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John C. Flickinger, Douglas Kondziolka, Ajay Niranjan, and L. Dade Lunsford

Object. The goal of this study was to define tumor control and complications of radiosurgery encountered using current treatment methods for the initial management of patients with unilateral acoustic neuroma.

Methods. One hundred ninety patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent gamma knife radiosurgery between 1992 and 1997. The median follow-up period in these patients was 30 months (maximum 85 months). The marginal radiation doses were 11 to 18 Gy (median 13 Gy), the maximum doses were 22 to 36 Gy (median 26 Gy), and the treatment volumes were 0.1 to 33 cm3 (median 2.7 cm3).

The actuarial 5-year clinical tumor-control rate (no requirement for surgical intervention) for the entire series was 97.1 ± 1.9%. Five-year actuarial rates for any new facial weakness, facial numbness, hearing-level preservation, and preservation of testable speech discrimination were 1.1 ± 0.8%, 2.6 ± 1.2%, 71 ± 4.7%, and 91 ± 2.6%, respectively. Facial weakness did not develop in any patient who received a marginal dose of less than 15 Gy (163 patients). Hearing levels improved in 10 (7%) of 141 patients who exhibited decreased hearing (Gardner-Robertson Classes II–V) before undergoing radiosurgery. According to multivariate analysis, increasing marginal dose correlated with increased development of facial weakness (p = 0.0342) and decreased preservation of testable speech discrimination (p = 0.0122).

Conclusions. Radiosurgery for acoustic neuroma performed using current procedures is associated with a continued high rate of tumor control and lower rates of posttreatment morbidity than those published in earlier reports.

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Zhishuo Wei, Arka N. Mallela, Andrew Faramand, Ajay Niranjan, and L. Dade Lunsford

BACKGROUND

Invasive sagittal sinus meningiomas are difficult tumors to cure by resection alone. Stereotactic radiosurgery (SRS) can be used as an adjuvant management strategy to improve tumor control after incomplete resection.

OBSERVATIONS

The authors reported the long-term retrospective follow-up of two patients whose recurrent parasagittal meningiomas eventually occluded their superior sagittal sinus. Both patients underwent staged radiosurgery and fractionated radiation therapy to achieve tumor control that extended to 20 years after their initial surgery. After initial subtotal resection of meningiomas that had invaded major cerebral venous sinuses, adjuvant radiosurgery was performed to enhance local tumor control. Over time, adjacent tumor progression required repeat SRS and fractionated radiation therapy to boost long-term tumor response. Staged multimodality intervention led to extended survival in these patients with otherwise unresectable meningiomas.

LESSONS

Multimodality management with radiosurgery and fractionated radiation therapy was associated with long-term survival of two patients with otherwise surgically incurable and invasive meningiomas of the dural venous sinuses.

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Sudesh S. Raju, Ajay Niranjan, Edward A. Monaco III, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

Multiple sclerosis (MS) is a neurodegenerative disease that can lead to severe intention tremor in some patients. In several case reports, conventional radiotherapy has been reported to possibly exacerbate MS. Radiosurgery dramatically limits normal tissue irradiation to potentially avoid such a problem. Gamma Knife thalamotomy (GKT) has been established as a minimally invasive technique that is effective in treating essential tremor and Parkinson’s disease–related tremor. The goal in this study was to analyze the outcomes of GKT in patients suffering from medically refractory MS-related tremor.

METHODS

The authors retrospectively studied the outcomes of 15 patients (mean age 46.5 years) who had undergone GKT over a 15-year period (1998–2012). Fourteen patients underwent GKT at a median maximum dose of 140 Gy (range 130–150 Gy) using a single 4-mm isocenter. One patient underwent GKT at a dose of 140 Gy delivered via two 4-mm isocenters (3 mm apart). The posteroinferior region of the nucleus ventralis intermedius (VIM) was the target for all GKTs. The Fahn-Tolosa-Marin clinical tremor rating scale was used to evaluate tremor, handwriting, drawing, and drinking. The median time to the last follow-up was 39 months.

RESULTS

After GKT, 13 patients experienced tremor improvement on the side contralateral to surgery. Four patients noted tremor arrest at a median of 4.5 months post-GKT. Seven patients had excellent tremor improvement and 6 had good tremor improvement. Four patients noted excellent functional improvement, 8 noted good functional improvement, and 1 noted satisfactory functional improvement. Three patients experienced diminished tremor relief at a median of 18 months after radiosurgery. Two patients experienced temporary adverse radiation effects. Another patient developed a large thalamic cyst 60 months after GKT, which was successfully managed with Ommaya reservoir placement.

CONCLUSIONS

Gamma Knife thalamotomy was found to be a minimally invasive and beneficial procedure for medically refractory MS tremor.

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John Y. K. Lee, Ajay Niranjan, James McInerney, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object. To evaluate long-term outcomes of patients who have undergone stereotactic radiosurgery for cavernous sinus meningiomas, the authors retrospectively reviewed their 14-year experience with these cases.

Methods. One hundred seventy-six patients harbored meningiomas centered within the cavernous sinus. Seventeen patients were lost to follow-up review, leaving 159 analyzable patients, in whom 164 procedures were performed. Seventy-six patients (48%) underwent adjuvant radiosurgery after one or more attempts at surgical resection. Eighty-three patients (52%) underwent primary radiosurgery. Two patients (1%) had previously received fractionated external-beam radiation therapy. Four patients (2%) harbored histologically verified atypical or malignant meningiomas. Conformal multiple isocenter gamma knife surgery was performed. The median dose applied to the tumor margin was 13 Gy.

Neurological status improved in 46 patients (29%), remained stable in 99 (62%), and eventually worsened in 14 (9%). Adverse effects of radiation occurred after 11 procedures (6.7%). Tumor volumes decreased in 54 patients (34%), remained stable in 96 (60%), and increased in nine (6%). The actuarial tumor control rate for patients with typical meningiomas was 93.1 ± 3.3% at both 5 and 10 years. For the 83 patients who underwent radiosurgery as their sole treatment, the actuarial tumor control rate at 5 years was 96.9 ± 3%.

Conclusions. Stereotactic radiosurgery provided safe and effective management of cavernous sinus meningiomas. We believe it is the preferred management strategy for tumors of suitable volume (average tumor diameter ≤ 3 cm or volume ≤ 15 cm3).

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Ajay Niranjan, Sudesh S. Raju, Edward A. Monaco III, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

Unilateral Gamma Knife thalamotomy (GKT) is a well-established treatment for patients with medically refractory tremor who are not eligible for invasive procedures due to increased risk of compications. The purpose of this study was to evaluate whether staged bilateral GKT provides benefit with acceptable risk to patients suffering from disabling medically refractory bilateral tremor.

METHODS

Eleven patients underwent staged bilateral GKT during a 17-year period (1999–2016). Eight patients had essential tremor (ET), 2 had Parkinson's disease (PD)–related tremor, and 1 had multiple-sclerosis (MS)–related tremor. For the first GKT, a median maximum dose of 140 Gy was delivered to the posterior-inferior region of the nucleus ventralis intermedius (VIM) through a single isocenter with 4-mm collimators. Patients who benefitted from unilateral GKT were eligible for a contralateral GKT 1–2 years later (median 22 months). For the second GKT, a median maximum dose of 130 Gy was delivered to the opposite VIM nucleus to a single 4-mm isocenter. The Fahn-Tolosa-Marin (FTM) clinical tremor rating scale was used to score tremor, drawing, and drinking before and after each GKT. The FTM writing score was assessed only for the dominant hand before and after the first GKT. The Karnofsky Performance Status (KPS) was used to assess quality of life and activities of daily living before and after the first and second GKT.

RESULTS

The median time to last follow-up after the first GKT was 35 months (range 11–70 months). All patients had improvement in at least 1 FTM score after the first GKT. Three patients (27.3%) had tremor arrest and complete restoration of function (noted via FTM tremor, writing, drawing, and drinking scores equaling zero). No patient had tremor recurrence or diminished tremor relief after the first GKT. One patient experienced new temporary neurological deficit (contralateral lower-extremity hemiparesis) from the first GKT. The median time to last follow-up after the second GKT was 12 months (range 2–70 months). Nine patients had improvement in at least 1 FTM score after the second GKT. Two patients had tremor arrest and complete restoration of function. No patient experienced tremor recurrence or diminished tremor relief after the second GKT. No patient experienced new neurological or radiological adverse effect from the second GKT. Statistically significant improvements were noted in the KPS score following the first and second GKT.

CONCLUSIONS

Staged bilateral GKT provided effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications. It is an appropriate strategy for carefully selected patients with medically refractory bilateral tremor who are not eligible for deep brain stimulation.

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Ajay Niranjan, Ahmed Kashkoush, Hideyuki Kano, Edward A. Monaco III, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

Seizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control.

METHODS

Patients with AVM who presented with a history of seizure and underwent SRS at the authors’ institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6–295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up.

RESULTS

Seizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0–27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4–23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15–0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16–0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test).

CONCLUSIONS

This study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

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Keisuke Maruyama, Douglas Kondziolka, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

Object. Management options for arteriovenous malformations (AVMs) of the brainstem are limited. The long-term results of stereotactic radiosurgery for these disease entities are poorly understood. In this report the authors reviewed both neurological and radiological outcomes following stereotactic radiosurgery for brainstem AVMs over 15 years of experience.

Methods. Fifty patients with brainstem AVMs underwent gamma knife surgery between 1987 and 2002. There were 29 male and 21 female patients with an age range of 7 to 79 years (median 35 years). Anatomical locations of these AVMs included the midbrain (39 lesions), pons (20 lesions), and medulla oblongata (three lesions). The radiation dose applied to the margin of the AVM varied from 12 to 26 Gy (median 20 Gy). Forty-five patients were followed up from 5 to 176 months (mean 72 months). The angiographically confirmed actuarial obliteration rate was 66% at the final follow-up examination. Two patients experienced a hemorrhage before obliteration. The annual hemorrhage rate was 1.7% for the first 3 years after radiosurgery and 0% thereafter. Patients who had received irradiation at two or fewer isocenters had higher obliteration rates (80% compared with 44% for > two isocenters, p = 0.006), and this was related to a more spherical nidus shape. The rate of persistent neurological complications in patients treated using magnetic resonance imaging—based dose planning after 1993 was 7%, compared with 20% in patients treated before 1993. An older patient age, a lesion located in the tectum, and a higher radiosurgery-based score were significantly associated with greater neurological complications.

Conclusions. Stereotactic radiosurgery provided complete obliteration of AVMs in two thirds of the patients with a low risk of latency-interval hemorrhage. Better three-dimensional imaging studies and conformal dose planning reduced the risk of adverse radiation effects. Younger patients harboring more spherical AVMs that did not involve the tectal plate had the best outcomes.

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Andrés Monserrate, Benjamin Zussman, Alp Ozpinar, Ajay Niranjan, John C. Flickinger, and Peter C. Gerszten

OBJECTIVE

Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined.

METHODS

Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained.

RESULTS

The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12–27 Gy) delivered in 1–3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment.

CONCLUSIONS

Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.

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Stephen Johnson, Hideyuki Kano, Andrew Faramand, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

Optimizing outcomes in the management of patients with vestibular schwannomas (VSs) requires consideration of the patient’s goals. Earlier recognition of VS by imaging has led to an evolution in management. Stereotactic radiosurgery (SRS) has emerged as a frequently used strategy designed to reduce management risks, obtain long-term tumor control, and preserve current neurological function. The authors analyzed features that impact hearing preservation rates in patients with serviceable hearing prior to SRS.

METHODS

The study included 307 patients who had serviceable hearing (Gardner-Robertson hearing scale [GR] grade 1 or 2, speech discrimination score ≥ 50%, pure tone average ≤ 50 dB) at the time of SRS. The authors evaluated parameters that included age, tumor volume, hearing status, disequilibrium, tinnitus, Koos class, sex, and tumor margin dose. The Pittsburgh Hearing Prediction Score (PHPS) was evaluated as a method to predict long-term hearing outcomes in these cases.

RESULTS

At a median of 7.6 years after SRS (range 1–23 years), tumor control was achieved in 95% of patients. The overall serviceable hearing preservation rate was 77.8% at 3 years, 68.8% at 5 years, and 51.8% at 10 years. The PHPS assigns a total of 5 points based on patient age (1 point if < 45 years, 2 points if 45–59 years, and 3 points if ≥ 60 years), tumor volume (0 points if < 1.2 cm3, 1 point if ≥ 1.2 cm3), and GR grade (0 points if grade 1 hearing, 1 point if grade 2 hearing) The serviceable hearing preservation rate was 92.3% at 10 years in patients whose score total was 1. In contrast, none of the patients whose PHPS was 5 maintained serviceable hearing at 10 years (p < 0.001).

CONCLUSIONS

SRS resulted in a high rate of long-term tumor control and cranial nerve preservation. The PHPS helped to predict long-term hearing preservation rates in patients who underwent SRS when they still had serviceable hearing. The best long-term hearing preservation rates were found in younger patients with smaller tumor volumes.