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The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy
Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).ORCID iD: 0000-0002-7101-240X
Karolinska Institutet, Sweden.
2011 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 23, 7585-7600 p.Article in journal (Refereed) Published
Abstract [en]

Theoretical modelling of tumour control probability (TCP) with respect to non-uniformity in the dose to the tumour, alternate fractionation schemes and tumour kinetics is a very useful tool for assessment of the influence of changes in dosimetric or radiobiological factors on the outcome of the treatment. Various attempts have been made to also include effects from non-uniform dose to the tumour volume, but the problem has not been fully solved and many factors were totally neglected or not accurately taken into account. This paper presents derivations of analytical expressions of TCP for macroscopic inter-cell dose variations and for random inter-fractional variations in average tumour dose, based on binomial statistics for the TCP and the well-known linear quadratic model for the cell survival. Numerical calculations have been performed to validate the analytical expressions. An analysis of the influence of the deterministic and stochastic heterogeneity in dose delivery on the TCP was performed. The precision requirements in dose delivery are discussed briefly with the support of the presented results. The main finding of this paper is that it is primarily the shape of the cell survival curve that governs how the response is affected by macroscopic dose variations. The analytical expressions for TCP accounting for heterogeneity in dose can quite well describe the TCP for varying dose from cell to cell and random dose in each fraction. An increased TCP is seen when a large number of fractions are used and the variations in dose to the cells are rather high for tissues with low alpha/beta.

Place, publisher, year, edition, pages
2011. Vol. 56, no 23, 7585-7600 p.
National Category
Physical Sciences
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-70644DOI: 10.1088/0031-9155/56/23/016ISI: 000297784400016OAI: oai:DiVA.org:su-70644DiVA: diva2:482971
Note

authorCount :3

Available from: 2012-01-24 Created: 2012-01-23 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Modeling of dose and sensitivity heterogeneities in radiation therapy
Open this publication in new window or tab >>Modeling of dose and sensitivity heterogeneities in radiation therapy
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The increased interest in the use of light ion therapy is due to the high dose conformity to the target and the dense energy deposition along the tracks resulting in increased relative biological effectiveness compared to conventional radiation therapy. In spite of the good clinical experience, fundamental research on the characteristics of the ion beams is still needed in order to be able to fully explore their use. Therefore, a Monte Carlo track structure code, KITrack, simulating the transport of electrons in liquid water, has been developed and used for calculation of parameters of interest for beam characterization. The influence of the choice of the cross sections for the physical processes on the electron tracks has also been explored. As an alternative to Monte Carlo calculations a semi-analytical approach to calculate the radial dose distribution from ions, has been derived and validated.

In advanced radiation therapy, accurate characterization of the beams has to be complemented by comprehensive radiobiological models, which relate the dose deposition into the cells to the outcome of the treatment. The second part of the study has therefore explored the influence of heterogeneity in the dose deposition into the cells as well as the heterogeneity in the cells sensitivity to radiation on the probability of controlling the tumor. Analytical expressions for tumor control probability including heterogeneous dose depositions or variation of radiation sensitivity of cells and tumors have been derived and validated with numerical simulations. The more realistic case of a combination of these effects has also been explored through numerical simulations.

The MC code KITrack has evolved into an extremely useful tool for beam characterization. The tumor control probability, given by the analytical derived expression, can help improve radiation therapy. A novel anisotropy index has been proposed. It is a measure of the absence of isotropy and provides deeper understanding of the relationship between beam quality and biological effects.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm University, 2012. 93 p.
Keyword
Monte Carlo simulations, Tumor control probability, Modeling, Beam characterization
National Category
Other Physics Topics
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-74719 (URN)978-91-7447-473-2 (ISBN)
Public defence
2012-05-04, the lecture hall, Radiumhemmet, Karolinska universitetssjukhuset, Solna, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2012-04-12 Created: 2012-03-21 Last updated: 2014-04-16Bibliographically approved

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