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Year : 2017  |  Volume : 65  |  Issue : 4  |  Page : 697--698

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations

Ajay Niranjan1, John C Flickinger2,  
1 Department of Neurological Surgery, Center of Image-Guided Neurosurgery, University of Pittsburgh, PA, USA
2 Department of Radiation Oncology, Center of Image-Guided Neurosurgery, University of Pittsburgh, PA, USA

Correspondence Address:
Ajay Niranjan
Department of Neurological Surgery, Center of Image-Guided Neurosurgery, University of Pittsburgh, PA

How to cite this article:
Niranjan A, Flickinger JC. Dose fractionated gamma knife radiosurgery for large arteriovenous malformations.Neurol India 2017;65:697-698

How to cite this URL:
Niranjan A, Flickinger JC. Dose fractionated gamma knife radiosurgery for large arteriovenous malformations. Neurol India [serial online] 2017 [cited 2022 Sep 27 ];65:697-698
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Full Text

The optimal management of large (volume >10 cm 3) brain arteriovenous malformations (AVMs) is controversial. As stand-alone treatment modality for large AVMs, microsurgery is associated with relatively high rates of morbidity and mortality, whereas embolization results in low rates of complete nidal obliteration. Stereotactic radiosurgery (SRS) is effective for many small- to-medium-sized AVMs but yields lower obliteration rates for large AVMs with increased rates of neurological morbidity. The volume of the surrounding normal brain covered in 12 Gy isodose is considered a significant predictor of adverse radiation effects following AVM radiosurgery.[1] As the 12 Gy volume increases, so are the chances of adverse radiation effects. In the cases of large AVMs where a single session radiosurgery (10 cc or more) is administered, invariably lower margin doses were prescribed in order to keep the 12 Gy volume within acceptable limits. Lowering prescribed margin doses is associated with reduced obliteration rates. In order to avoid complications (related to dose fall-off in the surrounding normal brain) and still maintain a reasonably high obliteration rate, the concepts of volume-staged stereotactic radiosurgery (VS-SRS) and dose-staged (DS) SRS (fractionated SRS) using more than one session were introduced. The goal for these strategies is to improve the risk-to-benefit profile for the radiosurgical treatment of large AVMs. Volume-staged SRS divides large AVMs into distinct volumes, each of which is independently targeted by SRS, with 3- to 9-month intervals between the sessions, until the entire AVM is treated. In contrast, DS-SRS involves repeated delivery of radiation to the entire AVM until a cumulative total dose has been delivered over a period of a few days or weeks. Either technique can be used as a stand-alone approach to achieve obliteration.

The authors reported their experience with dose fractionated gamma knife radiosurgery (DFGKSRS) for large volume AVMs. The authors treated 14 patients with three (8.9-11.5Gy per fraction) or two (11.3-15Gy per fraction) fraction scheme. These doses appear higher than that used in other studies using LINAC based fraction schedules. Out of seven patients who reached at least a 3-year follow-up, 3 had complete obliteration (43%). Six out of 14 patients (43%) developed headache requiring steroids and 2 required bevacizumab. One patient developed hemiparesis and the second showed behavioral changes. The rate of complications was not insignificant.[2]

While several studies on the outcome of staged SRS have been published, the data on DS-SRS using the gamma knife is sparse. Our study of VS-SRS showed an improved response with margin doses ≥17 Gy using VS-SRS.[3] VS-SRS, in comparison to single staged-SRS for large AVMs, significantly reduces the rates of permanently symptomatic adverse radiation effects. Although most reports have used a 3–8 month time interval between the VS-SRS stages, the optimal interval that is required between the stages remains unknown. A recent systematic review suggests that VS-SRS may afford higher rates of both complete and partial obliteration than DS-SRS.[4]

It is important to consider both the total delivered dose as well as the dose per fraction of DS-SRS. Previous reports have documented that a higher total dose is associated with an increased risk of complications without improving the potential for obliteration. Therefore, some studies have suggested that the total dose for DS-SRS be limited to [5] Thus, an efficient DS-SRS schedule appears to be 4 fractions at 7 Gy per fraction or 5 fractions at 6–6.5 Gy per fraction.[4] Estimating equivalent doses with the linear-quadratic model for changing from single fraction to fractionated radiosurgery is problematic for a number of reasons. The linear-quadratic formula leads to extrapolation errors with large fractions, which are evident when the alpha-beta ratios are calculated from single-fraction radiosurgery.[6] In addition, targeting errors frequently occur in AVM radiosurgery where part of the AVM nidus is not enclosed in the radiosurgery treatment volume.[6] This occurs more frequently when patients have undergone embolization. Targeting error makes it problematic to calculate the alpha-beta ratios for AVM obliteration with different dose-fractionation schemes.

The current study certainly proves that dose fractionation can be performed using the gamma knife.[2] Frameless gamma knife radiosurgery may be a better option for such fractionation. Although at the present time, angiograms cannot be incorporated into frameless mask-based radiosurgery, using gamma knife Ikon, it is certainly possible to treat the first fraction using the frame and deliver the 2nd and 3rd fractions using the mask. The management of large AVMs is challenging, and the role of VS-SRS and DS-SRS continues to evolve as the outcome data accrues. A large multicenter prospective study or randomized controlled trial is needed to prove the value of dose fractionation for large AVMs.


1Flickinger JC, Kondziolka D, Lunsford LD, Kassam A, Phuong LK, Liscak R, et al. Development of a model to predict permanent symptomatic postradiosurgery injury for arteriovenous malformation patients. Arteriovenous Malformation Radiosurgery Study Group. Int J Radiat Oncol Biol Phys 2000;46:1143-8.
2Mukherjee KK, Kumar N, Tripathi M, Oinam AS, Ahuja CK, Dhandapani S, Kapoor R, Ghoshal S, Kaur R, Bhat S. Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation. Neurol India 2017;65:826-35.
3Kano H, Kondziolka D, Flickinger JC, Park KJ, Parry PV, Yang HC, et al. Multistaged volumetric management of large arteriovenous malformations. Prog Neurol Surg 2013;27:73-80.
4Ilyas A, Chen CJ, Ding D, Taylor DG, Moosa S, Lee CC, et al. Volume-staged versus dose-staged stereotactic radiosurgery outcomes for large brain arteriovenous malformations: A systematic review. J Neurosurg 2017:1-11. doi: 10.3171/2016.9.JNS161571.
5Chen JC, Mariscal L, Girvigian MR, Vanefsky MA, Glousman BN, Miller MJ, et al. Hypofractionated stereotactic radiosurgery for treatment of cerebral arteriovenous malformations: Outcome analysis with use of the modified arteriovenous malformation scoring system. J Clin Neurosci 2016;29:155-61.
6Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD. An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration. Radiother Oncol 2002;63:347-54.