Faculty Bibliography

BACKGROUND:The degree of aneurysm occlusion following coil embolization has an impact on aneurysm recanalization. OBJECTIVE:To explain the natural history of intracranial aneurysms with neck remnant, Raymond-Roy Occlusion Classification (RROC) class II. METHODS:A single-center, retrospective study of 198 patients with 209 aneurysms treated with coil embolization that were initially either RROC class I or II. The angiographic outcomes at short- and long-term follow-up were compared as well as the complication/re-treatment rates. Atypical aneurysms and those that had been previously treated were excluded. RESULTS:Ninety-nine class I aneurysms were compared with 110 class II aneurysms. There was no difference in recanalization rate between the groups (class I 3.3% vs class II 8.5%, p=0.478) at short-term follow-up (8.2 months) and at subsequent follow-ups (21.7 and 52.1 months). There was also no difference in re-treatment rates (class I 3.3% vs class II 8.5%, p=0.196) or complication rates (class I 9.1% vs class II 4.6%, p=0.12). There were no aneurysm ruptures after treatment in either group. CONCLUSIONS:The angiographic outcome of aneurysms with neck remnant following coil embolization is similar to that of completely occluded aneurysms in that most remain stable and few recanalize. This understanding could potentially help the interventional neurosurgeon avoid complications such as coil herniation, vessel compromise, and stroke in selected cases. Further investigation with a larger patient population is warranted.

BACKGROUND:The Raymond-Roy Occlusion Classification (RROC) is the standard for evaluating coiled aneurysms (Class I: complete obliteration; Class II: residual neck; Class III: residual aneurysm), but not all Class III aneurysms behave the same over time. METHODS:This is a retrospective review of 370 patients with 390 intracranial aneurysms treated with coil embolization. A Modified Raymond-Roy Classification (MRRC), in which Class IIIa designates contrast within the coil interstices and Class IIIb contrast along the aneurysm wall, was applied retrospectively. RESULTS:Class IIIa aneurysms were more likely to improve to Class I or II than Class IIIb aneurysms (83.34% vs 14.89%, p<0.001) and were also more likely than Class II to improve to Class I (52.78% vs 16.90%, p<0.001). Class IIIb aneurysms were more likely to remain incompletely occluded than Class IIIa aneurysms (85.11% vs 16.67%, p<0.001). Class IIIb aneurysms were larger with wider necks while Class IIIa aneurysms had higher packing density. Class IIIb aneurysms had a higher retreatment rate (33.87% vs 6.54%, p<0.001) and a trend toward higher subsequent rupture rate (3.23% vs 0.00%, p=0.068). CONCLUSIONS:We propose the MRRC to further differentiate Class III aneurysms into those likely to progress to complete occlusion and those likely to remain incompletely occluded or to worsen. The MRRC has the potential to expand the definition of adequate coil embolization, possibly decrease procedural risk, and help endovascular neurosurgeons predict which patients need closer angiographic follow-up. These findings need to be validated in a prospective study with independent blinded angiographic grading.

Cervical-petrous internal carotid artery (CP-ICA) pseudoaneurysms are rare and have different etiologies, presentations, and treatment options. A middle-aged patient with a history of chronic otitis media presented with acute otorrhagia and was found to have a left-sided CP-ICA pseudoaneurysm. The patient was a poor surgical candidate with difficult arterial access. The pseudoaneurysm was treated with stand-alone coiling via a left brachial approach with persistent contrast filling seen only in the aneurysm neck at the end of the procedure. The patient re-presented 12 days later with repeat hemorrhage and rapid enlargement of the neck remnant, and was treated with a covered stent via a transcervical common carotid artery cut-down. A covered stent may provide a more definitive treatment for CP-ICA pseudoaneurysms compared with standalone coiling.

BACKGROUND:Changes in tumor volume are seen on magnetic resonance imaging within weeks after stereotactic radiosurgery (SRS), but it remains unclear what clinical outcomes early radiological changes portend. OBJECTIVE:We hypothesized that rapid, early reduction in tumor volume post-SRS is associated with prolonged local control and favorable clinical outcome. METHODS:A retrospective review of patients treated with CyberKnife SRS for brain metastases at the University of North Carolina from 2007 to 2009 was performed. Patients with at least 1 radiological follow-up, minimal initial tumor volume of 0.1 cm, no previous focal radiation, and no recent whole-brain radiation therapy were eligible for inclusion. RESULTS:Fifty-two patients with 100 metastatic brain lesions were analyzed and had a median follow-up of 15.6 months (range, 2-33 months) and a median of 2 (range, 1-8) metastatic lesions. In treated metastases in which there was a significant tumor volume reduction by 6 or 12 weeks post-SRS, there was no local progression for the duration of the study. Furthermore, patients with metastases that did not reduce in volume by 6 or 12 weeks post-SRS were more likely to require corticosteroids (P = .01) and to experience progression of neurological symptoms (P = .003). CONCLUSION/CONCLUSIONS:Significant volume reductions of brain metastases measured at either 6 or 12 weeks post-SRS were strongly associated with prolonged local control. Furthermore, early volume reduction was associated with less corticosteroid use and stable neurological symptoms.

PURPOSE/OBJECTIVE:Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. While acute post-SBRT urinary symptoms are well recognized, the late genitourinary toxicity of SBRT has not been fully described. Here, we characterize the clinical features of late urinary symptom flare and recommend conservative symptom management approaches that may alleviate the associated bother. METHODS:Between February 2008 and August 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Treatment was delivered using the CyberKnife with doses of 35-36.25 Gy in five fractions. The prevalence of each of five Common Terminology Criteria for Adverse Events (CTCAE) graded urinary toxicities was assessed at each follow-up visit. Medication usage was documented at each visit. Patient-reported urinary symptoms were assessed using the American Urological Association (AUA) symptom score and the Expanded Prostate Cancer Index Composite (EPIC)-26 at 1, 3, 6, 9, 12, 18, and 24 months. Late urinary symptom flare was defined as an increase in the AUA symptom score of ≥5 points above baseline with a degree of severity in the moderate to severe range (AUA symptom score ≥15). The relationship between the occurrence of flare and pre-treatment characteristics were examined. RESULTS:For all patients, the AUA symptom score spiked transiently at 1 month post-SBRT. Of the 216 patients, 29 (13.4%) experienced a second transient increase in the AUA symptom score that met the criteria for late urinary symptom flare. Among flare patients, the median age was 66 years compared to 70 for those without flare (p = 0.007). In patients who experienced flare, CTCAE urinary toxicities including dysuria, frequency/urgency, and retention peaked at 9-18 months, and alpha-antagonist utilization increased at 1 month post-treatment, rose sharply at 12 months post-treatment, and peaked at 18 months (85%) before decreasing at 24 months. The EPIC urinary summary score of flare patients declined transiently at 1 month and experienced a second, more protracted decline between 6 and 18 months before returning to near baseline at 2-year post-SBRT. Statistically and clinically significant increases in patient-reported frequency, weak stream, and dysuria were seen at 12 months post-SBRT. Among flare patients, 42.9% felt that urination was a moderate to big problem at 12 months following SBRT. CONCLUSION/CONCLUSIONS:In this study, we characterize late urinary symptom flare following SBRT. Late urinary symptom flare is a constellation of symptoms including urinary frequency/urgency, weak stream, and dysuria that transiently occurs 6-18 months post-SBRT. Provision of appropriate anticipatory counseling and the maintenance of prophylactic alpha-antagonists may limit the bother associated with this syndrome.

INTRODUCTION/BACKGROUND:CT-guided, frameless radiosurgery is an alternative treatment to traditional catheter-angiography targeted, frame-based methods for intracranial arteriovenous malformations (AVMs). Despite the widespread use of frameless radiosurgery for treating intracranial tumors, its use for treating AVM is not-well described. METHODS:Patients who completed a course of single fraction radiosurgery at The University of North Carolina or Georgetown University between 4/1/2005-4/1/2011 with single fraction radiosurgery and received at least one follow-up imaging study were included. All patients received pre-treatment planning with CTA ± MRA and were treated on the CyberKnife (Accuray) radiosurgery system. Patients were evaluated for changes in clinical symptoms and radiographic changes evaluated with MRI/MRA and catheter-angiography. RESULTS:Twenty-six patients, 15 male and 11 female, were included in the present study at a median age of 41 years old. The Spetzler-Martin grades of the AVMs included seven Grade I, 12 Grade II, six Grade III, and one Grade IV with 14 (54%) of the patients having a pre-treatment hemorrhage. Median AVM nidal volume was 1.62 cm(3) (0.57-8.26 cm(3)) and was treated with a median dose of 1900 cGy to the 80% isodose line. At median follow-up of 25 months, 15 patients had a complete closure of their AVM, 6 patients had a partial closure, and 5 patients were stable. Time since treatment was a significant predictor of response, with patients experience complete closure having on average 11 months more follow-up than patients with partial or no closure (p = 0.03). One patient experienced a post-treatment hemorrhage at 22 months. CONCLUSION/CONCLUSIONS:Frameless radiosurgery can be targeted with non-invasive MRI/MRA and CTA imaging. Despite the difficulty of treating AVM without catheter angiography, early results with frameless, CT-guided radiosurgery suggest that it can achieve similar results to frame-based methods at these time points.

OBJECT/OBJECTIVE:Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2-5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. METHODS:The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2-5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. RESULTS:There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83-6.91, p = 0.032). CONCLUSIONS:Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.

BACKGROUND:Artificial neural networks (ANNs) excel at analyzing challenging data sets and can be exceptional tools for decision support in clinical environments. The present study pilots the use of ANNs for determining prognosis in neuro-oncology patients. OBJECTIVE:To determine whether ANNs perform better at predicting 1-year survival in a group of patients with brain metastasis compared with traditional predictive tools. METHODS:: ANNs were trained on a multi-institutional data set of radiosurgery patients to predict 1-year survival on the basis of several input factors. A single ANN, an ensemble of 5 ANNs, and logistic regression analyses were compared for efficacy. Sensitivity analysis was used to identify important variables in the ANN model. RESULTS:A total of 196 patients were divided up into training, testing, and validation data sets consisting of 98, 49, and 49 patients, respectively. Patients surviving at 1 year tended to be female (P = .001) and of good performance status (P = .01) and to have favorable primary tumor histology (P = .001). The pooled voting of 5 ANNs performed significantly better than the multivariate logistic regression model (P = .02), with areas under the curve of 84% and 75%, respectively. The ensemble also significantly outperformed 2 commonly used prognostic indexes. Primary tumor subtype and performance status were identified on sensitivity analysis to be the most important variables for the ANN. CONCLUSION/CONCLUSIONS:ANNs outperform traditional statistical tools and scoring indexes for predicting individual patient prognosis. Their facile implementation, robustness in the presence of missing data, and ability to continuously learn make them excellent choices for use in complicated clinical environments.

BACKGROUND:Limited data exist regarding management of patients with a single brain lesion with extracranial disease due to non-small cell lung cancer (NSCLC). METHODS:Eighty-eight consecutive patients with a single brain lesion from NSCLC in the presence of extracranial disease were treated with stereotactic radiosurgery (SRS) alone. Local control (LC), distant intracranial failure (DIF), overall survival (OS), and toxicity were assessed. The logrank test was used to identify prognostic variables. RESULTS:Median OS was 10.6 months. One-year DIF was 61%; LC 89%. Treatments were delivered in 1-5 fractions to median BED10 = 60 Gy. Five patients developed radionecrosis. Factors associated with shortened OS included poor performance status (PS) (p = 0.0002) and higher Recursive Partitioning Analysis class (p = 0.017). For patients with PS 0, median survival was 22 months. DIF was associated with systemic disease status (progressive vs. stable) (p = 0.0001), as was BED (p = 0.021) on univariate analysis, but only systemic disease (p = 0.0008) on multivariate analysis. CONCLUSIONS:This study identifies a patient population that may have durable intracranial control after treatment with SRS alone. These data support the need for prospective studies to optimize patient selection for up-front SRS and to characterize the impact of DIF on patients' quality of life.