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Modeling of dose and sensitivity heterogeneities in radiation therapy
Stockholm University, Faculty of Science, Department of Physics.
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 [en]
Monte Carlo simulations, Tumor control probability, Modeling, Beam characterization
National Category
Other Physics Topics
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-74719ISBN: 978-91-7447-473-2 (print)OAI: oai:DiVA.org:su-74719DiVA: diva2:511523
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
List of papers
1. Radial secondary electron dose profiles and biological effects in light-ion beams based on analytical and Monte Carlo calculations using distorted wave cross sections
Open this publication in new window or tab >>Radial secondary electron dose profiles and biological effects in light-ion beams based on analytical and Monte Carlo calculations using distorted wave cross sections
2008 (English)In: Radiation Research, ISSN 0033-7587, Vol. 170, no 1, 83-92 p.Article in journal (Refereed) Published
Abstract [en]

To speed up dose calculation, an analytical pencil-beam method has been developed to calculate the mean radial dose distributions due to secondary electrons that are set in motion by light ions in water. For comparison, radial dose profiles calculated using a Monte Carlo technique have also been determined. An accurate comparison of the resulting radial dose profiles of the Bragg peak for (1)H(+), (4)He(2+) and (6)Li(3+) ions has been performed. The double differential cross sections for secondary electron production were calculated using the continuous distorted wave-eikonal initial state method (CDW-EIS). For the secondary electrons that are generated, the radial dose distribution for the analytical case is based on the generalized Gaussian pencil-beam method and the central axis depth-dose distributions are calculated using the Monte Carlo code PENELOPE. In the Monte Carlo case, the PENELOPE code was used to calculate the whole radial dose profile based on CDW data. The present pencil-beam and Monte Carlo calculations agree well at all radii. A radial dose profile that is shallower at small radii and steeper at large radii than the conventional 1/r(2) is clearly seen with both the Monte Carlo and pencil-beam methods. As expected, since the projectile velocities are the same, the dose profiles of Bragg-peak ions of 0.5 MeV (1)H(+), 2 MeV (4)He(2+) and 3 MeV (6)Li(3+) are almost the same, with about 30% more delta electrons in the sub keV range from (4)He(2+)and (6)Li(3+) compared to (1)H(+). A similar behavior is also seen for 1 MeV (1)H(+), 4 MeV (4)He(2+) and 6 MeV (6)Li(3+), all classically expected to have the same secondary electron cross sections. The results are promising and indicate a fast and accurate way of calculating the mean radial dose profile.

Keyword
Electrons, Ions, Light, Monte Carlo Method
National Category
Physical Sciences
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-17677 (URN)10.1667/RR0961.1 (DOI)000257298100009 ()18582149 (PubMedID)
Available from: 2009-01-19 Created: 2009-01-19 Last updated: 2012-03-22Bibliographically approved
2. A Monte Carlo program for the analysis of low-energy electron tracks in liquid water
Open this publication in new window or tab >>A Monte Carlo program for the analysis of low-energy electron tracks in liquid water
2011 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 56, no 7, 1985-2003 p.Article in journal (Refereed) Published
Abstract [en]

A Monte Carlo code for the event-by-event simulation of electron transport in liquid water is presented. The code, written in C++, can accommodate different interaction models. Currently it implements cross sections for ionizing collisions calculated with the model developed by Dingfelder et al (1998 Radiat. Phys. Chem. 53 1–18, 2008 Radiat. Res. 169 584–94) and cross sections for elastic scattering computed within the static-exchange approximation (Salvat et al 2005 Comput. Phys. Commun. 165 157–90). The latter cross sections coincide with those recommended in ICRU Report 77 (2007). Other included interaction mechanisms are excitation by electron impact and dissociative attachment. The main characteristics of the code are summarized. Various track penetration parameters, including the detour factor, are defined as useful tools to quantify the geometrical extent of electron tracks in liquid water. Results obtained with the present microdosimetry code are given in the form of probability density functions for initial electron kinetic energies ranging from 0.1 to 10 keV. The sensitivity of the simulated distributions to the choice of alternative physics models has been briefly explored. The discrepancies with equivalent simulations reported by Wilson et al (2004 Radiat. Res. 161 591–6) stem from the adopted cross sections for elastic scattering, which determine largely the spatial evolution of low-energy electron tracks.

Keyword
Monte Carlo track structure calculations, Cross sections
National Category
Physical Sciences
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-74718 (URN)10.1088/0031-9155/56/7/005 (DOI)
Available from: 2012-03-21 Created: 2012-03-21 Last updated: 2017-12-07Bibliographically approved
3. The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy
Open this publication in new window or tab >>The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy
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.

National Category
Physical Sciences
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-70644 (URN)10.1088/0031-9155/56/23/016 (DOI)000297784400016 ()
Note

authorCount :3

Available from: 2012-01-24 Created: 2012-01-23 Last updated: 2017-12-08Bibliographically approved
4. Impact of dose and sensitivity heterogeneity on TCP
Open this publication in new window or tab >>Impact of dose and sensitivity heterogeneity on TCP
2014 (English)In: Computational & Mathematical Methods in Medicine, ISSN 1748-670X, E-ISSN 1748-6718, 182935Article in journal (Refereed) Published
Abstract [en]

Purpose.The combined influence of heterogeneity in dose and radiation sensitivity on the probability of tumor control has not yet been fully explored, neither by numerical simulations nor by analytical modeling. The present paper adds to the current experience and presents an analytical description and numerical simulations of the influence of macroscopic intercell dose variations and intercell sensitivity variations on the probability of controlling the tumor. Methods. Computer simulations of tumour control probability (TCP) accounting for heterogeneity in dose and radiation sensitivity were performed based on Bernoulli trials including cell repopulation during the course of treatment in an explicit manner, without performing approximations.The dose heterogeneity was simulated by random sampling from a normal distribution with a specified mean dose and standard deviation. Two scenarios were considered for the simulation of intercell heterogeneity of the sensitivity described by the parameters of the linear-quadratic model (LQ) for cell killing. An analytical expression for TCP accounting for heterogeneity in sensitivity was also proposed and validated against simulations. Results. The results show good agreement between numerical simulations and the calculated TCP using the proposed analytical expression for the case of a heterogeneous dose and sensitivity distributions.When the intercellular variations of dose and sensitivity are taken into account, the total dose required for achieving the same level of control as for the case of homogeneous distribution is only slightly higher, the influence of the variations in the two factors taken into account being additive. For the case of interpatient variations in dose and sensitivity, the combined effects result in a coefficient of synergy of less than one. Conclusions.The results of this study show that the interplay between cell or tumor variation in the sensitivity to radiation and the inherent heterogeneity in dose distribution is highly complex and therefore should be taken into account when predicting the outcome of a given treatment.

Keyword
Tumor control probability, Sensitivity variation, Dose Heterogeneity, Modeling
National Category
Cancer and Oncology
Research subject
Medical Radiation Physics
Identifiers
urn:nbn:se:su:diva-102700 (URN)10.1155/2014/182935 (DOI)000336273000001 ()
Note

AuthorCount:3;

Available from: 2014-04-16 Created: 2014-04-16 Last updated: 2017-12-05Bibliographically approved

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