Asymptomatic Late-phase Radiographic Changes Among Chest-Wall Patients Are Associated With a Proton RBE Exceeding 1.1

Underwood, Tracy; Grassberger, Clemens; Bass, Rhedise; MacDonald, Shannon M.; Meyersohn, Nandini M.; Yeap, Beow Y.; Jimenez, Rachel; Paganetti, Harald

doi:10.1016/j.ijrobp.2018.03.037

“…Recently, Michelle et al reported a clear increasing trend of brainstem injury with the increasing RBE dose in brainstem for pediatric patients with posterior fossa tumors. And similar evidence was also reported in chest wall and pediatric cancer patients for lung injury and brain necrosis, respectively, which suggested that proton RBE can exceed 1.1 in vivo .…”

Section: Introductionsupporting

confidence: 78%

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

Deng

¹

,

Ding

²

,

Younkin

³

et al. 2019

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Purpose The dose‐averaged linear energy transfer (LETd) for intensity‐modulated proton therapy (IMPT) calculated by one‐dimensional (1D) analytical models deviates from more accurate but time‐consuming Monte Carlo (MC) simulations. We developed a fast hybrid three‐dimensional (3D) analytical LETd calculation that is more accurate than 1D analytical model. Methods We used the Geant4 MC code to generate 3D LETd distributions of monoenergetic proton beams in water for all energies and used a customized error function to fit the LETd lateral profiles at various depths to the MC simulation. The 3D LETd calculation kernel was a lookup table of these fitted coefficients, and LETd was determined directly from spot energies and voxel coordinates during analytical dose calculations. We validated our new method by comparing the calculated LETd distributions to MC results using 3D Gamma index analysis with 3%/2 mm criteria in 12 patient geometries. The significance of the improvement in Gamma index analysis passing rates over the 1D analytical model was determined using the Wilcoxon rank‐sum test. Results The passing rate of 3D Gamma analysis comparing LETd distributions from the hybrid 3D method and the 1D method to MC simulations was significantly improved from 94.0% ± 2.5% to 98.0% ± 1.0% (P = 0.0003). The typical time to calculate dose and LETd simultaneously using an Intel Xeon E5‐2680 2.50 GHz workstation was approximately 2.5 min. Conclusions Our new method significantly improved the LETd calculation accuracy compared to the 1D method while maintaining significantly shorter calculation time even comparing with the GPU‐based fast MC code.

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“…The current practice is to use a constant value of 1.1 to convert physical dose to RBE-weighted dose. And similar evidence was also reported in chest wall and pediatric cancer patients for lung injury 17 and brain necrosis, 18 respectively, which suggested that proton RBE can exceed 1.1 in vivo. While RBE~1.1 when LET d~1 keV/lm, RBE may be significantly higher (around 1.5) when LET d is high (around 10 keV/lm) near the end of the proton beam range and in the corresponding lateral penumbra regions due to multiple Coulomb scattering.…”

Section: Introductionsupporting

confidence: 71%

New Hybrid 3D Analytical Linear Energy Transfer (LET) Calculation Algorithm Based on the Pre-Calculated Data from Monte Carlo (MC) Simulations

Deng

¹

,

Ding

²

,

Younkin

³

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

0

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Purpose The dose‐averaged linear energy transfer (LETd) for intensity‐modulated proton therapy (IMPT) calculated by one‐dimensional (1D) analytical models deviates from more accurate but time‐consuming Monte Carlo (MC) simulations. We developed a fast hybrid three‐dimensional (3D) analytical LETd calculation that is more accurate than 1D analytical model. Methods We used the Geant4 MC code to generate 3D LETd distributions of monoenergetic proton beams in water for all energies and used a customized error function to fit the LETd lateral profiles at various depths to the MC simulation. The 3D LETd calculation kernel was a lookup table of these fitted coefficients, and LETd was determined directly from spot energies and voxel coordinates during analytical dose calculations. We validated our new method by comparing the calculated LETd distributions to MC results using 3D Gamma index analysis with 3%/2 mm criteria in 12 patient geometries. The significance of the improvement in Gamma index analysis passing rates over the 1D analytical model was determined using the Wilcoxon rank‐sum test. Results The passing rate of 3D Gamma analysis comparing LETd distributions from the hybrid 3D method and the 1D method to MC simulations was significantly improved from 94.0% ± 2.5% to 98.0% ± 1.0% (P = 0.0003). The typical time to calculate dose and LETd simultaneously using an Intel Xeon E5‐2680 2.50 GHz workstation was approximately 2.5 min. Conclusions Our new method significantly improved the LETd calculation accuracy compared to the 1D method while maintaining significantly shorter calculation time even comparing with the GPU‐based fast MC code.

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“…A study in 34 ependymoma patients found a correlation between incidence of post‐treatment image changes in magnetic resonance and both dose and LET . More recently, a similar study in chest wall patients reported a correlation between asymptomatic late‐phase radiographic changes within the lung and increased proton RBE . These new findings (along with accumulated clinical experience) have triggered several reviews of the existing knowledge on proton RBE.…”

Section: Introductionmentioning

confidence: 93%

“…8 More recently, a similar study in chest wall patients reported a correlation between asymptomatic late-phase radiographic changes within the lung and increased proton RBE. 9 These new findings (along with accumulated clinical experience) have triggered several reviews of the existing knowledge on proton RBE. While a few of them claim, in one way or another, that a variable RBE scheme should be implemented in clinical practice in the near future [14][15][16] many others agree that current evidence still does not support such a change of paradigm and propose alternative solutions for the consideration of this effect.…”

Section: Introductionmentioning

confidence: 99%

MultiRBE: Treatment planning for protons with selective radiobiological effectiveness

Sánchez-Parcerisa

¹

,

López-Aguirre

²

,

Llerena³

et al. 2019

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Purpose Clinical treatment planning protocols for protons recommend a uniform value radiobiological effectiveness (RBE) of protons of 1.1 throughout the treatment field, despite evidence from in‐vitro and animal studies that proton RBE increases with linear energy transfer (LET), causing tissues placed distally to the target location to receive a presumably higher biological dose than estimated. While several voices in the medical physics community have advocated for variable RBE‐based optimization, the uncertainties in RBE models have prevented its implementation in clinical practice, since an overestimation of RBE could cause significant target underdosage. Methods We propose a mixed RBE model (MultiRBE), where a uniform RBE is used in the target contours to ensure an adequate tumor coverage in terms of physical dose, but a variable RBE is used elsewhere. Our model was implemented in the open‐source treatment planning system matRad and three example cases were planned: a homogeneous phantom, a prostate tumor and a head‐and‐neck case. MultiRBE was used for plan optimization, and the produced plans were subsequently evaluated in terms of physical dose coverage (V95%) and variable RBE‐weighted dose in organs at risk and normal tissue complication probabilities (NTCP), where prediction models were available. Results The planning algorithm showed potential for reducing the biological dose in organs surrounding the planning target and thus decreasing the probability for complications in normal tissue (by up to 62% in the prostate case and 37% in the head‐and‐neck patient). This was achieved without compromising the target coverage or homogeneity in terms of physical dose, as a result of a smarter redistribution of dose among the surrounding tissues with regard to the optimization constraints. Conclusions The results prove the ability of the MultiRBE model to reduce biological dose at healthy tissues without compromising the dose coverage of the tumor, with independence of the variable RBE models used.

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Asymptomatic Late-phase Radiographic Changes Among Chest-Wall Patients Are Associated With a Proton RBE Exceeding 1.1

Cited by 93 publications

References 33 publications

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

New Hybrid 3D Analytical Linear Energy Transfer (LET) Calculation Algorithm Based on the Pre-Calculated Data from Monte Carlo (MC) Simulations

MultiRBE: Treatment planning for protons with selective radiobiological effectiveness

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