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Impact of dose and sensitivity heterogeneity on TCP
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.ORCID iD: 0000-0002-7101-240X
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.

Place, publisher, year, edition, pages
2014. 182935
Keyword [en]
Tumor control probability, Sensitivity variation, Dose Heterogeneity, Modeling
National Category
Cancer and Oncology
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-102700DOI: 10.1155/2014/182935ISI: 000336273000001OAI: oai:DiVA.org:su-102700DiVA: diva2:712660
Note

AuthorCount:3;

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