.
C Grassberger - One of the best experts on this subject based on the ideXlab platform.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
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variations in Linear Energy Transfer within clinical proton therapy fields and the potential for biological treatment planning
International Journal of Radiation Oncology Biology Physics, 2011Co-Authors: A Trofimov, C Grassberger, A J Lomax, Harald PaganettiAbstract:Purpose To calculate the Linear Energy Transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated or diminished biological effect. The location of such areas might be influenced in intensity-modulated proton therapy (IMPT) optimization. Methods and Materials Because Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated with simulations in water. The code was used in five patients, for each of them three planning and delivery techniques were simulated: passive scattering, three-dimensional modulation IMPT (3D-IMPT), and distal edge tracking IMPT (DET-IMPT). Results The inclusion of secondary particles led to significant differences compared with analytical techniques. In addition, passive scattering and 3D-IMPT led to largely comparable LET distributions, whereas the DET-IMPT plans resulted in considerably increased LET values in normal tissues and critical structures. In the brainstem, dose-averaged LET values exceeding 5 keV/μm were observed in areas with significant dose (>70% of prescribed dose). In noncritical normal tissues, even values >8 keV/μm occurred. Conclusion This work demonstrates that active scanning offers the possibility of influencing the distribution of dose-averaged LET ( i.e., the biological effect) without significantly altering the distribution of physical dose. On the basis of this finding, we propose a method to alter deliberately the LET distribution of a treatment plan in such a manner that the LET is maximized within certain target areas and minimized in normal tissues, while maintaining the prescribed target dose and dose constraints for organs at risk.
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mo g brc 05 impact of secondary particles on Linear Energy Transfer for biological treatment planning in proton therapy
Medical Physics, 2011Co-Authors: C Grassberger, H PaganettiAbstract:Purpose: To assess the contribution of secondary particles to pencil and passively scatteredproton beams, in particular to determine the impact on Linear Energy Transfer (LET), a central quantity in biological treatment planning. Methods: ProtonMonte Carlo simulations were performed directly in patient geometries considering all primary and secondary particles, including recoils stemming from inelastic nuclear interactions. Simulations were conducted for a prostate and a head&neck case to investigate the impact of different initial proton energies. Results: Examination of the results reveals that secondary protons exhibit LET‐ values up to a factor 10 higher than those of the primary protons in the same region. This causes significant changes to the dose‐averaged LET when including secondary protons, from 50% along the central axis of the beam to >200% in the penumbra. Furthermore the LET‐maximum increases from 12 to 15 MeV/mm. The contribution of recoils (A>3) was observed to be 1.2% in the entrance region of the prostate case, increasing slightly compared to the same beam in a water phantom. The degree of biological damage inflicted by recoils remains hard to quantify, but can be discussed on account of detailed Energy spectra of the preeminent particles. Conclusions: These results indicate that secondary protons have a significant influence on LET and should therefore be incorporated into RBE calculations for proton therapy, as well as into radiobiological experiments. The contribution of heavier secondary particles is complex, yet may have an impact on precise measurements of the radiobiological effectiveness (RBE) of protons, especially in the plateau region of high‐Energy beams. In addition the LET distributions presented demonstrate the impact of inhomogeneities on the LET and the subtle changes between the LET distributions of passively scattered and actively scanned beams. The latter observation suggests higher RBE variations in active scanning than in passively scattered fields. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.
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mo e brb 02 biologically optimized treatment planning for proton therapy monte carlo calculated Linear Energy Transfer distributions in patients
Medical Physics, 2010Co-Authors: C Grassberger, A Trofimov, H PaganettiAbstract:Purpose: To apply Monte Carlo simulations to simulate the Linear Energy Transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated biological effect. The location of such areas might be influenced in intensity‐modulated proton therapy (IMPT) optimization. Method and Materials:ProtonMonte Carlo calculations are performed using a code considering all relevant primary and secondary particles. Since Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated: simulations in a water phantom are compared to published data. The code was subsequently used to track particles through the patient geometry based on CT information for five patients. For each of them three different proton therapy planning and delivery techniques were simulated: passive scattering, 3D modulation IMPT (3D‐IMPT) and Distal Edge Tracking IMPT (DET‐IMPT). Results: Detailed examination of the LET distributions and LET‐Volume‐Histograms reveals significant differences between the treatment techniques. While passive scattering and 3D‐IMPT lead to largely comparable LET distributions, the DET‐IMPT plans result in considerably increased LET values in normal tissues and organs at risk. In the brainstem, dose‐averaged LET values exceeding 10 keV/ m are observed in areas with significant dose levels (above 70% of prescribed dose). In non‐critical normal tissues even values above 15 keV/ m occur, although in areas with low doses. Conclusion: This work demonstrates that active scanning offers the possibility to influence the distribution of dose averaged LET (i.e. the biological effect) without significantly altering the distribution of physical dose. Based on this finding, we propose a method to deliberately alter the LET distribution of a treatment plan in such a manner that the LET is maximized within the target and minimized in normal tissues, while leaving the prescribed dose to the target unchanged.
Andrzej Niemierko - One of the best experts on this subject based on the ideXlab platform.
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Brain Necrosis in Adult Patients After Proton Therapy: Is There Evidence for Dependency on Linear Energy Transfer?
International journal of radiation oncology biology physics, 2020Co-Authors: Andrzej Niemierko, Drosoula Giantsoudi, Jan Schuemann, Maximilian Niyazi, Genevieve Maquilan, Helen A. Shih, Harald PaganettiAbstract:Purpose To investigate if radiographic imaging changes defined as necrosis correlate with regions in the brain with elevated Linear Energy Transfer (LET) for proton radiation therapy treatments with partial brain involvement in central nervous system and patients with head and neck cancer. Methods and Materials Fifty patients with head and neck, skull base, or intracranial tumors who underwent proton therapy between 2004 to 2016 with a minimum prescription dose of 59.4 Gy (relative biological effectiveness) and with magnetic resonance imaging changes indicative of brain necrosis after radiation therapy were retrospectively reviewed. Each treatment plan was recalculated using Monte Carlo simulations to provide accurate dose distributions as well as 3-dimensional distributions of LET. To assess the effect of LET on radiographic imaging changes several voxel-based analyses were performed. Results In this patient cohort, LET adjusted for dose was not found to be associated with risk of brain necrosis. Conclusions A voxel-based analysis of brain necrosis as an endpoint is difficult owing to uncertainties in the origin of necrosis, timing of imaging, variability in patient specific radiosensitivity, and the simultaneous effect of dose and LET. Even though it is expected that the LET and thus relative biological effectiveness increases at the end of range, effects in patients might be small compared with interpatient variability of radiosensitivity and might be obscured by other confounding factors.
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patterns of failure after proton therapy in medulloblastoma Linear Energy Transfer distributions and relative biological effectiveness associations for relapses
International Journal of Radiation Oncology Biology Physics, 2014Co-Authors: Roshan V Sethi, Drosoula Giantsoudi, Andrzej Niemierko, Michael Raiford, Imran Malhi, Otto Rapalino, Paul A Caruso, Torunn I Yock, Nancy J Tarbell, H PaganettiAbstract:Purpose The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in Linear Energy Transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
A Trofimov - One of the best experts on this subject based on the ideXlab platform.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
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Linear Energy Transfer guided optimization in intensity modulated proton therapy feasibility study and clinical potential
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Drosoula Giantsoudi, David Craft, C Grassberger, Andrzej Niemierko, A Trofimov, Harald PaganettiAbstract:Purpose To investigate the feasibility and potential clinical benefit of Linear Energy Transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
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variations in Linear Energy Transfer within clinical proton therapy fields and the potential for biological treatment planning
International Journal of Radiation Oncology Biology Physics, 2011Co-Authors: A Trofimov, C Grassberger, A J Lomax, Harald PaganettiAbstract:Purpose To calculate the Linear Energy Transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated or diminished biological effect. The location of such areas might be influenced in intensity-modulated proton therapy (IMPT) optimization. Methods and Materials Because Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated with simulations in water. The code was used in five patients, for each of them three planning and delivery techniques were simulated: passive scattering, three-dimensional modulation IMPT (3D-IMPT), and distal edge tracking IMPT (DET-IMPT). Results The inclusion of secondary particles led to significant differences compared with analytical techniques. In addition, passive scattering and 3D-IMPT led to largely comparable LET distributions, whereas the DET-IMPT plans resulted in considerably increased LET values in normal tissues and critical structures. In the brainstem, dose-averaged LET values exceeding 5 keV/μm were observed in areas with significant dose (>70% of prescribed dose). In noncritical normal tissues, even values >8 keV/μm occurred. Conclusion This work demonstrates that active scanning offers the possibility of influencing the distribution of dose-averaged LET ( i.e., the biological effect) without significantly altering the distribution of physical dose. On the basis of this finding, we propose a method to alter deliberately the LET distribution of a treatment plan in such a manner that the LET is maximized within certain target areas and minimized in normal tissues, while maintaining the prescribed target dose and dose constraints for organs at risk.
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mo e brb 02 biologically optimized treatment planning for proton therapy monte carlo calculated Linear Energy Transfer distributions in patients
Medical Physics, 2010Co-Authors: C Grassberger, A Trofimov, H PaganettiAbstract:Purpose: To apply Monte Carlo simulations to simulate the Linear Energy Transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated biological effect. The location of such areas might be influenced in intensity‐modulated proton therapy (IMPT) optimization. Method and Materials:ProtonMonte Carlo calculations are performed using a code considering all relevant primary and secondary particles. Since Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated: simulations in a water phantom are compared to published data. The code was subsequently used to track particles through the patient geometry based on CT information for five patients. For each of them three different proton therapy planning and delivery techniques were simulated: passive scattering, 3D modulation IMPT (3D‐IMPT) and Distal Edge Tracking IMPT (DET‐IMPT). Results: Detailed examination of the LET distributions and LET‐Volume‐Histograms reveals significant differences between the treatment techniques. While passive scattering and 3D‐IMPT lead to largely comparable LET distributions, the DET‐IMPT plans result in considerably increased LET values in normal tissues and organs at risk. In the brainstem, dose‐averaged LET values exceeding 10 keV/ m are observed in areas with significant dose levels (above 70% of prescribed dose). In non‐critical normal tissues even values above 15 keV/ m occur, although in areas with low doses. Conclusion: This work demonstrates that active scanning offers the possibility to influence the distribution of dose averaged LET (i.e. the biological effect) without significantly altering the distribution of physical dose. Based on this finding, we propose a method to deliberately alter the LET distribution of a treatment plan in such a manner that the LET is maximized within the target and minimized in normal tissues, while leaving the prescribed dose to the target unchanged.