Faculty Bibliography

Selection of the prescription dose for arteriovenous malformation (AVM) radiosurgery is the final step in treatment planning. Physicians need to choose a prescription dose that provides an optimal middle ground between optimizing AVM obliteration with high radiation doses and limiting complication risks with the lowest doses. Accurately predicting complication risks for individual patients is a complex process that is highly dependent on the radiosurgery treatment volume, the target location and the nature of the target tissue. This article reviews the principles and data guiding dose selection for AVM radiosurgery.

Gamma Knife stereotactic radiosurgery was first applied for the treatment of an intracranial arteriovenous malformation (AVM) in 1968. Using biplane angiography to target a small-volume, deep-seated lesion, photons were cross-fired on the pathological shunt. The AVM was obliterated within 3 years. This began a cautious introduction of Gamma Knife radiosurgery in the 1970s. As the Gamma Knife technology spread to sites in Europe, South America and the USA in the 1980s, AVM radiosurgery became a primary indication. During the early years the usual standard was to deliver a single radiosurgical isocenter to the target defined by 2-dimensional angiography. Most patients had small-volume AVMs unsuitable for surgical excision. Over time the technique of Gamma Knife AVM surgery evolved to include: careful patient selection, discussion of appropriate treatment strategies, anticonvulsant administration for lobar locations and intraoperative targeting using both high-resolution axial plane imaging - usually magnetic resonance imaging - coupled with biplane digital subtraction angiography. High-speed computer dose planning integrated with more detailed imaging strategies facilitated conformal radiation delivery in a single treatment session coupled with high selectivity of the dose delivered. Multiple isocenters became routine. Long-term follow-up care included serial imaging evaluations to assess the response and to detect complications. Imaging was critical to confirm the desired radiobiological response - complete obliteration. Long-term follow-up after obliteration confirmed that AVM radiosurgery had a high success rate for properly selected patients and a risk-benefit profile that substantiated patient safety. Twenty-year results after Gamma Knife radiosurgery for AVMs are currently available. Established roles have been found for pediatric cases and for larger-volume AVMs unsuitable for surgical removal. The role and technique of embolization prior to radiosurgery continue to be evaluated. Current dose response data based on volume and predictions of adverse radiation effects guide current care.

Widespread availability of magnetic resonance imaging has helped our understanding of the natural history of cavernous malformations (CMs) of the brain. CMs present with diverse clinical manifestations. Supratentorial CMs are often identified incidentally. The clinical presentation corresponds with lesion location. Symptomatic, hemorrhagic CMs of the brainstem pose a challenging clinical problem as they are often associated with high surgical morbidity. In order to study the natural history of CM, we performed a prospective analysis on a series of patients who were sent to us for management. During the mean prospective follow-up interval of 34 months, 9 hemorrhages occurred. History of prior hemorrhage was the most important risk factor for subsequent hemorrhage. The annual hemorrhage was 0.6% in patients who never had a symptomatic hemorrhage. Patients who had prior hemorrhage have a higher (4.5%) annual hemorrhage rate.

Treatment options for symptomatic dural arteriovenous fistulas (DAVFs) include surgery, embolization and stereotactic radiosurgery (SRS). We reviewed our DAVF experience at the University of Pittsburgh and assessed the role of SRS. We evaluated 40 consecutive patients who underwent Gamma Knife SRS for 44 DAVFs. Twenty-eight patients had upfront SRS before or after embolization performed at our institution, and 12 patients underwent delayed SRS for recurrent or residual DAVFs after initial embolization. The median SRS target volume was 2.0 cm(3), and the median marginal dose was 21.0 Gy. At a median follow-up of 45 months (range, 23-116 months), a total of 28 patients with 32 DAVFs had obliteration. The obliteration rate was 83% for patients who had upfront SRS and embolization. The obliteration rate was lower (67%) for patients managed with SRS alone. The obliteration rate was 71% for patients who had delayed SRS for recurrent or residual DAVFs following prior embolization. In our experience cavernous/carotid fistulas were associated with higher rates of obliteration and symptomatic improvement compared to transverse/sigmoid sinus region fistulas. Our experience suggests that successful DAVF obliteration is possible in most patients with upfront SRS in conjunction with embolization. SRS alone is an effective treatment for selected patients with a small-volume, low-risk DAVF.

ABSTRACT: For skull base meningiomas, several treatment paradigms are available: Observation with serial imaging, surgical resection, stereotactic radiosurgery, radiation therapy or some combination of both. The choice depends on several factors. In this review we evaluate different treatment options, the outcome of modern irradiation techniques as well as the clinical results available, and establish recommendations for the treatment of patients with skull-base meningiomas.

Object The authors evaluated the potential role of environmental risk factors, including exposure to diagnostic or therapeutic radiation and to wireless phones that emit nonionizing radiation, in the etiology of vestibular schwannoma (VS). Methods A total of 343 patients with VSs who underwent Gamma Knife surgery performed between 1997 and 2007 were age and sex matched to 343 control patients from the outpatient degenerative spinal disorders service at the University of Pittsburgh Medical Center. The authors obtained information on previous exposure to medical radiation, use of wireless phone technologies, and other environmental factors thought to be associated with the development of a VS. Conditional multivariate logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results After adjusting for race, education, cigarette smoking, alcohol consumption, occupational exposure to noise, use of cell phones, and family history of cancer, the authors identified only a single factor that was associated with a higher risk of VS: individuals exposed to dental x-rays once a year (aOR = 2.27, 95% CI = 1.01-5.09) or once every 2-5 years (aOR = 2.65, 95% CI = 1.20-5.85), compared with those exposed less than once every 5 years. Of interest, a history of exposure to radiation related to head or head-and-neck computed tomography was associated with a reduced risk of VS (aOR = 0.52, 95% CI = 0.30-0.90). No relationship was found between the use of cell phones or cordless phones and VS. Conclusions Patients with acoustic neuromas reported significantly more exposure to dental x-rays than a matched cohort control group. Reducing the frequency of dental x-ray examinations may decrease the potential risk of VS.

Object Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS) for FMMs and to delineate its role in an overall management paradigm. Methods The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual tumors after a prior surgery. Results Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months (range 3-128 months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable. Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery. Conclusions Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or growing FMMs as well as for residual tumors following conservative microsurgical removal.

BACKGROUND AND PURPOSE: The purpose of this study was to define the risk of rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous malformations with or without associated intracranial aneurysms. METHODS: Between 1987 and 2006, we performed Gamma Knife SRS on 996 patients with brain arteriovenous malformations; 407 patients had sustained an arteriovenous malformation hemorrhage. Sixty-four patients (16%) underwent prior embolization and 84 (21%) underwent prior surgical resection. The median target volume was 2.3 mL (range, 0.1-20.7 mL). The median margin dose was 20 Gy (range, 13.5-27 Gy). RESULTS: The overall rate of total obliteration defined by angiography or MRI was 56%, 77%, 80%, and 82% at 3, 4, 5, and 10 years, respectively. Before obliteration, 33 patients (8%) sustained an additional hemorrhage after SRS. The overall annual hemorrhage rate until obliteration after SRS was 1.3%. The presence of a patent aneurysm was significantly associated with an increased rehemorrhage risk after SRS (annual hemorrhage rate, 6.4%) compared with patients with a clipped or embolized aneurysm (annual hemorrhage rate, 0.8%; P=0.033). CONCLUSIONS: When an aneurysm is identified in patients with arteriovenous malformations selected for SRS, additional endovascular or surgical strategies should be considered to reduce the risk of bleeding during the latency interval.