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Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note
Stockholm University, Faculty of Science, Department of Physics. (Medical Radiation Physics)
Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
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2009 (English)In: Journal of Neurosurgery, ISSN 0022-3085, Vol. 111, no 5, 919-926 p.Article in journal (Refereed) Published
Abstract [en]


Radiation treatment of large arteriovenous malformations (AVMs) remains difficult and not very effective, even though seemingly promising methods such as staged volume treatments have been proposed by some radiation treatment centers. In symptomatic patients harboring large intracranial AVMs not amenable to embolization or resection, single-session high-dose stereotactic radiation therapy is a viable option, and the special characteristics of high-ionization-density light-ion beams offer several treatment advantages over photon and proton beams. These advantages include a more favorable depth-dose distribution in tissue, an almost negligible lateral scatter of the beam, a sharper penumbra, a steep dose falloff beyond the Bragg peak, and a higher probability of vascular response due to high ionization density and associated induction of endothelial cell proliferation and/or apoptosis. Carbon ions were recently shown to be an effective treatment for skull-base tumors. Bearing that in mind, the authors postulate that the unique physical and biological characteristics of light-ion beams should convey considerable clinical advantages in the treatment of large AVMs. In the present meta-analysis the authors present a comparison between light-ion beam therapy and more conventional modalities of radiation treatment with respect to these lesions.


Dose-volume histograms and data on peripheral radiation doses for treatment of large AVMs were collected from various radiation treatment centers. Dose-response parameters were then derived by applying a maximum likelihood fitting of a binomial model to these data. The present binomial model was needed because the effective number of crucial blood vessels in AVMs (the number of vessels that must be obliterated to effect a cure, such as large fistulous nidus vessels) is low, making the Poisson model less suitable. In this study the authors also focused on radiobiological differences between various radiation treatments.


Light-ion Bragg-peak dose delivery has the precision required for treating very large AVMs as well as for delivering extremely sharp, focused beams to irregular lesions. Stereotactic light-ion radiosurgery resulted in better angiographically defined obliteration rates, less white-matter necrosis, lower complication rates, and more favorable clinical outcomes. In addition, in patients treated by He ion beams, a sharper dose-response gradient was observed, probably due to a more homogeneous radiosensitivity of the AVM nidus to light-ion beam radiation than that seen when low-ionization-density radiation modalities, such as photons and protons, are used.


Bragg-peak radiosurgery can be recommended for most large and irregular AVMs and for the treatment of lesions located in front of or adjacent to sensitive and functionally important brain structures. The unique physical and biological characteristics of light-ion beams are of considerable advantage for the treatment of AVMs: the densely ionizing beams of light ions create a better dose and biological effect distribution than conventional radiation modalities such as photons and protons. Using light ions, greater flexibility can be achieved while avoiding healthy critical structures such as diencephalic and brainstem nuclei and tracts. Treatment with the light ion He or Li is more suitable for AVMs <or= 10 cm(3), whereas treatment with the light ion Li, Be, or C may be more appropriate for larger AVMs. A binomial model based on the effective number of crucial vessels in the AVM may be used quite well to predict AVM obliteration probabilities for both small and large AVMs when therapies involving either photons or light ions are used.

Place, publisher, year, edition, pages
2009. Vol. 111, no 5, 919-926 p.
Keyword [en]
arteriovenous malformation, stereotactic ion beam therapy, radiosurgery
National Category
Medical and Health Sciences
URN: urn:nbn:se:su:diva-74967DOI: 10.3171/2007.10.17205ISI: 000271375500011OAI: diva2:513291
Available from: 2012-04-01 Created: 2012-04-01 Last updated: 2012-10-24Bibliographically 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, BahramMavroidis, Panayiotis
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