**5.5 Fractionated radiation/treatment**

FR strategy is intended for treating large lesions that carry increased mortality and morbidity using interventional methods and lower obliteration rates or longer obliteration time when treated using radiotherapy. Unfortunately, large AVM is not a well-defined or accepted criterion in the literature. SM refer to >6 cm along the nidus largest diameter. Other studies define a volumetric condition >10 (cm3 ) [62]. However, there is a consensus that high single-fraction doses as used in small AVMs increase radiation injury risks and associated neurological deficits when

large normal brain volume is exposed to high doses [89]. Two approaches exist to improve safety and efficacy in these cases: (1) **fractionation radiosurgery (FR)** where total dose is equally divided into fractions delivered over multiple sessions (days scale), so brain tissue adjacent to the lesion can tolerate higher integral doses. (2) **Volume staged radiosurgery** where the AVM is typically divided into 2–4 spatial regions each treated separately using a high single-fraction dose. Between treatments, a rest period (3–9 months) is imposed. Here, each AVM part is instantly treated with a clinically effective dose. Normal brain tissue recovers between treatments. This makes it possible to tackle the main disadvantage of FR—low fractional doses are relatively less effective at treating AVM and result in reduced obliteration rates unless the total dose is substantially increased [89]. However, a main concern of this approach is that partial AVM obliteration apparently alters blood flow patterns and increases hemorrhage risks [89]. Currently, there is a little evidence for the superiority of one approach over the other [89]. In general, it is highly recommended to minimize the integral dose to the normal brain of asymptomatic patients. Recently, Unkelbach et al. elegantly demonstrated that by boosting complementary parts of the target volume in different fractions, it may be possible to achieve a therapeutic advantage in FR since this approach facilitates mean dose reduction in the normal brain [89]. To date, FR has not been widely accepted as presenting a compelling advantage over multi-modality treatments such as initial size reduction using embolization.

#### **5.6 Summary**

While gaining popularity and presenting impressive treatment success rates of ~80%, radiosurgery still has distinct limitations that must be faced. Obliteration typically takes 2–3 years during which patients remain exposed to significant annual bleeding risks of 4–5% (twice that of conventional treatment) and overall morbidity rates reaching 12%. Large (SM grade ≥ 3) AVMs necessitate multi-modality or fractionated treatment. The latter shows promise but requires further study if efficient management is desired.
