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Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions
Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.ORCID iD: 0000-0002-7101-240X
2013 (English)In: Journal of radiation research, ISSN 0449-3060, E-ISSN 1349-9157, Vol. 54, no 1, 18-26 p.Article in journal (Refereed) Published
Abstract [en]

Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs. This paper presents a parameterization of the Repairable Conditionally-Repairable (RCR) cell survival model that can describe the survival of oxic and hypoxic cells over a wide range of LET values, and investigates the relationship between hypoxic radiation resistance and LET. The biological response model was tested by fitting cell survival data under oxic and anoxic conditions for V79 cells irradiated with LETs within the range of 30 – 500 keV/μm. The model provides good agreement with experimental cell survival data for the range of LET investigated, confirming the robustness of the parameterization method. This new version of the RCR model is suitable for describing the biological response of mixed populations of oxic and hypoxic cells and at the same time taking into account the distribution of doses and LETs in the incident beam and its variation with depth in tissue. The model offers a versatile tool for the selection of LET and dose required in the optimization of the therapeutic effect, without severely affecting normal tissue in realistic tumors presenting highly heterogeneous oxic and hypoxic regions.

Place, publisher, year, edition, pages
2013. Vol. 54, no 1, 18-26 p.
Keyword [en]
Hypoxia, LET dependence, Carbon ions
National Category
Cancer and Oncology
Research subject
Radiation Physics; Oncology; Medical Radiation Physics
URN: urn:nbn:se:su:diva-79121DOI: 10.1093/jrr/rrs070ISI: 000313127200002OAI: diva2:547468
Available from: 2012-08-28 Created: 2012-08-28 Last updated: 2015-06-15Bibliographically approved
In thesis
1. Radiobiological end-points for the theoretical evaluation of the effectiveness of carbon ions and photons in treating tumours with dynamic hypoxia
Open this publication in new window or tab >>Radiobiological end-points for the theoretical evaluation of the effectiveness of carbon ions and photons in treating tumours with dynamic hypoxia
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tumours are characterised by unorganised vasculature, which often results in hypoxic regions. Hypoxia is a common cause for photon radiotherapy (RT) treatment failure, as hypoxic cells require up to 2-3 times higher doses compared to well-oxygenated cells for the same effect in terms of cell kill. The increase in dose that would be required to treat the tumours of cancer patients is limited by the radiation sensitivity of surrounding normal tissues. Using carbon ions instead of photons, the radiation dose can be conformed to the tumour to a much higher degree, resulting in an improved sparing of normal tissues. In addition, carbon ions have a much higher radiobiological effectiveness near the end of their range, which is positioned in the tumour. Also, the radiation modes of action leading to cell death when carbon ions interact with living tissues, are less sensitive to the oxygen status compared with the action modes of photons.

The focus of this thesis lies in the development of models for the computation of the cell surviving fraction and tumour control probability (TCP) in hypoxic tumours after photon and carbon ion RT. The impact of fractionation was evaluated with regard to possible spatial changes in oxygenation, both for stereotactic body RT and for carbon ion RT. The feasibility of a method to determine and deliver the optimal photon dose for achieving a high TCP according to spatial variations in radiation sensitivity was evaluated in a treatment planning study. The radiobiological models were finally used for the theoretical quantification of the gain in using carbon ions instead of photons.

The results show that there are great possibilities to increase the number of positive outcomes of radiation treatment of tumours if the key influential factors are taken into account, such as level and distribution of hypoxia, radiation quality and choice of fractionation schedule.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm University, 2014. 50 p.
OER, hypoxia, LOC, RCR, hypofractionation, SBRT, carbon ion, fractionation, TCP, SF, RCE, RBE
National Category
Other Physics Topics
Research subject
Medical Radiation Physics
urn:nbn:se:su:diva-102731 (URN)978-91-7447-835-8 (ISBN)
Public defence
2014-05-27, CCK Lecture Hall, R8:00, Karolinska Sjukhuset, Solna, 13:00 (English)

At the time of the doctoral defence the following papers were unpublished and had a status as follows; Paper 3: Manuscript; Paper 4: Epubl ahead of print; Paper 5: Manuscript

Available from: 2014-05-05 Created: 2014-04-17 Last updated: 2014-05-05Bibliographically approved

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Antonovic, LauraFurusawa, YoshiyaToma-Dasu, Iuliana
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