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A decision to develop a stereotactic radiosurgery center and install the first 201 cobalt-60 Gamma Knife in Pittsburgh was made in 1981 after gathering regional and leadership support. This was part of a 7-year quest that required overcoming barriers to a new technology unfamiliar to US regulatory authorities and insurance companies. The first patient was treated in August 1987. Since that time our center has installed each succeeding Gamma Knife device developed. During an initial 30-year experience we performed more than 14,750 patient procedures. In addition to patient care our Center's goal was to develop a major teaching and clinical research program that eventually led to the training of more than 2,500 physicians and medical physicists, the publication of more than 600 peer-reviewed clinical outcome research studies, and 4 books. This report summarizes the rationale for acquisition, the challenges and the early years, and then the evolution of our center which installed the first US 201 source Gamma Knife.

Management of craniopharyngiomas remains challenging due to the tumor's often intimate relationship with the optic apparatus, the hypothalamus, and the pituitary gland. Often multimodal management is needed to achieve the best treatment outcome: tumor control coupled with endocrine, visual, and neurocognitive preservation. Many surgeons favor initial subtotal resection followed by adjunctive therapy to improve quality of life in a tumor with potentially long-term survival even if coupled with a need for periodic new interventions. During the patient's subsequent follow-up, solid or cystic tumor recurrence or progression often require additional management options. Leksell stereotactic radiosurgery (SRS) is a valuable adjuvant strategy that enhances long-term outcomes in patients with residual or recurrent craniopharyngiomas. Tumor control rates of 70-90% have been reported using 11- to 13-Gy tumor margin doses delivered using the Gamma Knife. Smaller tumors are associated with better radiosurgery outcomes. SRS is an effective management for residual or recurrent solid craniopharyngiomas with a favorable benefit-to-risk profile.

Leksell stereotactic radiosurgery has proven to be effective for less common tumors encountered in the brain, including hemangiomas of the orbit or cavernous sinus, recurrent hemangiopericytomas, and both sporadic hemangioblastomas as well as those encountered in the context of von Hippel-Lindau (VHL) disease. While all three tumors are responsive to single-session radiosurgery, hemangiomas and hemangiopericytomas are the most likely to demonstrate tumor regression. Hemangiopericytomas that recur after initial resection can be lower grade or anaplastic and have both higher local as well as distant recurrence risks. Sporadic hemangioblastomas undergo Leksell radiosurgery at the time of recurrence after initial surgery. In the context of VHL, growing or recurrent tumors are treated with tumor control rates exceeding 90%. Tumor control improves with higher dose delivery, typically15 Gy at the margin. Dose-limiting structures may include the optic apparatus for hemangiomas and brain stem locations for hemangioblastomas.

Stereotactic radiosurgery (SRS) is an effective treatment for patients with multiple brain metastases. Three decades of increasingly powerful scientific studies have shown that SRS improves outcomes and reduces toxicity when it replaces whole-brain radiation therapy (WBRT). Expert opinion surveys of clinicians have reported that the total intracranial tumor volume rather than the number of brain metastases is related to outcomes. As a result, an increasing number of treating and referring physicians have replaced the reflex use of WBRT with SRS, unless the patient has miliary disease or carcinomatous meningitis. In the current era of immunotherapy and targeted therapies with potentially increased systemic disease survival, 10 or more tumors are routinely treated with SRS alone at most academic medical centers. In a single SRS session we routinely treat patients with cumulative tumor volumes of 25 cm3 even if they have ≥10 metastases.

Low-grade gliomas represent a heterogeneous group of tumors. The goals of treatment include prolonged survival and reduced morbidity. Treatment strategies vary depending upon tumor histology, anatomic location, age, and the general medical condition of the patient. Safe surgical resection remains the first choice for the treatment of resectable tumors. In cases of unresectable lesions, adjuvant radiotherapy and chemotherapy are considered. Several reports in recent years have documented the safety and effectiveness of stereotactic radiosurgery (SRS) in controlling tumor growth and improving patients' survival for patients with low-grade gliomas. Patients with progressive, pilocytic, or grade 2 fibrillary astrocytomas, located in critical or deep areas of the brain, are ideal candidates for radiosurgery. The use of SRS as part of multimodal therapy for progressive, recurrent, or unresectable pilocytic or WHO grade 2 fibrillary astrocytomas is a safe and promising therapeutic modality. Gamma Knife radiosurgery has progressively gained more relevance in the management of low-grade gliomas.

Stereotactic radiosurgery using the Leksell Gamma Knife has proven to be a valuable alternative to orbital enucleation or fractionated radiation therapy for primary tumors of the orbit, metastatic tumors to the choroid, and primary uveal melanomas. With this approach in a single outpatient setting, the eye is immobilized by a local block after which high-definition MRI or CT is performed to define the target. After rapid dose planning, radiation delivery is completed before the local block dissipates. The tumor response is often dramatic. The risk of acute narrow-angle glaucoma, radiation-related retinopathy, or cataract formation has been relatively low. Other worldwide centers have confirmed that this approach is superior to either enucleation or fractionated radiation therapy for these relatively rare problems.

Vestibular schwannomas (VS) are benign tumors predominantly originating from the balance portion of cranial nerve VIII. These tumors have an incidence of 1-2 per 100,000 people. The growth of these tumors is approximately 1-2 mm per year. A VS can result in significant neurologic dysfunction from continued growth or the management paradigms designed to control this predominantly benign tumor. The impacts on the critical space within the auditory canal and cerebellopontine angle can lead to hearing deficits, tinnitus, vestibular dysfunction, facial nerve deficits, and brain stem compression.

For more than 65 years localization of brain targets suitable for stereotactic radiosurgery has been performed after application of an intracranial guiding device to the cranial vault. After imaging and dose planning the same frame is used to secure the target at the focus of the intersection of the ionizing radiation beams that create the radiobiological effect. Non-invasive immobilization systems first proposed for linear accelerator or proton radiation technologies have now been developed for the Leksell Gamma Knife ICON radiosurgical system. The ICON technology adds a cone-beam computed tomography (CBCT) scan to the original Perfexion radiosurgical device in order to define the brain stereotactic space. Marketed since 2015, the ICON can be used for standard radiosurgical procedures, most of which remain frame based, but also coupled with a non-invasive thermoplastic mask for carefully selected patients who undergo standard single-session radiosurgical procedures, as well as multisession procedures using repeat mask fixation. Both at UPMC as well as worldwide, mask immobilization has to date been used for approximately 10% of patients with specific characteristics: relatively simple dose plans, short radiation delivery times, and non-anxious patients, most of whom have metastatic or primary brain cancers. In certain cases, multisession radiosurgery is also performed using the mask. The workflow of frame versus frameless procedures is often altered, and is reliant on high-definition imaging, mostly MRI, done prior to dose planning. Since each CBCT takes 10-12 min to set up and acquire, co-register, and review with the treatment plan, and two CBCT scans are necessary to initiate the treatment plan, this workflow must be added to the beam on time. Although frame-based immobilization remains the predominant method to secure target fixation for problems suitable for single-session radiosurgery, the advent of a mask immobilization technique has proven valuable for a select group of patients. It also provides a non-invasive method to perform multisession or fractionated radiation in patients for whom traditional single-session radiosurgery is not feasible.

The classification of central neurocytoma (CN) by the WHO was upgraded to grade 2 in 1993 as it was recognized that at least some of these tumors can exhibit more aggressive behavior. Currently, as of 2016, CN is classified as WHO grade 2. Indeed, some atypical variants have been reported and residual postsurgical tumor is believed to have the potential for malignant transformation. Although gross total resection is usually curative for CN (5-year survival rate 99%), it is achieved in nearly 30-50% of cases due to its central location. Adjuvant treatments should be deliberately considered for the optimal management of CN. Recently, stereotactic radiosurgery is increasingly proposed as an adjuvant treatment for CN.

Tremor is the most prevalent movement disorder in adults. Patients who are refractory to medical management can explore surgical intervention. Deep-brain stimulation (DBS) and radiofrequency thalamotomy (RFT) are surgical procedures for intractable tremor that target the ventralis intermedius (VIM) nucleus to relieve contralateral tremor. For patients who are not candidates for surgical procedures, stereotactic radiosurgery (SRS) is a minimally invasive management option for tremor relief. SRS has been used for the elderly, those considered high surgical risk for other surgical procedures, those who are unresponsive to either DBS or RFT, and those who prefer a less invasive option. Radiosurgical thalamotomy is performed using a central dose of 130-140 Gy delivered to the VIM nucleus of the thalamus. The critical aspect of the dose planning procedure is the selection of the target, which requires a neurosurgeon experienced with movement disorder surgery. More than 90% of patients experience improvements in their tremor and quality of life after radiosurgical thalamotomy. Adverse radiation effects rates are low (4%). In selected cases, staged bilateral procedure can also be performed to relieve bilateral refractory tremor. In patients with tremor-predominant Parkinson's disease, VIM thalamotomy is also effective.

Chordomas and chondrosarcomas are rare locally aggressive skull base tumors with high progression or recurrence rates. Ultimately, they have high mortality rates unless they respond to multimodality management options that include one or more surgical resections, fractionated radiation therapy, and stereotactic radiosurgery (SRS). SRS has become a standard management option for recurrent or residual chordomas and chondrosarcomas after failed surgical resection and fractionated radiation therapy. This report examines the role of SRS in these skull base tumors.

Cavernous malformations (CM) represent a distinct subgroup of brain vascular malformations that are characterized by small sinusoidal vascular channels with hyaline degeneration and old blood pigments. Because of the increasing availability of magnetic resonance imaging (MRI) they are detected much more frequently in the present era. CM may be solitary or found in the context of a familial variant that results in an increasing number of CM developing as the patient ages. Because of the variable risk of subacute bleeding, their management options have been controversial. The annual risk of an incidentally detected CM bleeding is0.5% each year. Leksell radiosurgery is used for a subgroup of patients who have repeatedly bled. In general, CM best considered for stereotactic radiosurgery are deep seated and do not pre-sent to a pial or ependymal surface where microsurgical corridors for removal are feasible. When radiosurgery is used for patients at high risk for both re-bleeding as well as microsurgical resection, the risk of bleeding can be reduced from as high as 33% each year to0.5% each year after a 2-year latency interval. The target lies within the hemosiderin rim detected during the MRI that is part of planning. Marginal doses are significantly less than those used for angiographically visible arteriovenous malformations.

The outcome of patients with malignant gliomas has not substantially improved, even with advances in imaging, neurosurgery, molecular subtyping, and radiation, and newer oncologic options. Maximal safe resection when feasible remains the initial treatment of choice for most malignant gliomas. These tumors often recur and require additional therapy to control the tumor growth. Leksell stereotactic radiosurgery (SRS) is offered as salvage therapy in patients with recurrent or residual malignant gliomas. SRS is well tolerated and is associated with a relatively low risk of adverse radiation effects in malignant glial tumor patients who otherwise have relatively few options. SRS allows the surgeon more flexibility in terms of surgical options and may enhance quality of life for patients postoperatively. Although randomized controlled studies are lacking in the use of salvage SRS after the failure of initial standard of care management, preliminary data suggest that radiosurgery improves tumor control and overall survival for patients with recurrent malignant gliomas.

Management options for residual or recurrent glioblastoma multiforme (GBM) are limited despite advances in surgical, chemotherapeutic, and radiotherapeutic techniques. Stereotactic radiosurgery (SRS) is often beneficial in such cases providing improved survival of patients, but still remains underutilized as part of the multimodality management of malignant gliomas. During the last 20 years, 297 patients with histologically proven residual or recurrent GBM underwent Gamma Knife surgery in the University of Pittsburgh. Retrospective analysis of outcomes revealed median survival after initial diagnosis of 18 months, and 1- and 2-year survival rates of 72.5 and 29.5%, respectively. Median survival from the time of SRS was 9 months. The use of modified RPA (recursive partitioning analysis) classification demonstrated superior survival in our series in comparison with historical data. Important prognostic variables include tumor volume14 cm3, marginal radiation dose of ≥15 Gy, and younger age of the patients (60 years). Adverse radiation effects (ARE) were noted in 23% of cases and were mainly controlled with corticosteroids. Combining SRS with bevacizumab resulted in further improvement of the overall and progression-free survival and decreased incidence of ARE. Nevertheless, for future application of SRS in patients with GBM, evaluation of its efficacy in a well-designed prospective controlled clinical trials seems mandatory.

The first surgical procedures for abnormal movement disorders began in the 1930s, when surgeons first proposed ablative techniques of the caudate nucleus or transection of motor (pyramidal) pathways to reduce involuntary movements in patients with Parkinson's related tremor. During the 50-year interval between 1945 and 1995, the development of precise intracranial guiding devices, brain maps, and advanced imaging led to the refinement of appropriate deep brain targets affecting extrapyramidal pathways. Lesional surgery and subsequent neuroaugmentation using deep brain stimulation extended the role of deep brain surgery for a wider group of patients with tremor, rigidity, dyskinesia, and other involuntary movement disorders. Stereotactic radiosurgery has had wide application for tremor. The history of movement disorder surgery reads like a who's who of brilliant and resourceful surgeons who pushed the frontiers of neurosurgery. Even today, practitioners of functional brain surgery are among the most innovative practicing neurosurgeons.

Tremor is a common movement disorder that can be disabling, and its initial treatment is in the form of medical therapies. Often patients are refractory and seek surgical intervention. Treatment options for these patients include surgical radiofrequency thalamotomy and deep brain stimulation. There are a subset of patients who, for various reasons, are not candidates for open surgical procedures, or who opt to avoid them. For these patients, radiosurgical thalamotomy is a safe and useful alternative. Herein, we provide a review of the use of radiosurgical thalamotomy for the treatment of medically refractory tremor by discussing its history, defining the technique and its indications, evaluating its efficacy, and exploring its complications and shortcomings.

Radiosurgery is a minimally invasive technique designed to elicit a specific radiobiologic response at the target tissue using focused ionizing radiation delivered in single procedure. Radiosurgery was originally devised to treat intracranial lesions by delivering a high dose of radiation precisely at the intracranial target using stereotactic guidance. The term was coined and the field defined by Lars Leksell, a visionary leader of neurosurgery at the Karolinska Institute in Stockholm. Refinements in stereotactic methodologies, major improvements in dose planning software, and advances in neurodiagnostic imaging, all facilitated the increasingly broad application of brain radiosurgical methodologies. New technologies have continued to evolve and are still emerging. A variety of different radiosurgery techniques have been developed during the past 4 decades. Radiosurgery is now being used even for extracranial lesions such as spinal tumors, lung, liver, and prostate pathologies. Numerous studies have examined the benefits and risks of radiosurgery performed with various devices. The long-term results of radiosurgery are now available and have established it as an effective noninvasive management strategy for many brain disorders. Radiosurgery is now considered a mainstream neurosurgical modality for treatment of vascular malformations, tumors, trigeminal neuralgia, movement disorders, and perhaps epilepsy. Its role as a tool for spine and body surgery is also under evaluation.