Lars Fredrik Fjæra

Bio: Lars Fredrik Fjæra is an academic researcher from University of Bergen. The author has contributed to research in topics: Relative biological effectiveness & Proton therapy. The author has an hindex of 6, co-authored 11 publications receiving 153 citations. Previous affiliations of Lars Fredrik Fjæra include Haukeland University Hospital.

Exploration and application of phenomenological RBE models for proton therapy

Abstract: The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases. All models were analysed with respect to the distribution and range of linear energy transfer (LET) and reference radiation fractionation sensitivity ((α/β) x ) of their respective experimental databases. Proton therapy plans for a spread-out Bragg peak in water and three patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma) were optimised using an RBE of 1.1 in the Eclipse™ treatment planning system prior to recalculation and modelling in the FLUKA Monte Carlo code. Model estimated dose-volume parameters for the planning target volumes (PTVs) and organs at risk (OAR) were compared. The experimental in vitro databases for the various models differed greatly in the range of (α/β) x values and dose-averaged LET (LETd). There were significant variations between the model estimations, which arose from fundamental differences in the database definitions and model assumptions. The greatest variations appeared in organs with low (α/β) x and high LETd, e.g. biological doses given to late responding OARs located distal to the target in the treatment field. In general, the variation in maximum dose (D2%) was larger than the variation in mean dose and other dose metrics, with D2% of the left optic nerve ((α/β) x = 2.1 Gy) in the pituitary adenoma case showing the greatest discrepancies between models: 28-52 Gy(RBE), while D2% for RBE1.1 was 30 Gy(RBE). For all patient cases, the estimated mean RBE to the PTV was in the range 1.09-1.29 ((α/β) x = 1.5/3.1/10.6 Gy). There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models. These variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques. The results from the implementation of RBE models in dose planning studies should be evaluated in light of these deviations.

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer

Abstract: Background: For tumours near organs at risk, there is concern about unintended increase in biological dose from elevated linear energy transfer (LET) at the distal end of treatment fields. The obje...

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

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. This article is protected by copyright. All rights reserved.

Monte Carlo simulations of a low energy proton beamline for radiobiological experiments

Abstract: Background: In order to determine the relative biological effectiveness (RBE) of protons with high accuracy, radiobiological experiments with detailed knowledge of the linear energy transfer (LET) ...

The linear quadratic model: usage, interpretation and challenges

Abstract: The linear-quadratic model is one of the key tools in radiation biology and physics. It provides a simple relationship between cell survival and delivered dose: [Formula: see text], and has been used extensively to analyse and predict responses to ionising radiation both in vitro and in vivo. Despite its ubiquity, there remain questions about its interpretation and wider applicability-Is it a convenient empirical fit or representative of some deeper mechanistic behaviour? Does a model of single-cell survival in vitro really correspond to clinical tissue responses? Is it applicable at very high and very low doses? Here, we review these issues, discussing current usage of the LQ model, its historical context, what we now know about its mechanistic underpinnings, and the potential challenges and confounding factors that arise when trying to apply it across a range of systems.

American Association of Physicists in Medicine

Abstract: J. DAnwl B8NrL.nd, Ph.D., isIlssU14nt professor Andhed, Physic Section, Dep.:ntm ent ofR.4dUaion Oncology, Wa e Forest Unit/miry School of Medicine in Winston-Salem, N.G. He ischairman ofthe AAPM Electronic Media Coordinating Committee, chairman ofthe new AAPM Subcommitteeon MoieCHlaTImaging in Clinical Radiation Oncology, and aformer member ofthe AAPM RildiAtion Therllpy Committee. The AAPM is headqNllTtered in College PIlTk, Md. WHO WE ARE The America n Assoc iation of Physicists in Medicine (AAPM) h J S ap proximately 4.62S mcmbers who practice or arc associn ed with medical physics.

Exploration and application of phenomenological RBE models for proton therapy

Abstract: The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases. All models were analysed with respect to the distribution and range of linear energy transfer (LET) and reference radiation fractionation sensitivity ((α/β) x ) of their respective experimental databases. Proton therapy plans for a spread-out Bragg peak in water and three patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma) were optimised using an RBE of 1.1 in the Eclipse™ treatment planning system prior to recalculation and modelling in the FLUKA Monte Carlo code. Model estimated dose-volume parameters for the planning target volumes (PTVs) and organs at risk (OAR) were compared. The experimental in vitro databases for the various models differed greatly in the range of (α/β) x values and dose-averaged LET (LETd). There were significant variations between the model estimations, which arose from fundamental differences in the database definitions and model assumptions. The greatest variations appeared in organs with low (α/β) x and high LETd, e.g. biological doses given to late responding OARs located distal to the target in the treatment field. In general, the variation in maximum dose (D2%) was larger than the variation in mean dose and other dose metrics, with D2% of the left optic nerve ((α/β) x = 2.1 Gy) in the pituitary adenoma case showing the greatest discrepancies between models: 28-52 Gy(RBE), while D2% for RBE1.1 was 30 Gy(RBE). For all patient cases, the estimated mean RBE to the PTV was in the range 1.09-1.29 ((α/β) x = 1.5/3.1/10.6 Gy). There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models. These variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques. The results from the implementation of RBE models in dose planning studies should be evaluated in light of these deviations.