Radiation-Related Adverse Effects Observed on Neuro-Imaging Several Years After Radiosurgery for Cerebral Arteriovenous Malformations

doi:10.1016/S0090-3019(97)00531-4

Surgical Neurology

Volume 49, Issue 4, April 1998, Pages 385-398

https://doi.org/10.1016/S0090-3019(97)00531-4 Get rights and content

Abstract

Background

To our knowledge, there are no reported arteriovenous malformation (AVM) series in which detailed long-term follow-up results after radiosurgery were described based on the whole patient group.

Method

We performed a detailed long-term follow-up study of 53 patients with cerebral AVMs treated with gamma knife (GK) radiosurgery, with emphasis on radiation-related adverse effects detected on neuro-imaging after a long post-irradiation latency period (3–10 years). The post-GK follow-up period was 40–232 months excluding two mortalities, the mean being 112 and the median being 111 months.

Results

Three patients (5.6%) have, as yet, refused all neuro-imaging follow-up studies. Complete nidus obliteration was confirmed angiographically in 32 patients (60.4%) between 1 and 5 post-GK years. In the other 18 patients (34%), despite significant nidus shrinkage being angiographically demonstrated, complete obliteration was not achieved during a 2–7 year follow-up period. There were two mortalities, one AVM-related (massive re-bleeding during the latency period) and the other angiography-related. There were five radiation-related morbidities (9.4%), three of which—hemi-Parkinson syndrome, hemiparesis, and visual field disturbances attributable to delayed cyst formation—manifested at 5.5, 7 and 7 post-GK years, respectively. We also experienced five patients (9.4%) in whom, despite remaining asymptomatic to date, radiation-related adverse effects were seen on neuro-imaging: middle cerebral artery stenosis at 3 post-GK years in one patient; dural arteriovenous fistula at 7 post GK-years in one; delayed cyst formation in two, at 5 and 10 post-GK years; and a small cavitation at 9 post-GK years.

Conclusion

Long-term follow-up, particularly with neuro-imaging modalities, is essential even after the “treatment goal” has been attained.

Section snippets

Patient Population

We analyzed our own series of 53 AVM patients receiving gamma knife radiosurgery during the 1978–94 period: 32 patients at Karolinska Hospital, Stockholm; five at Clinica Del Sol, Buenos Aires; three at Presbyterian University Hospital, Pittsburgh; two at Tokyo University, Tokyo; four at Heisei Memorial Hospital, Fujieda; and seven at Tokyo Women’s Medical College, Tokyo. At the time of radiosurgery, the mean patient age was 28 years; range, 7 to 65 years. There were 29 males and 24 females.

Neuro-Imaging Follow-up

After the initial gamma knife radiosurgery, 50 (94.4%) patients periodically underwent angiographic examination until confirmation of total nidus obliteration (Table 3). In the other three patients (5.6%), neither follow-up angiography nor other neuro-imaging studies have as yet been performed because of patient refusal. Complete nidus obliteration was confirmed angiographically between 9.5 and 62 (mean, 24) months after radiosurgery in 32 patients (60.4%), in one of whom sequential MR studies

Discussion

We studied long-term post-treatment follow-up results based on our own series of AVM patients receiving gamma knife radiosurgery at three overseas centers, mainly the Karolinska Hospital, as well as at three centers in Japan. The study subjects include the 39 of these 53 patients who had radiosurgery before 1989, i.e., early in the “learning curve” for this procedure, and thus, before the development of advanced dose-planning systems augmented by three dimensional imaging techniques, as noted

Acknowledgements

The authors would like to thank Ladislau Steiner, M.D., Ph.D. University of Virginia Health Sciences Center, Charlottesville, Christer Lindquist, M.D., Ph.D.; Bengt Karlsson, M.D., Ph.D., and Lars Kihlström, M.D., Karolinska Hospital, Stockholm; Hernan J. Bunge, M.D., Ph.D., Centro de Radiocirugia Neurologica, Clinica Del Sol, Buenos Aires; L. Dade Lunsford, M.D. and Douglas Kondziolka, M.D., University of Pittsburgh School of Medicine, Pittsburgh; Shunsuke Kawamoto, M.D., University of Tokyo;

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Although delayed cystic formation has not been described in the LITT literature, late cyst formation has been described as a rare phenomenon after SRS for the treatment of multiple pathologies including AVM, metastatic tumor, meningioma, and schwannoma.8-13 It is hypothesized that radiation-induced cyst formation can result from several mechanistic pathways, such as increased vascular permeability secondary to breakdown of the blood-brain barrier and reactive gliosis resulting in degenerative changes in the surrounding vascular supply.8,14-17 The outcomes observed in SRS may inform further understanding of cystic formation in LITT.
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It has been gradually uncovered that late radiation-induced complications (LRICs) may occur after a long period. Cyst formation (CF) and encapsulated hematoma (EH)24-36 are major LRICs, considered to be of the same pathologic origin.28,33,37 Radiation-induced tumor (RIT) is extremely rare but could be life threatening because it is usually a malignant tumor.38-41
Stereotactic radiosurgery is widely used to treat brain arteriovenous malformation; however, detailed information on late radiation-induced complications (LRICs) is scarce. The goal of the present study was to characterize the incidence, risk factors, and clinical outcomes of LRICs based on our long-term follow-up data.
The outcomes of consecutive patients who underwent stereotactic radiosurgery for arteriovenous malformations at our institution in 1990–2010 were analyzed. Cyst formation/encapsulated hematoma (CF/EH) and radiation-induced tumor were defined as LRICs. Cumulative incidence rates were calculated using the Kaplan-Meier method. Risk factors for CF/EH were analyzed using a Cox proportional hazard model.
A total of 581 patients with mean and median follow-up periods of 11.8 and 10.1 years, respectively (range, 2.0–26.7 years), were analyzed. CF/EH was observed in 30 patients (5.2%). The median time to progression was 11.8 years (range, 1.9–23.9 years). Cumulative incidence rates were 0.8%, 2.8%, 7.6%, and 9.7% at 5, 10, 15, and 20 years, respectively. A multivariate analysis showed that lobar location and maximal diameter ≥22 mm were significant risk factors for CF/EH. Overall, the functional outcomes were mild, moderate, and severe/fatal in 26 (87%), 1 (3%), and 3 (10%) patients, respectively. Radiation-induced tumor was confirmed in only 1 patient (0.17%).
An increased nidus size and lobar location are risk factors for CF/EH. Although the CF/EH incidence is low, some LRICs develop after long periods. Extended follow-up is warranted, particularly of patients with risk factors.
Surgical Management of Adverse Radiation Effects After Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: A Population-Based Cohort Study
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The goal of this study is to report our experience in the surgical treatment of cerebral arteriovenous malformations (cAVMs) related permanent symptomatic adverse radiation effects (PSAREs), to clarify an appropriate surgical management and to identify the risk factors related to their development.
We evaluated 549 patients treated with Gamma Knife radiosurgery (GKRS) for cAVMs with a follow-up of at least 8 years. Univariate and multivariate analyses were used to test different risk factors related to the development of PSARE. We retrospectively reviewed the records of these patients to analyze the clinical outcome.
Fourteen patients (2.5%) developed PSARE and were submitted to surgery. Higher average treated volume represents a significant risk factors for the development of PSARE (P < 0.05); on the other hand, older age and higher average dose reduce the risk of PSARE (P < 0.05). A favorable clinical outcome was achieved in 13 patients (93%) after surgery; in 1 patient, the unfavorable outcome was due to hemorrhage that occurred months after GKRS. Serial MRI scans following either surgical removal of the nodule or Ommaya reservoir positioning showed progressive reduction of brain edema in all cases.
The management of PSARE is controversial, especially for cAVMs treated with SRS. Surgical removal is rarely needed, but—if unavoidable—it can be a valuable option in experienced hands. A careful preoperative planning is always necessary to detect pathologic blood flow through the PSARE.
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We retrospectively reviewed 214 consecutive patients who underwent a total of 1106 SRSs for BM. Demographic, clinical, dosimetric, and magnetic resonance imaging MRI data were reviewed. Statistical analysis was accomplished using Student's t test, and univariate and multivariate logistic regression.
The median patient age was 61 years (range, 19–91 years), and the median duration of follow-up was 424 days (range, 91–2934 days). Eleven cases of cyst formation (0.9% of 1106 treated lesions) were identified at SRS-treated BM sites among 9 patients (2 patients developed cysts at independent sites). The median interval between first SRS and first evidence of cyst was 218 days. Seven of the 9 patients (78%) sustained progressive cyst expansion and neurologic decline requiring steroid treatment. Four of these 7 patients (57%) experienced continued neurologic decline and needed surgical fenestration. On univariate analysis, receipt of >4 rounds of SRS was the sole variable associated with an increased risk of cyst formation (odds ratio, 16.58; P = 0.001). This association remained robust after adjusting for duration of follow-up (odds ratio, 13.59; P = 0.003).
In our experience with 1106 SRS-treated cases of BM, cyst formation was a rare phenomenon. However, 1 in 3 patients who underwent >4 rounds of SRS sustained cyst formation. A high proportion (78%) of SRS-associated cysts progressively expanded and required medical or surgical treatment.
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The risks and benefits of arteriovenous malformation (AVM) treatment should be considered cautiously in each patient since management strategy of it depends on various factors including age of the patient, location and volume of AVM and presence of other vascular abnormalities. Current management options of AVM include observation, endovascular embolization, radiosurgery and microsurgical resection or in combination of any two of the above procedures. Here, we have discussed a case of intracranial AVM with radiation induced early cyst formation, and performed a literature review to determine the optimum treatment of complex intracranial AVM. Standard search strategies were performed in PubMed/Medline using appropriate terms such as “intracranial arteriovenous malformation” radiosurgery, embolization and microsurgical resection as well as medical subject headings. The particular case in this study was retrospectively reviewed. Literature review revealed that the mean marginal radiation dose used by the different authors was 19 Gy, cysts were developed in 3.6% patients, the average time to form cyst was 6.6 years, average volume of cyst was 6.7 ml and maximum cysts were removed by resection. In our case, the cyst was developed 2.5 years after radiosurgery. Radiation induced cyst formation is a delayed complication of AVM management. However, cyst formation in this case was comparatively earlier in our case. Therefore, continuous follow-up after radiosurgery is required for early detection of cyst formation. In addition, the review revealed that embolization before radiosurgery was a poor strategy.
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Original ArticlesRadiation-Related Adverse Effects Observed on Neuro-Imaging Several Years After Radiosurgery for Cerebral Arteriovenous Malformations

Abstract

Section snippets

Patient Population

Neuro-Imaging Follow-up

Discussion

Acknowledgements

Surg Neurol

Surg Neurol

Int J Radiation Oncology Biol Phys

Surg Neurol

Surg Neurol

Surg Neurol

Surg Neurol

Intracranial dural arteriovenous malformations

Intracranial dural arteriovenous malformationsfactors predisposing to an aggressive neurological course

J Neurosurg

Intraoperative angiography in the management of neurovascular disorders

Neurosurgery

Stereotactic radiosurgery with the linear acceleratortreatment of arteriovenous malformations

Neurosurgery

Dural arteriovenous malformation of the major venous sinusesan acquired lesion

AJNR

Linear accelerator radiosurgery of cerebral arteriovenous malformations

Neurosurgery

Linear accelerator radiosurgery of cerebral arteriovenous malformationsan update

Neurosurgery

Intraoperative digital subtraction angiographya review of 112 consecutive examinations

AJNR

Stereotactic heavy charged-particle Bragg peak radiosurgery for intracranial arteriovenous malformations

Stereotactic heavy-ion Bragg peak radiosurgery for intracranial vascular disordersmethod for treatment of deep arteriovenous malformations

Br J Radiol

Etiologic factors in intracranial dural arteriovenous malformations

Linear accelerator radiosurgery for arteriovenous malformations

J Neurosurg

Linear accelerator radiosurgery for arteriovenous malformationsthe relationship of size to outcome

J Neurosurg

Arteriovenous malformation affecting the transverse dural venous sinusan acquired lesion

Mayo Clin Proc

Original Articles
Radiation-Related Adverse Effects Observed on Neuro-Imaging Several Years After Radiosurgery for Cerebral Arteriovenous Malformations