Faculty Bibliography

We sought 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 AVMs unsuitable for surgery. Two decades ago, we prospectively began to stage anatomical components in order to deliver higher single doses to AVMs >10 cm(3) in volume. Forty-seven patients with large AVMs underwent volume-staged SRS. The median interval between the two SRS procedures was 4.9 months (range, 3-14 months). The median nidus volume was 11.5 cm(3) (range, 4.0-26 cm(3)) in the first stage of SRS and 9.5 cm(3) in the second. The median margin dose was 16 Gy (range, 13-18 Gy) for both SRS stages. The actuarial rates of total obliteration after 2-staged SRS were 7, 20, 28 and 36% at 3, 4, 5 and 10 years, respectively. Sixteen patients needed additional SRS at a median interval of 61 months (range, 33-113 months) after the 2-staged SRS. After repeat procedure(s), the eventual obliteration rate was 66% at 10 years. 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. Symptomatic adverse radiation effects were detected in 13% of patients. Successful prospective volume-staged SRS for large AVMs unsuitable for surgery requires 2 or more procedures to complete the obliteration process. Patients remain at risk for hemorrhage if the AVM persists.

The authors outlined the treatment result of arteriovenous malformations (AVMs) inside the brainstem by reviewing the 4 existing studies in detail. The majority of patients with brainstem AVMs had a history of hemorrhage, leading to neurological deficits at the time of treatment in 72-73% of patients. The most frequent location was the midbrain or the pons depending on studies, while the medulla oblongata was the least common location throughout the series. The obliteration rate after radiosurgery was 44-73%, which was generally lower than in other locations, while the complication rate was 5-14%, which was expectedly higher than in other locations. No objective evidence for size is known, and therefore, patient selection and treatment planning should be carefully performed after judicious assessment of treatment risks and benefits among limited treatment options.

We sought to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) patients who underwent prior embolization. Between 1987 and 2006, we performed Gamma Knife(R) SRS on 120 patients with AVM who underwent embolization followed by SRS. Sixty-four patients (53%) had at least 1 prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm(3) (range, 0.2-26.3 cm(3)). The median margin dose was 18 Gy (range, 13.5-25 Gy). After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or magnetic resonance imaging were 35, 53, 55 and 59% at 3, 4, 5 and 10 years, respectively. Nine patients (8%) had a hemorrhage during the latency interval and 7 patients died due to hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8, 3.5, 5.4, 7.7 and 7.7% at 1, 2, 3, 5 and 10 years, respectively. Permanent neurological deficits due to adverse radiation effects developed in 3 patients (2.5%) after SRS. Using a case-match control technique, we found that embolization prior to SRS was associated with a lower rate of total obliteration (p = 0.028) in comparison to radiosurgery alone. In this 20-year experience, we found that prior embolization reduced the rate of total obliteration after SRS and latency interval hemorrhage risks were not affected by prior embolization. In the future, the role of embolization after SRS should be explored.

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.

Over the last two decades, stereotactic radiosurgery (SRS) has become a mainstay in the management of arteriovenous malformations (AVMs) of the brain. An extensive collective experience has demonstrated that SRS is a minimally invasive technique that can produce excellent AVM obliteration rates with only a modest risk of permanent adverse radiation effects (AREs). Controversy remains regarding the optimal treatment approach for AVMs, with much of the debate centered upon the risk:benefit ratios of microsurgical resection versus SRS. Proponents of surgery suggest that for appropriate Spetzler-Martin grade AVMs microsurgery harbors minimal morbidity and immediate cure. In contrast, supporters of SRS argue that many AVMs cannot be treated by microsurgery with limited morbidity, and that despite the possibility of hemorrhage during the latency to obliteration, the risk profile of SRS is more favorable. Unfortunately, a randomized clinic trial comparing microsurgery and SRS is not likely, so clinicians and patients must use available data to make their own decisions. Much effort has been expended to identify factors associated with AREs, defining their impact and predicting which patients are likely to have complete AVM obliteration in the absence of new neurological deficits. Refinement in an AVM management algorithm on these bases should better educate clinicians and patients about risk profiles, improve patient selection for different treatment strategies, and increase the likelihood of good therapeutic outcomes. Herein, we give a definition to the term ARE and review the suspected mechanisms that lead to them.

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.

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.

We evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm(3) (range 0.3-11.6). The marginal tumor dose (median = 15 Gy, range 12-25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12-185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined as a decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six (27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy.

BACKGROUND: As systemic therapies improve and patients live longer, concerns mount about the toxicity of whole-brain radiation therapy (WBRT) for treatment of brain metastases. Development of delayed white matter abnormalities indicative of leukoencephalopathy have been correlated with cognitive dysfunction. This study assesses the risk of imaging-defined leukoencephalopathy in patients whose management included WBRT in addition to stereotactic radiosurgery (SRS). This risk is compared to patients who only underwent SRS. METHODS: We retrospectively compared 37 patients with non-small cell lung cancer who underwent WBRT plus SRS to 31 patients who underwent only SRS. All patients survived at least 1 year after treatment. We graded the development of delayed white matter changes on magnetic resonance imaging using a scale to evaluate T(2) /FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. RESULTS: Patients treated with WBRT and SRS had a significantly greater incidence of delayed white matter leukoencephalopathy compared to patients who underwent SRS alone (P < .001). On final imaging, 36 of 37 patients (97.3%) treated by WBRT developed leukoencephalopathy (25% with grade 2; 70.8% with grade 3). Only 1 patient treated with SRS alone developed leukoencephalopathy. CONCLUSIONS: Risk of leukoencephalopathy in patients treated with SRS alone for brain metastases was significantly lower than that for patients treated with WBRT plus SRS. A prospective study is necessary to correlate these findings with neurocognition and quality of life. These data supplement existing reports regarding the differential effects of WBRT and SRS on normal brain structure and function. Cancer 2012. (c) 2012 American Cancer Society.