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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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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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L. Dade Lunsford, Aftab A. Khan, Ajay Niranjan, Hideyuki Kano, John C. Flickinger and Douglas Kondziolka

Object

A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal.

Methods

Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninety-eight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy.

Results

The follow-up ranged from 2 to 20 years. The annual hemorrhage rate—that is, a new neurological deficit associated with imaging evidence of a new hemorrhage—before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2-weighted MR imaging–defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS.

Conclusions

Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

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In-Young Kim, Douglas Kondziolka, Ajay Niranjan, John C. Flickinger and L. Dade Lunsford

Object

Schwannomas from the motor cranial nerves controlling eye movement are rare. The authors evaluated the role of Gamma Knife surgery (GKS) in the management of schwannomas originating from cranial nerves III, IV, and VI.

Methods

Over a 7-year period, 8 patients with schwannomas originating from the oculomotor (2 patients), trochlear (5 patients), or abducent (1) nerve underwent GKS. The mean patient age was 46.1 years (range 19–59 years). The presenting symptoms included diplopia in 5 patients, ptosis in 1 patient, ophthalmoplegia in 1 patient, and headache in 1 patient. Two patients had a history of neurofibromatosis Type 2. Gamma Knife surgery was performed as primary management in 7 patients and after prior resection in 1 patient. The median and mean tumor volumes were 0.22 and 1.32 cm3 (range 0.03–7.4 cm3). A median margin dose of 12.5 Gy (range 11.0–13.0 Gy) was prescribed to the tumor margin. Clinical and imaging follow-up data were available for all 8 patients.

Results

Magnetic resonance imaging showed tumor regression in all patients. The progression-free period varied from 4 to 42 months, with a mean of 21 months. Over a mean of 23 months, 4 of the 5 patients with a trochlear schwannoma and symptoms of diplopia noted symptomatic improvement. No improvement was noted in the 2 patients with oculomotor nerve palsies. Headache was improved in the 1 patient with an abducent neuroma.

Conclusions

Gamma Knife surgery is an effective and minimally invasive approach capable of inactivating schwannomas originating from the oculomotor, trochlear, and abducent nerves. Accompanying trochlear function may improve. Longer follow-up and larger patient samples are needed to confirm the authors' initial observations.

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

Object

To evaluate outcome predictors after stereotactic radiosurgery (SRS) in patients with trigeminal schwannomas, the authors compared tumor control, functional preservation, and complications with tumor grade, tumor volume, patient age, and tumor imaging characteristics.

Methods

The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1–82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5–18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12–20 Gy).

Results

At an average of 6 years (range 7.2–147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs.

Conclusions

Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment.

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Hideyuki Kano, Ajay Niranjan, Aftab Khan, John C. Flickinger, Douglas Kondziolka, Frank Lieberman and L. Dade Lunsford

Object

In this study the authors evaluated the role of stereotactic radiosurgery (SRS) in the management of progressive or newly diagnosed small-volume oligodendrogliomas. Tumor control, survival, and complications were assessed in patients with oligodendroglioma who underwent Gamma Knife radiosurgery as a primary or adjuvant procedure.

Methods

The authors retrospectively reviewed 30 patients with oligodendroglioma (12 Grade II and 18 Grade III) who underwent SRS between 1992 and June 2006 at the University of Pittsburgh. The median patient age was 43.2 years (range 10.8–75.4 years). Twenty-four patients had previously undergone resection of the tumor, whereas tumors in 6 were diagnosed based on biopsy findings. The SRS was performed in 25 patients who had imaging-defined tumor progression despite prior fractionated radiation (22 patients) and/or chemotherapy (20 patients). The median target volume was 15.4 cm3 (range 0.07–48.7 cm3) and the median margin dose was 14.5 Gy (range 11–20 Gy).

Results

At an average of 39.2 months of follow-up (range 12–133 months), 17 patients were dead and 13 were living. The overall survival rates from diagnosis to 5 and 10 years were 90.9 and 68.2%, respectively, for Grade II and 52.1% at 5 years and 26.1% at 10 years for Grade III. Factors associated with an improved progression-free survival included lower tumor grade and smaller tumor volume. In 13 patients who had loss of heterozygosity testing, patients with 1p19q loss of heterozygosity had a significantly improved survival after diagnosis (p = 0.04).

Conclusions

The SRS modality is a minimally invasive additional option for patients with residual or recurrent oligodendrogliomas. It may also be considered as an alternative to initial resection in small-volume tumors located in the cortical brain region.

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Juan J. Martin, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger, Karl A. Lozanne and L. Dade Lunsford

Object

Chordomas and chondrosarcomas of the skull base are aggressive and locally destructive tumors with a high tendency for local progression despite treatment. The authors evaluated the effect of stereotactic radiosurgery (SRS) on local tumor control and survival.

Methods

Twenty-eight patients with histologically confirmed chordomas (18) or chondrosarcomas (10) underwent Gamma Knife SRS either as primary or adjuvant treatment. Their ages ranged from 17 to 72 years (median 44 years). The most common presenting symptom was diplopia (26 patients, 93%). In two patients, SRS was the sole treatment. Twenty-six patients underwent between one and five additional surgical procedures. Two underwent an initial trans-sphenoidal biopsy. The average tumor volume was 9.8 cm3. The median dose to the tumor margin was 16 Gy.

Results

No patient was lost to follow-up. Transient symptomatic adverse radiation effects developed in only one patient. The actuarial local tumor control for chondrosarcomas at 5 years was 80 ± 10.1%. For chordomas both the actuarial tumor control and survival was 62.9 ± 10.4%.

Conclusions

Stereotactic radiosurgery is an important option for skull base chordomas and chondrosarcomas either as primary or adjunctive treatment. Multimodal management appears crucial to improve tumor control in most patients.

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Oren Berkowitz, Douglas Kondziolka, David Bissonette, Ajay Niranjan, Hideyuki Kano and L. Dade Lunsford

Object

The first North American 201 cobalt-60 source Gamma Knife surgery (GKS) device was introduced at the University of Pittsburgh Medical Center in 1987. The introduction of this innovative and largely untested surgical procedure prompted the desire to study patient outcomes and evaluate the effectiveness of this technique. The parallel advances in computer software and database technology led to the development of a registry to track patient outcomes at this center. The purpose of this study was to describe the registry's evolution and to evaluate its usefulness.

Methods

A team was created to develop a software database and tracking system to organize and retain information on the usage of GKS. All patients undergoing GKS were systematically entered into this database by a clinician familiar with the technology and the clinical indications. Information included patient demographics and diagnosis as well as the anatomical site of the target and details of the procedure.

Results

There are currently 11,738 patients in the database, which began to be used in August 1987. The University of Pittsburgh Medical Center has pioneered the evaluation and publication of the GKS technique and outcomes. Data derived from this computer database have facilitated the publication of more than 400 peer-reviewed manuscripts, more than 200 book chapters, 8 books, and more than 300 published abstracts and scientific presentations. The use of GKS has become a well-established surgical technique that has been performed more than 700,000 times around the world.

Conclusions

The development of a patient registry to track and analyze the use of GKS has given investigators the ability to study patient procedures and outcomes. The future of clinical medical research will rely on the ability of clinical centers to store and to share information.

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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.