Relating Proton Treatments to Photon Treatments via the Relative Biological Effectiveness—Should We Revise Current Clinical Practice?

Paganetti, Harald

doi:10.1016/j.ijrobp.2014.11.021

Cited by 54 publications

(46 citation statements)

References 11 publications

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“…Furthermore, the increasing use of IMPT could lead to variations in RBE as a function of delivery and/or planning parameters [48, 54–56]. …”

Section: Rbe Variations In Patientsmentioning

confidence: 99%

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Paganetti

2018

International Journal of Particle Therapy

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Proton therapy treatments are prescribed using a biological effectiveness relative to photon therapy of 1.1, that is, proton beams are considered to be 10% more biologically effective. Debate is ongoing as to whether this practice needs to be revised. This short review summarizes current knowledge on relative biological effectiveness variations and uncertainties in vitro and in vivo. Clinical relevance is discussed and strategies toward biologically guided treatment planning are presented.

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“…Furthermore, the increasing use of IMPT could lead to variations in RBE as a function of delivery and/or planning parameters [48, 54–56]. …”

Section: Rbe Variations In Patientsmentioning

confidence: 99%

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Paganetti

2018

International Journal of Particle Therapy

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“…This however assumes a spatially invariant RBE within all treatment fields and disregards strong experimental evidence (mostly based on cell survival) that suggests the RBE varies. It has been suggested that using a variable RBE may help improve proton therapy outcomes as well as help interpret clinical results from proton therapy (Carabe et al 2013, Tilly et al 2005, Wedenberg and Toma-Dasu 2014, Paganetti 2015). …”

Section: Introductionmentioning

confidence: 99%

A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all publishedin vitrocell survival data

2015

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Purpose Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies along the treatment field, i.e. with linear energy transfer (LET) and with tissue type. A recent review study collected over 70 experimental reports on proton RBE, providing a comprehensive dataset for predicting RBE for cell survival. Using this dataset we developed a model to predict proton RBE based on dose, LET and the ratio of the linear-quadratic model parameters for the reference radiation (α/β)x, as the tissue specific parameter. Methods and Materials The relationship of the RBE on dose, dose average LET (LETd) and (α/β)x was explored using 287 experimental data points. A RBE model based on the linear quadratic model was derived from a nonlinear regression fitting to the data. Results The proposed model predicts that the RBE increases with increasing LETd and decreases with increasing (α/β)x. The model additionally predicts a decrease in RBE with increasing dose. Conclusions The proposed phenomenological RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. The model agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x and also makes predictions on the relationship between RBE and dose. The proposed model shows a relationship between both α and β with LETd. Previously published phenomenological models, based on a limited data set, may have to be revised.

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“…In recent years, there has been a lively discussion as to whether a change in clinical practice toward a variable RBE is warranted [9][10][11]. The clinical evidence of RBE variations in patients is scarce owing the generally low complication rates for most treatment sites [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Paganetti

2017

Acta Oncologica

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Background: Proton therapy uses a constant relative biological effectiveness (RBE) of 1.1. The use of variable RBE values has been suggested but is currently not feasible due to uncertainties. The impact of variable RBE has solely been studied using dosimetric indices. This work elucidates the impact of RBE variations on tumor control and normal tissue complication probabilities (TCP/NTCP). Methods: Models to estimate TCP and NTCP were used in combination with an empirical proton RBE model. Variations in outcome as a function of linear-quadratic model parameters for cellular radiosensitivity were determined for TCP in prostate and ependymoma. In addition, NTCP analysis was done for brainstem necrosis. Results: Considering a variable proton RBE as a dose-modifying factor for prescription doses and dose constraints is misleading, as TCP/NTCP do not simply scale with RBE. The dependency of RBE on a/b cannot be interpreted independent of TCP/NTCP because variations in radiosensitivity affect both photon and proton treatments. Assuming interpatient variability in radiosensitivity results in lower TCP for patients with low a/b. In proton therapy, the magnitude of TCP variations is reduced due to an RBE increase as a/b decreases. The TCP in proton therapy is less affected by interpatient variability in a/b. On the other hand, patients with a lower a/b would have a lower complication probability, which is counteracted by an increase in RBE as a/b decreases. Toxicities in proton therapy would be more affected by a/b variations compared to photon therapy. Conclusions: Assessment of variable RBE in proton therapy should be based on TCP and NTCP. Potential interpatient variability in radiosensitivity causes a smaller variance in TCP but a larger variance in NTCP for proton patients. The relative TCP as a function of a/b was found to be higher than the RBE, whereas the relative NTCP was lower than a calculated RBE.

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Relating Proton Treatments to Photon Treatments via the Relative Biological Effectiveness—Should We Revise Current Clinical Practice?

Cited by 54 publications

References 11 publications

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Proton Relative Biological Effectiveness – Uncertainties and Opportunities

A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all publishedin vitrocell survival data

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

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