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H Paganetti - One of the best experts on this subject based on the ideXlab platform.
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brain specific Relative Biological Effectiveness of protons based on long term outcome of patients with nasopharyngeal carcinoma
International Journal of Radiation Oncology Biology Physics, 2021Co-Authors: Ying Y Zhang, H Paganetti, Judith Adams, Wan L Huo, Saveli Goldberg, Jason M Slater, Xiaowu Deng, Ying Sun, Barbara C Fullerton, Jay S LoefflerAbstract:Purpose Uncertainties in Relative Biological Effectiveness (RBE) constitute a major pitfall of the use of protons in clinics. An RBE value of 1.1, which is based on cell culture and animal models, is currently used in clinical proton planning. The purpose of this study was to determine RBE for temporal lobe radiographic changes using long-term follow-up data from patients with nasopharyngeal carcinoma. Methods and Materials Five hundred sixty-six patients with newly diagnosed nasopharyngeal carcinoma received double-scattering proton therapy or intensity modulated radiation therapy at our institutions. The 2 treatment cohorts were well matched. Proton dose distributions were simulated using Monte Carlo and compared with those obtained from the proton clinical treatment planning system. Late treatment effect was defined as development of enhancement of temporal lobe on T1-weighted magnetic resonance imaging, with or without accompanying clinical symptoms. The tolerance dose was calculated with receiving operator characteristic analysis and the Youden index. Tolerance curves, expressed as a cumulative dose-volume histogram, were generated using the cutoff points. Results With a median follow-up period >5 years for both cohorts, 10% of proton patients and 4% of patients undergoing intensity modulated radiation therapy developed temporal lobe enhancement in unilateral temporal lobe. There was no significant difference in dose distributions between the Monte Carlo method and treatment planning system. The tolerance dose-volume levels were V10 (26.1%), V20 (21.9%), V30 (14.0%), V40 (7.7%), V50 (4.8%), and V60 (3.3%) for proton therapy (P Conclusions Using long-term clinical outcome of patients with nasopharyngeal carcinoma, our data suggest that the RBE for temporal lobe enhancement is 1.18 at D1%. A prospective study in a large cohort would be necessary to confirm these findings.
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modelling variable proton Relative Biological Effectiveness for treatment planning
British Journal of Radiology, 2020Co-Authors: Aimee L Mcnamara, Henning Willers, H PaganettiAbstract:Dose in proton radiotherapy is generally prescribed by scaling the physical proton dose by a constant value of 1.1. Relative Biological Effectiveness (RBE) is defined as the ratio of doses required...
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report of the aapm tg 256 on the Relative Biological Effectiveness of proton beams in radiation therapy
Medical Physics, 2019Co-Authors: H Paganetti, Radhe Mohan, David R Grosshans, David J Carlson, Eleanor A Blakely, A Carabefernandez, Lei Dong, Kathryn D Held, Vitali Moiseenko, Andrzej NiemierkoAbstract:: The Biological Effectiveness of proton beams Relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual Relative Biological Effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as Biological parameters). The following task group aims were designed to guide the current clinical practice: Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained. Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit. Assess the potential clinical consequences of delivering Biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems. Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well-defined tumor types and critical structures.
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Relative Biological Effectiveness uncertainties and implications for beam arrangements and dose constraints in proton therapy
Seminars in Radiation Oncology, 2018Co-Authors: H Paganetti, D GiantsoudiAbstract:Current clinical implementation of proton radiation therapy assumes a constant Relative Biological Effectiveness (RBE) value of 1.1 throughout the treatment field, for both the target and organs at risks. Although few in vivo clinical data suggest that this approximation is clinically significant, in vitro studies demonstrate the dependency of RBE on dose, fractionation, proton energy, and linear energy transfer, as well as patient radiosensitivity and definition of endpoint. This article provides a brief review on the principles and individual factors contributing to RBE uncertainties, with emphasis on clinical practice. Clinical considerations regarding the effect of RBE uncertainties and implications for beam arrangements in proton therapy treatment planning are discussed through clinical examples for treatments of prostate cancer and posterior fossa tumors as well as craniospinal irradiation for medulloblastoma. Approaches on Biological optimization in proton therapy are presented, including a discussion on linear energy transfer-based optimization as an alternative method for Biological optimization and its implementation both in multicriteria optimization and inverse optimization modules.
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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: D Giantsoudi, Judith Adams, Shannon M Macdonald, H 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...
Radhe Mohan - One of the best experts on this subject based on the ideXlab platform.
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a simple model for calculating Relative Biological Effectiveness of x rays and gamma radiation in cell survival
British Journal of Radiology, 2020Co-Authors: Oleg N Vassiliev, Christine B Peterson, David R Grosshans, Radhe MohanAbstract:Objectives:The Relative Biological Effectiveness (RBE) of X-rays and γ radiation increases substantially with decreasing beam energy. This trend affects the efficacy of medical applications of this...
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report of the aapm tg 256 on the Relative Biological Effectiveness of proton beams in radiation therapy
Medical Physics, 2019Co-Authors: H Paganetti, Radhe Mohan, David R Grosshans, David J Carlson, Eleanor A Blakely, A Carabefernandez, Lei Dong, Kathryn D Held, Vitali Moiseenko, Andrzej NiemierkoAbstract:: The Biological Effectiveness of proton beams Relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual Relative Biological Effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as Biological parameters). The following task group aims were designed to guide the current clinical practice: Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained. Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit. Assess the potential clinical consequences of delivering Biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems. Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well-defined tumor types and critical structures.
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Using the Proton Energy Spectrum and Microdosimetry to Model Proton Relative Biological Effectiveness
International Journal of Radiation Oncology Biology Physics, 2019Co-Authors: Mark Newpower, Fada Guan, Pankaj Chaudhary, Stephen J. Mcmahon, Lawrence Bronk, Giuseppe Schettino, Kevin M. Prise, D Patel, David Randall Grosshans, Radhe MohanAbstract:Purpose We introduce a methodology to calculate the microdosimetric quantity dose-mean lineal energy for input into the microdosimetric kinetic model (MKM) to model the Relative Biological Effectiveness (RBE) of proton irradiation experiments. Methods and Materials The data from 7 individual proton RBE experiments were included in this study. In each experiment, the RBE at several points along the Bragg curve was measured. Monte Carlo simulations to calculate the lineal energy probability density function of 172 different proton energies were carried out with use of Geant4 DNA. We calculated the fluence-weighted lineal energy probability density function ( f w ( y ) ) , based on the proton energy spectra calculated through Monte Carlo at each experimental depth, calculated the dose-mean lineal energy y D ¯ for input into the MKM, and then computed the RBE. The radius of the domain (rd) was varied to reach the best agreement between the MKM-predicted RBE and experimental RBE. A generic RBE model as a function of dose-averaged linear energy transfer (LETD) with 1 fitting parameter was presented and fit to the experimental RBE data as well to facilitate a comparison to the MKM. Results Both the MKM and LETD-based models modeled the RBE from experiments well. Values for rd were similar to those of other cell lines under proton irradiation that were modeled with the MKM. Analysis of the performance of each model revealed that neither model was clearly superior to the other. Conclusions Our 3 key accomplishments include the following: (1) We developed a method that uses the proton energy spectra and lineal energy distributions of those protons to calculate dose-mean lineal energy. (2) We demonstrated that our application of the MKM provides theoretical validation of proton irradiation experiments that show that RBE is significantly greater than 1.1. (3) We showed that there is no clear evidence that the MKM is better than LETD-based RBE models.
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a mechanistic Relative Biological Effectiveness model based Biological dose optimization for charged particle radiobiology studies
Physics in Medicine and Biology, 2018Co-Authors: Fada Guan, Lawrence Bronk, David R Grosshans, Xiaochun Wang, David J Carlson, Changran Geng, Duo H, Drake Gates, Stephen F Kry, Radhe MohanAbstract:In charged particle therapy, the objective is to exploit both the physical and radioBiological advantages of charged particles to improve the therapeutic index. Use of the beam scanning technique provides the flexibility to implement Biological dose optimized intensity-modulated ion therapy (IMIT). An easy-to-implement algorithm was developed in the current study to rapidly generate a uniform Biological dose distribution, namely the product of physical dose and the Relative Biological Effectiveness (RBE), within the target volume using scanned ion beams for charged particle radioBiological studies. Protons, helium ions and carbon ions were selected to demonstrate the feasibility and flexibility of our method. The general-purpose Monte Carlo simulation toolkit Geant4 was used for particle tracking and generation of physical and radioBiological data needed for later dose optimizations. The dose optimization algorithm was developed using the Python (version 3) programming language. A constant RBE-weighted dose (RWD) spread-out Bragg peak (SOBP) in a water phantom was selected as the desired target dose distribution to demonstrate the applicability of the optimization algorithm. The mechanistic repair-misrepair-fixation (RMF) model was incorporated into the Monte Carlo particle tracking to generate radioBiological parameters and was used to predict the RBE of cell survival in the iterative process of the Biological dose optimization for the three selected ions. The post-optimization generated beam delivery strategy can be used in radiation biology experiments to obtain radioBiological data to further validate and improve the accuracy of the RBE model. This Biological dose optimization algorithm developed for radiobiology studies could potentially be extended to implement Biologically optimized IMIT plans for patients.
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impact of respiratory motion on variable Relative Biological Effectiveness in 4d dose distributions of proton therapy
Acta Oncologica, 2017Co-Authors: Silke Ulrich, Radhe Mohan, Hanspeter Wieser, Wenhua Cao, Mark BangertAbstract:Background: Organ motion during radiation therapy with scanned protons leads to deviations between the planned and the delivered physical dose. Using a constant Relative Biological Effectiveness (R...
Peter E Huber - One of the best experts on this subject based on the ideXlab platform.
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split dose carbon ion irradiation of the rat spinal cord dependence of the Relative Biological Effectiveness on dose and linear energy transfer
Radiotherapy and Oncology, 2015Co-Authors: Rebecca Grun, Peter E Huber, Michael Scholz, S Brons, Peter Peschke, Maria Saager, Christin GlowaAbstract:Abstract Purpose To measure the Relative Biological Effectiveness (RBE) of carbon ions Relative to 15MeV photons in the rat spinal cord for different linear energy transfers (LET) to validate model calculations. Methods and materials The cervical spinal cord of rats was irradiated with 2 fractions of carbon ions at six positions of a 6cm spread-out Bragg-peak (SOBP, 16–99keV/μm). TD 50 -values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300days after irradiation. Using previously published TD 50 -values for photons (Karger et al., 2006; Debus et al., 2003), RBE-values were determined and compared with predictions of two versions of the local effect model (LEM I and IV). Results TD 50 -values for paresis grade II were 26.7±0.4Gy (16keV/μm), 24.0±0.3Gy (21keV/μm), 22.5±0.3Gy (36keV/μm), 20.1±1.2Gy (45keV/μm), 17.7±0.3Gy (66keV/μm), and 14.9±0.3Gy (99keV/μm). RBE-values increased from 1.28±0.03 (16keV/μm) up to 2.30±0.06 at 99keV/μm. At the applied high fractional doses, LEM I fits best at 16keV/μm and deviates progressively toward higher LETs while LEM IV agrees best at 99keV/μm and shows increasing deviations, especially below 66keV/μm. Conclusions The measured data improve the knowledge on the accuracy of RBE-calculations for carbon ions.
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carbon ion irradiation of the rat spinal cord dependence of the Relative Biological Effectiveness on linear energy transfer
International Journal of Radiation Oncology Biology Physics, 2014Co-Authors: Maria Saager, Jurgen Debus, Peter E Huber, Michael Scholz, S Brons, Peter Peschke, Christin Glowa, Christian P KargerAbstract:Purpose To measure the Relative Biological Effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET). Methods and Materials As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD 50 values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD 50 for photons of our previous study. Results Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD 50 values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm. Conclusions The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning.
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Relative Biological Effectiveness of carbon ions in a rat prostate carcinoma in vivo comparison of 1 2 and 6 fractions
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Christian P Karger, Michael Scholz, Peter E Huber, Peter Peschke, Jurgen DebusAbstract:Purpose To determine the Relative Biological Effectiveness (RBE) and the effective α/β ratio for local tumor control of a radioresistant rat prostate tumor (Dunning subline R3327-AT1) after 6 fractions of carbon ions and photons. Methods and Materials A total of 82 animals with tumors in the distal thigh were treated with 6 fractions of either photons or carbon ions, by use of increasing dose levels and a 2-cm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for dose at 50% tumor control probability were used to determine RBE values. Including data for 1 and 2 fractions from a previous study, we estimated α/β ratios. Results For 6 fractions, the values for dose at 50% tumor control probability were 116.6 ± 3.0 Gy for photons and 43.7 ± 2.3 Gy for carbon ions and the resulting RBE was 2.67 ± 0.15. The α/β ratio was 84.7 ± 13.8 Gy for photons and 66.0 ± 21.0 Gy for carbon ions. Using these data together with the linear-quadratic model, we estimated the maximum RBE to be 2.88 ± 0.27. Conclusions The study confirmed the increased Effectiveness of carbon ions Relative to photons over the whole dose range for a highly radioresistant tumor. The maximum RBE below 3 is in line with other published in vivo data. The RBE values may be used to benchmark RBE models. Hypoxia seems to have a major impact on the radiation response, although this still has to be confirmed by dedicated experiments.
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application of constant vs variable Relative Biological Effectiveness in treatment planning of intensity modulated proton therapy
International Journal of Radiation Oncology Biology Physics, 2011Co-Authors: Malte C Frese, Jan J Wilkens, U Oelfke, Peter E Huber, Alexandra D Jensen, Zahra TaherikadkhodaAbstract:Purpose To investigate in a simulation study whether using a variable Relative Biological Effectiveness (RBE) in calculation and optimization of intensity-modulated proton therapy (IMPT) instead of using an RBE of 1.1 would result in significant changes in the RBE-weighted dose (RWD) distributions. Methods and Materials For 4 patients with head-and-neck tumors, three IMPT plans were prepared respectively. The first plan was physically optimized (IMPT-PO plan), and the RWD was calculated with a constant RBE of 1.1. Then the plan's RWD was recalculated (IMPT-R plan) using a variable RBE model taking into account the linear energy transfer (LET) and tissue-specific radioBiological parameters. The third IMPT plan was optimized using a Biological optimization routine (IMPT-BO plan). Results Comparing the IMPT-PO and IMPT-R plans, we observed that the RWD in radioresistant tissues was more sensitive to the LET than in radiosensitive tissues. The IMPT-R plans were in general more inhomogeneous than the IMPT-PO plans. The differences of RWD distributions for all volumes between IMPT-PO and IMPT-BO plans complied with predefined dose–volume constraints. The average LET was significantly lower in IMPT-BO plans than in IMPT-R plans. Conclusion In radioresistant normal tissues caution has to be used regarding the LET distribution because these are most sensitive to changes in the LET. Biological optimization of IMPT plans based on the organ-specific Biological parameters and LET distributions is feasible.
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Relative Biological Effectiveness of carbon ions for local tumor control of a radioresistant prostate carcinoma in the rat
International Journal of Radiation Oncology Biology Physics, 2011Co-Authors: Peter Peschke, Jurgen Debus, Peter E Huber, Michael Scholz, Christian P KargerAbstract:Purpose To study the Relative Biological Effectiveness (RBE) of carbon ion beams Relative to X-rays for local tumor control in a syngeneic rat prostate tumor (Dunning subline R3327-AT1). Methods and Materials A total of 198 animals with tumors in the distal thigh were treated with increasing single and split doses of either 12 C ions or photons using a 20-mm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for D 50 (dose at 50% tumor control probability) were used to determine RBE values. Results The D 50 values for single doses were 32.9 ± 0.9 Gy for 12 C ions and 75.7 ± 1.6 Gy for photons. The respective values for split doses were 38.0 ± 2.3 Gy and 90.6 ± 2.3 Gy. The corresponding RBE values were 2.30 ± 0.08 for single and 2.38 ± 0.16 for split doses. The most prominent side effects were dry and moist desquamation of the skin, which disappeared within weeks. Conclusion The study confirmed the Effectiveness of carbon ion therapy for severely radioresistant tumors. For 1- and 2-fraction photon and 12 C ion radiation, we have established individual D 50 values for local tumor control as well as related RBE values.
D Giantsoudi - One of the best experts on this subject based on the ideXlab platform.
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Relative Biological Effectiveness uncertainties and implications for beam arrangements and dose constraints in proton therapy
Seminars in Radiation Oncology, 2018Co-Authors: H Paganetti, D GiantsoudiAbstract:Current clinical implementation of proton radiation therapy assumes a constant Relative Biological Effectiveness (RBE) value of 1.1 throughout the treatment field, for both the target and organs at risks. Although few in vivo clinical data suggest that this approximation is clinically significant, in vitro studies demonstrate the dependency of RBE on dose, fractionation, proton energy, and linear energy transfer, as well as patient radiosensitivity and definition of endpoint. This article provides a brief review on the principles and individual factors contributing to RBE uncertainties, with emphasis on clinical practice. Clinical considerations regarding the effect of RBE uncertainties and implications for beam arrangements in proton therapy treatment planning are discussed through clinical examples for treatments of prostate cancer and posterior fossa tumors as well as craniospinal irradiation for medulloblastoma. Approaches on Biological optimization in proton therapy are presented, including a discussion on linear energy transfer-based optimization as an alternative method for Biological optimization and its implementation both in multicriteria optimization and inverse optimization modules.
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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: D Giantsoudi, Judith Adams, Shannon M Macdonald, H 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: D Giantsoudi, Judith Adams, Shannon M Macdonald, H 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...
Stephen J. Mcmahon - One of the best experts on this subject based on the ideXlab platform.
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Using the Proton Energy Spectrum and Microdosimetry to Model Proton Relative Biological Effectiveness
International Journal of Radiation Oncology Biology Physics, 2019Co-Authors: Mark Newpower, Fada Guan, Pankaj Chaudhary, Stephen J. Mcmahon, Lawrence Bronk, Giuseppe Schettino, Kevin M. Prise, D Patel, David Randall Grosshans, Radhe MohanAbstract:Purpose We introduce a methodology to calculate the microdosimetric quantity dose-mean lineal energy for input into the microdosimetric kinetic model (MKM) to model the Relative Biological Effectiveness (RBE) of proton irradiation experiments. Methods and Materials The data from 7 individual proton RBE experiments were included in this study. In each experiment, the RBE at several points along the Bragg curve was measured. Monte Carlo simulations to calculate the lineal energy probability density function of 172 different proton energies were carried out with use of Geant4 DNA. We calculated the fluence-weighted lineal energy probability density function ( f w ( y ) ) , based on the proton energy spectra calculated through Monte Carlo at each experimental depth, calculated the dose-mean lineal energy y D ¯ for input into the MKM, and then computed the RBE. The radius of the domain (rd) was varied to reach the best agreement between the MKM-predicted RBE and experimental RBE. A generic RBE model as a function of dose-averaged linear energy transfer (LETD) with 1 fitting parameter was presented and fit to the experimental RBE data as well to facilitate a comparison to the MKM. Results Both the MKM and LETD-based models modeled the RBE from experiments well. Values for rd were similar to those of other cell lines under proton irradiation that were modeled with the MKM. Analysis of the performance of each model revealed that neither model was clearly superior to the other. Conclusions Our 3 key accomplishments include the following: (1) We developed a method that uses the proton energy spectra and lineal energy distributions of those protons to calculate dose-mean lineal energy. (2) We demonstrated that our application of the MKM provides theoretical validation of proton irradiation experiments that show that RBE is significantly greater than 1.1. (3) We showed that there is no clear evidence that the MKM is better than LETD-based RBE models.
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the radiobiology of proton therapy challenges and opportunities around Relative Biological Effectiveness
Clinical Oncology, 2018Co-Authors: Bleddyn Jones, Stephen J. Mcmahon, Kevin M. PriseAbstract:Abstract With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the Relative Biological Effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful Biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2–1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radioBiological characteristics such as α/β, is proposed.
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we h bra 07 mechanistic modelling of the Relative Biological Effectiveness of heavy charged particles
Medical Physics, 2016Co-Authors: Stephen J. Mcmahon, Kevin M. Prise, Aimee L Mcnamara, J Schuemann, H PaganettiAbstract:Purpose Uncertainty in the Relative Biological Effectiveness (RBE) of heavy charged particles compared to photons remains one of the major uncertainties in particle therapy. As RBEs depend strongly on clinical variables such as tissue type, dose, and radiation quality, more accurate individualised models are needed to fully optimise treatments. MethodsWe have developed a model of DNA damage and repair following X-ray irradiation in a number of settings, incorporating mechanistic descriptions of DNA repair pathways, geometric effects on DNA repair, cell cycle effects and cell death. Our model has previously been shown to accurately predict a range of Biological endpoints including chromosome aberrations, mutations, and cell death. This model was combined with nanodosimetric models of individual ion tracks to calculate the additional probability of lethal damage forming within a single track. These lethal damage probabilities can be used to predict survival and RBE for cells irradiated with ions of different Linear Energy Transfer (LET). ResultsBy combining the X-ray response model with nanodosimetry information, predictions of RBE can be made without cell-line specific fitting. The model’s RBE predictions were found to agree well with empirical proton RBE models (Mean absolute difference between models of 1.9% and 1.8% for cells with α/β ratios of 9 and 1.4, respectively, for LETs between 0 and 15 keV/µm). The model also accurately recovers the impact of high-LET carbon ion exposures, showing both the reduced efficacy of ions at extremely high LET, as well as the impact of defects in non-homologous end joining on RBE values in Chinese Hamster Ovary cells.ConclusionOur model is predicts RBE without the inclusion of empirical LET fitting parameters for a range of experimental conditions. This approach has the potential to deliver improved personalisation of particle therapy, with future developments allowing for the calculation of individualised RBEs. SJM is supported by a Marie Curie International Outgoing Fellowship from the European Commission’s FP7 program (EC FP7 MC-IOF-623630)
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Relative Biological Effectiveness variation along monoenergetic and modulated bragg peaks of a 62 mev therapeutic proton beam a preclinical assessment
International Journal of Radiation Oncology Biology Physics, 2014Co-Authors: Pankaj Chaudhary, Stephen J. Mcmahon, Thomas I Marshall, Francesca M Perozziello, L Manti, F J Currell, F Hanton, Joy N Kavanagh, G A P Cirrone, Francesco RomanoAbstract:Purpose The Biological optimization of proton therapy can be achieved only through a detailed evaluation of Relative Biological Effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton Biological Effectiveness. Data were also used to validate a parameterized RBE model. Conclusions The predicted Biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.
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Relative Biological Effectiveness variation along monoenergetic and modulated bragg peaks of a 62 mev therapeutic proton beam a preclinical assessment
International Journal of Radiation Oncology Biology Physics, 2014Co-Authors: Pankaj Chaudhary, Stephen J. Mcmahon, Thomas I Marshall, Francesca M Perozziello, L Manti, F J Currell, F Hanton, Joy N Kavanagh, G A P Cirrone, Francesco RomanoAbstract:Purpose The Biological optimization of proton therapy can be achieved only through a detailed evaluation of Relative Biological Effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton Biological Effectiveness. Data were also used to validate a parameterized RBE model. Conclusions The predicted Biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.
