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A comparative analysis of radio-biological models for cell-surviving fractions at high doses
Stockholm University, Faculty of Science, Department of Physics.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the     Kavanagh-Newman (KN) and several generalizations of the LQ model, e.g. the Linear-Quadratic-Linear (LQL) model, the Padé Linear Quadratic (PLQ) model, etc. The purpose of the present study is to compare a number of models in order to find the best option(s) which could successfully be used as fractionation correction method in SRT.

In this work, six independent experimental data sets were used: CHOAA8 (Chinese hamster fibroblast), H460 (non-small cell lung cancer, NSLC), NCI-H841 (small cell lung cancer, SCLC), CP3 and DU145 (human     prostate carcinoma cell lines) and U1690 (SCLC). By detailed comparisons with these measurements, the validity of nine different radiobiological models was examined for the entire dose range, including high doses   beyond the shoulder of the survival curves.

Using the computed and measured cell surviving fractions, comparison of the goodness-of-fit for all the models was performed by means of the reduced χ2 test for a 95% confidence interval. The obtained results indicate that models with dose-independent final slopes and extrapolation numbers generally represent better choices for SRT. This is especially important at high doses where the final slope and extrapolation numbers are     presently found to play a major role.

The PLQ, USC and LQL models have the least number of shortcomings at all doses. The extrapolation      numbers and final slopes of these models do not depend on dose. Their asymptotes for the cell surviving      fractions are exponentials at low as well as high doses, and this is in agreement with the behaviour of the    corresponding experimental data. This is an important improvement over the LQ model which predicts a Gaussian at high doses. Overall and for the highlighted reasons, it was concluded that the PLQ, USC and LQL models are theoretically well-founded and, as such, could prove useful and practical choices compare to other proposed radiobiological models in clinical applications for obtaining uniformly accurate cell surviving fractions encountered in stereotactic high-dose radiotherapy as well as at medium and low doses.

National Category
Cancer and Oncology
URN: urn:nbn:se:su:diva-81077OAI: diva2:559342
Available from: 2012-10-09 Created: 2012-10-08 Last updated: 2012-10-09Bibliographically approved
In thesis
1. Improving the therapeutic ratio of stereotactic radiosurgery and radiotherapy
Open this publication in new window or tab >>Improving the therapeutic ratio of stereotactic radiosurgery and radiotherapy
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

New methods of high dose delivery, such as intensity modulated radiation therapy (IMRT), stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), hadron therapy, tomotherapy, etc., all make use of a few large fractions. To improve these treatments, there are three main directions: (i) improving physical dose distribution, (ii) optimizing radiosurgery dose-time scheme and (iii) modifying dose response of tumors or normal tissues.

Different radiation modalities and systems have been developed to deliver the best possible physical dose to the target while keeping radiation to normal tissue minimum. Although applications of radiobiological findings to clinical practice are still at an early stage, many studies have shown that   sublethal radiation damage repair kinetics plays an important role in tissue response to radiation.

The purpose of the present thesis is to show how the above-mentioned directions could be used to improve treatment outcomes with special interest in radiation modalities and dose-time scheme, as well as radiobiological modeling. Also for arteriovenous malformations (AVM), the possible impact of AVM network angiostructure in radiation response was studied.

Abstract [sv]

Nya och förbättrade metoder för precisionsbestrålning, såsom intensitetsmodulerad strålbehandling (IMRT), stereotaktisk strålbehandling (SRT), stereotaktisk strålkirurgi (SRS) eller hadronterapi etc., gör det möjligt att leverera behandlingen i ett fåtal fraktioner med höga doser. Dessa behandlingmetoder kan ytterligare förbättras genom att (i) förbättra den fysikaliska dosfördelningen, (ii) optimera dosrater och fraktioneringsscheman eller (iii) modifiera dosresponsen hos tumörer eller normalvävnad.

Olika strålmodaliteter och behandlingssystem har tagits fram för att kunna leverera bästa möjliga fysikaliska dosfördelning till targetvolymen samtidigt som dosen till frisk vävnad hålls så låg som möjligt. Även om användandet av radiobiologisk kunskap och modeller i klinisk rutin ännu är i sin linda så visar många studier att kinetiken för subletal reparation av strålskador har stor betydelse för strålresponsen.

Syftet med denna avhandling är att visa hur dessa olika utvecklingsvägar kan användas för att förbättra behandlingsresultatet speciellt genom att studera vald strålmodalitet, dosrat och fraktioneringsschema samt radiobiologisk modellering. För arteriovenösa missbildningar (AVM) har även  studerats hur strukturen hos angionätverket påverkar strålresponsen.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm Univeristy, 2012. 60 p.
optimization, stereotactic radiosurgery, stereotactic radiotherapy, radiobiology, modeling
National Category
Other Physics Topics
Research subject
Medical Radiation Physics
urn:nbn:se:su:diva-81079 (URN)978-91-7447-581-4 (ISBN)
Public defence
2012-11-16, föreläsningssalen, Radiumhemmet, Karolinska universitetssjukhuset, Solna, 10:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2012-10-25 Created: 2012-10-08 Last updated: 2012-10-31Bibliographically approved

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Andisheh, Bahram
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Cancer and Oncology

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