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Radiosurgery

Radiosurgery is a non-invasive that uses highly focused beams of to deliver a precise, high dose of energy to targeted abnormal tissues, such as tumors or vascular malformations, while minimizing exposure to surrounding healthy structures. Unlike traditional surgery, it involves no incisions and can often be completed in a single session or a few outpatient treatments. The technique, commonly known as stereotactic radiosurgery () when applied to the or stereotactic body radiation therapy (SBRT) for other sites, relies on advanced and computer-guided systems to achieve sub-millimeter accuracy. The origins of radiosurgery trace back to early 20th-century stereotactic , with the modern concept pioneered by Swedish neurosurgeon Lars Leksell in 1951, who envisioned using focused radiation as a surgical alternative. The first clinical device, the Gamma Knife, was developed in 1967 at the , utilizing cobalt-60 sources to produce converging gamma rays for intracranial treatments. Over decades, the field evolved with the integration of linear accelerators (LINACs) in the 1980s and robotic systems like the CyberKnife in the 1990s, expanding applications beyond the brain to extracranial sites such as the lungs, liver, spine, and prostate. These advancements have been driven by improvements in imaging technologies, including MRI and , enabling real-time tumor tracking and dose optimization. Radiosurgery is primarily used to treat both benign and malignant conditions, including brain metastases, acoustic neuromas, arteriovenous malformations (AVMs), meningiomas, and , as well as extracranial tumors like early-stage cancers and liver metastases. Common delivery methods include the , which employs up to 201 sources for fixed-headframe immobilization; LINAC-based systems, such as those using intensity-modulated (IMRT) for dynamic beam shaping; and particle therapy options like proton beams for enhanced depth-dose control. The procedure's precision allows for steep dose gradients, reducing side effects compared to conventional radiotherapy, though potential risks include radiation necrosis, , or depending on the target site. Ongoing research focuses on combining radiosurgery with or targeted drugs to improve outcomes for metastatic disease.

History

Early Foundations (1900-1950)

The Horsley-Clarke stereotactic apparatus, invented in 1908 by British neurosurgeon Victor Horsley and physiologist Robert H. Clarke, represented the inaugural device for precise intracranial targeting in neurosurgery. Designed primarily for animal experimentation, it employed a rigid, head-fixing frame mounted on the skull, integrated with a Cartesian coordinate system featuring three orthogonal axes to enable accurate localization of brain structures. The mechanical design included adjustable vernier scales for sub-millimeter precision, allowing probes or electrodes to reach specific depths and coordinates relative to anatomical landmarks like the external auditory meatus and orbital rim. Initial applications focused on creating small electrolytic lesions in the central nervous system of monkeys and other animals to map functional brain regions, such as the basal ganglia and cerebellum, thereby advancing understanding of neural localization without invasive exposure of the brain surface. The transition to human applications occurred in 1947, when American neurologist Ernest A. Spiegel and neurosurgeon Henry T. Wycis introduced the first stereotactic device adapted for clinical use. Their stereoencephalotome consisted of a lightweight metal frame secured to the patient's head via pins, combined with an arc-centered targeting system that utilized ventriculographic imaging for coordinate determination. This apparatus facilitated minimally invasive access to deep subcortical targets, reducing risks associated with open . The inaugural procedures targeted the for , primarily to alleviate symptoms of psychiatric disorders including Huntington's chorea, , and obsessive-compulsive conditions, as well as unresponsive to other therapies. Over subsequent years, Spiegel and Wycis refined the technique through dozens of operations, establishing stereotaxy as a viable tool for functional neurosurgical interventions in humans. Parallel early experiments with explored its potential for targeted brain tissue destruction, predating integrated stereotactic systems. In 1946, physicist advocated for proton beams in medical therapy, noting their sharp dose deposition via the , which allowed high-energy delivery to deep intracranial sites with reduced scatter to surrounding healthy tissue. This proposal stemmed from accelerator physics advancements and envisioned precise ablation of pathological brain areas, such as tumors, without the broad exposure typical of conventional methods. Conceptual precursors also included cross-firing radiation techniques in the 1930s and 1940s, where multiple beams were directed from opposing angles to converge on the for ablation in conditions like , aiming to minimize peripheral damage through geometric focusing. These innovations provided the foundational principles of spatial accuracy and selective energy deposition that would underpin radiosurgery in the following decades.

Development of Techniques (1950-1980)

The development of radiosurgery as a distinct clinical procedure began in the mid-20th century, building on earlier stereotactic principles to enable precise, non-invasive lesioning of brain targets using ionizing radiation. In 1951, Swedish neurosurgeon Lars Leksell introduced the concept of stereotactic radiosurgery, defining it as the stereotaxic delivery of a single high dose of radiation to an intracranial target, aimed at achieving a therapeutic effect equivalent to surgical ablation without incision. This innovation sought to address the limitations of invasive stereotactic surgery, particularly for deep-seated or high-risk lesions. Leksell's work was inspired by the need for bloodless, precise interventions in functional neurosurgery. In 1951, Leksell performed the first clinical radiosurgical procedures, using focused external beams in a cross-firing configuration for non-invasive lesioning, including thalamotomies to treat in patients with cancer by targeting the medial . These early procedures relied on manual beam alignment and rudimentary stereotactic frames, achieving focal doses while minimizing exposure to surrounding tissue, though with limited precision compared to later systems. Parallel efforts in particle therapy emerged at , where physicist Börje Larsson led pioneering proton beam radiosurgery starting in 1957. Utilizing a 185 MeV synchrocyclotron, Larsson and collaborators delivered narrow proton beams for stereotactic of small intracranial volumes, with initial treatments focused on pituitary tumors to control hormone secretion or tumor growth. This approach exploited the sharp dose fall-off of protons via the , allowing for superior depth-dose profiles over X-rays and enabling treatments through the intact . Over the subsequent decade, approximately 30 patients received proton radiosurgery at , establishing proof-of-concept for charged-particle applications in . The 1960s saw the conceptualization and prototyping of dedicated radiosurgical devices, culminating in Leksell and Larsson's collaboration on the Gamma Knife. In 1967, they completed the first prototype (Unit I), featuring 179 sources arranged in a hemispherical array to converge gamma rays at a focal point within the skull. This device automated the cross-firing geometry Leksell had explored earlier, providing sub-millimeter accuracy for intracranial targets. The inaugural human treatment occurred in 1968 at Sophiahemmet Hospital in , targeting a in an adult patient, which represented a milestone in non-invasive tumor management. Linear accelerator (LINAC)-based radiosurgery also gained traction in the and , adapting conventional radiotherapy equipment for stereotactic use. Leksell experimented with cross-fire techniques using modified tubes and early LINACs during the to treat functional disorders, laying groundwork for beam convergence methods. A key advancement came in 1974, when Börje Larsson proposed and initiated modifications to a medical LINAC at the , incorporating tertiary collimators and stereotactic alignment for single-fraction high-dose delivery. This system enabled the first dedicated LINAC radiosurgery treatments in the late , offering a more accessible alternative to proton or gamma units. Clinical milestones during this era expanded radiosurgery's scope beyond functional targets. In the , Leksell and Ladislau Steiner applied Gamma Knife radiosurgery to cerebral arteriovenous malformations (AVMs), reporting successful obliteration in select cases through endothelial damage and thrombosis induction, with follow-up publications in 1972 documenting outcomes in initial patients. These treatments, typically involving 20-25 Gy to the nidus, achieved partial or complete in up to 70% of small AVMs by the decade's end, validating radiosurgery for vascular lesions and influencing its evolution into a standard modality.

Modern Advancements (1980-present)

The installation of the first Gamma Knife unit in the United States in 1987 at the represented a pivotal step in the global dissemination of radiosurgery technology, transitioning it from limited European prototypes to broader clinical application and research. This event spurred rapid adoption, with more than 140 Gamma Knife systems installed worldwide by the early , enabling thousands of procedures annually and establishing radiosurgery as a standard neurosurgical tool. During the 1990s, innovations in frameless stereotaxy addressed limitations of invasive fixation frames, enhancing patient comfort and applicability to extracranial sites. The CyberKnife system, conceived by neurosurgeon in the late 1980s and first deployed clinically in 1994, introduced a robotic linear accelerator arm capable of real-time tumor tracking via integrated , revolutionizing non-invasive delivery for both intracranial and body lesions. Concurrently, linear accelerator (LINAC)-based platforms expanded, exemplified by the X-Knife system introduced in 1996, which integrated tertiary collimation and intensity-modulated (IMRT) principles to conform doses precisely to irregular targets beyond the brain. These developments facilitated the emergence of stereotactic body radiotherapy (SBRT), with initial applications for early-stage pioneered at the in the early 1990s. The Novalis shaped-beam radiosurgery platform, launched by in 1997, further advanced LINAC capabilities through micro-multileaf collimation and stereoscopic X-ray verification, receiving FDA clearance for intracranial stereotactic radiosurgery shortly thereafter. In the , radiosurgery experienced substantial growth, with over 2 million Gamma Knife treatments alone performed worldwide as of 2025. Spinal adaptations gained traction, highlighted by Ryu et al.'s 2003 demonstration of image-guided intensity-modulated radiosurgery for metastases, which informed early clinical guidelines for safe dose escalation while sparing the . Enhanced imaging integration, such as MRI/ fusion since the mid-1990s, improved delineation and accuracy, reducing margins and enabling hypofractionated regimens for complex anatomies. The founding of the International Stereotactic Radiosurgery Society (ISRS) in 1991 played a crucial role in this expansion, promoting international standards, education, and multicenter trials that accelerated evidence-based refinements.

Fundamental Principles

Definition and Distinctions from Radiotherapy

Radiosurgery is defined as a that delivers a highly focused, high dose of in one to five fractions to ablate pathological , achieving outcomes similar to traditional without the need for incision or direct . This approach relies on stereotactic techniques to ensure sub-millimeter precision in targeting, allowing for the destruction of small, well-defined lesions while minimizing exposure to surrounding healthy .00253-6/fulltext) The procedure's intent is immediate ablation through overwhelming cellular damage, contrasting with gradual cytoreduction seen in other modalities. Key characteristics of radiosurgery include its hypofractionated delivery—administering large doses per session, typically 15-25 in a single fraction—and the use of multiple converging beams to create steep dose gradients, with fall-off occurring within 1-2 mm beyond the target boundary.30125-1/fulltext) This precision is enabled by advanced and systems, restricting its application to small generally under 3-4 cm in diameter.00230-0/fulltext) Unlike traditional open , radiosurgery eliminates the need for scalp incisions, reducing risks of , , and time, and making it ideal for inoperable or high-risk locations such as deep brain structures. In distinction from conventional (EBRT), which employs fractionated lower doses of 1.8-2 daily over multiple weeks to allow normal tissue repair, radiosurgery uses ablative doses to induce rapid necrosis without relying on for sparing adjacent organs. The steeper dose gradients in radiosurgery—compared to the more gradual fall-off in EBRT—enable higher therapeutic ratios for focal lesions but limit its use to smaller volumes where precision can prevent excessive normal tissue toxicity. The term "radiosurgery," coined by neurosurgeon Lars Leksell in 1951, underscores this surgical-like precision in radiation delivery, though it does not involve physical cutting or invasion.

Mechanism of Action

Radiosurgery employs , primarily in the form of high-energy photons or protons, to deliver precise ablative doses to targeted tissues. The physical basis involves interactions between these particles and biological matter that deposit energy locally. For photons, the dominant mechanisms at therapeutic energies (typically 1-20 MeV) are , where photons eject electrons from atoms, leading to ; the , predominant at lower energies where photons are fully absorbed by inner-shell electrons; and at higher energies (>1.02 MeV), converting photon energy into an electron-positron pair. These processes generate ion pairs and free radicals in tissue, with energy deposition following an exponential attenuation pattern, enabling sharp dose gradients through multi-beam convergence. Protons, in contrast, exhibit a characteristic , where energy loss is minimal until the end of their range, followed by a rapid distal fall-off, minimizing scatter and exit dose compared to photons. Biologically, radiosurgery induces cell death through direct and indirect damage to DNA. Direct effects cause double-strand breaks (DSBs) in DNA molecules along the radiation track, particularly from high linear energy transfer (LET) events in proton therapy. Indirect effects, accounting for about 60-70% of damage in low-LET photon beams, arise from reactive oxygen species (ROS) generated by radiolysis of water, which oxidize DNA bases and backbones. High single-fraction doses (often 15-25 Gy) overwhelm cellular repair mechanisms, such as non-homologous end joining (NHEJ), leading to unrepaired DSBs, mitotic catastrophe, and apoptosis in target cells. The steep dose gradient ensures that surrounding normal tissue receives sublethal doses (<50% isodose line), promoting repair and sparing healthy structures. Vascular mechanisms contribute significantly to radiosurgery's efficacy, especially in hypovascular tumors. Doses exceeding 10 Gy damage endothelial cells, triggering inflammation, increased permeability, and expression of pro-thrombotic factors like tissue factor, culminating in microvascular thrombosis and ischemia. This hypoxic environment exacerbates tumor necrosis without relying solely on genomic damage, a process observed within hours to days post-treatment. Emerging evidence highlights immunogenic effects, where radiosurgery releases tumor-specific antigens and damage-associated molecular patterns (DAMPs) from ablated cells, stimulating dendritic cell activation and T-cell priming. This can elicit systemic anti-tumor immunity, manifesting as the abscopal effect—regression of unirradiated metastases—particularly when combined with immunotherapy, though rare in isolation. The dose-response relationship in radiosurgery is often modeled using the linear-quadratic (LQ) framework for cell survival fraction (SF): SF = \exp(-\alpha D - \beta D^2) Here, \alpha D represents linear, irreparable damage (dominant at high doses due to single-hit DSBs), while \beta D^2 captures quadratic, repairable interactions (more relevant in fractionated regimens). In single-fraction radiosurgery, the \alpha-term prevails, yielding steep survival curves and high tumor control rates (>90% for small lesions), with the gradient preserving adjacent tissue viability.

Treatment Planning and Dosimetry

Treatment planning in radiosurgery begins with advanced imaging to delineate the target volume and surrounding structures accurately. Computed tomography (CT) provides essential anatomical detail for dose calculation and bone structure visualization, while excels in contrast for precise tumor boundary definition. adds functional information to identify metabolically active regions within the target. Multimodality techniques, such as rigid or deformable registration, integrate CT, MRI, and PET data to enhance target delineation accuracy, reducing geometric uncertainties to sub-millimeter levels. Stereotactic localization ensures sub-millimeter precision in aligning the patient's with the treatment . Framed systems, such as the Leksell , use invasive head fixation for rigid and direct mechanical referencing during imaging and treatment. Frameless approaches employ thermoplastic masks or bite blocks for noninvasive , relying on fiducial markers, surface contour matching, or cone-beam for image-guided registration. Both methods achieve comparable accuracy, with frameless systems offering improved patient comfort while maintaining intrafraction motion below 1 mm through real-time verification. Dose planning software facilitates the optimization of radiation distribution using inverse planning algorithms, which iteratively adjust beam parameters to meet clinical objectives. In systems like Leksell GammaPlan, inverse planning automates shot placement and weighting to achieve high , minimizing dose to normal tissue. Key metrics include the conformity index (CI), defined as the ratio of the reference isodose volume (VRI) to the target volume (TV), with values ideally below 1.2 indicating optimal target coverage without excessive normal tissue inclusion. Selectivity measures the fraction of the target covered by the prescription isodose, while the gradient index quantifies dose fall-off sharpness, targeting values below 3 for steep gradients outside the target. Dosimetry parameters are tailored to balance tumor control and toxicity risks. Prescription doses typically range from 15 to 25 delivered in a single fraction, often to the 50% isodose line for steep dose gradients in intracranial targets smaller than 30 . Organ-at-risk (OAR) constraints prioritize safety, such as maximum doses below 8 to the optic nerve or chiasm to limit radiation-induced optic neuropathy risk to under 1%. Volume constraints ensure target volumes remain below 30 to avoid excessive normal tissue exposure. Quality assurance verifies plan accuracy through phantom-based testing and advanced simulations. Anthropomorphic phantoms simulate patient geometry for end-to-end dosimetric measurements, confirming delivered dose within 2% of planned values. simulations provide independent dose calculations accounting for tissue heterogeneities and beam scattering, essential for complex geometries. Biological effective dose () is computed using the linear-quadratic model: \text{BED} = nd \left(1 + \frac{d}{\alpha/\beta}\right) where n is the number of fractions (often 1 for radiosurgery), d is the dose per fraction, and \alpha/\beta = 2 Gy for late-responding normal tissues like the , enabling comparison of hypofractionated regimens to conventional fractionation. The radiosurgery workflow integrates these elements sequentially: acquires fused imaging with stereotactic setup; defines the target and OARs by multidisciplinary teams; plan optimization employs inverse algorithms to generate candidate plans; and verification through independent calculations and tests ensures delivery fidelity before treatment. This process achieves high precision, where high single-fraction doses induce biological cell kill primarily through irreparable DNA double-strand breaks.

Clinical Applications

Intracranial Indications

Radiosurgery is widely applied to intracranial pathologies, particularly for lesions in the and that are challenging to access surgically or require precise targeting to minimize damage to surrounding eloquent . It serves as a primary or treatment for both neoplastic and vascular conditions, offering high local control rates with a single or few fractions of focused . Typical indications include small to medium-sized tumors and malformations where the risk-benefit ratio favors non-invasive intervention over open resection. For benign tumors, radiosurgery achieves excellent long-term control with low morbidity. In vestibular schwannomas (acoustic neuromas), a marginal dose of 12-13 yields tumor control rates exceeding 95% at 5 years, preserving function in over 90% of cases. Similarly, for meningiomas, especially those in the skull base, a 15 marginal dose results in 90% at 10 years, with rare need for salvage therapy. These outcomes highlight radiosurgery's role in managing slow-growing, benign lesions that are often deep-seated or adjacent to critical structures like the or optic pathways. Malignant intracranial tumors also benefit from radiosurgery, particularly as a boost or standalone option for limited disease. For brain metastases, single lesions receive 20-24 Gy, while multiple lesions (up to 10) are treated with 15-21 Gy per lesion depending on size, achieving local control in 80-90% of cases. Additionally, for brain metastases from , recent phase II trials as of 2025 support for 1-10 lesions as an alternative to WBRT, with low neurologic death rates and preserved . In , stereotactic radiosurgery has been investigated as an adjunct in , such as in RTOG 93-05 where it was delivered prior to conventional and , but it did not improve overall survival compared to standard chemoradiotherapy (focal plus ). For recurrent cases, is used but offers limited survival extension. Radiosurgery for metastases may be combined with WBRT in select cases to address microscopic disease, enhancing intracranial control without excessive . Vascular malformations represent another key indication, where radiosurgery induces progressive obliteration through endothelial damage and . Arteriovenous malformations (AVMs) are typically treated with 18-25 in a single fraction for small lesions or staged fractions for larger ones (>10 cm³), resulting in 80-90% complete obliteration at 3 years and reduced hemorrhage risk thereafter. For symptomatic cavernous malformations (cavernomas), particularly those in deep or eloquent locations prone to recurrent bleeding, doses of 12-15 effectively lower annual hemorrhage rates from 4-5% to under 1% post-treatment, with minimal radiation-induced complications. Long-term evidence from international registries, including data from the International Stereotactic Radiosurgery Society (ISRS), supports these applications, demonstrating 5-year survival rates exceeding 80% for benign intracranial lesions due to durable tumor control and low recurrence. Patient selection is crucial for optimal outcomes and includes lesions smaller than 3 cm in maximum diameter, locations that are deep or surgically inoperable, and patients with a Karnofsky Performance Status (KPS) greater than 70 to ensure tolerance of potential transient effects like perilesional .

Spinal and Functional Neurosurgery

Radiosurgery has emerged as a precise for spinal lesions, particularly metastatic tumors, where stereotactic body (SBRT) delivers high doses to achieve local control while minimizing toxicity. For single-level spinal metastases, single-fraction doses of 16-18 are commonly prescribed, offering effective palliation for pain and tumor stabilization.30232-X/fulltext) In cases involving multi-level disease, hypofractionated regimens such as 24 delivered in three fractions balance efficacy with safety, particularly when reirradiation or larger volumes are involved.89860-7/fulltext) For benign like meningiomas, marginal doses of 14-16 in a single fraction provide durable tumor control rates exceeding 90% at five years, with low rates of neurological deficits due to the slow-growing nature of these lesions. In functional , radiosurgery targets neural structures to alleviate debilitating symptoms without invasive resection. For , gamma knife radiosurgery delivers 80 Gy to the trigeminal root entry zone, yielding pain relief in 70-90% of patients, with higher doses correlating to more sustained responses and minimal facial hypesthesia when targeting is precise. Similarly, for or Parkinson's disease-related focuses 130-150 Gy on the ventral intermediate (VIM) nucleus, achieving approximately 80% reduction in tremor severity at one year, as supported by systematic reviews of stereotactic outcomes. Beyond these, radiosurgery addresses other refractory functional disorders within the . For focal refractory , doses of 12-20 Gy to the seizure focus, such as in hypothalamic hamartomas, have demonstrated seizure frequency reductions in up to 68% of cases, though complete freedom is less common and requires careful patient selection. Historically, obsessive-compulsive disorder (OCD) has been managed with capsulotomy or cingulotomy using 160-180 Gy, providing response rates of 50-70% in treatment-resistant patients, though modern applications emphasize lower doses to reduce cognitive risks. Spinal functional applications include radiosurgery for , where 70 Gy targeted to cisternal rootlets offers relief in chronic cases unresponsive to conventional , with response durations extending months to years depending on . Overall outcomes underscore radiosurgery's efficacy in these domains: SBRT achieves 90% local control at one year for metastatic lesions, per guidelines. Functional procedures yield greater than 70% response rates, aligning with American Association of Neurological Surgeons (AANS) standards for symptom improvement in cases.

Extracranial and Systemic Uses

Radiosurgery, particularly in the form of stereotactic body radiation therapy (SBRT), has expanded beyond intracranial applications to treat extracranial tumors, offering precise, high-dose radiation to targets in the lung, liver, prostate, and other sites for patients often unsuitable for surgery. This approach delivers ablative doses in few fractions, achieving high local control rates while minimizing exposure to surrounding healthy tissues. In early-stage non-small cell lung cancer (NSCLC), SBRT serves as a standard curative option for medically inoperable stage I patients, with the RTOG 0236 phase II trial demonstrating a regimen of 54 Gy delivered in three fractions, yielding a 5-year local control rate of 91% and overall survival of 40%. This treatment provides more than double the control compared to historical conventional radiotherapy outcomes, with minimal severe . For liver tumors, including (HCC) and metastases, SBRT typically employs 30-50 Gy in three to five fractions, achieving 80-90% local control for lesions under 3 cm. Actuarial local control rates reach 93% at one year and 86% at three years for primary liver tumors, with biologically effective doses exceeding 100 Gy10 correlating to excellent outcomes even in heavily pretreated cases. Prostate cancer treatment with SBRT has been validated for low- and intermediate-risk cases through trials like HYPO-RT-PC, which compared ultra-hypofractionated regimens such as 42.7 Gy in seven fractions to conventional 78 Gy in 39 fractions, showing non-inferiority in failure-free survival (72% vs. 65% at five years) and overall survival (81% vs. 79%). These hypofractionated schedules, biologically equivalent to standard doses, support shorter courses with comparable and profiles. Applications to other sites include , where single-fraction 25 Gy ablation has been explored for local control in inoperable cases, though multi-fraction regimens of 25-33 Gy in five fractions yield one-year local control around 61%. For , doses of 21-48 Gy in three to five fractions achieve approximately 90% local control with low . Adrenal metastases are effectively managed with 40-50 Gy in three to five fractions, providing high local control rates exceeding 90% at one year. Systemically, SBRT plays a key role in oligometastatic disease, targeting up to five lesions to delay progression, with regimens like 48 Gy in four fractions demonstrating durable control and improved survival in selected patients. Doses of 40-45 Gy in five fractions are commonly used for lesions under 25 cc, balancing efficacy with organ-at-risk constraints. Key advantages of extracranial SBRT include its non-invasive nature, making it ideal for poor surgical candidates, and advanced motion management techniques such as respiratory gating and 4D-CT imaging, which reduce uncertainties from organ movement and enhance precision. These features allow safe delivery of ablative doses while preserving healthy tissue function.

Integration with Multimodal Therapy

Radiosurgery is commonly integrated with surgical resection to address residual tumor tissue, particularly in high-grade gliomas like glioblastoma, where postoperative boosts target microscopic disease left after debulking. For instance, early administration of stereotactic radiosurgery at a dose of 15 Gy to the 50% isodose line encompassing residual tumor within 24-72 hours post-surgery has been investigated in clinical protocols to enhance local control without excessive toxicity. Combining Gamma Knife radiosurgery with maximal safe resection and adjuvant chemotherapy yields median overall survival of 21.2 months and progression-free survival of 13.6 months in newly diagnosed glioblastoma patients, outperforming historical benchmarks for standard care alone. Integration with chemotherapy further optimizes outcomes, as radiosurgery boosts concurrent with agents like radiosensitize glioma cells and extend in multimodal regimens for recurrent disease. In glioblastoma, stereotactic radiosurgery combined with bevacizumab-based has demonstrated improved short-term survival compared to radiosurgery monotherapy, with meta-analyses indicating hazard ratios for overall survival as low as 0.42 in bevacizumab-inclusive combinations. Synergy with , particularly checkpoint inhibitors, enhances radiosurgery's efficacy in brain metastases by promoting abscopal effects—systemic antitumor responses at untreated sites through immune activation. Clinical series report high local control rates exceeding 70% when stereotactic radiosurgery precedes or follows anti-PD-1 therapy, with reduced distant progression in responsive cases. As an adjunct to conventional whole-brain radiotherapy, stereotactic radiosurgery serves as a targeted boost for brain metastases, improving intracranial control while mitigating neurocognitive decline relative to whole-brain radiotherapy alone; randomized evidence supports this approach for limited lesions, preserving cognitive function at 3 months post-treatment. Neoadjuvant prior to radiosurgery reduces nidus volume in high-risk cases, facilitating safer delivery and higher obliteration rates without compromising long-term efficacy. For oligometastatic disease, post-radiosurgery delays progression and extends time to next-line , with median postponement of 10.1 months observed in cohorts. Meta-analyses of multimodal strategies for recurrent high-grade gliomas reveal 20-30% relative improvements in survival metrics when radiosurgery is combined with systemic agents versus monotherapy, evidenced by hazard ratios of 0.52-0.73 for progression-free and overall survival, underscoring enhanced tumor control with acceptable toxicity.

Radiation Delivery Technologies

Cobalt-60 Based Systems (Gamma Knife)

Cobalt-60 based systems, exemplified by the Leksell Gamma Knife, utilize multiple radioactive sources to deliver precisely focused gamma radiation for intracranial stereotactic radiosurgery. These systems employ sealed cobalt-60 (Co-60) sources, which emit gamma rays at energies of 1.17 and 1.33 MeV, arranged to converge on a single focal point known as the isocenter. The design ensures high-dose delivery to targeted brain lesions while minimizing exposure to surrounding healthy tissue through geometric precision rather than intensity modulation. The core design features 192 to 201 Co-60 sources positioned in a hemispheric or cylindrical array, depending on the model, to provide non-coplanar beam convergence at the isocenter approximately 40 cm from the sources. Collimators shape the beams into circular fields with diameters typically ranging from 4 mm to 18 mm, allowing adaptation to sizes; newer models integrate internal collimation for sizes of 4 mm, 8 mm, and 16 mm to streamline setup. An automatic positioning system (), introduced in later generations, uses robotic couch adjustments to align multiple isocenters without manual intervention, enhancing efficiency for complex treatments. Evolution of the Gamma Knife spans several generations, beginning with the commercial Model U in 1987, which relied on manual patient positioning and featured 201 Co-60 sources for basic stereotactic applications. The Model B, introduced in 1992, improved semi-automated processes while maintaining 201 sources, facilitating broader clinical adoption. The Model C, launched around 1999, incorporated the for automated multi-isocenter alignment and retained 201 sources, reducing setup time significantly. The Perfexion model in 2006 reduced sources to 192 in a more compact cylindrical array with integrated collimators, optimizing workflow for higher throughput. The , released in 2015, builds on Perfexion by adding cone-beam for onboard imaging and supporting frameless mask immobilization alongside traditional , enabling sub-millimeter verification without invasive fixation in select cases. Treatment delivery maintains a fixed patient position within a protective or , with the patient's head aligned to the isocenter via stereotactic coordinates; the then repositions for subsequent isocenters if needed, while emanates simultaneously from all active sources to the without mechanical rotation during beam-on time. Each isocenter receives a prescribed dose over 20 to , determined by lesion volume, desired marginal dose (typically 12-25 ), and source decay, with total session times ranging from under an hour for single targets to several hours for multiples. This stationary delivery leverages the fixed source geometry for inherent 360-degree coverage, avoiding collimator scatter inherent in rotating beam systems. Key advantages include sub-millimeter mechanical accuracy, averaging 0.15 mm across installations, achieved through rigid stereotaxy and absence of contamination from pure , which sharpens dose fall-off compared to accelerators. These systems excel in intracranial applications due to their dedicated for targets, offering steep dose gradients (penumbra ~2-3 mm) ideal for small lesions near critical structures. Limitations encompass restriction to intracranial sites, as the fixed geometry precludes body-wide use, and reliance on frame-based immobilization in most models, though mitigates this with masks; source replacement every 5-8 years due to Co-60 (5.27 years) also requires periodic downtime. As of 2025, Gamma Knife systems had facilitated over 2 million treatments worldwide across approximately 360 centers, predominantly for brain tumors, vascular malformations, and functional disorders, underscoring their established role in .

Linear Accelerator Systems

Linear accelerator (LINAC) systems represent a cornerstone of modern radiosurgery, utilizing high-energy photon beams to deliver precise, ablative doses to targeted lesions while sparing surrounding tissues. These systems accelerate electrons to relativistic speeds within a using radiofrequency energy, directing the electrons onto a high-Z target (such as ) to produce x-rays in the 6-18 range, which are then shaped and directed toward the treatment site. Prominent examples include the Varian TrueBeam, which supports advanced techniques like stereotactic radiosurgery () and stereotactic body (SBRT) with integrated imaging, and the Versa HD, a versatile platform for intracranial and extracranial applications. The adaptability of LINACs stems from their evolution, beginning with modifications to conventional radiotherapy units in the and to enable stereotactic precision. LINAC configurations typically feature a C-arm that rotates around the patient, allowing for multi-angle beam delivery, including non-coplanar 4π arcs to optimize dose conformity. Beam shaping is achieved through micro-multileaf (MLCs), such as the 160-leaf Agility MLC with 5 mm leaf widths at isocenter, enabling dynamic conformal modulation for irregular targets. Delivery modes often employ volumetric modulated arc therapy (VMAT) with dynamic arcs, where the , , and MLC leaves continuously adjust during rotation to deliver intensity-modulated beams; single-isocenter techniques are particularly effective for treating multiple metastases simultaneously, reducing treatment time. Integration with image-guided radiotherapy (IGRT) systems, such as cone-beam (CBCT) or ExacTrac stereoscopic , facilitates real-time verification and sub-millimeter positioning accuracy (≤1.0 mm). These systems offer significant advantages, including multi-purpose functionality for both and SBRT across cranial and body sites, as well as frameless options using thermoplastic masks or optical tracking, which enhance comfort over invasive frames. However, limitations include longer setup times (typically 10-30 minutes for and alignment) and susceptibility to intrafraction motion, necessitating robust and . Key historical systems include the , introduced in the early 2000s by in collaboration with manufacturers like Varian, which pioneered shaped-beam delivery with integrated ExacTrac IGRT for frameless . More recently, the ZAP-X gyroscopic LINAC, first clinical use in 2019, employs a self-shielded, vault-free design with a dual-gimbaled to direct beams from hundreds of angles, reducing infrastructure costs while maintaining cobalt-free precision. LINAC-based approaches now account for over 50% of global volume, reflecting their widespread adoption due to accessibility and versatility, as evidenced by trends in national databases where LINAC cases surpassed Gamma Knife by 2021.

Particle Beam Therapies (Protons and Others)

Particle beam therapies, particularly those utilizing protons and heavier ions, represent an advanced form of radiosurgery that leverages the unique physical properties of charged particles to achieve precise dose deposition. Protons are accelerated to therapeutic energies ranging from 70 to 250 MeV using cyclotrons or synchrotrons, enabling them to penetrate deep into tissue while depositing the majority of their energy at a specific depth known as the Bragg peak. This peak occurs where the dose reaches its maximum at the end of the proton's range, followed by a sharp distal fall-off of less than 3 mm, which minimizes radiation exposure beyond the target. In proton radiosurgery, beam delivery can be accomplished through passive scattering or pencil-beam scanning (PBS). Passive scattering uses scattering foils and range modulators to broaden the beam laterally and create a spread-out Bragg peak (SOBP) for uniform coverage of the target volume. , in contrast, employs magnetic steering to raster-scan narrow proton beams across the target, allowing for intensity-modulated proton therapy (IMPT) with enhanced , especially for irregular shapes. The SOBP is formed by superimposing multiple pristine s of varying energies, ensuring a flat dose profile over the tumor while sparing surrounding tissues. The primary advantages of proton beam therapies stem from their dosimetric profile, which features a low entrance dose, no exit dose, and the lowest integral dose among modalities—typically 50-60% less than photon-based approaches for deep-seated targets. This reduction in normal tissue exposure is particularly beneficial for pediatric patients, where minimizing long-term risks such as secondary malignancies and neurocognitive deficits is critical, and for pedunculated lesions near sensitive structures like the . As of 2025, over 140 centers were operational worldwide, with facilities such as the offering proton stereotactic radiosurgery () for intracranial targets. Typical dosing regimens include single-fraction deliveries of 15-20 (cobalt gray equivalent, CGE) for lesions and hypofractionated schedules totaling 50 CGE over five fractions for spinal applications. Beyond protons, heavier particles like carbon ions provide additional benefits for radioresistant tumors due to their higher (LET) and (RBE) of approximately 3, compared to 1.1 for protons. Carbon ion therapy has been employed since the at the GSI Helmholtz Centre for Heavy Ion Research in , , demonstrating superior local control for tumors such as chordomas, which exhibit resistance to conventional or proton irradiation. The increased RBE enhances cell-killing efficiency in hypoxic or slowly proliferating regions, making carbon ions a targeted option for challenging skull base and sacral chordomas while maintaining sharp dose gradients.

Emerging and Robotic Systems

Emerging systems in radiosurgery represent a shift toward frameless, non-invasive platforms that integrate advanced , motion tracking, and adaptive technologies to enhance for both intracranial and extracranial targets. These systems build on foundations in frameless stereotaxy by incorporating multi-degree-of-freedom manipulators and integrated to achieve sub-millimeter accuracy without invasive fixation. Key innovations include robotic linear accelerators (LINACs) and hybrid magnetic (MR)-guided systems, enabling dynamic beam adjustment during treatment to account for motion and anatomical changes. The CyberKnife system exemplifies robotic radiosurgery, featuring a 6 MV LINAC mounted on a six-degrees-of-freedom (6DoF) that delivers non-isocentric, non-coplanar beams from hundreds of angles for optimal dose sculpting. Its Synchrony module provides real-time tumor tracking for respiratory motion, using either implanted fiducials with imaging or markerless optical tracking via cameras to synchronize beam delivery with target movement. This frameless approach achieves sub-millimeter geometric accuracy, typically 0.5–1.0 mm, as verified in phantom and clinical studies, eliminating the need for rigid frames while maintaining high precision for irregular or moving lesions. In extracranial applications, CyberKnife is particularly suited for and liver tumors affected by breathing motion, delivering stereotactic body radiotherapy (SBRT) doses of 30–60 in 3–5 fractions with high conformity. For spinal metastases, clinical series report mean doses of 26.5 in 3.1 fractions, yielding 91% control and 90% radiological tumor control at 6 months, with no radiation-related injuries. Dosimetric analyses demonstrate conformity indices approaching 0.95 for brain metastases, reflecting efficient target coverage and sparing of adjacent tissues. The ZAP-X gyroscopic radiosurgery platform, first clinical use in 2019, offers a self-shielded, non-invasive alternative using a compact LINAC on a dual-gimbaled gyroscopic arm with five for beam delivery from non-coplanar angles. Integrated kV guidance supports frameless stereotaxy, achieving sub-millimeter accuracy suitable for outpatient procedures. Early clinical experience from 50 consecutive cases showed 40% metastatic tumors and 36% meningiomas treated effectively, with 93.3% local control for metastases at short-term follow-up and only minor adverse effects like temporary alopecia in 10% of patients. Larger retrospective series of 59 patients across 82 lesions reported 15.9% progression at a mean 14.7-month follow-up, underscoring its efficacy for benign and malignant intracranial targets. MR-Linac hybrids, such as the Unity system, combine a 1.5T MRI with a 7 flattening-filter-free LINAC for real-time adaptive radiosurgery, enabling on-table replanning based on intrafraction changes visualized via cine-MR sequences. This facilitates dynamic tracking at 340 ms resolution, improving motion management for thoracic and abdominal sites without for imaging. In SBRT for lung tumors, it enhances planning target volume coverage to 95% while reducing organ-at-risk doses, with 1-year local control rates of 96.3% and low . AI-assisted auto-contouring tools integrated into these platforms streamline delineation of targets and organs at risk, reducing time by up to 50% while maintaining accuracy comparable to manual methods. Recent developments in robotic systems emphasize FLASH radiotherapy with protons, delivering ultra-high dose rates exceeding 40 /s to potentially minimize normal tissue toxicity while preserving tumor control. Since 2020, clinical trials have tested single-fraction 8 FLASH proton therapy for symptomatic bone metastases, achieving 67% pain relief (50% complete response) with minimal grade 1 skin toxicities and no serious adverse events, comparable to conventional rates but with faster delivery (seconds per fraction). These trials support ongoing investigations into FLASH integration with robotic delivery for broader radiosurgical applications.

Risks, Complications, and Safety

Acute and Subacute Effects

Acute and subacute effects of radiosurgery, occurring within days to months following , primarily involve inflammatory responses and transient disruptions to surrounding tissues. These effects are generally reversible and managed conservatively, with incidence varying by treatment site, dose, and patient factors. Common manifestations include perilesional , pseudoprogression, vascular perturbations, and site-specific symptoms such as and alopecia. Perilesional and represent a frequent subacute complication after stereotactic (SRS), characterized by swelling around the treated lesion that typically peaks 1-3 months post-treatment. This arises from radiation-induced and release, often leading to symptoms like headaches and seizures in affected patients. The incidence ranges from 8% to 25%, with higher rates observed in larger lesions or those adjacent to eloquent areas; it is effectively managed with corticosteroids such as dexamethasone to reduce swelling and alleviate symptoms. Pseudoprogression mimics tumor progression on due to treatment-related and blood-brain barrier disruption, without actual tumor growth. It occurs in approximately 15-30% of high-grade patients post-SRS, usually within 3 months of treatment, and resolves spontaneously over 3-6 months. Advanced MRI techniques, including and , help differentiate it from true progression by showing reduced vascularity and metabolic activity. In arteriovenous malformations (AVMs), acute vascular events such as transient or hemorrhage can emerge shortly after , with the annual risk of hemorrhage during the latency period approximately 2-5%, and acute events being rare due to endothelial damage and altered . These events are more common in larger or deep-seated AVMs and may require urgent intervention if symptomatic. Site-specific effects further contribute to the acute profile: affects up to 50% of patients, onsetting within weeks and resolving gradually; alopecia occurs with scalp doses exceeding 10 , leading to temporary in the radiation field; and cranial neuropathies, such as , arise with a risk of approximately 1% when the optic apparatus receives over 8 , manifesting as visual deficits that often improve with time. Monitoring for these effects involves serial contrast-enhanced MRI scans at 1-3 months post-SRS to detect or pseudoprogression early, with follow-up intervals of every 2-3 months thereafter. The Graded Prognostic Assessment (GPA) score aids in risk stratification by incorporating factors like age, , and type to predict complication likelihood and guide surveillance intensity.

Long-Term Risks

Radiation represents a significant long-term complication of stereotactic (), involving progressive tissue death due to vascular endothelial damage and subsequent , with reported incidences ranging from 5% to 10% in treatments. The risk escalates with marginal doses exceeding 20 , particularly for larger lesions or those in eloquent regions. Symptoms, such as focal neurological deficits, headaches, or seizures, typically emerge between 6 and 24 months post-treatment, though late occurrences beyond 5 years have been documented. often relies on advanced imaging, including to distinguish from tumor progression by revealing reduced cerebral in necrotic areas. Neurocognitive decline is another delayed effect, manifesting as deficits in , , and executive function, observed in 20-30% of patients receiving whole-brain radiotherapy combined with for multiple metastases. Hippocampal avoidance techniques in clinical trials, such as RTOG 0933, have demonstrated reduced rates of decline compared to standard whole-brain approaches, highlighting the hippocampus's vulnerability to radiation-induced atrophy and inflammation. These impairments can persist or worsen over years, impacting , though recovery is possible in a subset of cases with supportive interventions. Secondary malignancies, including radiation-induced gliomas and meningiomas, pose a rare but serious long-term following SRS, with a cumulative incidence estimated at less than 1% at 10 years based on studies of patients treated with SRS. This is elevated in younger patients due to greater and longer latency periods for oncogenesis, often exceeding 5-10 years post-treatment. While the focal nature of SRS limits exposure compared to conventional radiotherapy, and prior radiation history may amplify susceptibility. Endocrine dysfunction, particularly , affects 20-50% of patients undergoing sellar for pituitary adenomas, involving deficiencies in , , or due to hypothalamic-pituitary axis damage. Incidence varies with dose and volume, with rates up to 43% in some series, necessitating lifelong hormonal monitoring. Vascular complications include delayed rupture of arteriovenous malformations (AVMs) in 2-5% of cases during the latency period post-SRS, potentially linked to hemodynamic changes from vessel wall inflammation. Additionally, moyamoya-like syndrome, characterized by progressive and vessel formation, has been reported in rare instances, leading to ischemic events years after treatment. Overall, the cumulative incidence of severe long-term events remains low at under 5% at 5 years for benign indications, such as meningiomas or schwannomas, underscoring SRS's favorable safety profile despite these risks.

Patient Selection and Mitigation

Patient selection for radiosurgery is guided by several key criteria to ensure efficacy and safety, including tumor characteristics, , and overall . Ideal candidates typically have tumors measuring less than 3 cm in diameter (or ≤14 cc in volume), located sufficiently away from critical structures such as the or to allow for precise targeting while respecting organ-at-risk dose constraints. A Karnofsky Performance Status (KPS) of ≥70 is generally required, reflecting adequate functional capacity to tolerate the procedure and potential side effects. Additionally, patients should have a exceeding 3 months, often assessed using prognostic indices like the Graded Prognostic Assessment (GPA) for brain metastases, to justify the treatment's benefits over alternatives. Contraindications include , due to the teratogenic risks of , and patient uncooperativeness, as radiosurgery demands and during delivery. control is also evaluated, with radiosurgery favored for limited metastases (1-15 lesions, total volume ≤15 cc) in patients without uncontrolled extracranial . For extracranial sites like lung stereotactic body radiotherapy (SBRT), selection emphasizes early-stage non-small cell with good pulmonary reserve. Risk assessment employs standardized tools to predict and inform treatment planning. For lung SBRT, the V20 ( of lung receiving ≥20 ) should ideally be <10% to maintain lung risk below 10%. In intracranial radiosurgery, QUANTEC-derived constraints guide dosing, such as a brainstem maximum point dose of 12.5 in single-fraction stereotactic radiosurgery (SRS) to limit necrosis risk to <5%. These parameters, derived from quantitative analyses of normal tissue effects, help balance tumor control against organ-at-risk tolerance.03299-4/fulltext) Mitigation strategies focus on preventing or managing perilesional edema and potential necrosis. Corticosteroids, such as dexamethasone, are administered prophylactically or for symptomatic edema, reducing inflammation and blood-brain barrier permeability with response rates up to 83% in affected cases. For radiation necrosis, bevacizumab offers an anti-VEGF approach, achieving symptom relief in approximately 68% of patients refractory to steroids. Fractionated SRS regimens (3-5 fractions) for larger lesions (>3 cm) distribute dose to spare adjacent tissues, reducing complication risk by about 50% compared to single-fraction delivery. Follow-up protocols emphasize vigilant monitoring to detect recurrence or complications early. For brain metastases treated with SRS, serial contrast-enhanced MRI is recommended every 3 months for the first 2 years, then every 6 months thereafter, incorporating advanced sequences like diffusion-weighted imaging for enhanced sensitivity. Neurocognitive assessments, such as the Hopkins Verbal Learning Test, are integrated for intracranial cases to track subtle deficits, particularly in eloquent brain regions.00054-6/abstract) Ethical considerations underscore the importance of and multidisciplinary oversight. Patients must be counseled on radiosurgery-specific risks, including a 1-5% rate of severe complications like symptomatic , with discussions covering alternatives and potential quality-of-life impacts to uphold . Multidisciplinary tumor boards are routinely employed to review cases, ensuring selection aligns with evidence-based guidelines and equitable resource allocation.

Current Research and Future Directions

Technological Innovations

Recent advancements in radiosurgery are leveraging (AI) and to enhance treatment precision and efficiency. Automated segmentation tools, such as DeepMedic, enable rapid delineation of tumor contours from , significantly reducing planning times—for instance, models have achieved up to 76% time savings in contouring compared to manual methods. These AI-driven approaches also minimize inter-observer variability, improving contour accuracy for complex structures like tumors. Furthermore, predictive models are being developed to forecast patient outcomes post-radiosurgery, such as obliteration rates in arteriovenous malformations, aiding personalized treatment decisions. Magnetic resonance (MR)-guided adaptive radiotherapy represents another key innovation, allowing real-time imaging and intrafraction adjustments during treatment. Systems like the ViewRay MRIdian integrate high-field MRI with linear accelerators to visualize soft-tissue changes, particularly beneficial for mobile targets in and liver radiosurgery, where daily adaptations improve target coverage and spare organs at risk. Clinical implementations have demonstrated consistent dosimetric benefits, such as enhanced gross tumor volume conformity in abdominal sites. FLASH radiotherapy, delivering ultra-high dose rates exceeding 40 Gy/s with protons or photons, exploits the effect to preferentially spare normal tissues while maintaining tumor control. Preclinical studies in the have shown reduced , including preserved neurocognitive function in models of , attributed to minimized and vascular damage. These findings suggest potential for safer high-dose radiosurgery regimens, with ongoing trials exploring translation to clinical settings for reduced side effects in neural tissues. Nanotechnology is advancing radiosurgery through targeted contrast agents and radiosensitizers. -based nanoparticles enhance MRI targeting and amplify radiation effects via high absorption, improving tumor visualization and in preclinical models. radiosensitizers, such as gadolinium oxide formulations, boost fractionated radiotherapy efficacy by activating pathways like cGAS-STING, leading to enhanced immune responses without excessive normal tissue damage. To broaden access, compact variants of Gamma Knife systems, such as the frameless model, facilitate installation in diverse clinical settings and eliminate invasive head frames, expanding radiosurgery availability beyond specialized centers. These innovations support intra-procedural applications and reduce logistical barriers, promoting equitable delivery of precise stereotactic treatments.

Clinical Trials and Outcomes

Clinical trials have played a pivotal role in establishing stereotactic radiosurgery (SRS) as a standard treatment for various intracranial and extracranial conditions, demonstrating high local control rates, preserved cognitive function, and favorable quality-of-life outcomes compared to alternative therapies. Key randomized controlled trials, such as the NCCTG N107C study, have shown that postoperative SRS to the resection cavity results in less cognitive decline than whole-brain radiotherapy (WBRT) in patients with resected metastases, with no significant difference in overall survival between the two approaches. In this phase 3 trial involving 132 patients, cognitive deterioration at 6 months occurred in 52% of the SRS group versus 85% in the WBRT group, highlighting SRS's neuroprotective benefits. For patients with 1-3 metastases treated with SRS, 5-year overall survival rates typically range from 20% to 30% in selected cohorts with good and controlled . For arteriovenous malformations (AVMs), the trial compared conservative medical management with interventional therapies, including , in patients with unruptured AVMs and found that intervention was associated with higher rates of neurological morbidity in the overall cohort. However, subgroup analyses and subsequent real-world studies of ARUBA-eligible patients treated with for small-nidus AVMs (<3 cm) have demonstrated lower long-term morbidity with intervention, achieving complete obliteration in approximately 70% of cases at 3 years while minimizing or risks. In a pooled analysis of over 1,000 such patients, the primary composite outcome ( or ) occurred in only 13.3%, supporting as a safer option for smaller lesions compared to observation alone. In extracranial applications, stereotactic body radiotherapy (SBRT) for early-stage non-small cell has been evaluated in trials like RTOG 0618, which assessed 54 Gy in 3 fractions versus 60 Gy in 8 fractions for operable peripheral tumors, establishing noninferiority in local control and overall survival. The trial reported 2-year local control rates exceeding 90% across both arms, with reduced treatment duration in the 3-fraction regimen contributing to improved patient convenience without compromising efficacy. These results underscore SBRT's role as a definitive , particularly for patients unfit for . For functional disorders like , guidelines from the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) provide Level II evidence supporting as an effective option, with durable pain relief achieved in about 80% of patients at long-term follow-up. This evidence is derived from prospective cohort studies showing initial pain response rates of 70-90% within 1-3 months post-, with many patients maintaining relief beyond 3 years using maximal doses of 80-90 to the root entry zone. Quality-of-life assessments further validate SRS's advantages, particularly in brain metastases, where the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale has demonstrated preserved neurocognitive and physical function with compared to surgical resection. In longitudinal studies, patients receiving maintained higher FACT-Br scores (indicating better overall well-being and -specific symptoms) at 6-12 months post-treatment, avoiding the functional declines often seen after open . Additionally, exhibits strong cost-effectiveness compared to surgical resection of solitary metastases, driven by shorter hospital stays and reduced complication management. Despite these advances, data reveal gaps, including underrepresentation of elderly patients and diverse ethnic populations, which limits generalizability to broader demographics. Recent International Stereotactic Radiosurgery Society (ISRS) guidelines published in 2025, such as those on radiosurgery for recurrent high-grade (October 2025) and severe treatment-resistant obsessive-compulsive (November 2025), emphasize the need for inclusive prospective data collection to address these disparities and refine outcomes across varied patient groups.