Management of Adverse Radiation Effects after Radiosurgery for Arteriovenous Malformations

Author(s):  
Edward A. Monaco III ◽  
Ajay Niranjan ◽  
Hideyuki Kano ◽  
John C. Flickinger ◽  
Douglas Kondziolka ◽  
...  
2015 ◽  
Vol 123 (4) ◽  
pp. 945-953 ◽  
Author(s):  
Or Cohen-Inbar ◽  
Cheng-Chia Lee ◽  
Zhiyuan Xu ◽  
David Schlesinger ◽  
Jason P. Sheehan

OBJECT The authors review outcomes following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs) and their correlation to postradiosurgery adverse radiation effects (AREs). METHODS From a prospective institutional review board–approved database, the authors identified patients with a minimum of 2 years of follow-up and thin-slice T2-weighted MRI sequences for volumetric analysis. A total of 105 AVM patients were included. The authors analyzed the incidence and quantitative changes in AREs as a function of time after GKRS. Statistical analysis was performed to identify factors related to ARE development and changes in the ARE index. RESULTS The median clinical follow-up was 53.8 months (range 24–212.4 months), and the median MRI follow-up was 36.8 months (range 24–212.4 months). 47.6% of patients had an AVM with a Spetzler-Martin grade ≥ III. The median administered margin and maximum doses were 22 and 40 Gy, respectively. The overall obliteration rate was 70.5%. Of patients who showed complete obliteration, 74.4% developed AREs within 4–6 months after GKRS. Late-onset AREs (i.e., > 12 months) correlated to a failure to obliterate the nidus. 58.1% of patients who developed appreciable AREs (defined as ARE index > 8) proceeded to have a complete nidus obliteration. Appreciable AREs were found to be influenced by AVM nidus volume > 3 ml, lobar location, number of draining veins and feeding arteries, prior embolization, and higher margin dose. On the other hand, a minimum ARE index > 8 predicted obliteration (p = 0.043). CONCLUSIONS ARE development after radiosurgery follows a temporal pattern peaking at 7–12 months after stereotactic radiosurgery. The ARE index serves as an important adjunct tool in patient follow-up and outcome prediction.


2020 ◽  
Vol 132 (1) ◽  
pp. 122-131
Author(s):  
Ching-Jen Chen ◽  
Kathryn N. Kearns ◽  
Dale Ding ◽  
Hideyuki Kano ◽  
David Mathieu ◽  
...  

OBJECTIVEArteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.METHODSThe authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.RESULTSThe study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).CONCLUSIONSSRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.


2012 ◽  
Vol 116 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Hideyuki Kano ◽  
L. Dade Lunsford ◽  
John C. Flickinger ◽  
Huai-che Yang ◽  
Thomas J. Flannery ◽  
...  

Object The aim of this paper was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I and II arteriovenous malformations (AVMs). Methods Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs, including 217 patients with AVMs classified as Spetzler-Martin Grade I or II. The median maximum diameter and target volumes were 1.9 cm (range 0.5–3.8 cm) and 2.3 cm3 (range 0.1–14.1 cm3), respectively. The median margin dose was 22 Gy (range 15–27 Gy). Results Arteriovenous malformation obliteration was confirmed by MR imaging in 148 patients and by angiography in 100 patients with a median follow-up of 64 months (range 6–247 months). The actuarial rates of total obliteration determined by angiography or MR imaging after 1 SRS procedure were 58%, 87%, 90%, and 93% at 3, 4, 5, and 10 years, respectively. The median time to complete MR imaging–determined obliteration was 30 months. Factors associated with higher AVM obliteration rates were smaller AVM target volume, smaller maximum diameter, and greater marginal dose. Thirteen patients (6%) suffered hemorrhages during the latency period, and 6 patients died. Cumulative rates of AVM hemorrhage 1, 2, 3, 5, and 10 years after SRS were 3.7%, 4.2%, 4.2%, 5.0%, and 6.1%, respectively. This corresponded to rates of annual bleeding risk of 3.7%, 0.3%, and 0.2% for Years 0–1, 1–5, and 5–10, respectively, after SRS. The presence of a coexisting aneurysm proximal to the AVM correlated with a significantly higher hemorrhage risk. Temporary symptomatic adverse radiation effects developed in 5 patients (2.3%) after SRS, and 2 patients (1%) developed delayed cysts. Conclusions Stereotactic radiosurgery is a gradually effective and relatively safe option for patients with smaller volume Spetzler-Martin Grade I or II AVMs who decline initial resection. Hemorrhage after obliteration did not occur in this series. Patients remain at risk for a bleeding event during the latency interval until obliteration occurs. Patients with aneurysms and an AVM warrant more aggressive surgical or endovascular treatment to reduce the risk of a hemorrhage in the latency period after SRS.


2008 ◽  
Vol 109 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Jung Ho Han ◽  
Dong Gyu Kim ◽  
Hyun-Tai Chung ◽  
Chul-Kee Park ◽  
Sun Ha Paek ◽  
...  

Object In this paper the authors analyzed the clinical and neuroimaging outcomes of patients with cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS), focusing on the analysis of the radiation injury rate depending on the AVM volume. Methods Between 1997 and 2004, 277 consecutive patients with cerebral AVMs were treated with GKS. Of these patients, 218 were followed up for ≥ 2 years. The mean age was 31 ± 15 years, the median AVM volume was 3.4 cm3 (range 0.17–35.2 cm3), the median marginal dose was 18.0 Gy (range 10.0–25.0 Gy), and the mean follow-up duration was 44 ± 20 months. The authors reduced the prescription dose by various amounts, depending on the AVM volume and location as prescribed in the classic guideline to avoid irreversible radiation injuries. Results The angiographic obliteration rate was 66.4% overall, and it was 81.7, 53.1, and 12.5% for small, medium, and large AVMs, respectively. The overall annual bleeding rate was 1.9%. The annual bleeding rate was 0.44 and 4.64% for small and large AVMs, respectively. Approximately 20% of the patients showed severe postradiosurgery imaging (PRI) changes. The rate of PRI change was 11.4, 33.3, and 9.5% for small, medium, and large AVM volume groups, respectively, and a permanent radiation injury developed in 5.1% of patients. Conclusions By using the reduced dose from what is usually prescribed, the authors were able to obtain outcomes in small AVMs that were comparable to the outcomes described in previous reports. However, medium AVMs appear to still be at risk for adverse radiation effects. Last, in large AVMs, the authors were able to attain a tolerable rate of radiation injury; however, the clinical outcomes were quite disappointing following administration of a reduced dose of GKS for large AVMs.


2012 ◽  
Vol 116 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
John C. Flickinger ◽  
Kyung-Jae Park ◽  
Phillip V. Parry ◽  
...  

Object The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. Methods In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm3. Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8–13.8 months). The median target volume was 11.5 cm3 (range 4.0–26 cm3) in the first-stage SRS and 9.5 cm3 in the second-stage SRS. The median margin dose was 16 Gy (range 13–18 Gy) for both stages. Results In 17 patients, AVM obliteration was confirmed after 2–4 SRS procedures at a median follow-up of 87 months (range 0.4–209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33–113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0–1, 1–5, and 5–10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. Conclusions Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.


Neurosurgery ◽  
2017 ◽  
Vol 80 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Bruce E. Pollock ◽  
Michael J. Link ◽  
Scott L. Stafford ◽  
Giuseppe Lanzino ◽  
Yolanda I. Garces ◽  
...  

Abstract BACKGROUND: Radiation-based treatment options of large intracranial arteriovenous malformations (AVM) must balance the likelihood of obliteration with the risk of adverse radiation effects (ARE). OBJECTIVE: To analyze the efficacy and risks of volume-staged stereotactic radiosurgery (VS-SRS) for AVM. METHODS: Retrospective study of 34 AVM patients having VS-SRS between 1997 and 2012. A median of 2 stages (range, 2-4) was used to treat a median AVM volume of 22.2 cm3 (range, 7.4-56.7). The median AVM margin dose was 16 Gy (range, 14-18); the median radiosurgery-based AVM score was 2.81 (range, 1.54-6.45). The median follow-up after VS-SRS was 8.2 years (range, 3-13.3). RESULTS: Nidus obliteration was noted in 18 patients (53%) after VS-SRS. The rate of obliteration was 14% at 3 years, 54% at 5 years, and 75% at 7 years. Six patients (18%) had 11 bleeds after VS-SRS. Two patients (6%) remained neurologically stable, 2 (6%) patients had significant deficits, and 2 patients (6%) died. The actuarial risk of a first bleed after VS-SRS was 6% at 1 year, 12% at 3 years, and 19% at 7 years. Six patients (18%) underwent repeat SRS; all achieved nidus obliteration for an overall cure rate of 71%. Two patients (6%) had a permanent ARE after VS-SRS or repeat SRS. CONCLUSION: VS-SRS permitted large volume intracranial AVM to be treated with a low rate of ARE. Further study is needed on dose escalation and decreasing the treatment volume per stage to determine if this will increase the rate of obliteration with this technique.


2012 ◽  
Vol 116 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
John C. Flickinger ◽  
Huai-che Yang ◽  
Thomas J. Flannery ◽  
...  

Object The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs). Methods Between 1987 and 2006, Gamma Knife surgery was performed in 996 patients with AVMs. During this period, repeat SRS was performed in 105 patients who had incompletely obliterated AVMs at a median of 40.9 months after initial SRS (range 27.5–139 months). The median AVM target volume was 6.4 cm3 (range 0.2–26.3 cm3) at initial SRS but was reduced to 2.3 cm3 (range 0.1–18.2 cm3) at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 18 Gy. Results The actuarial rate of total obliteration by angiography or MR imaging after repeat SRS was 35%, 68%, 77%, and 80% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographic or MR imaging obliteration after repeat SRS was 39 months. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume (p = 0.038) and a volume reduction of 50% or more after the initial procedure (p = 0.014). Seven patients (7%) had a hemorrhage in the interval between initial SRS and repeat SRS. Seventeen patients (16%) had hemorrhage after repeat SRS and 6 patients died. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.9%, 8.1%, 10.1%, 10.1%, and 22.4% at 1, 2, 3, 5, and 10 years, respectively, which translate to annual hemorrhage rates of 4.05% and 1.79% of patients developing new post–repeat-SRS hemorrhages per year for Years 0–2 and 2–10 following repeat SRS. Factors associated with a higher risk of hemorrhage after repeat SRS were a greater number of prior hemorrhages (p = 0.008), larger AVM target volume at initial SRS (p = 0.010), larger target volume at repeat SRS (p = 0.002), initial AVM volume reduction less than 50% (p = 0.019), and a higher Pollock-Flickinger score (p = 0.010). Symptomatic adverse radiation effects developed in 5 patients (4.8%) after initial SRS and in 10 patients (9.5%) after repeat SRS. Prior embolization (p = 0.022) and a higher Spetzler-Martin grade (p = 0.004) were significantly associated with higher rates of adverse radiation effects after repeat SRS. Delayed cyst formation occurred in 5 patients (4.8%) at a median of 108 months after repeat SRS (range 47–184 months). Conclusions Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate. Hemorrhage after obliteration did not occur in this series. The best results for patients with incompletely obliterated AVMs were seen in patients with a smaller residual nidus volume and no prior hemorrhages.


2014 ◽  
Vol 120 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Greg Bowden ◽  
Hideyuki Kano ◽  
Daniel Tonetti ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
...  

Object Arteriovenous malformations (AVMs) of the posterior fossa have an aggressive natural history and propensity for hemorrhage. Although the cerebellum accounts for the majority of the posterior fossa volume, there is a paucity of stereotactic radiosurgery (SRS) outcome data for AVMs of this region. The authors sought to evaluate the long-term outcomes and risks of cerebellar AVM radiosurgery. Methods This single-institution retrospective analysis reviewed the authors' experience with Gamma Knife surgery during the period 1987–2007. During this time 64 patients (median age 47 years, range 8–75 years) underwent SRS for a cerebellar AVM. Forty-seven patients (73%) presented with an intracranial hemorrhage. The median target volume was 3.85 cm3 (range 0.2–12.5 cm3), and the median marginal dose was 21 Gy (range 15–25 Gy). Results Arteriovenous malformation obliteration was confirmed by MRI or angiography in 40 patients at a median follow-up of 73 months (range 4–255 months). The actuarial rates of total obliteration were 53% at 3 years, 69% at 4 years, and 76% at 5 and 10 years. Elevated obliteration rates were statistically higher in patients who underwent AVM SRS without prior embolization (p = 0.005). A smaller AVM volume was also associated with a higher rate of obliteration (p = 0.03). Four patients (6%) sustained a hemorrhage during the latency period and 3 died. The cumulative rates of AVM hemorrhage after SRS were 6% at 1, 5, and 10 years. This correlated with an overall annual hemorrhage rate of 2.0% during the latency interval. One patient experienced a hemorrhage 9 years after confirmed MRI and angiographic obliteration. A permanent neurological deficit due to adverse radiation effects developed in 1 patient (1.6%) and temporary complications were seen in 2 additional patients (3.1%). Conclusions Stereotactic radiosurgery proved to be most effective for patients with smaller and previously nonembolized cerebellar malformations. Hemorrhage during the latency period occurred at a rate of 2.0% per year until obliteration occurred.


2012 ◽  
Vol 116 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
John C. Flickinger ◽  
Huai-che Yang ◽  
Thomas J. Flannery ◽  
...  

Object In this paper, the authors' goal was to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the medulla, pons, and midbrain. Methods Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 67 patients had AVMs in the brainstem. In this series, 51 patients (76%) had a prior hemorrhage. The median target volume was 1.4 cm3 (range 0.1–13.4 cm3). The median margin dose was 20 Gy (range 14–25.6 Gy). Results Obliteration of the AVMs was eventually documented in 35 patients at a median follow-up of 73 months (range 6–269 months). The actuarial rates of documentation of total obliteration were 41%, 70%, 70%, and 76% at 3, 4, 5, and 10 years, respectively. Higher rates of AVM obliteration were associated only with a higher margin dose. Four patients (6%) suffered a hemorrhage during the latency period, and 2 patients died. The rate of AVM hemorrhage after SRS was 3.0%, 3.0%, and 5.8% at 1, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.9%. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 7 patients (10%) after SRS, and a delayed cyst developed in 2 patients (3%). One patient died at an outside institution with symptoms of AREs and unrecognized hydrocephalus. Higher 12-Gy volumes and higher Spetzler-Martin grades were associated with a higher risk of symptomatic AREs. Ten of 22 patients who had ocular dysfunction before SRS had improvement, 9 were unchanged, and 3 were worse due to AREs. Eight of 14 patients who had hemiparesis before SRS improved, 5 were unchanged, and 1 was worse. Conclusions Although hemorrhage after obliteration did not occur in this series, patients remained at risk during the latency interval until obliteration occurred. Thirty-eight percent of the patients who had neurological deficits due to prior hemorrhage improved. Higher dose delivery in association with conformal and highly selective SRS is required for safe and effective radiosurgery.


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