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Hideyuki Kano, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Daniel Tonetti, Ajay Niranjan and L. Dade Lunsford

Object

The purpose of this study was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs).

Methods

Between 1987 and 2009, SRS was performed in 474 patients with SM Grade III AVMs. The AVMs were categorized by scoring the size (S), drainage (D), and location (L): IIIa was a small AVM (S1D1L1, N = 282); IIIb was a medium/deep AVM (S2D1L0, N = 44); and IIIc was a medium/eloquent AVM (S2D0L1, N = 148). The median target volume was 3.8 ml (range 0.1–26.3 ml) and the margin dose was 20 Gy (range 13–25 Gy). Eighty-one patients (17%) underwent prior embolization, and 58 (12%) underwent prior resection.

Results

At a mean follow-up of 89 months, the total obliteration rates documented by angiography or MRI for all SM Grade III AVMs increased from 48% at 3 years to 69% at 4 years, 72% at 5 years, and 77% at 10 years. The SM Grade IIIa AVMs were more likely to obliterate than other subgroups. The cumulative rate of hemorrhage was 2.3% at 1 year, 4.4% at 2 years, 5.5% at 3 years, 6.4% at 5 years, and 9% at 10 years. The SM Grade IIIb AVMs had a significantly higher cumulative rate of hemorrhage. Symptomatic adverse radiation effects were detected in 6%.

Conclusions

Treatment with SRS was an effective and relatively safe management option for SM Grade III AVMs. Although patients with residual AVMs remained at risk for hemorrhage during the latency interval, the cumulative 10-year 9% hemorrhage risk in this series may represent a significant reduction compared with the expected natural history.

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Cheng-Chia Lee, Hideyuki Kano, Huai-Che Yang, Zhiyuan Xu, Chun-Po Yen, Wen-Yuh Chung, David Hung-Chi Pan, L. Dade Lunsford and Jason P. Sheehan

Object

Nonfunctioning pituitary adenomas (NFAs) are the most common type of pituitary adenoma and, when symptomatic, typically require surgical removal as an initial means of management. Gamma Knife radiosurgery (GKRS) is an alternative therapeutic strategy for patients whose comorbidities substantially increase the risks of resection. In this report, the authors evaluated the efficacy and safety of initial GKRS for NFAs.

Methods

An international group of three academic Gamma Knife centers retrospectively reviewed outcome data in 569 patients with NFAs.

Results

Forty-one patients (7.2%) underwent GKRS as primary management for their NFAs because of an advanced age, multiple comorbidities, or patient preference. The median age at the time of radiosurgery was 69 years. Thirty-seven percent of the patients had hypopituitarism before GKRS. Patients received a median tumor margin dose of 12 Gy (range 6.2–25.0 Gy) at a median isodose of 50%. The overall tumor control rate was 92.7%, and the actuarial tumor control rate was 94% and 85% at 5 and 10 years postradiosurgery, respectively. Three patients with tumor growth or symptom progression underwent resection at 3, 3, and 96 months after GKRS, respectively. New or worsened hypopituitarism developed in 10 patients (24%) at a median interval of 37 months after GKRS. One patient suffered new-onset cranial nerve palsy. No other radiosurgical complications were noted. Delayed hypopituitarism was observed more often in patients who had received a tumor margin dose > 18 Gy (p = 0.038) and a maximum dose > 36 Gy (p = 0.025).

Conclusions

In this study, GKRS resulted in long-term control of NFAs in 85% of patients at 10 years. This experience suggests that GKRS provides long-term tumor control with an acceptable risk profile. This approach may be especially valuable in older patients, those with multiple comorbidities, and those who have endocrine-inactive tumors without visual compromise due to mass effect of the adenoma.

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Greg Bowden, Hideyuki Kano, Daniel Tonetti, Ajay Niranjan, John Flickinger and L. Dade Lunsford

Object

Arteriovenous malformations (AVMs) of the posterior fossa have an aggressive natural history and propensity for hemorrhage. Although the cerebellum accounts for the majority of the posterior fossa volume, there is a paucity of stereotactic radiosurgery (SRS) outcome data for AVMs of this region. The authors sought to evaluate the long-term outcomes and risks of cerebellar AVM radiosurgery.

Methods

This single-institution retrospective analysis reviewed the authors' experience with Gamma Knife surgery during the period 1987–2007. During this time 64 patients (median age 47 years, range 8–75 years) underwent SRS for a cerebellar AVM. Forty-seven patients (73%) presented with an intracranial hemorrhage. The median target volume was 3.85 cm3 (range 0.2–12.5 cm3), and the median marginal dose was 21 Gy (range 15–25 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MRI or angiography in 40 patients at a median follow-up of 73 months (range 4–255 months). The actuarial rates of total obliteration were 53% at 3 years, 69% at 4 years, and 76% at 5 and 10 years. Elevated obliteration rates were statistically higher in patients who underwent AVM SRS without prior embolization (p = 0.005). A smaller AVM volume was also associated with a higher rate of obliteration (p = 0.03). Four patients (6%) sustained a hemorrhage during the latency period and 3 died. The cumulative rates of AVM hemorrhage after SRS were 6% at 1, 5, and 10 years. This correlated with an overall annual hemorrhage rate of 2.0% during the latency interval. One patient experienced a hemorrhage 9 years after confirmed MRI and angiographic obliteration. A permanent neurological deficit due to adverse radiation effects developed in 1 patient (1.6%) and temporary complications were seen in 2 additional patients (3.1%).

Conclusions

Stereotactic radiosurgery proved to be most effective for patients with smaller and previously nonembolized cerebellar malformations. Hemorrhage during the latency period occurred at a rate of 2.0% per year until obliteration occurred.

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Seong-Hyun Park, Hideyuki Kano, Ajay Niranjan, John C. Flickinger and L. Dade Lunsford

Object

To assess the long-term outcomes of stereotactic radiosurgery (SRS) for cerebellopontine angle (CPA) meningiomas, the authors retrospectively reviewed data from a 20-year experience. They evaluated progression-free survival as well as improvement, stabilization, or deterioration in clinical symptoms.

Methods

Seventy-four patients with CPA meningiomas underwent SRS involving various Gamma Knife technologies between 1990 and 2010. The most common presenting symptoms were dizziness or disequilibrium, hearing loss, facial sensory dysfunction, and headache. The median tumor volume was 3.0 cm3 (range 0.3–17.1 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 11–16 Gy). The median follow-up period was 40 months (range 4–147 months).

Results

At last imaging follow-up, the tumor volume had decreased in 46 patients (62%), remained stable in 26 patients (35%), and increased in 2 patients (3%). The progression-free survival after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years. At the last clinical follow-up, 23 patients (31%) showed neurological improvement, 43 patients (58%) showed no change in symptoms or signs, and 8 patients (11%) had worsening symptoms or signs. The neurological improvement rate after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years. The post-SRS deterioration rate was 5% at 1 year, 10% at 3 years, and 16% at 5 years. A multivariate analysis demonstrated that trigeminal neuralgia was the symptom most likely to worsen after SRS (HR 0.08, 95% CI 0.02–0.31; p = 0.001). Asymptomatic peritumoral edema occurred in 4 patients (5%) after SRS, and symptomatic adverse radiation effects developed in 7 patients (9%).

Conclusions

Stereotactic radiosurgery for CPA meningiomas provided a high tumor control rate and relatively low risk of ARE. Tumor compression of the trigeminal nerve by a CPA meningioma resulted in an increased rate of facial pain worsening in this patient experience.

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Douglas Kondziolka, Phillip V. Parry, L. Dade Lunsford, Hideyuki Kano, John C. Flickinger, Susan Rakfal, Yoshio Arai, Jay S. Loeffler, Stephen Rush, Jonathan P. S. Knisely, Jason Sheehan, William Friedman, Ahmad A. Tarhini, Lanie Francis, Frank Lieberman, Manmeet S. Ahluwalia, Mark E. Linskey, Michael McDermott, Paul Sperduto and Roger Stupp

Object

Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown.

Methods

The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment.

Results

The actual median patient survival was 10.3 months (95% CI 6.4–14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12–18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months.

Conclusions

Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.

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Neal Luther, Douglas Kondziolka, Hideyuki Kano, Seyed H. Mousavi, John C. Flickinger and L. Dade Lunsford

Object

The authors sought to better define the clinical response of patients who underwent stereotactic radiosurgery (SRS) for brain metastases located in the region of the motor cortex.

Methods

A retrospective analysis was performed in 2026 patients with brain metastasis who underwent SRS with the Gamma Knife between 2002 and 2012, and multiple factors that affect motor function before and after SRS were evaluated. Ninety-four patients with tumors ≥ 1.5 cm in diameter located in or adjacent to the motor strip were identified, including 2 patients with bilateral motor strip metastases.

Results

Motor function improved after SRS in 30 (31%) of 96 cases, remained stable in 48 (50%), and worsened over time in 18 (19%) instances. Forty-seven patients had no motor weakness prior to radiosurgery; 10 (22%) developed new Grade 3/5–4/5 weakness. Thirty (68%) of 44 patients with ≥ 3/5 pre-SRS weakness improved, 6 (14%) remained stable, and 8 (18%) worsened. Three of 5 patients with < 3/5 pre-SRS motor function improved. Motor deficits prior to SRS did not correlate with a worse outcome; however, worse outcomes were associated with larger tumor volumes. The median tumor volume in patients whose function improved or remained stable was 5.3 cm3, but it was 9.2 cm3 in patients who worsened (p < 0.05). Tumor volumes > 9 cm3 were associated with a higher risk of worsening motor function. Adverse radiation effects occurred in 5 patients.

Conclusions

Most intact patients with brain metastases in or adjacent to motor cortex maintained neurological function after SRS, and most patients with symptomatic motor weakness remained stable or improved. Larger tumor volumes were associated with less satisfactory outcomes.

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Jason P. Sheehan, Robert M. Starke, David Mathieu, Byron Young, Penny K. Sneed, Veronica L. Chiang, John Y. K. Lee, Hideyuki Kano, Kyung-Jae Park, Ajay Niranjan, Douglas Kondziolka, Gene H. Barnett, Stephen Rush, John G. Golfinos and L. Dade Lunsford

Object

Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population.

Methods

Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1–223 months).

Results

Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02–1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96–4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score.

Conclusions

Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

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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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Douglas Kondziolka, Seyed H. Mousavi, Hideyuki Kano, John C. Flickinger and L. Dade Lunsford

Object

Management recommendations for patients with smaller-volume or newly diagnosed vestibular schwannomas (< 4 cm3) need to be based on an understanding of the anticipated natural history of the tumor and the side effects it produces. The natural history can then be compared with the risks and benefits of therapeutic intervention using a minimally invasive strategy such as stereotactic radiosurgery (SRS).

Methods

The authors reviewed the emerging literature stemming from recent recommendations to “wait and scan” (observation) and compared this strategy with published outcomes after early intervention using SRS or results from matched cohort studies of resection and SRS.

Results

Various retrospective studies indicate that vestibular schwannomas grow at a rate of 0–3.9 mm per year and double in volume between 1.65 and 4.4 years. Stereotactic radiosurgery arrests growth in up to 98% of patients when studied at intervals of 10–15 years. Most patients who select “wait and scan” note gradually decreasing hearing function leading to the loss of useful hearing by 5 years. In contrast, current studies indicate that 3–5 years after Gamma Knife surgery, 61%–80% of patients maintain useful hearing (speech discrimination score > 50%, pure tone average < 50).

Conclusions

Based on published data on both volume and hearing preservation for both strategies, the authors devised a management recommendation for patients with small vestibular schwannomas. When resection is not chosen by the patient, the authors believe that early SRS intervention, in contrast to observation, results in long-term tumor control and improved rates of hearing preservation.

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Jason Sheehan and Chun Po Yen