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Brian J. Williams, Patrick J. Karas, Ganesh Rao, Laurence D. Rhines, and Claudio E. Tatsui

The authors present the first report of laser interstitial thermal therapy (LITT) ablation of a recurrent chordoma metastasis to the cervical spine. This patient was a 75-year-old woman who was diagnosed and treated for a sacral chordoma, and then developed metastases to the lung and upper thoracic spine. Unfortunately she experienced symptomatic recurrence at the C-7 spinous process. She underwent an uncomplicated LITT to the lesion. The patient convalesced without incident and was discharged on postoperative Day 1. She received stereotactic spinal radiosurgery to the lesion at a dose of 24 Gy in 1 fraction. At the 3-month follow-up evaluation she had radiographic response and improvement in her symptoms.

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Brian J. Williams, Deric M. Park, and Jason P. Sheehan

The authors present a case of an arteriovenous malformation of the central sulcus treated with Gamma Knife surgery. The patient developed perilesional edema 9 months after treatment and experienced severe headache and hemiparesis. Her symptoms were refractory to corticosteroid therapy and pain management. She was subsequently treated with bevacizumab with striking improvement in her symptoms and results of neuroimaging studies. This is the first time that bevacizumab has been used to control severe refractory perilesional edema related to an intracranial arteriovenous malformation.

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Robert M. Starke, Brian J. Williams, John A. Jane Jr., and Jason P. Sheehan

Object

Nonfunctioning pituitary macroadenomas often recur after microsurgery and thereby require further treatment. Gamma Knife surgery (GKS) has been used to treat recurrent adenomas. In this study, the authors evaluated outcomes following GKS of nonfunctioning pituitary macroadenomas and assessed predictors of tumor control, neurological deficits, and delayed hypopituitarism.

Methods

Between June 1989 and March 2010, 140 consecutive patients with nonfunctioning pituitary macroadenomas were treated using GKS at the University of Virginia. The median patient age was 51 years (range 21–82 years), and 56% of patients were male. Mean tumor volume was 5.6 cm3 (range 0.6–35 cm3). Thirteen patients were treated with GKS as primary therapy, and 127 had undergone at least 1 open resection prior to GKS. Ninety-three patients had a history of hormone therapy prior to GKS. The mean maximal dose of GKS was 38.6 Gy (range 10–70 Gy), the mean marginal dose was 18 Gy (range 5–25 Gy), and the mean number of isocenters was 9.8 (range 1–26). Follow-up evaluations were performed in all 140 patients, ranging from 0.5 to 17 years (mean 5 years, median 4.2 years).

Results

Tumor volume remained stable or decreased in 113 (90%) of 125 patients with available follow-up imaging. Kaplan-Meier analysis demonstrated radiographic progression free survival at 2, 5, 8, and 10 years to be 98%, 97%, 91%, and 87%, respectively. In multivariate analysis, a tumor volume greater than 5 cm3 (hazard ratio = 5.0, 95% CI 1.5–17.2; p = 0.023) was the only factor predictive of tumor growth. The median time to tumor progression was 14.5 years. Delayed hypopituitarism occurred in 30.3% of patients. No factor was predictive of post-GKS hypopituitarism. A new or worsening cranial nerve deficit occurred in 16 (13.7%) of 117 patients. Visual decline was the most common neurological deficit (12.8%), and all patients experiencing visual decline had evidence of tumor progression. In multivariate analysis, a tumor volume greater than 5 cm3 (OR = 3.7, 95% CI 1.2–11.7; p = 0.025) and pre-GKS hypopituitarism (OR = 7.5, 95% CI 1.1–60.8; p = 0.05) were predictive of a new or worsened neurological deficit.

Conclusions

In patients with nonfunctioning pituitary macroadenomas, GKS confers a high rate of tumor control and a low rate of neurological deficits. The most common complication following GKS is delayed hypopituitarism, and this occurs in a minority of patients.

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Brian J. Williams, Zhiyuan Xu, David J. Salvetti, Ian T. McNeill, James Larner, and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) is a safe and effective treatment for patients with small to moderately sized vestibular schwannomas (VSs). Reports of stereotactic radiosurgery for large VSs have demonstrated worse tumor control and preservation of neurological function. The authors endeavored to assess the effect of size of VSs treated using GKS.

Methods

This study was a retrospective comparison of 24 patients with large VSs (> 3 cm in maximum diameter) treated with GKS compared with 49 small VSs (≤ 3 cm) matched for age, sex, radiosurgical margin and maximal doses, length of follow-up, and indication.

Results

Actuarial tumor progression-free survival (PFS) for the large VS cohort was 95.2% and 81.8% at 3 and 5 years, respectively, compared with 97% and 90% for small VSs (p = 0.009). Overall clinical outcome was better in small VSs compared with large VSs (p < 0.001). Patients with small VSs presenting with House-Brackmann Grade I (good facial function) had better neurological outcomes compared with patients with large VSs (p = 0.003). Treatment failure occurred in 6 patients with large VSs; 3 each were treated with resection or repeat GKS. Treatment failure did not occur in the small VS group. Two patients in the large VS group required ventriculoperitoneal shunt placement. Univariate analysis did not identify any predictors of treatment failure among the large VS cohort.

Conclusions

Patients with large VSs treated using GKS had shorter PFS and worse clinical outcomes compared with age-, sex-, and indication-matched patients with small VSs. Nevertheless, GKS has efficacy for some patients with large VSs and represents a reasonable treatment option for selected patients.

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Robert M. Starke, Brian J. Williams, Claire Hiles, James H. Nguyen, Mohamed Y. Elsharkawy, and Jason P. Sheehan

Object

Skull base meningiomas are challenging tumors owing in part to their close proximity to important neurovascular structures. Complete microsurgical resection can be associated with significant morbidity, and recurrence rates are not inconsequential. In this study, the authors evaluate the outcomes of skull base meningiomas treated with Gamma Knife surgery (GKS) both as an adjunct to microsurgery and as a primary treatment modality.

Methods

The authors performed a retrospective review of a prospectively compiled database detailing the outcomes in 255 patients with skull base meningiomas treated at the University of Virginia from 1989 to 2006. All patients had a minimum follow-up of 24 months. The group comprised 54 male and 201 female patients, with a median age of 55 years (range 19–85 years). One hundred nine patients were treated with upfront radiosurgery, and 146 patients were treated with GKS following resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results

Meningiomas were centered over the cerebellopontine angle in 43 patients (17%), the clivus in 40 (16%), the petroclival region in 28 (11%), the petrous region in 6 (2%), and the parasellar region in 138 (54%). The median duration of follow-up was 6.5 years (range 2–18 years). The mean preradiosurgery tumor volume was 5.0 cm3 (range 0.3–54.8 cm3).

At most recent follow-up, 220 patients (86%) displayed either no change or a decrease in tumor volume, and 35 (14%) displayed an increase in volume. Actuarial progression-free survival at 3, 5, and 10 years was 99%, 96%, and 79%, respectively. In Cox multivariate analysis, pre-GKS covariates associated with tumor progression included age greater then 65 years (HR 3.41, 95% CI 1.63–7.13, p = 0.001) and decreasing dose to tumor margin (HR 0.90, 95% CI 0.80–1.00, p = 0.05).

At most recent clinical follow-up, 230 patients (90%) demonstrated no change or improvement in their neurological condition and the condition of 25 patients had deteriorated (10%). In multivariate analysis, the factors predictive of new or worsening symptoms were increasing duration of follow-up (OR 1.01, 95% CI 1.00–1.02, p = 0.015), tumor progression (OR 2.91, 95% CI 1.60–5.31, p < 0.001), decreasing maximum dose (OR 0.90, 95% CI 0.84–0.97, p = 0.007), and petrous or clival location versus parasellar, petroclival, and cerebellopontine angle location (OR 3.47, 95% CI 1.23–9.74, p = 0.018).

Conclusions

Stereotactic radiosurgery offers a high rate of tumor control and neurological preservation in patients with skull base meningiomas. After radiosurgery, better outcomes were observed for those receiving an optimal radiosurgery dose and harboring tumors located in a cerebellopontine angle, parasellar, or petroclival location.

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Ahmad Alhourani, Zaid Aljuboori, Mehran Yusuf, Shiao Y. Woo, Eyas M. Hattab, Norberto Andaluz, and Brian J. Williams

OBJECTIVE

The purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.

METHODS

The authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.

RESULTS

The authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.

CONCLUSIONS

AMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.

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Mayur Sharma, Beatrice Ugiliweneza, Enzo M. Fortuny, Nicolas K. Khattar, Noberto Andaluz, Robert F. James, Brian J. Williams, Maxwell Boakye, and Dale Ding

OBJECTIVE

The development and recent widespread dissemination of flow diverters may have reduced the utilization of surgical bypass procedures to treat complex or giant unruptured intracranial aneurysms (UIAs). The aim of this retrospective cohort study was to observe trends in cerebral revascularization procedures for UIAs in the United States before and after the introduction of flow diverters by using the National (Nationwide) Inpatient Sample (NIS).

METHODS

The authors extracted data from the NIS database for the years 1998–2015 using the ICD-9/10 diagnostic and procedure codes. Patients with a primary diagnosis of UIA with a concurrent bypass procedure were included in the study. Outcomes and hospital charges were analyzed.

RESULTS

A total of 216,212 patients had a primary diagnosis of UIA during the study period. The number of patients diagnosed with a UIA increased by 128% from 1998 (n = 7718) to 2015 (n = 17,600). Only 1328 of the UIA patients (0.6%) underwent cerebral bypass. The percentage of patients who underwent bypass in the flow diverter era (2010–2015) remained stable at 0.4%. Most patients who underwent bypass were white (51%), were female (62%), had a median household income in the 3rd or 4th quartiles (57%), and had private insurance (51%). The West (33%) and Midwest/North Central regions (30%) had the highest volume of bypasses, whereas the Northeast region had the lowest (15%). Compared to the period 1998–2011, bypass procedures for UIAs in 2012–2015 shifted entirely to urban teaching hospitals (100%) and to an elective basis (77%). The median hospital stay (9 vs 3 days, p < 0.0001), median hospital charges ($186,746 vs $66,361, p < 0.0001), and rate of any complication (51% vs 17%, p < 0.0001) were approximately threefold higher for the UIA patients with bypass than for those without bypass.

CONCLUSIONS

Despite a significant increase in the diagnosis of UIAs over the 17-year study period, the proportion of bypass procedures performed as part of their treatment has remained stable. Therefore, advances in endovascular aneurysm therapy do not appear to have affected the volume of bypass procedures performed in the UIA population. The authors’ findings suggest a potentially ongoing niche for bypass procedures in the contemporary treatment of UIAs.

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Dale Ding, Robert M. Starke, John Hantzmon, Chun-Po Yen, Brian J. Williams, and Jason P. Sheehan

Object

WHO Grade II and III intracranial meningiomas are uncommon, but they portend a significantly worse prognosis than their benign Grade I counterparts. The mainstay of current management is resection to obtain cytoreduction and histological tissue diagnosis. The timing and benefit of postoperative fractionated external beam radiation therapy and stereotactic radiosurgery remain controversial. The authors review the stereotactic radiosurgery outcomes for Grade II and III meningiomas.

Methods

A comprehensive literature search was performed using PubMed to identify all radiosurgery series reporting the treatment outcomes for Grade II and III meningiomas. Case reports and case series involving fewer than 10 patients were excluded.

Results

From 1998 to 2013, 19 radiosurgery series were published in which 647 Grade II and III meningiomas were treated. Median tumor volumes were 2.2–14.6 cm3. The median margin doses were 14–21 Gy, although generally the margin doses for Grade II meningiomas were 16–20 Gy and the margin doses for Grade III meningiomas were 18–22 Gy. The median 5-year PFS was 59% for Grade II tumors and 13% for Grade III tumors, which may have been affected by patient age, prior radiation therapy, tumor volume, and radiosurgical dose and timing. The median complication rate following radiosurgery was 8%.

Conclusions

The current data for radiosurgery suggest that it has a role in the management of residual or recurrent Grade II and III meningiomas. However, better studies are needed to fully define this role. Due to the relatively low prevalence of these tumors, it is unlikely that prospective studies will be feasible. As such, well-designed retrospective analyses may improve our understanding of the effect of radiosurgery on tumor recurrence and patient survival and the incidence and impact of treatment-induced complications.

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Colin J. Przybylowski, Robert F. Dallapiazza, Brian J. Williams, I. Jonathan Pomeraniec, Zhiyuan Xu, Spencer C. Payne, Edward R. Laws, and John A. Jane Jr.

OBJECTIVE

The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods.

METHODS

The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS).

RESULTS

The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test).

CONCLUSIONS

Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.

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Robert M. Starke, James H. Nguyen, Jessica Rainey, Brian J. Williams, Jonathan H. Sherman, Jesse Savage, Chun Po Yen, and Jason P. Sheehan

Object

Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression.

Methods

A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12–82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results

Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2–16 years). The mean preradiosurgical tumor volume was 5.7 cm3 (range 0.3–33 cm3), and mean postradiosurgical tumor volume was 4.9 cm3 (range 0.1–33 cm3). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12–9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60–0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72–100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1–13.7; p = 0.03).

Conclusions

Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.