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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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Edward A. Monaco III, Aftab A. Khan, Ajay Niranjan, Hideyuki Kano, Ramesh Grandhi, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object

The authors performed a retrospective review of prospectively collected data to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) for the treatment of patients harboring symptomatic solitary cavernous malformations (CMs) of the brainstem that bleed repeatedly and are high risk for resection.

Methods

Between 1988 and 2005, 68 patients (34 males and 34 females) with solitary, symptomatic CMs of the brainstem underwent Gamma Knife surgery. The mean patient age was 41.2 years, and all patients had suffered at least 2 symptomatic hemorrhages (range 2–12 events) before radiosurgery. Prior to SRS, 15 patients (22.1%) had undergone attempted resection. The mean volume of the malformation treated was 1.19 ml, and the mean prescribed marginal radiation dose was 16 Gy.

Results

The mean follow-up period was 5.2 years (range 0.6–12.4 years). The pre-SRS annual hemorrhage rate was 32.38%, or 125 hemorrhages, excluding the first hemorrhage, over a total of 386 patient-years. Following SRS, 11 hemorrhages were observed within the first 2 years of follow-up (8.22% annual hemorrhage rate) and 3 hemorrhages were observed in the period after the first 2 years of follow-up (1.37% annual hemorrhage rate). A significant reduction (p < 0.0001) in the risk of brainstem CM hemorrhages was observed following radiosurgical treatment, as well as in latency period of 2 years after SRS (p < 0.0447). Eight patients (11.8%) experienced new neurological deficits as a result of adverse radiation effects following SRS.

Conclusions

The results of this study support a role for the use of SRS for symptomatic CMs of the brainstem, as it is relatively safe and appears to reduce rebleeding rates in this high-surgical-risk location.

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

✓ Stereotactic radiosurgery is commonly used for selected patients with benign cranial base tumors. The goal of radiosurgery is cessation of tumor growth and preservation of neurological function. Over the last 2 decades, the technique of radiosurgery has evolved due to improved imaging, better radiosurgical devices and software, and the continued analysis of results. In this report, the authors discuss technical concepts and dose selection in skull base radiosurgery.

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Douglas Kondziolka and L. Dade Lunsford

Object

In the management of trigeminal neuralgia (TN), physicians seek rapid and long-lasting pain relief, together with preservation of trigeminal nerve function. Percutaneous retrogasserian glycerol rhizotomy (PRGR) offers distinct advantages over other available procedures. The aim of this report was to provide details of the PRGR procedure and its expected outcome.

Methods

The authors reviewed their experience with PRGR in 1174 patients to evaluate the procedural technique, results, and complications. Although it is clear that TN is not a static disorder but one characterized by remissions and recurrences, long-lasting pain relief was noted in 77% of patients, with 55% discontinuing all medications and 22% requiring some drug usage.

Conclusions

The authors discuss the role of PRGR in their practice, along with other procedures such as microvascular decompression and gamma knife surgery, for idiopathic or multiple sclerosis–related TN. They conclude that PRGR had distinct advantages over other procedures, which include eliminating the need for intraoperative confirmatory sensory testing, and a lower risk of facial sensory loss.

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

Management options for patients with vestibular schwannomas (acoustic neuromas) include observation, tumor resection, stereotactic radiosurgery, and fractionated radiotherapy. In this report the authors review their 15-year experience with radiosurgery and discuss indications and expectations in relation to the different approaches. They conducted a survey of neurosurgeons to determine management preferences in two different cases of intra- and extra-canalicular tumor presentations. Patient decisions must be based on quality information derived from peer-reviewed literature.

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Jason P. Sheehan, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

Object

Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study was to evaluate the efficacy and role of gamma knife surgery (GKS) in the treatment of these lesions.

Methods

The authors conducted a review of cases in which GKS was performed at the University of Pittsburgh between 1987 and 2001. Forty-six patients with nonfunctioning pituitary adenomas and with at least 6 months of follow-up data were identified. In 41 of these patients some form of prior treatment such as transsphenoidal resection, craniotomy and resection, or conventional radiation therapy had been conducted. Five patients were deemed ineligible for microsurgery, and GKS served as the primary treatment modality. Endocrinological, ophthalmological, and radiological responses were evaluated. The mean radiation dose to the margin was 16 Gy.

In all patients with microadenomas and 91% of those with macroadenomas tumor control was demonstrated after radiosurgery. Gamma knife surgery had essentially equal efficacy in terms of achieving tumor control in cases of adenomas with cavernous sinus invasion and suprasellar extension. No new endocrinopathies were noted following radiosurgery. In two patients, however, tumor growth and decline in visual function occurred.

Conclusions

Gamma knife surgery is safe and effective in treating nonfunctioning pituitary adenomas. Radiosurgery may serve as a primary treatment modality in some or as a salvage treatment in others. Treatment must be tailored to meet the patient's symptoms, overall health, and tumor morphometry.

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Costas G. Hadjipanayis, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object

This study was conducted to examine the role of radiosurgery in the management of patients with recurrent or unresectable low-grade astrocytomas.

Methods

During a 13-year interval, 49 patients underwent stereotactic radiosurgery as part of multimodal treatment of their recurrent or unresectable low-grade astrocytomas. Thirty-seven of these patients (median age 14 years) harbored pilocytic astrocytomas and 12 patients harbored World Health Organization (WHO) Grade II fibrillary astrocytomas (median age 25 years). Tumors involved the brainstem in 22 cases, cerebellum in four, thalamus in six, temporal lobe in five, frontal lobe in four, and parietal lobe in three, as well as the hypothalamus, corpus callosum, insular cortex, optic tract, and third ventricle in one patient each. Each diagnosis was confirmed with the aid of stereotactic biopsy sampling in 17 patients, open biopsy sampling in five, partial resection in 13, and near-total resection in 14. Multimodal treatment included fractionated radiotherapy in 14 patients, stereotactic intracavitary irradiation in five, chemotherapy in two, cyst drainage in eight, ventriculoperitoneal shunt placement in five, and additional cytoreductive surgery in five. Tumor volumes ranged from 0.42 to 45.1 cm3. The median radiosurgical dose to the tumor margin was 15 Gy (range 9.6–22.5 Gy).

After radiosurgery, serial neuroimaging demonstrated complete tumor resolution in 11 patients, reduced tumor volume in 12, stable tumor volume in 10, and delayed tumor progression in 16. No procedure-related death was encountered. Forty-five of 49 patients are alive at a median follow-up period of 32 months after radiosurgery and 63 months after diagnosis. Sixteen patients participated in follow-up review for more than 60 months. Three patients died of local tumor progression.

Conclusions

Stereotactic radiosurgery is a potential alternative or adjunctive intervention in the management of selected patients with pilocytic or WHO Grade II fibrillary astrocytomas, usually performed for small-volume tumors in an attempt to avoid larger-field fractionated radiotherapy.

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Douglas Kondziolka, Atul Patel, L. Dade Lunsford, and John C. Flickinger

Object

Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with whole-brain radiation therapy (WBRT), is poor, with an average expected survival time of less than 6 months. Investigators at numerous centers have evaluated the role of stereotactic radiosurgery in retrospective case series of patients harboring solitary or multiple tumors. Tumor resection is used mainly for patients with large tumors that cause acute neurological syndromes. The authors conducted a randomized trial in which they compared radiosurgery combined with WBRT with WBRT alone.

Methods

Twenty-seven patients were randomized (14 to recieve WBRT alone and 13 to receive WBRT combined with radiosurgery). The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients in whom boost radiosurgery was performed. The median time to local failure was 6 months after WBRT alone (95% confidence interval (CI) 3.5–8.5) in comparison to 36 months (95% CI 15.6–57) after WBRT and radiosurgery (p = 0.0005). The median time to the development of any brain failure was improved in the combined modality group (p = 0.002). Survival was shown to be related to the extent of extracranial disease (p = 0.02).

Conclusions

Combined WBRT and radiosurgery for the treatment of patients with two to four brain metastases significantly improves control of brain disease. Whole-brain radiation therapy alone does not provide lasting and effective care when treating most patients. Surgical resection remains important for patients with large symptomatic tumors and in whom limited extracranial disease has been demonstrated.

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Brian R. Subach, Douglas Kondziolka, L. Dade Lunsford, David J. Bissonette, John C. Flickinger, and Ann H. Maitz

Object

Stereotactically guided radiosurgery is one of the primary treatment modalities for patients with acoustic neuromas (vestibular schwannomas). The goal of radiosurgery is to arrest tumor growth while preserving neurological function. Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2) represent a special challenge because of the risk of complete deafness. To better define the tumor control rate and long-term functional outcome, the authors reviewed their 10-year experience in treating these lesions.

Methods

Forty patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35 of them for solitary tumors. The other five underwent staged procedures for bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors) had undergone a median of two prior resections. The mean tumor volume at radiosurgery was 4.8 ml and the mean tumor margin dose was 15 Gy (range 12–20 Gy).

The overall tumor control rate was 98%. During the median follow-up period of 36 months, 16 (36%) tumors regressed, 28 (62%) remained unchanged, and one (2%) grew. In the 10 patients for whom more than 5 years of clinical and neuroimaging follow-up results were available (median 92 months), five tumors were smaller and five remained unchanged. Surgical resection was performed in three patients (7%) after radiosurgery; only one showed radiographic evidence of progression. Useful hearing (Gardner-Robertson Class I or II) was preserved in six (43%) of 14 patients and this rate improved to 67% after modifications made in 1992. Normal facial nerve function (House-Brackmann Grade 1) was preserved in 25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34 (94%) of 36 patients.

Conclusions

Stereotactically guided radiosurgery is a safe and effective treatment for patients with acoustic tumors in the setting of NF2. The rate of hearing preservation may be better with radiosurgery than with other available techniques.