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Bruce E. Pollock and Robert L. Foote

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Brian D. Milligan, Bruce E. Pollock, Robert L. Foote and Michael J. Link

Object

Gamma Knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors.

Methods

Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm3 (range 5.3–19.1 cm3). The median maximum posterior fossa diameter was 2.8 cm (range 2.5–3.8 cm). The median tumor margin dose was 12 Gy (range 12–14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26–121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection.

Results

Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction.

Conclusions

Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.

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Bruce E. Pollock, Michael J. Link and Robert L. Foote

Object

The decline in cranial nerve morbidity after radiosurgery for vestibular schwannoma (VS) correlates with dose reduction and other technical changes to this procedure. The effect these changes have had on tumor control has not been well documented.

Methods

The authors performed a retrospective review of 293 patients with VSs who underwent radiosurgery between 1990 and 2004 and had a minimum of 24 months of imaging follow-up (90% of the entire series). The median radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as progressive tumor enlargement noted on 2 or more imaging studies. The mean postradiosurgical follow-up was 60.9 ± 32.5 months.

Results

Tumor growth was noted in 15 patients (5%) at a median of 32 months after radiosurgery. Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years after radiosurgery. Univariate analysis revealed 2 factors that correlated with failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and tumor margin radiation doses ≤ 13 Gy (p = 0.02). Multivariate analysis showed that only an increasing number of isocenters correlated with failed VS radiosurgery (hazard ratio 1.1, 95% CI 1.02–1.32, p < 0.05). The tumor margin radiation dose (p = 0.22) was not associated with tumor growth after radiosurgery.

Conclusions

Distortion of stereotactic MR imaging coupled with increased radiosurgical conformality and progressive dose reduction likely caused some VSs to receive less than the prescribed radiation dose to the entire tumor volume.

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Akio Morita, Robert J. Coffey, Robert L. Foote, David Schiff and Deborah Gorman

Object. In this study the authors sought to determine the neurological risks and potential clinical benefits of gamma knife radiosurgery for skull base meningiomas.

Methods. A consecutive series of 88 patients harboring skull base meningiomas were treated between 1990 and 1996 by using the Leksell gamma knife in a prospective clinical study that included a strict dose—volume protocol. Forty-nine patients had previously undergone surgery, and six had received external-beam radiotherapy. The median treatment volume was 10 cm3, and the median dose to the tumor margin was 16 Gy. The radiosurgical dosage to the optic nerve, the cavernous sinus, and Meckel's cave was calculated and correlated with clinical outcome. The median patient follow-up time was 35 months (range 12–83 months).

Two tumors (2.3%) progressed after radiosurgery; the progression-free 5-year survival rate was 95%. At last follow-up review, 60 (68%) tumors were smaller and 26 (29.5%) remained unchanged. Clinical improvement (in vision, trigeminal pain, or other cranial nerve symptoms) occurred in 15 patients. Functioning optic nerves received a median dose of 10 Gy (range 1–16 Gy), and no treatment-induced visual loss occurred. Among nine patients with new trigeminal neuropathy, six received doses of more than 19 Gy to Meckel's cave.

Conclusions. Gamma knife radiosurgery appeared to be an effective method to control the growth of most skull base meningiomas in this intermediate-term study. The risk of trigeminal neuropathy seemed to be associated with doses of more than 19 Gy, and the optic apparatus appeared to tolerate doses greater than 10 Gy. Considering the risks to cranial nerves associated with open surgery for comparable tumors, the authors believe that gamma knife radiosurgery is a useful method for the management of properly selected recurrent, residual, or newly diagnosed skull base meningiomas.

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Robert L. Foote, Bruce E. Pollock, Michael J. Link, Yolanda I. Garces and Robert W. Kline

Object. The aim of this study was to determine the incidence and magnitude of coordinate setting slippage during gamma knife surgery (GKS).

Methods. Thirty-six consecutive patients undergoing GKS with a Leksell unit between June and December 2000 had their coordinates (right and left x-, y-, and z-coordinates; 1548 coordinates; 258 isocenters) and gamma angles checked after the delivery of treatment to each isocenter to determine whether the coordinate settings had slipped and, if so, which settings and the magnitude of the slippage.

Conclusions. Coordinate setting slippage during GKS with a Leksell unit does occur but is rare. The magnitude of such slippage is typically within the error of the stereotactic system and coordinate reading. The authors noted that coordinate setting slippage is significantly correlated with patient weight.

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Bruce E. Pollock, Scott L. Stafford, Michael J. Link, Yolanda I. Garces and Robert L. Foote

Object

Stereotactic radiosurgery (SRS) is an important treatment option for patients with cavernous sinus meningiomas (CSM). To analyze factors associated with local tumor control and complications after single-fraction SRS, the authors reviewed cases involving patients treated with Gamma Knife SRS between 1990 and 2008.

Methods

Excluded were patients with WHO Grade II or III tumors, radiation-induced tumors, multiple meningiomas, neurofibromatosis Type 2, and prior or concurrent radiotherapy. Five patients were lost to follow-up and 3 patients refused research authorization. The remaining 115 patients (29 men, 86 women) had either histologically confirmed WHO Grade I (n = 46, 40%) or presumed (n = 69, 60%) CSM. The median treatment volume was 9.3 cm3 (range 1.3–42.2 cm3). The median margin dose was 16 Gy (range 12–20 Gy). The median follow-up after SRS was 89 months (range 12–251 months). Thirty-nine patients (34%) had 10 or more years of follow-up after SRS.

Results

Six patients (5%) had tumor progression (in field, n = 3; marginal, n = 3) at a median of 74 months (range 42–145 months) after SRS. The local tumor control rate was 99% at 5 years and 93% at 10 years after SRS. No analyzed factor was associated with local control after SRS. Fourteen patients (12%) had permanent complications at a median onset of 23 months (range 2–146 months) including trigeminal dysfunction (n = 9), diplopia (n = 2), ischemic stroke (n = 2), and hypopituitarism (n = 1). The 2-year, 5-year, and 10-year rates of complications were 7%, 10%, and 15%, respectively. Multivariate analysis found larger treatment volume (HR 1.1, 95% CI 1.02–1.2, p = 0.01) to be associated with complications after SRS. The complication rate for patients with a treatment volume of 9.3 cm3 or less was 3% (2 of 58 cases) compared with 21% (12 of 57 cases) for patients with a treatment volume greater than 9.4 cm3.

Conclusions

Single-fraction SRS at the radiation doses used in this series provided durable tumor control for patients with benign CSM. Larger tumor volume remains the primary factor associated with complications after single-fraction SRS of benign CSM despite advancements in SRS technique.

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Bruce E. Pollock, Loi K. Phuong, Deborah A. Gorman, Robert L. Foote and Scott L. Stafford

Object. Each year a greater number of patients with trigeminal neuralgia (TN) undergo radiosurgery, including a large number of patients who are candidates for microvascular decompression (MVD).

Methods. The case characteristics and outcomes of 117 consecutive patients who underwent radiosurgery were retrieved from a prospectively maintained database. The mean patient age was 67.8 years; and the majority (58%) of patients had undergone surgery previously. The dependent variable for all analyses of facial pain was complete pain relief without medication (excellent outcome). Median follow-up duration was 26 months (range 1–48 months). The actuarial rate of achieving and maintaining an excellent outcome was 57% and 55% at 1 and 3 years, respectively, after radiosurgery. A greater percentage of patients who had not previously undergone surgery achieved and maintained excellent outcomes (67% at 1 and 3 years) than that of patients who had undergone prior surgery (51% and 47% at 1 and 3 years, respectively; relative risk [RR] = 1.77, 95% confidence interval [CI] 1.01–3.13, p = 0.04). New persistent trigeminal dysfunction was noted in 43 patients (37%). Tolerable numbness or paresthesias occurred in 29 patients (25%), whereas bothersome dysesthesias developed in 14 patients (12%). Only a radiation dose of 90 Gy correlated with new trigeminal deficits or dysesthesias (RR = 3.10, 95% CI 1.64–5.81, p < 0.001). Excellent outcomes in patients with new trigeminal dysfunction were achieved and maintained at rates of 76% and 74% at 1 and 3 years, respectively, after radiosurgery, compared with respective rates of 46% and 42% in patients who did not experience postradiosurgery trigeminal dysfunction (RR = 4.53, 95% CI 2.03–9.95, p < 0.01).

Conclusions. Radiosurgical treatment provides complete pain relief for the majority of patients with idiopathic TN. There is a strong correlation between the development of new facial sensory loss and achievement and maintenance of pain relief after this procedure. Because the long-term results of radiosurgery still remain unknown, MVD should continue to be the primary operation for medically fit patients with TN.

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Bruce E. Pollock, Todd B. Nippoldt, Scott L. Stafford, Robert L. Foote and Charles F. Abboud

Object. The goal of this study was to determine factors associated with endocrine normalization after radiosurgery is performed in patients with hormone-producing pituitary adenomas.

Methods. Between 1990 and 1999, 43 patients with hormone-producing pituitary adenomas underwent radiosurgery: 26 patients with growth hormone (GH)—producing tumors, nine with adrenocorticotrophic hormone—producing tumors, seven with tumors that produced prolactin (PRL) alone, and one with a tumor that secreted both GH and PRL. The median patient age was 42 years. Thirty-seven patients (86%) had undergone surgery earlier and in 30 (70%) there was tumor extension into the cavernous sinus. The product-limit method was used to calculate endocrine normalization while patients were not receiving any hormone-suppressive medication. The median follow-up period after radio-surgery was 36 months (range 12–108 months).

In 20 patients (47%) there was normalization of hormone secretion at a median of 14 months (range 2–44 months) after radiosurgery; no correlation was found between tumor type and cure. Actuarial cure rates were 20, 32, and 61% at 1, 2, and 4 years posttreatment. Multivariate analysis demonstrated that the absence of hormone-suppressive medications at the time of radiosurgery (relative risk 8.9, 95% confidence interval [CI] 1.2–68.7, p = 0.04) and maximum radiation doses greater than 40 Gy (relative risk 3.9, 95% CI 1.3–11.7, p = 0.02) correlated with an endocrine cure. A new anterior pituitary deficiency developed in seven patients (16%), temporal lobe necrosis was identified in two patients, an asymptomatic internal carotid artery stenosis was detected in two patients, and unilateral blindness occurred in one patient.

Conclusions. Radiosurgery provides an endocrine cure for many patients with persistent or recurrent hormone-producing pituitary adenomas. Further study is needed to determine whether pituitary hormone—suppressive medications have a radioprotective effect.

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Ritesh Banerjee, James P. Moriarty, Robert L. Foote and Bruce E. Pollock

Object

The best approach to the management of vestibular schwannoma (VS) remains controversial. The aim of this study is to analyze the initial and follow-up costs of resection and stereotactic radiosurgery for patients with VS.

Methods

Initial and follow-up costs in 53 cases in which patients with unilateral, previously unoperated VSs > 3 cm underwent resection (21 cases) or radiosurgery (32 cases) at the Mayo Clinic from June 2000 until July 2002 were analyzed for 36 months. Follow-up treatment-specific utilization records were gathered prospectively for patients not returning to the Mayo Clinic after treatment. Six-month moving averages of incremental follow-up costs were calculated for the 2 patient groups.

Results

The mean cost of surgery in the microsurgery group was $23,788 (95% confidence interval $22,280–$24,842) compared with $16,143 (95% confidence interval $15,277–$17,545) for the radiosurgical group. Mean incremental follow-up costs per month for patients in the microsurgery group started just > $1000 per month, decreased steadily, and remained < $70 per month by the 10th month of follow-up. Mean incremental follow-up costs per month for patients in the radiosurgery group were <$10 per month for the first few months and thereafter increased to as much as $200 per month.

Conclusions

Although the total cost of microsurgery is higher due to the costs of hospitalization, follow-up costs for radiosurgery are greater in general. From a societal perspective, radiosurgery is less expensive than microsurgical resection provided that the rate of tumor progression after radiosurgery remains low with long-term follow-up.

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Bruce E. Pollock, Curtis B. Storlie, Michael J. Link, Scott L. Stafford, Yolanda I. Garces and Robert L. Foote

OBJECTIVE

Successful stereotactic radiosurgery (SRS) for the treatment of arteriovenous malformations (AVMs) results in nidus obliteration without new neurological deficits related to either intracranial hemorrhage (ICH) or radiation-induced complications (RICs). In this study the authors compared 5 AVM grading scales (Spetzler-Martin grading scale, radiosurgery-based AVM score [RBAS], Heidelberg score, Virginia Radiosurgery AVM Scale [VRAS], and proton radiosurgery AVM scale [PRAS]) at predicting outcomes after SRS.

METHODS

The study group consisted of 381 patients with sporadic AVMs who underwent Gamma Knife SRS between January 1990 and December 2009; none of the patients underwent prior radiation therapy. The primary end point was AVM obliteration without a decline in modified Rankin Scale (mRS) score (excellent outcome). Comparison of the area under the receiver operating characteristic curve (AUC) and accuracy was performed between the AVM grading scales and the best linear regression model (generalized linear model, elastic net [GLMnet]).

RESULTS

The median radiological follow-up after initial SRS was 77 months; the median clinical follow-up was 93 months. AVM obliteration was documented in 297 patients (78.0%). Obliteration was 59% at 4 years and 85% at 8 years. Fifty-five patients (14.4%) had a decline in mRS score secondary to RICs (n = 29, 7.6%) or ICH (n = 26, 6.8%). The mRS score declined by 10% at 4 years and 15% at 8 years. Overall, 274 patients (71.9%) had excellent outcomes. There was no difference between the AUC for the GLMnet (0.69 [95% CI 0.64–0.75]), RBAS (0.68 [95% CI 0.62–0.74]), or PRAS (0.69 [95% CI 0.62–0.74]). Pairwise comparison for accuracy showed no difference between the GLMnet and the RBAS (p = 0.08) or PRAS (p = 0.16), but it did show a significant difference between the GLMnet and the Spetzler-Martin grading system (p < 0.001), Heidelberg score (p < 0.001), and the VRAS (p < 0.001). The RBAS and the PRAS were more accurate when compared with the Spetzler-Martin grading scale (p = 0.03 and p = 0.01), Heidelberg score (p = 0.02 and p = 0.02), and VRAS (p = 0.03 and p = 0.02).

CONCLUSIONS

SRS provides AVM obliteration without functional decline in the majority of treated patients. AVM grading scales having continuous scores (RBAS and PRAS) outperformed integer-based grading systems in the prediction of AVM obliteration without mRS score decline after SRS.