Stereotactic Radiation Surgery Research Articles

Growth speed of large brain metastases between diagnostic and radiosurgical planning MRI and predictors of rapid tumor growth

PurposeWe aimed to assess volumetric changes of large brain metastases (≥ 2 cm) between their diagnosis and planning for treatment with fractionated stereotactic radiation surgery (fSRS). Predictors of rapid tumor growth were also analyzed.Materials and methodsOne hundred nine patients harboring 126 large brain metastases were retrospectively evaluated. Tumor characteristics were evaluated on diagnostic magnetic resonance imaging (dMRI) and MRI performed when planning fSRS (pMRI). Average tumor growth rate and percentage growth rate were calculated. Predictors of rapid growth (percentage growth rate > 5%) were determined using multivariate logistic regression.ResultsBoth tumor diameter and volume were significantly larger on pMRI than on dMRI (P < 0.001). Median tumor percentage growth rate was 2.6% (range, − 10.8–43.3%). Eighty-eight tumors (70%) were slow-growing (percentage growth rate < 5%) and 38 (30%) grew rapidly (percentage growth rate ≥ 5%). Major peritumoral edema and no steroids were predictors of rapid tumor growth.ConclusionLarge brain metastases can grow considerably between the time of diagnosis and the time of fSRS treatment planning. We recommend the time between dMRI and fSRS treatment initiation be as short as possible.

Palliative Whole Brain Radiotherapy: International State of Practice 2022

Increasing technology of radiation treatment planning and delivery, better systemic therapies, and randomized trials in the population of patients (pts) with brain metastases have provided robust targeted options. This has resulted in palliative whole brain radiation therapy (WBRT) being used far less frequently than previously. Most centers preferentially use stereotactic radiation surgery (SRS) for pts with several lesions and may reserve WBRT for those with poor performance, with rapidly progressive disease, or with leptomeningeal presentation. We hypothesize that different trends in current WBRT regimens exist across different continents with varying rates of use of hippocampal avoidance (HA) and memantine. Despite differences in dose, fractionation, and treatment technique, we predict that survival post-WBRT will remain poor-indicating appropriate application of whole brain treatment in this era of SRS and improved systemic therapies. A multi-center international analysis of pts receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. Participating centers were located in Belgium, the United Kingdom, Hong Kong, Cyprus, Italy, Germany, Ghana, and the United States. De-identified data were collected and analyzed centrally. Pts receiving WBRT as part of a curative regimen (e.g., medulloblastoma, primary CNS lymphomas), prophylactically in small cell lung cancer, or as bridging prior to CAR-T were excluded. The collected data consisted of pt parameters including prior stereotactic radiosurgery (SRS), prescription dose and fractionation, use of HA technique with or without memantine, and survival after WBRT. Survival was calculated via the Kaplan-Meier method. Of 23,332 RT prescriptions written at these centers in 2022, 399 (1.7%) were for palliative WBRT. Most frequent primary cancers were lung (42%) and breast (28%). Twenty-seven different dose regimens were used. The most common prescriptions were for 3 Gy daily fractions for 10 fractions (45%) and 4 Gy daily for 5 fractions (37%). Prior CNS SRS was delivered in 32 pts (7%). HA technique was used in 44 pts (10%); this technique was almost exclusively used in the United States. Memantine was prescribed in 93 pts (20%). Survival ranged from zero days to still surviving. The global median overall survival was 84 days after completion of treatment (95% CI: 68.0-104.0). Cumulative 3-month and 6-month actuarial survivals were 48% and 32%. This "moment in time" analysis confirms that pts with poor expected survival are being appropriately selected for WBRT and demonstrates the variance in global practice. Since poor survival precludes these pts from deriving much benefit, memantine and HA may be best suited only for carefully selected cases; use of these is not Standard of Care in the participating European, Asian, and African centers.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases

Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P=.46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P=.26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

Historical Progress of Stereotactic Radiation Surgery.

Radiosurgery and stereotactic radiotherapy have established themselves as precise and accurate areas of radiation oncology for the treatment of brain and extracranial lesions. Along with the evolution of other methods of radiotherapy, this type of treatment has been associated with significant advances in terms of a variety of modalities and techniques to improve the accuracy and efficacy of treatment. This paper provides a comprehensive overview of the progress in stereotactic radiosurgery (SRS) over several decades, and includes a review of various articles and research papers, commencing with the emergence of stereotactic techniques in radiotherapy. Key clinical aspects of SRS, such as fixation methods, radiobiology considerations, quality assurance practices, and treatment planning strategies, are presented. In addition, the review highlights the technological advancements in treatment modalities, encompassing the transition from cobalt-based systems to linear accelerator-based modalities. By addressing these topics, this study aims to offer insights into the advancements that have shaped the field of SRS, that have ultimately enhanced the accuracy and effectiveness of treatment.

A Case of Pembrolizumab (Anti-PD-1) Induced Encephalitis

Objective N/A. Background PD-1 Immune checkpoint inhibitors (ICI) have been associated with neurologic immune-related adverse events including meningoencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of suspected pembrolizumab (anti PD-1) induced limbic encephalitis presenting as episodic aphasia. Design/Methods N/A. Results A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases post thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation surgery presented with recurrence of brain metastases one year after the diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region causing right homonymous hemianopsia. The metastases initially improved in size and number with radiation and serial brain MRIs were stable. Biopsy of the mets revealed a poorly differentiated carcinoma. He was subsequently treated with pembrolizumab for six months. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia concerning for seizures. Continuous EEG monitoring revealed a left-sided focus without seizures, and the episodes persisted despite levetiracetam and clobazam. Four lumbar punctures revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48–68 mg/dl), negative cytology, flow cytometry and viral studies including JC virus. Paraneoplastic panels in serum and cerebrospinal fluid were negative. Repeat MRIs findings were most consistent with radionecrosis and noted improvement of the metastatic lesions. Suspicion was raised for pembrolizumab-induced encephalitis and he received high-dose steroids with minimal response however, clinical improvement noted with reduced episode frequency after intravenous immunoglobulin induction therapy and rituximab maintenance therapy. Conclusions PD-1 ICI-related encephalitis is a diagnosis of exclusion that should be considered in patients with encephalopathy or other neurological deficits following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences are reported in males. Early recognition is crucial to prevent long-term neurologic damage. Outcomes are depend on patient characteristics and clinical presentation.

Susceptibility weighted imaging for qualitative grading of persistent arteriovenous shunting in deep-seated arteriovenous malformations after stereotactic radiation surgery.

To investigate Susceptibility Weighted Imaging (SWI) signal changes in the draining vein of deep-seated arterio-venous malformations (AVMs) following stereotactic radiosurgery (SRS). This is a retrospective study of 32 patients with deep-seated AVMs who were treated with SRS. Pre-SRS treatment and post-SRS treatment MRI were performed at 6, 12, and 24-month intervals. Deep-seated AVMs were classified based on their anatomical location and venous drainage pattern. AVM nidal volume (cm3) was estimated using the ABC/2 method. AV shunting of the AVM draining veins were graded according to its SWI signal intensity: hyperintense (grade III), mixed signal intensity (grade II), hypointense (grade I) and absent (grade 0). Conventional time-of-flight (TOF)-MRA and contrast enhanced (CE)-MRA sequences were performed to document the patency of the vein. Pre-SRS treatment AVM draining veins were either grade III 18/32 (56%) or grade II 14/32 (44%). Using mixed effects analysis, we demonstrate that each month following the SRS treatment nidal volumes decreased at the rate of 0.51cm3/per month (CI -0.61 to (-0.40)) p =.00. Following the treatment, there was a clinically significant relationship between the signal and nidal volume: signal 0 corresponded with average nidal volume of 1.81cm3 (CI 1.40-2.21), signal 1 with nidal volume of 2.06cm3 (CI 1.69-2.44), signal 2 with nidal volume 2.73cm3 (CI 2.35-3.11) and signal 3 with nidal volume 3.13cm3 (CI 2.70-3.56) p = .00. Post-SRS AVM draining veins shows a stepwise regression of the SWI signal grades which can be reliably used as a surrogate to monitor the reduction of AV shunting.

A measure tool for evaluating dose falloff outside the target volume in high precision radiotherapy

IntroductionA reliable and high resolution systemic with all aspects plan evaluation indices has been proposed in this study to measure the dose falloff outside the target volume. The essential goal of this study is to compensate the shortcomings for the judgment of planning target volume and dose-volume histogram by visual verification slice by slice in high precision modern radiotherapy techniques like stereotactic radiation surgery, volumetric arc therapy, and stereotactic body radiation therapy. Materials and methodsDynamic Gradient Index has been proposed both geometric and dosimetric orientated in all aspects plan evaluation indices to measure the dose falloff outside the target volume. Organ at Risk Integral Dose, and Target Specific Gain Ratio are created for evaluating highly conformal plans and provide better sparing of normal tissue. Users can do the plan evaluation indices calculation proposed in this study just simply with a sequence of exported data including normal tissue volume covered by every isodose line, target volume covered by every isodose line, and organ at risk volume covered by every isodose line from the approved planning system. The results here were also compared with several indices usually used such as gradient index developed by various authors. ResultsDGI avoids the mistaken judgment counted on a single gradient index on one referenced isodose line recommended by other published results for the evaluation of SRS, SBRT high precision needed plan. Dynamic Gradient Index is a measure of steep dose gradient outside the target volume; therefore; this index plays a significant role in SRS as a measure of plan quality, especially a judgment of complication cases. Furthermore, taking into consideration the Organ at Risk Integral Dose and normal tissue integral dose to evaluate the target therapeutic gain lets Target Specific Gain Ratio becomes a comprehensive evaluation tool for pros and cons tangled cases. ConclusionsThe function of DGI successfully reflects the advantage of fast expanded isodose lines (low dose gradient) could be easily examined. The plan superiority is determined by how close the DGI and the other indices are to the line of the benchmark. The growing speed of DGI for the SRS curve is slower similar to VMAT than the other two treatment techniques. The DGI of SRS beyond 100% inside the target area shows the advantage of the plateau between 100% and 110%, which means the change of dose gradient is smaller and this phenomenon could not be checked in DVH as well in other plan evaluation indices.

Cost Comparison From a Patient Perspective for Intracranial Stereotactic Radiation Therapy

PurposeHistorically, opaque health care pricing in the US has prevented patients from identifying opportunities to lower costs. Attempting to promote price transparency, the US government recently mandated that hospitals publish prices for all services in a document called a chargemaster. Patients often travel to tertiary centers for intracranial stereotactic radiation therapy (SRT), but cost comparison is complicated by multiple delivery systems and fractionation schemes. We hypothesized that prices published in chargemasters vary widely between SRT techniques and institutions. Methods and MaterialsWe obtained chargemasters published online by National Cancer Institute–designated clinical centers. Technical charges for Gamma Knife single-fraction stereotactic radiosurgery (GK), single-fraction linear-accelerator stereotactic radiation surgery (SRS), and 3-fraction fractionated stereotactic radiation therapy (FSRT) were obtained from chargemasters by billing code and keyword searches. Prices were adjusted by the Medicare geographic cost price index (GPCI). Pairwise comparisons were conducted to compare prices between modalities and geographic regions. Relationships with cost index were examined using Spearman correlations, as was the price interrelationship between modalities across institutions. ResultsOf 62 chargemasters obtained, 58 listed SRT prices. Median prices were $49,529 for GK, $31,834 for FSRT, and $22,915 for SRS. Prices varied widely, with large ranges corresponding to 2 to 9 times the magnitude of median prices (GK, $111,298; FSRT, $312,480; and SRS, $104,396). Adjusting for GPCI, GK (P = .0003) and FSRT (P = .001) were more expensive than SRS, and no difference in price was noted between regions. The FSRT price was positively correlated with GPCI (P = .033), but prices for the other techniques were not. Modality prices were all positively correlated (all P < .001), meaning that institutions with prices greater than the median price for SRS were similarly expensive for GK and FSRT. ConclusionsPublished prices for SRT vary by delivery system, fractionation, and institution without a clear explanation. Obtaining personalized price estimates may offer cost savings for patients. Policy changes encouraging reliable access to insurer-negotiated cost estimates for SRT are needed.

PO-1654 Quality Assurance of C-Arm CBCT Angiography for Stereotactic Radiation Surgery

PO-1654 Quality Assurance of C-Arm CBCT Angiography for Stereotactic Radiation Surgery

Paraspinal Myosistis After Stereotactic Radiation Surgery

Myositis of the paraspinal muscles can be a clinically significant side effect of spinal radiation surgery. This report describes the typical clinical scenario, relevant radiologic findings, treatment, and management with the best available evidence.

Automatic Detection and Segmentation of Multiple Brain Metastases on MR Images Using Simultaneous Optimized Double-UNET Architecture

Brain metastases (BM) develops in approximately one third of patients throughout their disease course and can be a major cause of morbidity and mortality if not caught and treated early. BM is commonly detected using MRI. Once diagnosed, stereotactic radiation surgery (SRS) can offer effective local control. However, BM tends to be multifocal; 80% of the diagnosed patients have more than one BM and 50% have three or more. Moreover, the size and radiological appearance of BM can be highly heterogeneous. Detecting and segmenting multiple BM thus is challenging and dependent on clinicians’ experience. Here, we aim to develop an automated BM detection and segmentation method using a novel simultaneous optimized double-UNET architecture. With an IRB approval, contrast-enhanced T1 MR images from 195 patients with multiple BM were solicited from our institutional SRS database. The BM segmentations were verified by radiation oncologists with >5 years of experience. Of all 195 patients, 1034 BMs had been manually contoured for SRS planning. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions) and testing (15 patients, 89 lesions) datasets. A double 3D-UNET architecture, each with a down-sampling and an up-sampling arm, was constructed to capture the spatial information. The inputs include channel (T1 MR) and 3D volumetric image size. The double 3D-UNET was trained using two different kernels (3x3x3 and 1x1x3 respectively). The weightings of the two UNETs were optimized to achieve the best detection sensitivity on the validation set. Dice similarity coefficient [defined as DSC(S, T) = 2|S∩T| / (|S| + |T|); S and T are automatic and manual segmentation respectively] and detection sensitivity [defined as TT/(TT+TN); TT and TN are number of correctly detected and undetected BM] were used as quantitative assessment metrics. The lesions in the testing set were further divided into 3 sub-groups based on the lesion sizes (A = 1-4mm, B = 5-8mm and C = 9-26mm) for performance reporting. As a comparison, a traditional single 3D-UNET was trained and evaluated using the same datasets. In the testing dataset, there were 47, 21 and 21 BM in the A, B and C sub-groups, respectively. The numbers of undetected BM using single 3D-UNET were 28, 2 and 0 for A, B and C. The single 3D-UNET achieved sensitivity of 0.40 and 0.90, and DSC of 0.44 and 0.69 for A and B respectively. The numbers of undetected BM using our double 3D-UNET are 24, 1 and 0 for A, B and C. Our double 3D-UNET improved sensitivity to 0.49 and 0.95, and DSC to 0.49 and 0.70 for A and B. For the C sub-group with relatively larger lesions, both models achieved 100% detection sensitivity and DSC of 0.82. A double-UNET architecture was successfully constructed for automated detection and segmentation of the multiple BM on contrast enhanced T1 MR images. Preliminary results showed more pronounced improvement in hard-to-detect small BMs comparing to single 3D-UNET.

Outcomes of Using a Hypofractionated Dose to treat Ependymomas in Pediatric Patients using Fractionated Stereotactic Radiosurgery (FSRS)

This study aims to determine if Fractionated Stereotactic Radiation Surgery (FSRS) reduces the recurrence of pediatric ependymomas, is efficacious and is safe.

An open-source tool to visualize potential cone collisions while planning SRS cases.

PurposeTo create an open‐source visualization program that allows one to find potential cone collisions while planning intracranial stereotactic radiosurgery cases.MethodsMeasurements of physical components in the treatment room (gantry, cone, table, localization stereotactic radiation surgery frame, etc.) were incorporated into a script in MATLAB (MathWorks, Natick, MA) that produces three‐dimensional visualizations of the components. A localization frame, used during simulation, fully contains the patient. This frame was used to represent a safety zone for collisions. Simple geometric objects are used to approximate the simulated components. The couch is represented as boxes, the gantry head and cone are represented by cylinders, and the patient safety zone can be represented by either a box or ellipsoid. These objects are translated and rotated based upon the beam geometry and the treatment isocenter to mimic treatment. A simple graphical user interface (GUI) was made in MATLAB (compatible with GNU Octave) to allow users to pass the treatment isocenter location, the initial and terminal gantry angles, the couch angle, and the number of angular points to visualize between the initial and terminal gantry angle.ResultsThe GUI provides a fast and simple way to discover collisions in the treatment room before the treatment plan is completed. Twenty patient arcs were used as an end‐to‐end validation of the system. Seventeen of these appeared the same in the software as in the room. Three of the arcs appeared closer in the software than in the room. This is due to the treatment couch having rounded corners, whereas the software visualizes sharp corners.ConclusionsThis simple GUI can be used to find the best orientation of beams for each patient. By finding collisions before a plan is being simulated in the treatment room, a user can save time due to replanning of cases.

Stereotactic Body Radiation Therapy (SBRT) or Surgery in Early Stage Non-Small-Cell Lung Cancer: The Radiation Oncologist’s Point of View

Stereotactic Body Radiation Therapy (SBRT) or Surgery in Early Stage Non-Small-Cell Lung Cancer: The Radiation Oncologist’s Point of View

Stereotactic Body Radiation Therapy (SBRT) or Surgery in Early Stage Non-Small-Cell Lung Cancer: The Surgeon’s Point of View

Stereotactic Body Radiation Therapy (SBRT) or Surgery in Early Stage Non-Small-Cell Lung Cancer: The Surgeon’s Point of View

Radiation Necrosis in Intracranial Lesions.

Radiation necrosis (RN) is a challenging potential complication of cranial radiation therapy. Believed to result from a complex interplay of vascular, glial, and immunologic factors, the exact mechanism of RN remains unclear. Patients who develop RN typically have a history of treatment with stereotactic radiation surgery or some other form of radiation-based therapy. The time frame for its development is variable, but it most often occurs one to three years following radiation therapy. Reported treatment doses capable of inducing radiation necrosis are variable, with higher doses per fraction more likely to induce RN. Furthermore, RN remains a challenging diagnosis for clinicians to make, as its presentation is often nonspecific and imaging studies might not clearly differentiate RN from tumor recurrence or pseudoprogression. RN is initially managed with corticosteroids, followed by bevacizumab, surgical resection, or laser interstitial thermal therapy if symptoms persist. In this review, we examine the literature regarding pathophysiology, incidence, imaging characteristics, and management strategies for radiation necrosis.

Radiotherapy in combination with systemic therapies for brain metastases: current status and progress.

Brain metastases (BMs) are the most common cause of intracranial neoplasms in adults with poor prognosis. Most BMs originate from lung cancer, breast cancer, or melanoma. Radiotherapy (RT), including whole brain radiotherapy (WBRT) and stereotactic radiation surgery (SRS), has been widely explored and is considered a mainstay anticancer treatment for BMs. Over the past decade, the advent of novel systemic therapies has revolutionized the treatment of BMs. In this context, there is a strong rationale for using a combination of treatments based on RT, with the aim of achieving both local disease control and extracranial disease control. This review focuses on describing the latest progress in RT as well as the synergistic effects of the optimal combinations of RT and systemic treatment modalities for BMs, to provide perspectives on current treatments.

82Rubidium chloride positron emission tomography discrimination of recurrent intracranial malignancy from radiation necrosis.

Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride (82RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy. Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain 82RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain 82RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. 82RbCl PET time activity curve analysis was performed which comprised lesion SUV<inf>max</inf>, contralateral normal brain SUV<inf>max</inf>, and tumor to background ratios (TB<inf>max</inf>). 82RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of 82RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUV<inf>max</inf> compared to radiation necrosis, no statistically significant difference between lesion SUV<inf>max</inf> nor TB<inf>max</inf> was found (P>0.05). 82RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Clinical Perspectives in Brain Metastasis.

Brain metastases (BMs) are responsible for decline in neurological function, reduction in overall quality of life, and mortality from recurrent or untreatable lesions. Advances in diagnostics and imaging have led to increased detection of central nervous system (CNS) metastases in patients with progressive cancers. Improved control of extracranial systemic disease, and the limited ability of current therapeutics to cross the blood-brain barrier (BBB) also contribute to the increase in incidence of brain metastases, as tumor cells seek refuge in the brain. Surgery, chemotherapy, and/or radiation (whole-brain radiation therapy and stereotactic radiation surgery [WBRT/SRS]) are a clinically established treatment paradigm for patients with brain metastases. With the advent of genetic and molecular characterization of tumors and their immune microenvironment, clinical trials seek to include targeted drugs into the therapeutic regimen for eligible patients. Several challenges, like treatment of multiple CNS lesions, superior uptake of chemotherapy into the brain, and trials with multidisciplinary approaches, are now being clinically addressed.

Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death

To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS. Irradiation with doses higher than approximately 10Gy/fraction causes significant vascular injury in tumors, leading to secondary tumor cell death. Irradiation of tumors with high doses has also been reported to increase the antitumor immunity, and various approaches are being investigated to further elevate antitumor immunity. The mechanism of normal tissue damage by high-dose irradiation needs to be further investigated. In addition to directly killing tumor cells, high-dose irradiation used in SBRT and SRS induces indirect tumor cell death via vascular damage and antitumor immunity. Further studies are warranted to better understand the biological mechanisms underlying the high efficacy of clinical SBRT and SRS and to further improve the efficacy of SBRT and SRS.