Early versus late arteriovenous malformation responders after stereotactic radiosurgery: an international multicenter study

Abstract

OBJECTIVE The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM. METHODS Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7-324.7 months). RESULTS Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems. CONCLUSIONS Early obliteration (≤ 18 months post-SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy.

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

“…22,51,55 A literature review revealed that the most commonly reported factors associated with favorable outcome of SRS for AVMs were ruptured AVMs, lower AVM grade, smaller AVM volume, and a higher marginal dose. 11,19,52,[56][57][58][59] The present study showed that Spetzler-Martin grades I to III, AVM volumes 10 cc, and, more significantly, the appearance of perinidal T2 hyperintensity signal in post-SRS follow-up MRIs were independent predictors of AVM obliteration, which is consistent with other AVM SRS series. 11,19,22,52,[56][57][58][59][60] The importance of the MRI appearance of perinidal high T2 signal, after SRS of AVMs, in predicting nidal obliteration was highlighted by other investigators.…”

“…11,19,52,[56][57][58][59] The present study showed that Spetzler-Martin grades I to III, AVM volumes 10 cc, and, more significantly, the appearance of perinidal T2 hyperintensity signal in post-SRS follow-up MRIs were independent predictors of AVM obliteration, which is consistent with other AVM SRS series. 11,19,22,52,[56][57][58][59][60] The importance of the MRI appearance of perinidal high T2 signal, after SRS of AVMs, in predicting nidal obliteration was highlighted by other investigators. 19,22,60 Arrese Regańón et al 19 reported that the development of hyperintensity on T2 MRI after the treatment was among the strongest predictive factors of achieved nidal obliteration in 77% of their series of 59 radiosurgically treated AVMs.…”

“…These changes, usually observed from 6 to 18 months after SRS, are frequently transient and reversible (i.e., resolving over weeks or a few months). 4,11,22,26,27,[51][52][53][54] Ilyas et al, 53 based on pooled data from 51 studies, reported that $ 1 in 3 patients with AVMs treated with SRS develops radiologically evident RIC, and of those, 1 in 4 patients develops neurologic symptoms. The present study showed 20.9%, 33.9%, and 12.9% rates of transient, persistent, and symptomatic RICs, respectively.…”

“…Such complications are attributed to the delivery of clinically significant radiation doses to normal brain tissues lying immediately adjacent to the AVM nidus or embedded within the nidus itself. 4,11,12 As the SRS target volume increases, the volume of normal tissue receiving a clinically significant dose rapidly increases, and consequently the higher the complication rate. [13][14][15] Thus the selection of patients with cerebral AVMs for SRS should be based on weighing the benefits versus the risks of SRS, with respect to the natural history and to those of other treatment modalities (i.e., microsurgery and endovascular surgery).…”

“…However, Arrese Regańón et al 19 reported that many AVMs showed complete obliteration between 3 and 5 years after SRS and recommended waiting until 5 years after treatment before considering a new therapeutic approach for an observed residual AVM nidus by the end of 3 years after treatment. An international multicenter study, conducted by Cohen-Inbar et al, 11 recently reported that documentation of AVM obliteration can extend to as long as 5 years after SRS. Unlike microsurgery, in which the risk of hemorrhage is completely eliminated right after surgery, SRS has no significant influence on the rate of bleeding, when compared with the natural history, at any time during the latency period before complete obliteration of the AVM nidus is achieved.…”