Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations.

Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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