Journal ArticleDOI
A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.
Eivind Rørvik,S. Thörnqvist,S. Thörnqvist,Camilla H. Stokkevåg,Tordis J. Dahle,Lars Fredrik Fjæra,Lars Fredrik Fjæra,Kristian S. Ytre-Hauge +7 more
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TLDR
Analysis indicated that non‐linear models could give a better representation of the RBE‐LET relationship, as differences between the models were observed for the SOBP scenario, and both non‐ linear LET spectrum‐ and linear LETd based models should be further evaluated in clinically realistic scenarios.Abstract:
Purpose
The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LETd) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model.
Method
The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LETd based models for a simulated spread out Bragg peak (SOBP) scenario.
Results
The statistical analysis of the weighted regression analysis favoured a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (p=0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (p=0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22).
Conclusion
The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were observed for the SOBP scenario, both non-linear LET spectrum- and linear LETd based models should be further evaluated in clinically realistic scenarios.
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Citations
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Journal ArticleDOI
Exploration and application of phenomenological RBE models for proton therapy
Eivind Rørvik,Lars Fredrik Fjæra,Tordis J. Dahle,Jon Espen Dale,G.M. Engeseth,Camilla H. Stokkevåg,S. Thörnqvist,S. Thörnqvist,Kristian S. Ytre-Hauge +8 more
TL;DR: There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models and these variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques.
Journal ArticleDOI
New insights in the relative radiobiological effectiveness of proton irradiation
TL;DR: How RBE depends on the dose, different biological endpoints and physical properties is analyzed and there is an urgent need for more coordinated in vitro and in vivo experiments that concentrate on a realistic dose range of in clinically relevant tissues like lung or spinal cord.
Journal ArticleDOI
Is the dose-averaged LET a reliable predictor for the relative biological effectiveness?
TL;DR: The analysis showed that LETD is a sufficiently accurate predictor for RBE only in regions with comparably narrow, but not in areas with broad, LET distribution as in a single SOBP or in multiple overlapping fields.
Journal ArticleDOI
Proton therapy for head and neck squamous cell carcinomas: A review of the physical and clinical challenges.
A. Beddok,Anthony Vela,Valentin Calugaru,Thomas Tessonnier,Jiri Kubes,Pauline Dutheil,A. Gérard,M. Vidal,F. Goudjil,C. Florescu,Emmanuel Kammerer,Karen Benezery,Joel Herault,Philip Poortmans,Jean Bourhis,Juliette Thariat +15 more
TL;DR: The effects of these uncertainties and their management for developing a robust and optimized IMPT treatment delivery plan to achieve clinical outcomes that are superior to those for IMRT are explored.
Journal ArticleDOI
Modelling variable proton relative biological effectiveness for treatment planning.
TL;DR: The models that have been developed to better predict RBE variations in tissue based on experimental data as well as using a mechanistic approach are reviewed.
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