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Improving the therapeutic ratio in stereotactic radiosurgery: optimizing treatment protocols based on kinetics of repair of sublethal radiation damage
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
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2013 (English)In: Technology in Cancer Research & Treatment (Trykt), ISSN 1533-0346, E-ISSN 1533-0338, Vol. 12, no 4, 349-361 p.Article in journal (Refereed) Published
Abstract [en]

Sublethal damage after radiation exposure may become lethal or be repaired according to repair kinetics. This is a well-established concept in conventional radiotherapy. It also plays an important role in single-dose stereotactic radiotherapy treatments, often called stereotactic radiosurgery, when duration of treatment is extended due to source decay or treatment planning protocol. The purpose of this study is to look into the radiobiological characteristics of normal brain tissue and treatment protocols and find a way to optimize the time course of these protocols. The general problem is nonlinear and can be solved numerically. For numerical optimization of the time course of radiation protocol, a biexponential repair model with slow and fast components was considered. With the clinically imposed constraints of a fixed total dose and total treatment time, three parameters for each fraction (dose-rate, fraction duration, time of each fraction) were simultaneously optimized. A biological optimization can be performed by maximizing the therapeutic difference between tumor control probability and normal tissue complication probability. Specifically, for gamma knife radiosurgery, this approach can be implemented for normal brain tissue or tumor voxels separately in a treatment plan. Differences in repair kinetics of normal tissue and tumors can be used to find clinically optimized protocols. Thus, in addition to considering the physical dose in tumor and normal tissue, we also account for repair of sublethal damage in both these tissues.

Place, publisher, year, edition, pages
2013. Vol. 12, no 4, 349-361 p.
Keyword [en]
Biologically effective dose, Sublethal radiation damage, Cell survival, Radiobiological modeling
National Category
Cancer and Oncology
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-81078DOI: 10.7785/tcrt.2012.500324ISI: 000322611300008OAI: oai:DiVA.org:su-81078DiVA: diva2:559344
Available from: 2012-10-09 Created: 2012-10-08 Last updated: 2017-12-07Bibliographically 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.
Keyword
optimization, stereotactic radiosurgery, stereotactic radiotherapy, radiobiology, modeling
National Category
Other Physics Topics
Research subject
Medical Radiation Physics
Identifiers
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)
Opponent
Supervisors
Note

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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